Drugs Flashcards

Question 1

Q

Albumin-bound sirolimus (Fyarro)

Answer

A

Sarcoma

Perivascular epithelioid cell tumors

Dose reduce for hepatic impairment

DLT: mucositis/stomatitis

Question 2

Q

Atezolizumab (tecentriq)

Answer

A

Sarcoma, bladder (first-cisplatin ineligible PD-L1 cps >5% or second line), melanoma, NSCLC PD-L1 >/=1%, SCLC, HCC (with bev)

Alveolar soft part sarcoma

Anti-PDL-1 antibody

ADR: severe life threatening immune mediated rxn, infusion rxn-premeditate

Question 3

Q

Avapritinib (Ayvakit)

Answer

A

Sarcoma-NEOADJUVANT if resectable! Also for for metastatic unresectable GISTwith PDGFRA exon 18 mutation including D842V

Tyrosine kinase inhibitor that blocks PDGFRA and KIT D842V

-Cyp3A4 interactions
-electrolytes abnormalities with diarrhea
-take on empty stomach
-cognitive impairment: memory impairment and confusion
-brain bleeds, seizures
-300 mg daily on empty stomach

Question 4

Q

Dacarbazine (DTIC)

Answer

A

Sarcoma, HL

Alkylating agent - triazine

-renal and hepatic dose adjustment
-flu-like syndrome
-DTI: myelosuppression

Question 5

Q

Dactinomycin (actinomycin D, cosmegen)

Answer

A

Sarcoma

Antineoplastic ABX

-Max: 2500 mcg
-hepatic dose adjustment
-extravasation
DLT: myelosuppression

Question 6

Q

Denosumab (Xgeva)

Answer

A

Sarcoma

Giant cell tumor of bone: 120 mg q4weeks- first week give additional 120 mg on d8 and d15

-hypocalcemia, hypophosphatemia

Question 7

Q

Doxorubicin (adriamycin)

Answer

A

Sarcoma, bladder, uterine sarcoma, endometrial, breast, AML, ALL, DLBCL, BL, HL, MM, thyroid, SCLC

Anthracycline, topo-2 inhibitor (cell cycle specific)

-Lifetime dose: 450 mg/m2
-emetogenicity
-high: >60mg/m2
-moderate: <60mg/m2
-LVEF before/during/after tx
-radiation recall skin rxn
-extravasation-WORST VESICANT!
-dose reduce for hepatic impairment-for bili 1.2 or more
-can stain urine and contact lenses for 24 hours after last dose
-DLT: myelosuppression, cardiomyopathy , hepatotoxicity

-hyperbaric oxygen therapy is contraindicated

Question 8

Q

Pegylated Doxorubicin liposomal (doxil)

Answer

A

Kaposi sarcoma, recurrent gyn CA, breast

-20 mg/m2 q21d
-LVEF prior to use
-monitor hepatic function
-DLT: hand foot syndrome- more than conventional!
-do not sub for conventional on mg per mg basis
-less cardio toxicity than conventional
-not a vesicant like normal doxorubicin
-infusion reactions

Question 9

Q

Eribulin (halaven)

Answer

A

Sarcoma, breast cancer

Microtubule inhibitor

Breast: metastatic after 2+ linesof therapy (like trabectedin) including anthracycline
-soft tissue liposomal (NOT LMS) sarcoma- refractory to 2+ regimens

-renal and hepatic adjustment
-QTc
-peripheral neuropathy
-electrolyte abnormalities
-DLT: myelosuppression

Question 10

Q

Entrectinib (Rozlytrek)

Answer

A

TRK inhibitor, also inhibits ROS1 and ALK

NTRk gene fusion positive: sarcoma(GIST), met breast, NSCLC (NTRK or ROS1), recurrent ovarian, thyroid, pancreatic, gastric/esophageal (rare), colorectal (NRTK +)

-QTc, cardiac ADRs
-better CNS penetration than larotrectenib so better for CNS tumors
-increased CNS toxicity
-Edema
-pain withdraw
-hematologic toxicity
-capsules only

Adults and peds 12+ y/o (larotrectinib doesn’t have age minimum)

Question 11

Q

Gemcitabine (gemzar)

Answer

A

Sarcoma, non-muscle invasive bladder ca, ovarian, cervical , breast, R/R NHL, HL, head/neck, NSCLC, SCLC, biliary tract, pancreatic

Antimetabolite (pyramidine analog),

-Fixed dose infused over 10 mg/m2/minute- (sarcoma) increase in retention but more toxicity so we don’t use it!- although it is used, at least with sarcomas

-DLT: myelosuppression, thrombocytopenia!
-rarely- TTP, hepatic uremic syndrome
-flu-like symptoms

Cell cycle specific (mostly s)

“The cytarabine of solid tumors”

Usually over 30 mins- fast phosphylation and cellular uptake- DONT GIVE LONGER LIKE ANNA SMH, increases cellular retention and toxicity

Hepatotoxicity- hematologically safe in hepatic impairment but may cause added hepatotoxicity

Question 12

Q

Ifosfamide (ifex)

Answer

A

Sarcoma, testicular, uterine sarcoma, R/R NHL, HL

Alkylating agent- nitrogen mustard

-DLT: hemorrhagic cystitis (acrolein)
-hydrate 2-3L/Day, IVF NS not D5W!!
-ALWAYS WITH mesna: 60-100% dose of ifos, cont 12-24 hr after ifos
-daily urine samples
-neurotoxicity- d/t chloracetaldehyde 2-48 hr after infusion- pretreat with albumin. STOP infusion if it happens and give methylene blue
-note: monitor electrolytes especially sodium to decrease risk of neurotoxicity (ifos can cause siadh)
-Avoid with aprepitant and fosaprepitant
-cardiotox at very high doses
-renal tubular acidosis- tx with sodium bicarb or sodium acetate based fluid

Cell cycle non-specific

Question 13

Q

Imatinib (gleevec)

Answer

A

Sarcoma, ALL, CML (1st line chronic phase), melanoma

BCR-ABL TKI- gen 1

-400 mg daily->inc to BID
-800 mg: KIT exon 9 mutation

With food and large glass of water

-3A4 substrate
-3A4 and 2D6 inhibitor (like nilotinib)

Question 14

Q

Larotrectinib (vitrakvi)

Answer

A

TRK inhibitor

Sarcoma-gist, breast cancer, recurrent ovarian, thyroid
TRK inhibitor, TKI, NSCLC, pancreatic, gastric/esophageal (rare), colorectal (NTRK+)

-CNS penetration
-hematologic toxicity
-pain withdraw
-capsules and oral solution

Adults AND pediatrics (note that for entrectinib must be 12+ y/o)

Question 15

Q

Methotrexate (MTX)

Answer

A

Pyrimidine analog
Sarcoma, CNS tumors, bladder, breast, AML, ALL, BL, DLBCL, CNS ppx (HD and IT), MCL (hyperCVAD)

Antimetabolite- pyramidine analog- cell cycle specific

-large VD- delayed clearance
-avoid in ascites, edema, pleural effusions (if must be given use prolonged leucovorin until completely cleared)
-nephrotoxicity- via crystallization-renal tubule necrosis (do urinary alkalinization and hydration, 2-3 L/m2/day)
-hepatotoxicity (bump in LFTs is normal and ok)
-mucositis-prevent w/ leucovorin
-myelosuppression- prevent w/ leucovorin
-neurotoxicity 10-14 d after, seizures/stroke like symptoms
-DI: bactrim (HOLD FOR PJP PPX UNTIL MTX CLEARED, cipro, thiazides, salicylates, NSAIDs, PCNs (including cephalosporins), PPIs- can delay clearance, vit C, phenytoin, tetracycline
-high dose: leucovorin rescue, hydration (minimum rate 100 mL/hr) goal UOP 100 mL/hr, urinary alkalinization- ph > 7 (bicarb in IVF or acetazolamide if fluid overloaded)- prevents precipitation
-continue hydration/urine alkalinization x3 day after lvls good

-lvls drawn 24, 48, 72 hr post dose and should be <5 or 10?, <1, and <0.1 respectively

Note: once weekly dose is for RA not cancer

MTX is hydrophilic (need high doses to cross BBB)

Bac to siping thias, saliciting PPIs, I NSAID what I said and it ain’t PCN, like vitamin C, phenytoin, tetracycline

Hold x1 day: cipro (only 1 sip of death)
Hold x2 day: bactrim, thiazides (2 thighs and 2 sides of back)
Avoid if possible, if take me Hold day of: PPI, PCN, NSAID
Hold 10 days: salycilate (unless Asa 81 mg, hold day of

Question 16

Q

Pazopanib (Votrient)

Answer

A

Sarcoma, kidney, recurrent uterine leiomyosarcoma

Catch all for NON-LIPO sarcoma

TKI, VegF inhibitor, PDGFR a and b, c-KIT

-empty stomach (1hr before, 2hr after)
-DI:
-acid reducing agents
-Cyp3A4
-QTc

ADRs: nausea, diarrhea, HTN, HA, low blood cell counts, hair color change, *hepatotoxicity!!!, bleeding, clotting, wound healing, arrhythmia

DLT: HTN, diarrhea, hepatotoxicity (caution with simvastatin)

Question 17

Q

Pembrolizumab (keytruda)

Answer

A

Sarcoma, bladder (first-cisplatin ineligible PD-L1 cps >10% or second line (cat 1 for OS benefit)), kidney, prostate if MSI high or dMMR dx and progressed through docetaxel and novel HT, testicular 3rd line MSI-H/dMMR or TMB-H, cervical, endometrial , breast (high risk early stage TNBC, R/R HL, melanoma, head/neck, NSCLC, SCLC, HCC, biliary tract, pancreatic, gastric/esophageal, SCC, colorectal

Anti-pd1 antibody

-severe life threatening immune related ADRs

Question 18

Q

Pexidartinib (turalio)

Answer

A

Sarcoma-250 BiD- take with food, LOW fat meal

Reduces symptoms but does NOT cure!

TKI against CSF1 receptors.

-adult symptomatic tenosynovial giant cell tumor (TGCT)- severe and not. Amenable to improvement w/ surgery
-BBW: hepatotoxicity (DLT)- REMS!
-ADR: ocular issues, fatigue, high cholesterol, hair discoloration, dyguesia
-DI: Cyp3A4, PPI

Question 19

Q

Regorafenib (stivarga)

Answer

A

Sarcoma, CNS tumors, HCC, colorectal

TKI, VEGF

-dermatological toxicity
-hand foot syndrome
-hepatotoxicity
-wound healing
-photosensitivity
-HTN
-fatigue
-diarrhea
-mucositis

Question 20

Q

Ripretinib (Qinlock)

Answer

A

Sarcoma

KIT inhibitor, PDGFR-alpha blocker, TKI

-monitor BP
-echo or MUGA prior and during tx
-cyp3A4 interactions

Question 21

Q

Tazematostat (tazverik)

Answer

A

Sarcoma, R/R FL after 2 prior therapies (irrespective of EZH2 mutation)

Need EZH2 mutation

EZH2 inhibitor, HMT inhibitor

-epithelioid sarcoma not eligible for complete resection- 800 mg BID
-cyp3A4 interactions
-need INI-1 loss

Pain, fatigue, nausea, decreased appetite, vomiting, diarrhea, constipation

Weak cyp3A4 inducer

Cyp3A4 and pgp substrate

Question 22

Q

Temozolomide (temodar)

Answer

A

Sarcoma, CNS tumors, melanoma (last line of CNS Mets), SCLC, pancreatic in PNET

Alkylating agent- triazine

-100% bioavailability
-crosses BBB
-myelosuppression
-lymphopenia!!
-skin rash
-peripheral edema
-fatigue!!
-constipation
-mod-highly emetogenic

-give at bedtime with 5HT3 blocker
-pjp ppx needed if given w/ RT

Question 23

Q

Trabectedin (yondelis)

Answer

A

Sarcoma- myxoid liposarcoma and leimyosarcoma (unlike Eribulin which only covers liposomal NOT LMS)- after 2 lines of therapy, recurrent uterine LMS, platinum resistant ovarian CA

Alkylating agent

-premeditate dex 20 mg iv to prevent hepatotoxicity
-premeditate zofran 16 mg iv (CINV)
-monitor cpk and alkphos prior to each dose
-rhabdo- check cpk. >2.5 ULN hold x3 wks, >5 ULN hold x3 wks then dose reduce
-LVEF (echo): BL and q2-3 mo
-LFTs and bili prior to each cycle
-vesicant!
-24h cont infusion for sarcoma

Question 24

Q

Vinorelbine (navelbine)

Answer

A

Sarcoma, breast, NSCLC, SCLC

Vinca alkaloid, antimicrotubule

-cell cycle specific
-vesicant - central line
-give in mini bag
-neurotoxicity
-peripheral neuropathy
-hepatic adjustment
-myelosuppressive
-constipation- BR

Question 25

Q

Soft tissue sarcoma chemo regimen

Answer

A

First line: doxorubicin + ifosfamide

Second line: Gemcitabine + docetaxel

Question 26

Q

Angiosarcoma chemo regimen

Answer

A

Docetaxel/Paclitaxel + vinorelbine

Question 27

Q

Sunitinib (Sutent)

Answer

A

Sarcoma- GIST second line, kidney, pancreatic in PNET

TKI- VEGF 1, 2, and 3 inhibitor, PDGFR a and b, c-KIT, FLT-3, CSF-1R, RET

ADRs: Nausea, diarrhea, skin/hair color changes, mouth sores, weakness, low wbc/rbc,, HTN, CHF, bleeding, hand/foot syndrome, low thyroid hormone, taste changes

Question 28

Q

Bevacizumvab (avastin)

Answer

A

VEGF inhibitor

CNS tumors, clear cell RCC (rarely), frontline/recurrent ovarian and cervical, recurrent endometrial, non-squamous cell NSCLC, HCC, colorectal

-impaired wound healing-hold for 6 weeks before and 6-8 weeks after surgery (not including port-A-Cath)
-bleeding !
-clotting- avoid if stroke hx
-nephrotic syndrome- hold for urine protein 2+ and do 24hr urine collection
-GI perforation
-HTN! HTN does NOT preclude people from getting bevacizumab especially if it’s controlled
-proteinuria- okay if scr is fine

-tracheoesophageal fistula

Question 29

Q

Carboplatin (paraplatin)

Answer

A

CNS tumors, bladder, testicular AUC 7 x1- only time AUC 7 is used, ovarian, endometrial, cervical, Breast, RR NHL, HL, head/neck, NSCLC, SCLC, gastric/esophageal

Alkylating agent

-nausea
-pancytopenia
-fatigue
-renal toxicity
-DLT: thombocytopenia
-use instead of cisplatin if SIADH

Question 30

Q

Carmustine (BiCNU)

Answer

A

CNS tumors

Alkylating agent- nitrosourea

-nausea
-fatigue
-thrombocytopenia
-lymphopenia
-pulmonary toxicity

-equivalent to lomustine but IV so less preferred
-wafer rarely ever used
-great BBB permeability

Question 31

Q

Cisplatin (platinol)

Answer

A

CNS tumors, bladder, cervical, breast, HL, NHL, MM, head/neck, NSCLC, SCLC, biliary tract, pancreatic, gastric/esophageal

-N/V- biphasic
-nephrotoxicity-hydrate with NS only
-ototoxicity
-neuropathy!
-infertility! (Testicular cancer >400 mg/m2)
-highly emetogenic
-Thrombocytopenia
-relative lack of myelosuppression
-less tolerated than Carboplatin
-do not give if crcl< 30
-50% dose reduce for crcl 30-60
-use carbo instead if SIADH

-Hydrate with NS and can use forced hydration with loop diuretic or mannitol
-mannitol only shown benefit with cycle 1 and overall not compelling evidence, and diuretics don’t have convincing data to recommend
-supplemental k and mg- electrolyte wasting d/t renal tubule damage
-Amifostine to decrease nephrotoxicity, don’t use if good chance of survival advantage

Question 32

Q

Cyclophosphamide

Answer

A

CNS tumors, breast, AML, ALL, CLL with Fludarabine and rituximab
-lymphomas: DLBCL, Burkitts, PMBL, HL, indolent lymphomas, MM, SCLC

Alkylating agent- nitrogen mustard

-N/V
-myelosuppression
-mucositis
-hemorrhagic cystitis- hydrate, give with Mesna if:
-BMT
-hyperCVAD- 1.8 g/m2
-renal dysfunction
-immunosuppressant
-SIADH
-nasal congestion if given too fast

Prodrug activated by liver
-caution w/ dose adjustments, not clear

Cell cycle non-specific

Nadir d7-12 (a bit earlier)

DI:
-inducers may increase bio activation and increase toxicity
-3A4 inhibitors

Question 33

Q

Etoposide (Vepsid, VP-16)

Answer

A

CNS tumors, recurrent ovarian, AML, DLBCL, PMBL, BL, HL, MM, NSCLC, SCLC

Topoisomerase II inhibitor, epipidophylotoxin

-hypotension- slow infusion
-DLT-myelosuppression
-N/V- low-mod
-secondary malignancy AML

There is a PO option - very erratic absorption

Cell cycle specific

non-PCV bag and low sorting infusion set

Works in G2 (like bleomycin) phase and S phase of cell cycle

Question 34

Q

Irinotecan (camptosar)

Answer

A

CNS tumors, SCLC, pancreatic, gastric/esophageal, colorectal

Topoisomerase I inhibitor -camptothecan

Prodrug- SN38 is active metabolite

ADRs:
-diarrhea (acute within 24hrs d/t cholinergic storm- tx w/ atropine, late >24h tx w/ loperamide)
-pancytopenia/neutropenia!!
-nausea/vomiting is big
-fatigue
-does NOT cause hypotension
-myelosuppression is big

-Cell cycle specific
-Smoking decreases activity (at least toxicity and likely efficacy)
-Use 70% of standard dose if know HOMOZYGOUS UGT1A128*

-3A4 substrate- CI with inhibitors (don’t ignore this!!)

Don’t use with Gilbert’s dx

There is a liposomal form

Fun fact: bacterial in gut can convert irinotecan back to active for- so if refractory diarrhea could try cephalosporin/FQ could help

Glucuronidated in liver to SN38G which is eliminated via biliary excretion into GI tract, however can be deactivated back to SN38 here

Question 35

Q

Leucovorin

Answer

A

MTX rescue therapy- rescues healthy cells- GIVE WITHIN 42 HOURS! But usually started 20-24 hours after start of MTX

Should prevent mucositis and neutropenia

Rescue: 15 mg/m2 iv starting 24h after starting MTX- may end up needing much higher doses

Required for MTX>500 mg/m2 (HD-MTX) but consider for 100-500 mg/m2

IV to PO is 1:1 unless at higher doses like >35 mg

Used until MTX <0.1

Don’t give within 2hr of glucarpidase. Also, first 48h after glucarpidase use pre glucarpidase luecovorin dose- then dose leucovorin base on MTX lvls

Also used to enhance activity of 5FU- allows it to bind to target enzyme better- IV over 2 hours (not PO)

-also levoleucovorin which is usually used if leucovorin is not available (dosed at 50% of leucovorin dose)

Question 36

Q

Lomustine

Answer

A

CNS tumors

Alkylating agent- nitrosourea

-oral so preferred over carmustine
-nausea
-fatigue
-thrombocytopenia
-lymphopenia
-pulmonary toxicity
-dispense 1 RX at a time to avoid patient overdose possibility
-prolonged nadir 4-6 wks

-give at night with 5HT3 blocker
-great BBB permeability

Question 37

Q

Procarbazine

Answer

A

CNS tumors, HL

Alkylating agent- methylhyderazine

-PO
-MAO-I activity- seratonin syndrome- beware DIs, low tyramine diet and x1 week after taking drug
-nausea-give at night with 5HT3 blocker
-rash

Question 38

Q

Rituximab

Answer

A

B cell Lymphomas- DLBCL, PMBL, BL, CNS lymphoma, chronic leukemias, indolent lymphomas (FL, MCL, MZL, WM)

-infusion rxn- (fever, chills, rigors, changes in BP)- most commons with first dose- don’t stop infusion, slow it down
-hypersensitivity rxn (chimeric mAb) but this is quite rare
-hep b reactivation
-PML- due to long immunosuppression
-can decrease efficacy of vaccines
-risk IgM tumor flare in WM- caution if high IgM (>4000)
-rapid infusion- if tolerated start with cycle 2- over 90 minutes (20% in 30 mins and 80% over next 60). Don’t do
If CV dx or lymphocyte count >5000.

Question 39

Q

Teniposide (vumon, VP-26)

Answer

A

CNS tumors

Topoisomerase II inhibitor - epipodophyllotoxin

-Myelosuppression
-mucositis
-N/V
-diarrhea
-hypotension!

Not used for glioma

Works in G2 (like bleomycin) phase and S phase of cell cycle

Question 40

Q

Vincristine (oncovin)

Answer

A

CNS tumors, mostly just hematologic CAs, also ITP, ALL, DLBCL, PMBL, BL, HL, indolent lymphomas, SCLC

Antimicrotubule

-cell cycle specific
-neuropathy- can be reversible!
-constipation-DLT (autonomic neuropathy)!
-NOT myelosuppressive!
-hepatic-dose reduce for elevated bili
-3a4 interactions- fluconazole ok but other azoles interact
-SIADH-hyponatremia
-CI in Charcot Marie tooth disease

-Vocal cord palsy: tx with pyridoxime or pyridostigmine
-jaw pain, trigeminal neuralgia
-Veno-occlusive dx

Question 41

Q

Glucarpidase

Answer

A

Tx of toxic MTX levels with evidence of new renal impairment - 48-60 hrs from start of MTX infusion

Continuous infusions
-36h level>30
-42h level>10
-48h level>5

Infusions over <6h
-24h level >50
-36h level>30
-42h level >10
-48h level >5

you still need leucovorin for intracellular MTX- glucarpidase only eliminates extra cellular MTX

*and scr must be elevated (50%+ increase from BL)

hour markers a measured from the *start of the MTX infusion

-don’t give leucovorin within 2 hours
-don’t repeat glucarpidase within 48 hours of first dose
-immunoassay for MTX lvls are inaccurate for 48 hrs after glucarpidase.

Question 42

Q

Avelumab (bavencio)

Answer

A

Bladder, kidney, metastatic merkel cell carcinoma
PD-L1 inhibitor

Bladder- second line for maintenance following platinum based chemo could become SO

Downside: dosed twice weekly, requires premeds when initiating therapy

Question 43

Q

BCG (Tice BCG)

Answer

A

Biological response modulator (similar to IL-2)- need intact immune system-no immunosuppressants

Non-muscle invasive bladder cancer

Given intravesically

Used as induction and maintenance x1-3 yrs for high risk

Give at least 7-14 d after TURBT- to avoid systemic absorption and BCG sepsis (tx with anti-tuberculosis therapy)

Flu-like symptoms (after 3rd dose)- give APAP/NSAIDs, dysuria, bladder spasms (oxybutynin/tolterodine, hematuria (hold until resolution), allergic rxn (H1 ppx), exposure precautions x48hrs

Don’t use in people w/ infections on ABX

Compound separately from other IV and use containment device or respiratory protection

Exposure precautions- caution when voiding x48h, wash hands if urine on them, bleach in toilet before flush

NOT used preoperatively

Question 44

Q

Docetaxel (Taxotere)

Answer

A

Antimicrotubule

Cell cycle specific

Bladder, prostate (with pred), gyn, breast, head/neck, NSCLC, SCLC, gastric/esophageal

DLT: neutropenia, neuropathy, (less than paclitaxel)

ADRs: tearing, edema (give steroids!!)myalgias, more neutropenia than paclitaxel, skin rxns, irritant

-Dose reduce for hepatotoxicity!
-3A4 substrate
-Dex 8 mg BID x3 d starting the day before
-controversy over dose in Asians

Other:
-inflammatory moa
-free radicals (stop vit C)

Question 45

Q

Enfortumab vedotin (Padcev)

Answer

A

Antibody drug conjugate - antimicrotubule

-Nectin-4 targeting antibody-drug conjugate with MMAE payload
–MMAE (antimicrotubule)

Metastatic Bladder- 1st line with pembro
-second line: post ICI and cisplatin ineligible

ADRs: skin reactions/ rash, pruritis, neuropathy, hyperglycemia (DKA), ocular toxicity (eye exam), diarrhea

Loperamide prn, fragrance free lotion, ppx artificial tears, blood glucose monitoring

Question 46

Q

Erdafitnib (Balversa)

Answer

A

FGFR inhibitor

Metastatic Bladder-FGFR/FGFR2 mutations and progressed on at least 1 line of platinum therapy (second line )

eye disorders

Question 47

Q

Mitomycin (mutamycin, jelmyto)

Answer

A

Anti tumor antibiotic

Bladder-NMIBC, MIBC if w/ 5-fu + RT

Question 48

Q

Nadofaragene firadenovec-vngc
(Adstiladrin)

Answer

A

Gene therapy- intravesical

High risk BCG unresponsive NMIBC w/ Cis w/ or w/o papillary tumors

Delivers gene copy to bladder lining that encodes interferon-Alfa 2b that stimulates immune system to attack

Question 49

Q

Nivolumab (Opdivo)

Answer

A

Bladder, kidney, R/R HL, HL, melanoma, head/neck, NSCLC, SCLC, HCC, gastric/esophageal, colorectal (dMMR/MSI-H or POLE/POLD1)

Immune checkpoint inhibitor -PD-1 inhibitor

Bladder-2nd line, no PDL1 required

Give first

Nivo 1 mg/ ipi 3 mg (could consider reverse to decrease ADR)

For melanoma follow with nivo maintenance (240 mg q2wk or 480 mg q4wk)

Question 50

Q

Penbrolizumab (Keytruda)

Answer

A

PD-1 inhibitor

Bladder- 1st line for platinum ineligible, or 2nd line, other indications

Question 51

Q

Sacituzumab govitecan (Trodelvy)

Answer

A

Antibody drug conjugate- SN38 (active metabolite of irinotecan) payload is topo-I inhibitor- targets trop-2

Bladder/ mUC after platinum and IO

-1) Refractory metastatic TNBC after 2 lines or 2) metastatic HR+ HER2- endocrine refractory dx or visceral crisis ( not HER2 low-l). Used instead of fam-trastuzumab if not HER2 low

-Treat diarrhea with loperamide

Increased risk neutropenia with ugt1A1*28

Question 52

Q

Vinblastine

Answer

A

Antimicrotubule

HL, bladder

-cell cycle specific

Myelosuppression

Increases cisplatin ototoxicity

Question 53

Q

Durvalumab

Answer

A

PD-L1 inhibitor

Bladder- second line, NSCLC, SCLC, cholangiocarcinoma, HCC

Question 54

Q

Trilaciclib

Answer

A

CDK 4/6 inhibitor

Myelosuppression prevention-given before platinum/etoposide containing regimens or a topotecan regimen for ES-SCLC

Question 55

Q

Defibrotide

Answer

A

Treats Veno-occlusive dx which is emergency type of hepatotoxicity often caused by drugs that have ozagamicin

Gemtuzumab ozagamicin
Inotuzumab ozagamicin

VOD usually happens in first 3 weeks after transplant

Question 56

Q

Brigatinib (Alunbrig)

Answer

A

ALK inhibitor, ROS-1

Sarcoma, NSCLC-ALK

ADRs: fatigue, constipation, edema, myalgia, visual disturbance, pneumonitis, GI toxicity, hepatotoxicity, bradycardia, QTc, ILD

-early pulmonary toxicity- dose titration: 90 mg QD x7 d—> 180 mg QD
-CNS penetration

Question 57

Q

Crizotinib (Xalkori)

Answer

A

ALK inhibitor, ROS1

Sarcoma, NSCLC- ALK/ROS1, MET exon 14 skipping mutation

ADRs: fatigue, constipation, edema, myalgia, visual disturbance, pneumonitis, GI toxicity, hepatotoxicity, bradycardia, QTc, IL, low testosterone

-moderately emetogenic
-renal dose

Question 58

Q

Lorlatinib (Lorbrena)

Answer

A

ALK inhibitor

NSCLC- ALK, ROS1

ADRs: fatigue, constipation, edema, myalgia, visual disturbance, pneumonitis, GI toxicity, hepatotoxicity, bradycardia, QTc, ILD

-MOST CNS penetration
-CNS ADRs (nightmares, hallucinations, depression)
-NEUROPATHY
-hypercholesterolemia- tx with statins don’t dose reduce
-weight gain

-option for resistant mutations: ALk G1202R, L1196M, (except compound L1196M/G1202R)

Question 59

Q

Axitinib (Inlyta)

Answer

A

Kidney

TKI- VEGF inhibitor

ADRs: HTN, fatigue, N/V/D, poor appetite/wt loss, voice changes, hand/foot syndrome, constipation. HTN, bleeding, clotting, wound healing, lfts, hypothyroidism

Short t1/2: quick onset of large dx burden and quick offset if ADRs

Question 60

Q

Belzutifan (welireg)

Answer

A

Von-hippel-lindau (VHL) associated RCC after PD-L1 and VegF

Also VHL associated: CNS hemangioblastoma, pancreatic neuroendocrine tumors

Hypoxia inducible factor inhibitor

ADRs: anemia (hold for Hgb<8), fetal embryo toxicity, fatigue, dyspnea, nausea, HA, hyperglycemia, hypoxia

3A4 Enzyme Inducer- birth control failure!

Question 61

Q

Cabozantinib (cabometyx- tablets) ( cometriq- capsules)

Answer

A

Kidney, thyroid, HCC (2nd line)

TKI- VEGF inhibitor, MET, AXL, RET

ADRs: N/V/D, diarrhea, fatigue, poor appetite/ wt loss, HTN, hand/foot syndrome, constipation. Bleeding, clots, intestinal perforation, fistulas
-hold 3 weeks before and 2 weeks after surgery (wound healing)
-mod-high emetogenic
-empty stomach
-higher risk of hand/foot syndrome than other VEGF inhibitors

Thyroid:
Tablets (cabometyx-140 mg QD) and capsules (cometriq- 60 mg QD) are not interchangeable

Question 62

Q

Everolimus

Answer

A

Kidney, recurrent endometrial (w/ letrozole), breast cancer, WM, pancreatic

mTOr kinase inhibitor

ADRs: immunosuppressive, mouth sores (use dex mouthwash), nausea, loss of appetite, rash, diarrhea, fatigue, edema, hyperglycemia, hypercholesterol. Rare lung damage
DLT: mucositis- use dexamethasone mouth rinse (solution NOT elixir- (etoh free)) QID no food within an hour

NOT hand/foot syndrome

Question 63

Q

IL-2

Answer

A

Kidney Ca

Rarely used d/t AE and better therapies available

*need excellent PFS and good renal function

Question 64

Q

Ipilimumab (Yervoy)

Answer

A

Kidney, Melanoma, NSCLC, HCC, -colorectal (if dMMR/MSI-H, or POLE/POLD1. Only in combo with nivo)

Immune checkpoint inhibitor- anti CTLA4 mAb

First FDA approved ICI

Answer 65

A

Kidney, recurrent endometrial, melanoma, thyroid, HCC, biliary tract

TKI- VEGF 1, 2, and 3 inhibitor; FGFR 1, 2, 3, and 4 inh, PDGFRa; c-KIT, and RET

ADRs: , diarrhea, N/V/D, proteinuria, fatigue, decreased appetite. joint/muscle pain, swelling of arms/legs. Bleeding, clots, severe HTN, intestinal perforation, kidney/liver/heart failure, hypothyroid, mucositis, hypocalcemia
-voice hoarseness (reversible and not dose related)
-mod-high emetogenic- GIVE with ANTIEMETIC
-hold 1 wk before and 2 wks after surgery (wound healing)

Answer 66

A

-Kidney- historically used but not anymore except certain circumstances
-Thyroid
-HCC cat 1

TKI- VEGF inhibitor, FLT-3-ITD, RET

ADRs: fatigue, rash, diarrhea, HTN, hand/foot syndrome, cardiotoxicity, LFTs, QTc, wound healing impairment, bleeding
-empty stomach

Answer 67

A

Kidney- historically used but now only under certain circumstances, endometrial

mTOR kinase inhibitor

ADRs: mouth sores, rash, nausea, loss of appetite, edema in face/legs, hyperglycemia, hypercholesterol,

Answer 68

A

Kidney- after 2 prior therapies

TKI-VEGF inhibitor- blocks all three VEGF receptors, c-KIT, PDGFR-beta

ADRs: nausea, diarrhea, HTN, poor appetite, cough, mouth sores, fatigue, voice changes, bleeding, clotting, wound healing, thyroid, kidney, heart problems, allergy to excipient (yellow 5)

3A4 substrate

Answer 69

A

Prostate- only for de novo metastatic dx

Anti-androgen

mCSPC and mCRPC

Give with prednisone:
-non-metastatic: once daily
-mCSPC: 5 mg PO daily
-mCRPC: 5 mg PO Twice daily

500 mg fine particle formulation=1000 mg of original- give w/ Methylprednisolone 4 mg BID

Food affects absorption: 1000 mg give on empty stomach, 250 mg give with breakfast

Adrs: hepatotoxicity, HTN, hyper/hypoglycemia

caution if cardiac history

Answer 70

A

Prostate

Antiandrogen

m0CRPC (delays mets), m1CSPC

240 mg PO daily

ADR:
-crosses BBB- falls, seizures. This is CLASS EFFECT
-diarrhea, rash, hypothyroidism, HTN, fractures

Drug interaction! Inducer!!!

Answer 71

A

Prostate

Antiandrogen

No monotherapy- use with LHRH agonist or antagonist to prevent tumor flare

ADR:
-class effect- crosses BBB: falls, seizures, diarrhea

Answer 72

A

Prostate (give with pred or dex)

Taxane- antimicrotubule

m1CRPC, must try docetaxel first

20 mg/m2 standard- if 25 mg/m2 give with G-CSF

Less fatigue and asthenia than docetaxel

DIARRHEA, and FN (intermediate)

Contains polysorbate 80 and ethanol

Non-PCV and low sorting infusion set

Premeds: steroid, h1, h2

Answer 73

A

Prostate- m0CRPC, m1CSPC with docetaxel

Antiandrogen

m0CRPC, evidence for triple therapy for newly diagnosed, de novo metastatic, high risk/volume CSPC

Different from enazalutamde and apalutamide- different structure

Reduced CNS toxicity- doesn’t cross BBB penetration- less fatigue and falls

May be more effective in long run-works against mutated receptors

Give with food!

Less drug interactions: weak inducer

Renal and hepatic dose adjustment

600 my BID with food

HTN

Only one that is TWICE DAILY

Answer 74

A

Prostate

GnRH antagonist - SubQ, monthly

Cornerstone of therapy- continue throughout dx regardless of progression

Monthly injections

Adrs:
-inj site rxns- can be pretty nasty
-anaphylaxis
-hot flashes
-metabolic syndrome

Preferred over LHRH agonist when tumor flare is big concern (spinal cord compression/injury)- no need for antiandrogen

Achieved castration in <7d, unlike 28 days for agonist

Monthly only- LHRH agonists can be given much less often depending on dose

May have cv benefit over LHRH agonists in pts with high cv risk

Answer 75

A

Prostate

Anti-Androgen

m0CSPC, m0CRPC, m1CRPC, m1CSPC

CNS ADRs: falls, seizures, HTN, fractures

Drug interactions! Inducer!

160 mg daily

Answer 76

A

Prostate, breast

GnRH agonist

Prostate: Cornerstone of therapy and should be continued throughout dx course regardless of progression

Breast: premenopausal with AI of tamoxifen for ovarian suppression

Adrs:
-tumor flare (bone pain, urinary sx)
-hot flashes
-metabolic syndrome

give with first gen antiandrogen for first few weeks

-SubQ

Answer 77

A

discontinued by manufacturer

Prostate

GnRH agonist

Cornerstone of therapy and should be continued throughout dx course regardless of progression

Adrs:
-tumor flare (bone pain, urinary sx)
-hot flashes
-metabolic syndrome

give with first gen antiandrogen for first few weeks

Not listed in guidelines but approved for palliative tx

Answer 78

A

Prostate, breast

GnRH agonist

Prostate: Cornerstone of therapy and should be continued throughout dx course regardless of progression

Breast: premenopausal, in combo with AI or tamoxifen for ovarian suppression

Adrs:
-tumor flare (bone pain, urinary sx)
-hot flashes
-metabolic syndrome

give with first gen antiandrogen for first few weeks

Not all leuprolide products are the same regarding formulation, dosing, and route

-SubQ, IM
-can cause hyperglycemia

Answer 79

A

Prostate

Radiopharmaceutical

PSMA-positive mCRPC previously treated with ADT and taxanes!!

ADrs: fatigue, dry mouth, nausea, anemia, kidney injury, myelosuppression, GI-constipation, infertility, embryo fetal toxicity, wt loss, radiation exposure

-Avoid close contact x3-7d
-premed w/ antiemetic

Answer 80

A

Prostate- m1CRPC- for palliation with no other tx options. QOL benefit but no OS benefit, AML

Topo-II inhibitor, anthracycline

Very cardiotoxic

Different structure from other anthracyclines so less cross resistance (why it’s used in refractory setting in AML)

Blue

Answer 81

A

PARP inhibitor

Prostate- m1CRPC with any HRRm mutation except PPP2R2A- after androgen receptor therapy, ovarian

Breast: if germline BRCA 1/2 mutation, early stage, and HER2-negative
-adjuvant x1year- started after surgery, RT and chemo (start at least 2 wks after RT)

Pancreatic- if germline BRCA mutation

Myelosuppression!!! fatigue, nausea, bowel changes (constipation)

Pneumonitis, increased scr

Drug interactions, no grapefruit

Tablets and capsules are NOT interchangeable- capsules mostly phased out of US market

With or without food

Answer 82

A

Prostate m1CRPC- symptomatic bone dx

Radiopharmaceutical

Not used often

Targets bone mets, not for visceral Mets!

IV monthly x6 months

Not just a palliative drug like some other radiopharmaceuticals

Myelosuppression!

First dose requires:
-anc >1500, plt >100, Hgb >10,
Subsequent:
-anc>1000, plt >50,

Don’t use with chemo or other drugs other than ADT and BMA- d/t additive myelosuppression

Give with BMA

Answer 83

A

NCCN states not to use with other prostate cancer meds at this time (no interaction studies- so probably better for m0CSPC- great for intermittent ADT

Prostate

GnRH antagonist

Requires loading dose, reload if stopped for >7days

Fast onset and offset- compliance is critical- don’t give if pt with poor compliance!!

Potential for less CV ADRs than leuprolide

Qtc, diarrhea

Only oral option for ADT

Used as a single agent!

no need for antiandrogen- used for pts who need ADT alone!

Dont use in combination with other prostate drugs!!

Answer 84

A

Prostate-m1CRPC w/ BRCA mutation- after androgen receptor and taxane therapy , ovarian (BRCAm)

Pancreatic- germline or somatic BRCA of PALB mutation

PARP inhibitor

Myelosuppression, fatigue, nausea, bowel changes (constipation)

-Hypercholesterolemia, elevated AST/ALT, increased scr, photosensitivity, MONTHLY CBC

Drug interactions - less than Olaparib, grapefruit ok

With or without food

Answer 85

A

Prostate

CA vaccine

Metastatic CRPC, No visceral mets, need good PFS and >6 mo life expectancy and minimal symptoms

Not used often

3 doses are given

Well tolerated

Answer 86

A

Prostate- m1CRPC- given in combination with enzalutamide for HRR+ dx

Breast: metastatic germline BRCA1/2 mutation

PARP inhibitor

ADRs:
-myelosuppression-more than Olaparib!!!!esp anemia!
-fatigue
-nausea

Oral

Dose reduce with p-gp inhibitors

Renal dose adjustment

Answer 87

A

Prostate

GnRG agonist

Cornerstone of therapy and should be continued throughout dx course regardless of progression

Adrs:
-tumor flare (bone pain, urinary sx)
-hot flashes
-metabolic syndrome

Not frequently used

give with first gen antiandrogen for first few weeks

Intramuscular

Answer 88

A

Pediatric Neuroblastoma

Anti-GD2 mAb- it’s a type of immunotherapy

10-20 hr infusion x4 days (do not exceed 20 hr infusion)

-pain- need continuous opioid infusion!, infusion rxn, hypotension, capillary leak (give with albumin), cough, ocular/visual issues, electrolyte disturbances, myelosuppression

bleeding, electrolyte abnormalities, increased risk infection, vision changes,
No pregnancy or breastfeeding, pre-meds with NS, APAP Benadryl (not dex- reduces efficacy), and antiemetics, infusion rxn, n/v

pre meds, pre-hydration, opioid infusion, albumin (keep albumin >3)

Slow infusion to increase tolerance

contraindicated with steroids

Answer 89

A

Testicular CA, Hodgkin’s lymphoma

-not myelosuppressive
-max lifetime dose of 400 units
-anaphylactiod rxn- do test dose for lymphoma (debatable) and premeds with APAP and h1!!!
-hyperpigmentation of skin
-NS only
-reynauds
-CI w/ brentuximab vedotin and w/in 24h G-CSF (debatable)
-measure DLCO- consider stopping if >25% decrease from BL (workbook says decrease of 40-60%)
-avoid if BL DLCO <75% predicted (in general DLCO >60% is acceptable)
-G-CSF- ok with testicular cancer, not ok if HL (unless BEACOPP)
-note: NCCN specifically speaks to 60% rule but doesn’t discuss how much DLCO must decrease in order to stop
-works in G2 phase of cell cycle (like topo inhibitors)
-RENAL dose adjust!!

GLYCOPEPTIDE antibiotic

Binds iron and oxygen to for free radicals and kills dna in g2

Answer 90

A

May be substituted for etoposide in patients with etoposide allergy

Equivalent doses

Answer 91

A

Platinum- alkylating agent

-Testicular CA-3rd line with gemzar
-R/R NHL, HL, pancreatic, gastric/esophageal, colorectal

-Qtc!!

-cold sensitivity- resolves in 3-5days but this can lengthen with each infusion
-peripheral neuropathy- can be permanent (related to cumulative dose)
-neurotoxicity/neuropathy- can prolong infusion to 6hr and can give ca/mg (not recommended d/t lack of evidence
-there is acute (paresthesias, dysesthesias, hypoesthesias, breathing sensation loss, etc.) and chronic PN) neurotoxicity
-neuropathy d/t oxalate metabolite chelating ca/mg and opening voltage gated ca channels
-could use heat, acupuncture, or duloxetine
-coasting- neuropathy may worse over first 3 months of discomtinuation
-PN could be permanent in some cases

Answer 92

A

Antimicrotubule

Testicular ca-second line, ovarian, endometrial, Breast cancer, head/neck, NSCLC, SCLC, gastric/esophageal

Myelosuppression- worse with 24h infusion- so we don’t do this, Less if given weekly vs q21d

DLT: Peripheral neuropathy - worse with weekly compared to q21d

Hypersensitivity rxn d/t cremephor -premed: diphen, famot, dex
-non-PVC Line w/ 0.22 micro filter bc cremephor can leach DEHP

Mild vesicant-warm v cold debatable

DI:
-increases dox when given after, so give dox—->paclitaxel
-cisplatin increases paclitaxel, so give paclitaxel —->cisplatin

Taxol syndrome- arthralgias/myalgias, likely a type of neuropathy

Cell cycle specific

Caution in liver impairment

Cremephor now called Kolliphor

Answer 93

A

Vinca alkaloid- antimicrotubule

Testicular CA

Answer 94

A

Hemorrhagic cystitis protectant agent

-always with ifos- 20% ifos dose at hr 0, 4, and 8 (for bolus doses<2.5mg/m2/d
-unless for ICE regimen you do 1:1
-for cont inf: 20% as bolus then 40% as cont inf for 12-24h after ifos completion
-sometimes with cyclophosphamide
-available PO but double the dose and it takes bad d/t sulfur moiety
-do 20% as iv at hr 0, then 40% at hr 2 and 40% at hr 6. Repeat if vomit within 2 hr (total 100%)

IV Mesna dose is equal to 60-100% of ifos dose

contraindicated in breastfeeding due to benzyl etoh

Bad taste- take with juice or something

Answer 95

A

Cardioprotectant
-generally for dox >300 mg/m2
-dose 10:1
-give 15-30 mins prior

*metastatic BC but not adjuvant d/t possible decreases efficacy

Testicular atrophy and infertility

Answer 96

A

Chemo protectant
-prevention cisplatin nephrotoxicity
-consider for decreased neutropenia- usually use g-CSF
-910 mg/m2 iv over 15 mins or less, 30 mins before chemo- monitor BP (0 , 5, 10, 15, and 15 mins after)
-prevention of radiation proctitis in rectal cancer
-200 mg/m2 IVP over 3 mins before each fx of RT
-Can also prevent xerostomia and mucositis in RT pts for head/neck cancer- actually don’t use for mucositis…?
-avoid if good chance of cure
-can cause hypotension (hold BP meds x24 hrs before)
-premeds with NS, 5HT3, and dex
-must give chemo within 30 mins (short half life)
-not really used in clinical practice anymore due to inconsistent data and poor tolerability

Answer 97

A

Decreases severe mucositis in pts undergoing autologous SCT for a hematologic CA with total body irradiation AND HD chemo conditioning

-60 mcg/kg IV x3 d before start of conditioning regimen and x3 d starting day if stem cell infusion
-don’t give within 24 hours of initiation of conditioning regimen

This is a keratinocyte growth factor

Answer 98

A

IDH 1 inhibitor

-IDH1 mutated conventional and dedifferentiated chondrosarcoma
-IDH1 mutated de novo or relapsed refractory AML. Given in combo with HMA or alone for unfit pts older than 75y
-IDH1 mutated cholangiocarcinoma

Serious ADR: differentiation syndrome, QTC prolongation, high WBC, GBS, pulmonary and/or renal dysfunction

3A4 inducer

Once daily (unlike olutasidenib)

Answer 99

A

Bladder Tis in pts who received x2 prior courses of BCG

-800 mg intravesical weekly x6

Answer 100

A

Aromatase inhibitor- non-steroidal

Ovarian CA maintenance, metastatic or recurrent endometrial Ca -Should be ER/PR positive

Breast- post-menopausal, only pre-menopause if used with ovarian suppression or ablation

DLT: arthralgias/myalgias

Answer 101

A

Anti-PD-L1 mab

-Advance Endometrial w/ dMMR after platinum failure
-pancreatic MSI-H or dMMR
-primary advanced or recurrent dMMR or MSI-H endometrial CA combo w/ carbo and pacli —-> single agent dostarlimab
-breast- MSI-H/dMMR
-colorectal (dMMR, MSI-H, or POLE/POLD)

Answer 102

A

Aromatase inhibitor - non-steroidal

-Recurrent endometrial CA
-maintenance in ER/PR recurrent ovarian
-breast: post menopausal (only premenopausal if ovarian suppression or ablation)

DLT: arthralgias/myalgias

Answer 103

A

Anti-neoplastic progestin w/ anti estrogenic properties

Low grade endometrial cancer

Answer 104

A

Anti-folate receptor alpha (75%), antibody drug conjugate- anti-microtubule (DM4)

FR-a positive (75%+ of cells with PS2+ staining)- platinum RESISTANT ovarian, fallopian, or primary peritoneal CA- who have received 1-3 prior systemic tx

Dose in adjusted body wt due to ocular toxicity - for all BMIs!!- Don’t dose round!!

Ocular toxicity - steroid eye drops day -1 x5d (6x/day)—>x4d (4x/d), lubricating drops; warm compress before sleep, sunglasses, no contact lenses
-eye exam before and then every other cycles for 8 cycles

D5W only
Need 0.22 micro filter

DM4 is a cyp3A4 substrate

Answer 105

A

Antimicrotubule

Albumin bound paclitaxel

Not used often- exhaust paclitaxel and docetaxel first

Recurrent ovarian CA, endometrial, breast, NSCLC- better response in squamous

pancreatic, NSCLC, metastatic breast

Answer 106

A

PARP inhibitor

Ovarian:
Dose on wt and plt: 200 mg instead of 300 mg for wt<77kg or plt<150k (this is for first line maintenance only, if starting at a reduced dose in secondary maintenance setting, you may increase back if no thrombocytopenia

DLT: thrombocytopenia

Myelosuppression, fatigue, nausea, bowel changes (constipation), WEEKLY CBC

HTN, palpitations

No cyp interactions

With or without food

Answer 107

A

Antimetabolite (pyramidine analog), inhibits thymidylate synthase

-non-squamous NSCLC
-Gyn- recurrent dx

-Give folic acid and B12- prevent severe hematologic toxicity(Start 1 wk before and continue x3 weeks after completion) (neutropenia)
-Give dex 4 bid day before, of and after-prevent skin rash
-crcl cut off is 45 ml/min
-interacts with NSAIDs- increased pemetrexed

Doesnt work in squamous cell bc there’s more thymidylate synthetase so you would need much higher doses

Answer 108

A

SERM

Ovarian maintenance in ER/PR positive

Breast: pre/post menopausal

Estrogenic in bones, lipids, endometrium

Anti-estrogenic in breast and vaginal mucosa

Increase BMD in post-menopausal but decreased in pre-menopausal

Increased endometrial cancer in post-menopausal

VTE, hot flashes, cataracts, hypertriglyceridemia, DECREASES LDL/TC, inc HLD

Contraindicated in pregnancy

Interacts with warfarin- 2c9 inhibitor

Answer 109

A

Antimicrotubule- antibody conjugated to MMAE, target is CD142
–MMAE (antimicrotubule)

Cervical cancer- recurrent or metastatic with dx progression on chemo

ADR: ocular, peripheral neuropathy, fatigue, nausea, epistaxis, alopecia, hemorrhage, rash

-eye exam before each infusion
-steroid, vasoconstrictor (prior to infusion), and lubricating eye drops
-ice packs during infusion

-interaction with 3A4 inhibitor s

Answer 110

A

Topo-I inhibitor

Gyn- recurrent dx, SCLC

Answer 111

A

Anti-HER-2 mab

-Endometrial with carbo/taxane for HER2+

-Breast:
-neoadjuvant and adjuvant
-for T>1 cm (consider if < 1cm)
-prefer to give with chemo except anthracyclines
-x1 year
-HER-2+ obviously

-Biliary tract- with Pertuzumab
-gastric/esophageal- adenocarcinoma only

-colorectal (give with lapatinib, tucatinib, or pertuzumab)

Cardiotoxic , pulmonary toxicity, infusion rxn, fetal toxicity , diarrhea

IV

Answer 112

A

-prevents cisplatin ototoxicity in kids with non-metastatic hepatoblastoma and other non-metastatic cancers
-meclorethamine extravasation

don’t use is metastatic dx

Answer 113

A

Vinca alkaloid extravasation

Answer 114

A

Topoisomerase I inhibitor

Answer 115

A

Azathioprine, mercaptopurine, thioguanine, cladrabine, clofarabine, Fludarabine, nelarabine, pentostatin

Answer 116

A

CAR-T (anti-CD-19)

->/= 2nd relapsed or refractory B-ALL on pts up to 25 y/o (only indication with this age restriction)
-R/R DLBCL- adults
-R/R FL (after 2+ lines of therapy)- adults

Answer 117

A

Bispecific T-cell engager (anti-CD19/CD3)

-Relapsed ALL, MRD+ ALL (after 3 months/cycles- after consolidation I think) frontline for ph+ given with tki

-Risk for cytokine release syndrome and neurotoxicity (ICANS)

-Works best with low dx burden (<50% blasts)

-For R/R ALL28 day continuous infusion followed by 2 week break: Can do 7 day bag for home infusion (has preservative so can’t use this bag if <22kg)
-For MRD+ hospitalize for first 3 days of cycle 1 and first 2 days of cycle 2

Answer 118

A

Radioconjugate for patients with relapsed or refractory Neuroblastoma

Answer 119

A

-NSCLC- better response in squamous
-pancreatic
-Bound to albumin to help dissolve in solution better (normal paclitaxel needs cremephor)-
-NO Premeds or inline filter/special tubing
-can give faster w/o hypersensitivity rxn
-kinetics are different- more free paclitaxel
-better uptake into tumor cells bc CA needs amino acids
-approvals: met breast ca, NSCLC, pancreatic ca
-very expensive- data doesn’t necessarily show that it’s better except for…
most benefit in pancreatic cancer d/t better penetration

Cremephor now called Kolliphor

Answer 120

A

Antimetabolite (pyramidine analog)
-inhibits thymidylate synthetase (continuous infusion) AND
-RNA false base pair (bolus)

Breast cancer, bladder, head/neck, pancreatic, gastric/esophageal, colorectal

Continuous infusion for head/neck ca

May need dose reduction for DPD deficiency (DPYD intermediate or poor metabolizer)

ADRs:
-infusion: hand-foot syndrome, diarrhea
-bolus: myelosuppression so if neutropenia and pt is getting infusion, wouldn’t make sense to decrease dose
-mucositis (cryotherapy w/ ice chips-30 mins before bolus)
-coronary vasospasm- may rechallenge (but premeds with nitrate and calcium channel blocker- continue x48h after)

Often given with leucovorin to increase efficacy

-Topical form for basal cell carcinoma
-radiosensitizer
-photosensitizer (avoid sun)
-major interaction with warfarin- inhibits cyp2c9- INCREASES warfarin!
-Mainly metabolized in liver via DPD
-darkening if skin along veins and nails

Answer 121

A

CDK4/6 inhibitor

Breast cancer:
-use in combination with endocrine therapy !!
-adjuvant therapy x2 y for high risk HR+ HER2 negative that spread to LN and high risk of recurrence:
-4+ LN OR
-1-3 LN + (grade 3 or T=5+cm (T3), or ki67>/=20)
-OR MBC: 1st line (with AI), 2nd line (with fulvestrant +/- LHRH agonist if premenopausal)

diarrhea-more than others!
-less neutropenia than others in class
-hepatotoxicity, VTE
-increased scr (not due to renal
Impairment- it inhibits tubular secretion transporter

Anemia, thrombocytopenia, fatigue, infections, n/v, alopecia, weakness, interstitial lung dx

For MBC with fulvestrant, preferred over Palbociclib

Only CDK4/6 that is continuous therapy rather than 3 wks on 1 wk off

RB1 mutation confers resistance to CKD 4/6

Answer 122

A

HER-2 mAb

Breast cancer: 1) early stage in pts who got trastuzumab and docetaxel/paclitaxel neoadjuvant, then surgery and had cancer remaining at surgery-ADJUVANT ONLY
2) met HER2+ MBC 3rd line +

Trastuzumab link to small amount of chemo to deliver chemo directly to tumor

IV

Emtansine is a microtubule inhibitor

-Extravasation!
-can give with RT (unlike capecitabine)
-tx cardiotoxicity the same as trastuzumab/Pertuzumab combo

Answer 123

A

PIK3CA inhibitor , (PI3K)

Breast- HR+, HER2 neg-, metastatic dx-second line post CDK4/6+AI after progression
-for post-menopause (or pre menopause with OAS (like all ET in metastatic breast ca))

In combination *with fulvestrant (REPLACES THE CDK4/6 INHIBITOR, and AI get switched to fulvestrant)

Only for patient with PIK3CA mutation

Second line and beyond (DONT GET TRIPPED UP!)

ADR: *hyperglycemia!! (Will usually need Metformin), diarrhea, rash (consider h1 blocker), hepatotoxicity, pneumonitis

Answer 124

A

Antimetabolite (pyramidine analog)

Breast cancer, head/neck (1250 mg/m2 BID), pancreatic, gastric/esophageal, colorectal

ADR: think golf man- hand foot syndrome, diarrhea, photosensitivity
-rare cardio toxicity (unlike 5FU)
-ADRs worse if DPD deficiency
-hyperbilirubin, angina, mild myelosuppression
-don’t use if crcl<30 (use 5FU instead)
-coronary vasospasm (like 5FU)

DI: warfarin (2c9 inhibitor)- warfarin- inhibits cyp2c9- INCREASES warfarin- more than 5FU), phenytoin, allopurinol (decreased conversion to 5FU), PPIs

-More toxicity in US (like folate deficiency) so we give 1000 mg/m2
-available as 150 mg and 500 mg tabs
-consider barriers in pt with upper GI cancer (crush-ability, absorption)
-I think more diarrhea and hand foot syndrome than 5FU

Mainly metabolized in liver via DPD

Answer 125

A

AKT inhibitor

Breast HR+, HER-2 (-), with one or more PIK3CA or AKT1/PTEN alteration

Second line

Give with fulvestrant

VERY similar to alpelisib but addition of AKT1/PTEN

ADRs: hyperglycemia, rash

Answer 126

A

Endocrine therapy- SERD

HR+, HER2 neg, must have ESR1 mutation-metastatic breast ca- post menopausal after at least 1 prior line of therapy (in the metastatic setting)- not first line (DONT GET TRIPPED UP)

Given alone, unlike alpelesib which is with fulvestrant

First oral SERD

Oral- Take with food

Adr: dyslipidemia

emetogenic

Answer 127

A

Anthracycline

Breast cancer

Answer 128

A

Aromatase inhibitor -steroidal

Breast- post menopausal (only premenopausal if ovarian suppression or ablation)

Answer 129

A

HER-2 mAb
-Dxd/DX8951 (MAAA-1181a) topo-1 inhibitor

Breast cancer: (5.4 mg/kg)
-metastatic ONLY: HR+/HER2- (really HER-2 low) AND endocrine refractory- this is second line if HER2 low (IHC 1+ or 2+ and fish negative)

-NSCLC-HER2 (lower dose- 5.4 mg/kg)
-gastric/GEJ: prior trastuzumab (5.4 mg/kg)
-gastric: 6.4 mg/kg
-colorectal (HER2+, 5.4 mg/kg)
-now any solid tumor with no other options

Monitor for interstitial lung dx! (more than emtansine)

IV

Deruxtecan is topo-1 inhibitor

cardiotoxicity- hold for LVEF drop below 40% or >20% from BL or
If LVEF 40-45 and drop is 10-20% recheck it in 3 wks and permanently stop if not recovered

Answer 130

A

Endocrine therapy-SERD (kinda like elacastrant)

Breast- post menopausal (premenopausal if ovarian suppression or ablation) not previously tx with ET and in women w/ progression on ET

Intramuscular- thick/viscous and painful, 2 injections

Answer 131

A

Antimicrotubule, epothilone B analog

Metastatic breast cancer after failure of anthracycline, taxane, and capecitabine …
or in combination with capecitabine after anthra and taxane failure

ADR: neutropenia, neuropathy, hypersensitivity (give premeds- h1/h2)

Non-PVC and low sorting infusion set

Answer 132

A

HER-2 oral TKI

-Breast cancer metastatic only: (with trastuzumab or capecitabine)
-colorectal (HER-2 + and RAS/BRAF wildtype. Must give w/ trastuzumab)

ADR: diarrhea

Oral

QTc

Without food

Answer 133

A

HER2 targeted

-Metastatic only Breast cancer- after at least 2+ HER2 therapies (one in metastatic setting )
-given with chemo, replaces trastuzumab

IV

Cardiotoxic- monitor LVEF within 4 wks before and q3 months during and after tx. Hold for dec 16% or 10% to below 50%/hospital limits (like trastuzumab). D/c if >8 wks or 3+ holds

CD16A-158F may predict benefit over trastuzumab

Answer 134

A

HER2 oral TKI

Breast- ADJUVANT ONLY

X1 yr following 1 yr of trastuzumab: LN+, HR+, HER-2+

Diarrhea- prophylactic loperamide for *first 2 cycles (8 weeks)
or 2 week dose escalation (120 mg—>160 mg—>240 mg)

Oral

With food

PPI/h2 interactions

Answer 135

A

CDK4/6 inhibitor

Breast: MBC: in combo with endocrine therapy (AI (1st line) or fulvestrant (2nd line) +/- LHRH agonist if premenopausal)

-Primary toxicity is neutropenia

-QTc prolongation , anemia, thrombocytopenia, fatigue, n/v, infxns, alopecia, weakness, interstitial lung dx

RB1 mutation confers resistance to CKD 4/6

Answer 136

A

Her2

-Breast cancer- must give with trastuzumab
-biliary tract cancers- must give with trastuzumab
-colorectal (RAS/BRAF wildtype. Also must give with trastuzumab)

Neoadjuvant and adjuvant

Early stage: Add to trastuzumab if T > 2cm or LN positive

Give x1 year

Preferentially give with chemo (except anthracyclines)

diarrhea more than trastuzumab

IV

Answer 137

A

HER2

Breast-neoadjuvant and adjuvant

SubQ

Answer 138

A

SERM

Breast cancer in post menopausal

Use over AI if poor BMD, use over tamoxifen if intact uterus

Clotting risk

Answer 139

A

CDK4/6 inhibitor -PREFERRED OUT OF THE 3

Metastatic Breast- MBC in combination with endocrine therapy (AI (1st line) or fulvestrant (2nd line) +/- LHRH agonist if premenopausal)

Qtc prolongation, neutropenia/leukopenia, hepatobilliary toxicity,

N/V, infxns, alopecia, anemia, thrombocytopenia, fatigue, weakness, interstitial lung dx

RB1 mutation confers resistance to CKD 4/6

3A4 inhibitor (Pablo is weak inhibitor and abem is not at all)

Answer 140

A

RET kinase inhibitor, also VEGF

Metastatic breast cancer RET+, thyroid, NSCLC- RET, HCC-RET+, pancreatic-RET+, colorectal (off label, RET+

ADR: hypersensitivity, HTN, interstitial lung dx, hemorrhagic events, liver toxicity, impaired wound healing, edema, QTc (unlike pralsetinib!! Caution with afib), inc TC, hypothyroidism

-avoid acid reducing agents
-take with food if taking with PPI
-3A4 interactions (like pralsetinib)
-wt based dosing
-good response with brain Mets
-50 kg+ 160 mg bid, <50 kg 120 mg bid

Answer 141

A

SERM

Metastatic breast cancer- infrequently used

Answer 142

A

LHRH agonist

Breast: premenopausal in combination with AI or tamoxifen for ovarian suppression

IM

Answer 143

A

HER2 oral TKI- more selective than others (like Neratinib, so less ADRs)

-Breast: refractory metastatic only: HER2+ in combo with trastuzumab + capecitabine
-colorectal (RAS wildtype, HER2+, unresectable/metastatic that progressed on fluoropyrimidine, Oxaliplatin and irinotecan based chemo

Good activity with brain mets

Oral

*strong 3a4 inhibitor, increases scr!!, diarrhea, lfts

Answer 144

A

Alkylating agent (nitrogen mustard)- has purine analog in structure

-Chronic leukemia in combo with rituximab or obinutuzumab
-DLBCL and HL
-indolent lymphomas, WM
-SCLC

Nadir- 3 wks- so we usually give q28d

-Infections, severe rash (3%), infusion rxn, extravasation, secondary malignancy, TLS (incr risk rash w/ allopurinol), hepatotoxicity
-DLT: myelosuppressive
(lymphompenia, neutropenia, thrombocytopenia)
-consider pjp and HSV ppx

-bendeka (over 10 mins) has largely replaced treanda (over 60 minutes)

-cyp1A2
-omit when bridging to CAR-T
-not recommended if crcl <40 (generally decrease by 20% for crcl <50 or 40% for crcl<30)
-smoking can affect metabolism (like erlotinib and irinotecan)

Answer 145

A

Alkylating agent- nitrogen mustard

Uveal Melanoma (hepatic delivery kit for liver directed therapy)- Liver is most common site of metastases for uveal melanoma REMS d/t peri procedural complications

ADRs: Extreme hematologic toxicity, GI toxicity, black box (hemorrhage, hepatocellular injury, thromboembolic events), hypersensitivity, VOD

MM (oral) in non-transplant eligible pts

Answer 146

A

Alkylating agent- nitrogen mustard

-Non-preferred option in chronic leukemias
-FL- historical tx

Answer 147

A

Alkylating agent- nitrogen mustard

-FDA discontinued manufacture of IV form d/t low demand
-there is a topical form for cutaneous T cell lymphoma

Answer 148

A

Alkylating agent- alkyl sulfonate

Answer 149

A

Anti tumor antibiotic, alkylating agent-ethylene imine

Do not use if crcl<30 or scr>1.7

Answer 150

A

Alkylating agent-ethylene imine

Answer 151

A

-great for delayed n/v ppx and TREATMENT
-transient increase in wbc d/t demarginalization (also causes immune suppression)
-antipyretic-masks fever
-lymphocytic
-decreases gut and brain edema
-get bx before giving dex for suspected PCNSL (lymphocytic and can cause false negative)
-spinal cord compression: 4 mg IV q6
-use 12 mg instead of 20 mg if with aprepitant/fosaprepitant
-iv push: perineal burning
-eye drops for HD-Cytarabine
-for Pemetrexed rash
-myopathy/muscle weakness
-thrush
-energy/euphoria
-agitation/psychosis
-gi ulcers
-hyperglycemia
-HTN
-caution in n/v for brain tumors bc it decreases BBB inflammation and increases BBB integrity which decreases chemo exposure

-Used in lymphomas (WM- DHAP, MCL- hyperCVAD)
-MM

Answer 152

A

More with paclitaxel
-peripheral neuropathy
-more lipophilic (hard to get onto solution)

More with docetaxel
-neutropenia
-mucositis
-docetaxel is stronger

Both:
-nail changes
-full body alopecia
-neuropathy is reversible

Answer 153

A

ALL

Not myelosuppressive

ADRs: hypersensitivity (can be allergic or non-allergic (d/t ammonia from asparagine breakdown)
-allergic: usually not first dose. Don’t just increase premeds- drug isn’t working if real allergic rxn. Check activity level and Switch to different bacteria (erwinia instead of ecoli) for grade 3+ rxn
-non-allergic: often first dose. Increase premeds

hyperglycemia, Hypertriglyceridemia, hyperammonium, coagulopathy (clotting more and bleeding), hepatotoxicity often transient, pancreatitis

Want enzyme activity level to be at least 0.1 units/mL on day 7

MOA: depletes asparaginase in blood (normal cells can make their own but CA cells need to import it from outside the cell)

Note: Do NOT switch to erwinia for ADRs! Only switch for inactivation or grade 3+ rxn (ADRs also often worse with erwinia)

In adults cap long acting doses at 3750 units

Peg q2wks
Cal q3wks

-Monitor fibrinogen twice weekly (FFP/cryo if <50-70)
-lactulose/metronidazole/rifaximin for ammonioum but generally abates with time
-hepatotoxicity-if t. Bili> 3, hold until bili<2

Answer 154

A

Immunosuppressant

MDS- Aplastic anemia

-infusion rxns
-serum sickness

Answer 155

A

MDS, AML

Hypomethylating agent

Oral form should not be substituted where IV/SQ is used

-IV/SQ for MDS and low intensity AML tx
-PO for AML maintenance ONLY! (int/poor risk who can’t get allo HCT)

Take oral with antiemetic for at least first 2 cycles

renally cleared- use decitabine instead of renal impairment

Oral has poor bioavailability (~10%)

Answer 156

A

MDS NOT AML!!!

Cytosine deaminase inhibitor/hypomethylating agent

Oral

Answer 157

A

MDS- aplastic anemia

Calcineurin inhibitor

Answer 158

A

MDS, AML

Hypomethylating agent

-IV (but the PO combination product can be used in MDS as well)
-NO SubQ for like azacitadine

use instead of azacitadine if ESRD

Answer 159

A

MDS- for iron overload

Chelating agent

Oral

*CI in high risk MDS d/t ADRs: liver/kidney damage and GI bleeding

don’t use if crcl<40 (like deferoxamine)

Answer 160

A

MDS- Second line for iron overload

Chelating agent

Oral

Can cause agranulocytosis- so use is controversial unlike others

Answer 161

A

MDS- for iron overload

Chelating agent

IM/SQ

Avoid in crcl<40 (like deferasirox)

Eye, ear, pulmonary toxicity

Answer 162

A

MDS- for thrombocytopenia if blasts are low, also for aplastic anemia

Thrombopoetin agonist

Oral

Role unclear in MDS- c/f dx transformation and narrow fibrosis. Consider if severe or refractory thrombocytopenia

Answer 163

A

-MDS- del5q (consider first BEFORE epo level)- Unless ch 7 abnormality
-R/R DLBCL
-indolent lymphomas (FL, MCL)
-MM

Immune modulating agent

REMs: pt (even men), MD, pharmacy

ADR: fetal embryo toxicity (even men), thrombotic events may need ppx of Asa or AC-use saved score), hepatotoxicity, cutaneous rxns, TLS, tumor flare, decreased ability to mobilize for HCT w/ >4 cycles for MM, thyroid issues, diarrhea (use bile acid sequestrant), skin hyperpigmentation (black pts), dermatological rxns (rash), peripheral neuropathy,
-secondary malignancies!!
-with or without food

MM
-tx 25 mg QD
-maintenance: 10 mg daily
-dose reduce for renal impairment
-crcl 30-60: 10 mg/d
-crcl <30: 15 mg QOD
-HD: 5 mg QD
should be able to use if crcl >30

Answer 164

A

MOA: IgG1, TGF-B, smad 2/3 signaling

MDS- ring sideroblasts (15%+ or 5%+ if SF3B1 mutation)

Activin receptor ligand trap

Helps w/ anemia but doesn’t modify the disease course

SubQ injection

hypertension- monitor before giving

Thromboembolic events

If inadequate response after 2 cycles (6 weeks) increase the dose (2 increases and if still no response then d/c)

If Hgb 11.5+ in absence of transfusion- HOLD
If inc of 2 within 3 weeks in absence of transfusion- dose reduce

Answer 165

A

Can be used in MDS

Note: always start filgrastim within 72hs

Answer 166

A

Thrombopoetin agonist

MDS- thrombocytopenia if blasts are low, more commonly used in ITP

SQ

Role unclear in MDS- c/f dx transformation and narrow fibrosis. Consider if severe or refractory thrombocytopenia

Seem to be choice over eltrombopag for thrombocytopenia

Goals plt 100-150k

2 mcg/kg

Answer 167

A

AML

FLT3 inhibitor

FLT3-ITD/TKD mutation in de novo AML

ADRs: pulmonary toxicity, cardiac issues, anemia, nausea

Daily premedications for nausea and air out capsules (bad taste/smell)

Severe 3A4 interaction- avoid w/ Azoles

Answer 168

A

AML

FLT3 inhibitor

FLT3-ITD only mutation in de novo AML

Serious ADRs: cardiac toxicity/arrhythmia (EKG), CNS (seizures, confusion), prolonged myelosuppression, higher incidence of early death (first 30 days)

REMS!!

3A4 substrate

Answer 169

A

AML

FLT3 inhibitor

FLT3-ITD or TKD mutation in relapse or refractory AML

Serious ADRs: differentiation syndrome, arrhythmia (EKG), liver, fever, PRES, myalgia/arthralgias , orthostatic hypotension, inc cpk , pancreatitis, cytopenias

Long half life

Answer 170

A

IDH1 inhibitor

Relapsed/refractory AML with IDH1 mutation

Serious ADR: differentiation syndrome, hepatotoxicity

-empty stomach- otherwise absorption is increased and you get ADRs (like QTc-unlike at normal doses)
-3A4 inducer

-twice daily- unlike ivosidenib

For differentiation syndrome you need to definitely hold even for less severe symptoms unlike other agents

Answer 171

A

IDH2 inhibitor

De novo or relapsed refractory AML with IDH2 mutation

Serious ADR: differentiation syndrome, can produce Gilbert’s like indirect hyperbilirubinemia, cytopenias, high WBC, pulmonary and/or renal dysfunction

Answer 172

A

BCL-2 inhibitor

-AML- 28 day courses
-but get marrow at d21-28 and give 7-14 day break if no dx
-CLL- 1st line
-R/R indolent lymphomas (MCL, WM)
-R/R MM- with dex if t(11;14)- dose is higher (800 mg and no ramp up)

ADRs: GI toxicity, PNA, TLS (do ramp up), serious infxns, cytopenias

-DI with azoles! Must dose reduce venetoclax to 70 mg- in AML stop azole when remission attained
-other DIs: carvedilol (50% dec), digoxin (give dig 6 hrs prior)
-PO only
-take **WITH Food!* affects
Absorption

Note: re-ramp up may be needed if interrupted for >1 week

CLL weekly ramp up: 20, 50, 100, 200, 400 mg

AML can consider 3 day ramp up

purpose of ramp up is to decrease TLS risk

Answer 173

A

Hedgehog pathway inhibitor

AML- unfit for intensive therapy- give with LDAC

-need to take birth control!
-cardio toxicity/QTc
-nausea, dysgeusia

Answer 174

A

APL

adr: differentiation syndrome, dry skin, LFTs, hypertriglyceridemia, pseudotumor cerebri (increases ICP, give acetazolamide), myositis- give steroid

Induces differentiation of APL cells

PO only (can put in suspension if intubated)

Answer 175

A

APL

Serious adr: differentiation syndrome, LFTs, QTc (monitor twice weekly)

Supplement with k+ and mg+ during tx

MOA: DNA fragmentation —>apoptosis
-also degrades fusion protein PML (promyelocytic leukemia)-retinoids receptor alpha)

use freimingham or fredericka
-QTc- stop for >450 mg (men) or 460 mg (women)
-it’s ok to use with zofran
-headache*- extend infusion duration

Answer 176

A

ALL

Use only in severe hypersensitivity (grade 3) or antibody inactivation to Peg-asparginase

Answer 177

A

CAR-T therapy: Anti-CD19

Relapsed/ refractory B-cell precursor ALL or R/R mantle cell lymphoma (third line after BTK-I)

Risk for CRS and ICANS

Pts shouldn’t drive x8 weeks after infusion

Answer 178

A

ALL

Longer half life than peg Asparginase but minimal data in adults and AYA so use with caution

Hydrolysis asparagine (normal cells can make but leukemia cells cannot)

Cap dose in adults

No more than q3wks

</=21 yrs

Answer 179

A

Antimetabolite (purine analog)

AML, hairy cell leukemia, WM

Answer 180

A

Antimetabolite (purine analog)

AML, ALL

Answer 181

A

Antimetabolite (pyramidine analog)

Cell cycle specific

AML, ALL, NHL

ADRs:
-cerebellar toxicity (increased risk with renal impairment, females, and elderly)- THIS IS FOR HIGH DOSE ONLY (1000 mg/m2+)- DISCONTINUE!
-conjuctivitis/keratoconjunctivitis (water soluble)- pre-tx (and continue for a few days after) w/ steroid eye drops (lubricating drops,dex + nsaid gtts)- ok to rechallenge. (This is also from HD-Cytarabine)- TRUE
-Ara-C syndrome: give steroids
-avoid if renal failure!
-diarrhea

Pearls:
-metabolized by cytidine deaminase- which is everywhere- happens FAST- why we give it continuously otherwise metabolized to ara-U
-rate limiting step in conversion is deoxy-cytidine-kinase-this can be saturated at higher doses (debate about high doses)- after saturation the rest is metabolized to ara-U
-ara-U is responsible to cerebellar toxicity (why it’s seen with high dose but not standard dose)

-liposomal form for IT
-HIDAC 3000 mg/m2 over 3 hr q12 hr x6 doses (on day 1, 3, and 5)
-DLT- myelosuppression

In FLAG-IDA Fludarabine upregulates deoxycytidine kinase which converts Cytarabine to its active form. Also G-CSF is used for priming here

Answer 182

A

BCR-ABL TKI- gen 2

ALL, CML chronic phase first line

ADR: pleural effusion (risk does NOT decrease over time-could use diuretics), PAH (d/c therapy), myelosuppression, QTc!!, PLT inhibition

Better BBB penetration -preferred in lymphoid variant blast phase

contraindicated in V299L mutation

-3A4 substrate

Answer 183

A

Anthracycline

AML, ALL

Red urine

Cardiotoxicity seen at 550 mg/m2

Answer 184

A

AML- CPX351

this is a LIPOSOMAL product so for secondary AML

-higher rates of prolonged thrombocytopenia and neutropenia (but lower rates of serious infxn- maybe protective of microbiota)
-hemorrhage
-copper overload

Answer 185

A

Steroids are part of backbone of tx in ALL- has anti leukemic activity

Answer 186

A

Antimetabolite (purine analog)

-AML, CLL 1st line with cyclophos and/or rituximab
-indolent lymphomas (WM, FL)

Dose reduce for crcl<80

Could cause autoimmune hemolytic anemia- stop drug if occurs

Answer 187

A

Antibody drug conjugate - anti-CD33, calicheamicin (alkylation?)

AML- if core binding fx: inv (16), t(16;16), t(8;21) (don’t need CD33+ listed)

Risk of venoocclusive dx-permanently d/c, infusion rxn (give premeds)

Answer 188

A

AML, ALL

Used to reduced WBC (>50-100k) when acute leukemia is suspected (cytoreduction)-generally prior to confirmation of subtype

Also for chronic leukemias

Goal is to decrease complications associated with leukostasis (pulmonary and neurological, stroke)

Answer 189

A

Anthracycline

AML

Many “theoretical” advantages over daunorubicin (uptake, potency, etc.) but not proven to be better

Red urine

Answer 190

A

BCR-ABL TKI- gen 1

ALL, CML (1st line chronic phase), melanoma

Minor: Diarrhea-self limiting, rash, arthralgia, periorbital edema, fatigue

Severe: myelosuppression- transient, hepatotoxicity, worsening hypothyroidism, mild anemia, fetal embryo toxicity (men can still conceive), bone formation. Expensive

With food and large glass of water

-3A4 substrate
-3A4 and 2D6 inhibitor (like nilotinib)

Answer 191

A

Antibody drug conjugate (anti-CD22), calicheamicin (alkylation?)

R/R- ALL

Black box warnings
-Veno-occlusive dx
-higher post HSCT non-relapse mortality
-better than blinatumomab with higher dx burden

Answer 192

A

Antimetabolite (purine analog)

ALL maintenance daily (goal ANC 500-1500)- dose adjust in alternative fashion with MTX by 25% for out of range ANC

Aka 6-MP

Must dose reduce 50-90% if given with allopurinol

Same time every day with or without food

Increased serum lvls in hepatic impairment

Answer 193

A

Antimetabolite (purine analog)

ALL- good for R/R T-cell ALL

Neurotoxicity

Answer 194

A

ALL

Hydrolyses asparagine (leukemic cells cannot make)

Cap at 3750 units in adults

No more than q2wks

Answer 195

A

Biological response modulator (anti-CD123)

Indication: blastic plasmacytoid dendritic cell neoplasm (BPDCN)

Warning: capillary leak syndrome

Answer 196

A

Antimetabolite (purine analog)

ALL

-sinosoidal obstructive syndrome: may need allopurinol (plus dose modification) if skewed metabolism- but dose reduce 50-75% since they interact

Allopurinol shift metabolism from hepatotoxic and ineffective metabolite 6-MMP to 6TGN

Answer 197

A

Car-T cell therapy

CD-19

Adults with relapsed/refractory B-cell NHL or R/R follicular lymphoma, R/R MZL

REMS

Pts should not drive x8 weeks after infusion

ICANS-worse than other CAR-T

Answer 198

A

CAR-T cell therapy

CD19

Relapsed refractory B-cell NHL

Answer 199

A

CAR-T cell therapy targeting BCMA

Relapsed/ refractory multiple myeloma

ADR: Parkinsonism

Lymphodeplete with cyclophos and Fludarabine for 3 days, then start 2-4 days later

Premed with APAP and diphen but NOT dex (decreased efficacy)

Answer 200

A

BTK inhibitor

CLL- 1st line, R/R
MCL- R/R

ADR: headache (occurs early and resolves in 4-8wks)
Low incidence of bleeding, HTN, and afib (so less ADRs than ibrutinib)

-tablet form released which does NOT interact with PPI/H2- capsule DOES interact- separate 2h before and after

-3A4 substrate

Answer 201

A

Anti-CD52 mAb

Chronic leukemia via compassionate use program

Answer 202

A

BCR-ABL and STAMP TKI

Chronic phase CML with:
-T315I mutation OR
-resistance or intolerance to 2 prior TKIs

Dose:
-40 mg BID or 80 mg QD
-T315I mutation- 200 mg BID

-3A4 and 2C9 substrate

Does NOT prolong QTc- only one that doesnt

Answer 203

A

BCR-ABL TKI- gen 2

CML- chronic phase 1st line

Bone marrow suppression, diarrhea/GI issues

contraindicated in V299L mutation

With food and large glass of water

-3A4 substrate

Answer 204

A

P13K inhibitor

CLL- R/R after 2 prior lines of therapy

Black box: infection, diarrhea/colitis, cutaneous rxns, pneumonitis

-Cyp3A4 substrate

-with or without food

Answer 205

A

BTK inhibitor

-CLL- 1st line
-R/R DLBCL (non-germinal center)
-indolent lymphomas (WM, MZL, R/R MCL)

ADR: bleeding, afib (don’t hold unless grade 3+), HTN
-arthralgia, diarrhea

-NO warfarin- use alternative AC (Apixaban preffered)

-3A4 substrate

Answer 206

A

P13K Inhibitor

CLL- relapsed, in combo with rituximab

Hepatotoxicity, diarrhea, hematological

-cyp3A4 substrate AND inhibitor (unlike duvelisib which is just a substrate)

-with or without food

Answer 207

A

BCR-ABL TKI- gen 2

CML- 1st line chronic phase)

ADR: QTc!!!-BLACK BOX GI and liver toxicity, peripheral arterial occlusive dx, metabolic syndrome, pancreatitis (like Ponatinib)

Empty stomach

Only one that is twice daily- so not good option if adherence is bad!!

Ok in V299L mutation

-3A4 substrate
-3A4 and 2D6 inhibitor (like imatinib)

Answer 208

A

Anti-CD20 mAb

-Chronic leukemias
-FL

Could split 1st dose over 2 days on CLL to decrease infusion rxn

Answer 209

A

Anti-CD20 mAb

Chronic leukemias CLL?

Exclusively available via patient access Novartis oncology program (PANO)

Answer 210

A

Cephalotaxine; protein synthesis inhibitor

CML:
-chronic phase OR
-pts who PROGRESS to accelerated phase (not for de novo- don’t get tripped up)
for resistant or intolerant to 2 TKIs

SubQ BID-ouch!

Hyperglycemia

Answer 211

A

Adenosine deaminase (ADA) inhibitor

Hairy cell leukemia- one of the preferred initial options

Answer 212

A

BTK inhibitor

-CLL -R/R
-MCL- R/R after 2+ lines of therapy including BTK-I

Novel mechanism (non-covalent binding)- allows it to work in patients that progressed in prior BTK-I

-ADR: bleeding, afib, cytopenias

-3A4 substrate, increases digoxin (pgp)

Answer 213

A

BCR-ABL TKI

ALL
CML- chronic phase with:
-T315I mutation drug of choice- 45 mg but decrease to 15 mg when bcr-abl <1%
-resistance or intolerance to 2 TKIs

Risk for arterial thromboembolic events (it has pan-VegF inhibition), pancreatitis, HF, hepatotoxicity

Obtain via Takeda oncology Here2Assist program

-3A4 substrate

Answer 214

A

BTK inhibitor

-CLL- category 1 preferred for second line and subsequent therapy with or without del(17p)/TP53 mutation
-R/R MCL
-First line WN
-second line MZL

ADR: myelosuppression, PNA, upper respiratory tract infxns, cytopenias
-low incidence of bleeding, HTN, and afib (like Acalabrutinib)

-3A4 substrate

-160 BID or 320 daily

Answer 215

A

Bispecific t-cell engager

Brings two antibodies together- one side targets t-cell and the other targets the antigen - then T cell kills antigen

Bypasses need to co-stimulation

Usually tried after CAR-T therapy

Off the shelf- no crazy manufacturing like CAR-T

Answer 216

A

R/R hairy cell leukemia after 2+ systemic therapies including purine analogs

Anti-CD22 mAb conjugated to PSA endotoxin

ADR: infusion rxns, capillary leak syndrome, hemolytic uremic syndrome

Give ASA in d1-8 of each cycle

Product provided as two separate vials- so be careful when making!

Drug no longer available for new starts after 7/2023

Answer 217

A

Antibody drug conjugate -CD30

Hodgkin’s lymphoma

Answer 218

A

Bispecific antibody- CD20/CD3

R/R DLBCL- third line
R/R follicular lymphoma- third line

-Step up dosing
-SubQ
-hospitalize x24h following first dose of 48 mg (full dose)
-premed: steroid, diphen, APAP for cycle 1
-premed with steroid for all cycles
-continue steroid x3 days following each dose
-CRS, ICANS
-nausea , diarrhea, pyrexia, MSK pain, abdominal pain, serious infxns

Answer 219

A

Bispecific antibody- CD20/CD3

R/R DLBCL- third line

-Step up dosing
-MUST get pretreatment dose of obinituzumab 7 days prior to first dose
-max 12 cycles (this is finite unlike epcoritimab)
-premeds: steroid, diphen, APAP for first 3 cycles
-APAP and antihistamine in all subsequent cycles
-CRS, ICANS
-serious infection, tumor flare, MSK pain, rash, fatigue
-hospitalization required for the first 2.5 mg step up dose

Answer 220

A

Antibody drug conjugate -CD19 directed antibody with alkylating agent conjugate (SG3199)

R/R DLBCL (2+ prior tx)-third line

-Premeditate with dex 4 mg bid x3 days beginning day before
-dex is used to mitigate edema because LOOP DIURETICS WONT HELP WITH EDEMA (try spironolactone)

Other:
-photosensitivity
-infection
-extravasation
-serious rash

Answer 221

A

Antibody drug conjugate -CD79B
-MMAE (antimicrotubule)

R/R DLBCL: PBR regimen

ADR: thombocytopenia, peripheral neuropathy, infusion rxns (90 minute observation and premed), FN (consider G-CSF), opportunistic infections (HSV/PJP ppx), PML, TLS, hepatotoxicity, PNA

3A4 interactions d/t vedotin!!

Answer 222

A

Used in DLBCL, PMBL, BL, HL, indolent lymphomas, MM

Answer 223

A

Anti-CE 19 mAb

R/R DLBCL ineligible for auto HCT; tafasitamab w/ Lenalidomide

Answer 224

A

Selective inhibitor of Nuclear export (SINE)

MM, 3rd line DLBCL

ADRs: hyponatremia, neurotoxicity, GI toxicity (diarrhea ~14 days in) hemorrhagic events, N/V

-use dual antiemetic ppx (5HT3 + NK-1/OLZ)
-tablets- with or without food

Answer 225

A

SubQ

CLL, DLBCL, FL: all have different administration times and vial sizes

Must have tolerated at least one full dose of IV

Answer 226

A

R/R cutaneous T-cell lymphoma after at least one prior therapy

Selectively binds to CCR4

-worsens autoimmune mediated things like any autoimmune disorder or GVHD- so caution in these patients!
-rash
-infections
-infusion rnxs

Answer 227

A

Radiotherapy

Follicular lymphoma

Answer 228

A

Proteosome inhibitor

-MM
-WM

-Can be inactivated by high intake of vitamin C
-peripheral neuropathy (IV>SQ) (usually within 1st 5 cycles it starts)
-reactivation of HSV/VZV- need ppx
-minimum 72h b/w doses
-blepharitis- tx w/ ketotifen or doxycycline
-thrombocytopenia, hypotension, TMA
-weekly preferred for MM tx

Dose adjust in hepatic impairment

Rare hearing loss

Answer 229

A

Proteosome inhibitor

WM, MM

ADR: cardiac and pulmonary toxicity and renal

-Screen for hep b
-HSV/HSV ppx
-Infusion rxn- premeditate w dex (can be immediate or delayed)
-hydration- decrease TLS and AKI
-slower rate decreases cardiopulmonary tox
-need VTE ppx if given w/ dex!
-max BSA 2.2 to calculate dose
-once weekly may be ok
-watch: EF, BP, electrolytes, liver and renal function, thrombocytopenia, TMA, TTP, HUS, PRES, inc tox w/ Melphalan
-much less neuropathy
-IV not SQ
-hydration before 1st cycle (TLS)

Dose adjust in hepatic impairment

Answer 230

A

P13K inhibitor

withdrawn from US market

IV

Answer 231

A

Bispecific antibody - CD20/CD3

FL- R/R after 2+ lines of therapy

-step up dosing
-q21 days x8 cycles (up to 17 cycles of only PR)
-premeds: steroid, APAP, h1 blocker (for cycle 1 and 2, optional beyond that
-hospitalization for monitoring is NOT required
-CRS
-neurologic toxicity
-fatigue, rash, pyrexia, HA, Dec lymphocytes and myelosuppression

Infections!! Consider PJP and HSV ppx

Answer 232

A

Relugolix is oral

Answer 233

A

Antiandrogens, less commonly used that bicalutamide d/t tolerability

Flutamide: diarrhea, hematuria, give with LHRH agonist, most hepatotoxic

Nilutamide: diarrhea, disulfiram like rxn avoid if etoh drinker, visual issues, interstitial PNA, give with orchiectomy

hot flashes are common

Answer 234

A

Darolutamide: prostate

Daratumumab: MM

Durvalumab: bladder second line

Answer 235

A

Antibody drug conjugate

Targets BCMA

Removed from market- available for
Compassion use only for relapsed refractory multiple myeloma

Infusion rxns, ocular toxicity (lubricating eye drops), thrombocytopenia

REMs

Need eye exam before each infusion, need lubricant eye drops, avoid contact lenses

Answer 236

A

Human IgG1k mAb target ring CD38

-HSV/VSV ppx during tx and for 3 months after
-Upper respiratory tract infections
-screen for hep B
-infusion rnxs (more with IV than SQ, more with faster infusions)
-could split 1st dose over 2 days to reduce infusion rxn
-premeds with APAP, dex, diphen (may omit for SQ staring with 4th dose)
-could use montelukast to decrease infusion rxn
-different volumes for doses 1 v 2 v 3
-SQ is flat dose
-don’t need IV test dose like rituxan
-abdomen over 3-5 mins
-can interfere with blood type and screening
-after 2 tolerated doses you can do rapid administration over 90 mins

Answer 237

A

Humanized IgG1 mAb that targets SLAMF7 protein

Multiple myeloma -NOT given alone (usually with IMID)
-after 1-3 failed therapies (sooner than car-t and BiTEs)

-GI toxicity
-infusion rxns- premed with dex, diphen, APAP, H2

Options:
-elo + Len + dex
-elo + Pom + dex
-elo + bor + dex

Answer 238

A

Bispecific antibody, BCMA, CD3

R/R MM- at least 4 prior lines of therapy including PI, immunomodulatory agent, and Anti CD38

Step up dosing (like teclistimab), hospitalize and monitor x48 and 24h for doses 1 and 4 respectively

Premeditate with dex, APAP, and diphen before step up doses (prevents CRS)

REMs for CRS and ICANS

Given alone (like teclistimab and talquetamab, unlike elotuzumab)

Infections!! Consider PJP and HSV ppx

Answer 239

A

CAR-T targeting BCMA

MM

Lymphodeplete with cyclophos and Fludarabine for 3 days, then start 2 days later

Premed with APAP and diphen but NOT dex (decreased efficacy)

Answer 240

A

Chimeric IgG1 mAb that binds CD38

R/R MM

-HSV/VZV ppx during tx and for 3 months after
-premeds for infusion rxn
-hep B screening
-can interfere w/ blood typing
-infusion rxns
-upper respiratory tract infections
-diarrhea

Answer 241

A

Proteosome inhibitor

MM

-HSV/VZV ppx
-ADRs: GI toxicity (N/V/D), fluid retention, dermatological toxicity, peripheral neuropathy (less than velcade)
-oral- capsules
-take on Empty stomach- 2hr after or 1 he before a meal with a glass of water

Answer 242

A

Immunomodulating agent

MM

ADR: dermatological toxicity, myelosuppression, VTE (ppx)
(Less diarrhea and rash than revlimid)

REMS- teratogen

Answer 243

A

Bispecific GPRC5D directed CD3 t-cell engager

R/R MM- at least 4 prior therapies including PI, immunomodulatory agent, anti-CD38

Step up dosing for CRS- hospitalized x48h after each step up

Premeds with dex, APAP, diphen (CRS PPX)

REMs for CRS and ICANS

skin and nail toxicity

taste changes and weight loss

Given alone (like teclistimab and elrantamab , unlike elotuzumab)

Infections- not quite as bad as BCMAs

Answer 244

A

Bispecific antibody- BCMA and CD3

R/R MM- 4+ prior therapies including PI, immunomodulatory agent, anti- CD38 mAb

CRS ppx: dex + APAP + diphenhydramine (PREVENTS CRS)

ADR: infections (acyclovir, often pjp ppx too), CRS, neurotoxicity

Step up dosing and hospitalization x48h after each dose increase

REMs- CRS/neurotoxicity (ICANS)

Given alone (like elrantamab and talquetamab, unlike elotuzumab)

Approved for new technology add on payment for limited time

Infections!! Consider PJP and HSV ppx

Answer 245

A

Immunomodulatory agent

MM

ADR: constipation, peripheral neuropathy, neurotoxicity (sedation), VTE (give ppx)

REMs- teratogen

-Capsules- empty stomach at bedtime
-does not require week off like Lenalidomide and pomalidomide
-no renal or hepatic adjustments

Answer 246

A

Hypercalcemia of malignancy

4-8 units/kg q6-12hr IM or SQ

Onset: 2-4 hrs

Tachyplylaxis- limit to 48h max

nasal form is NOT effective

Not used alone!!

avoid if fish allergy

Probably for more severe cases (ca2+ >14)

Answer 247

A

-Start within 6 hours
-remove cold packs for at least 15 minutes before, and during tx
-iron chelator that works by preventing formation of free radicals which inhibits necrosis

Testicular atrophy and infertility

Answer 248

A

IL-2

Melanoma

Not used much d/t toxicity and low response

Capillary leak syndrome

Answer 249

A

MEK inhibitor

Melanoma, NSCLC

Ocular toxicity, decrease LVEF

Answer 250

A

MEK inhibitor

Melanoma (with vemurafenib)

Highest rates of ADRs of all BRAF/MEK inhibitors: rash, transaminitis, may decreased LVEF

Answer 251

A

BRAF inhibitor

Melanoma, ovarian, thyroid, NSCLC, HCC

ADRs: fever, chills, flu-like symptoms, QTc, hand/foot syndrome, ocular toxicity

-empty stomach
-DDIs: clarithromycin, estrogens/progestins
-hyperglycemia
-alopecia
-arthralgias
-fever- antipyretics, steroids, maybe dose reduction

Answer 252

A

PD-1 inhibitor + lymphocyte activation gene-3 (LAG3) blocking antibody

Melanoma

Relatlimab only available in this combination

Answer 253

A

Oncolytic virus

Melanoma- unresectable stage III, satellite or in transit lesion

Local injection site rxns

-caution: viral transmission:
-blood may be infectious
-urine is infections day of inj
-avoid contact w/ tx site
-wear gloves, keep covered x 1 wk
-dispose of stuff in sealed plastic bag
-keep covered x1 week
-wash hands
-avoid acyclovir and antiherpetics
-intralesional injection
-fever, chills, fatigue, cellulitis

Answer 254

A

gp100 targeted Bispecific T cell engager

Melanoma- HLA-A*02:01 pts only - I believe this is uveal melanoma

ADRs: itching/rash (give topical steroid, antihistamine, and maybe oral steroid), CRS

First BiTE for solid tumor

First 3 doses require observation for 16 hours

Answer 255

A

BRAF inhibitor

Highest rate of AES of all BRAF/MEK combos: rash, transaminitis, QTc

Melanoma (with Cobimetinib)

Answer 256

A

MEK inhibitor

Ovarian, Melanoma, thyroid, NSCLC-MEK, HCC

ADR: may decrease LVEF, dermatological toxicity (rash), fevers, ocular toxicity, anemia
-empty stomach
-Refrigerate

Answer 257

A

Nk1 blocker

Not an inhibitor of cyp3a4

Does inhibit bcrp- watch mtx, mitoxantrone, imatinib, lapatinib, gefitinib, topotecan, irinotecan

Oral

Iv removed from marker for hypersensitivity rxns

Long half life 130hr- only one dose needed

Answer 258

A

GM-CSF

Stimulates granulocytes and macrophages

-Primarily for HCT
-also indicated in AML

Answer 259

A

Long acting G-CSF

Answer 260

A

EGFR inhibitor

-Head/neck
-colorectal (KRAS wildtype)

-Rash, acneform rash, skin/hair/nail toxicity, diarrhea, low mg
-Hypersensitivity- this is IgE (inc risk in southeast US, more than with panitumumab d/t chimeric structure opposed to humanized)- Need Benadryl premed. Usually fast it 1st or 2nd cycle. Switch to panitumumab!!
-check alpha gal IgE (don’t tx if positive)-from lone star tick bite, or develops antibodies!
-hypomagnesemia!!!
-rare aseptic meningitis

Answer 261

A

PD-1 inhibitor

Metastatic/recurrent nasopharyngeal carcinoma (with cisplatin/Gemcitabine)- or single agent if progression on platinum

Answer 262

A

RET kinase inhibitor, also VEGF

Thyroid, NSCLC- RET

ADRs: interstitial lung dx, HTN, hemorrhagic events, liver toxicity, wound healing impairment, HTN, edema, TLS, bone marrow suppression, electrolyte abnormalities, increased CK, edema, hypothyroidism

-empty stomach
-many 3A4 interactions

Answer 263

A

Multi kinase inhibitor (VEGF, EGFR, RET)

Thyroid- mainly MTC

ADR: cardiotoxicity, HTN, HF, dermatological toxicity, GI toxicity, bleeding risk, hypothyroidism
-REMS: d/t QTc risk

-obtain k, ca2+, mg, TSH, and ecg before initiation and regularly throughout tx

Answer 264

A

Mucositis prevention in RT

Not approved in United States

Answer 265

A

Papillary and follicular thyroid cancer

NOT for MTC or anaplastic

-stop levoxyl and do iodine free diet beforehand
-N/V
-xerostomia
-infertility (especially men) no preganancy x1 yr after- pregnancy test for all women regardless of sexual hx and birth control
-no pregnancy or breastfeeding
-risk of secondary cancer
-there is a max lifetime dose
-no contrast dye- blocks uptake of RAI
-give with beta blocker or methimazole in elderly or cv risk pts

Answer 266

A

Give in BC concurrently with WBRT and x6 months after to delay cognitive decline

Answer 267

A

KRAS inhibitor

-NSCLC- KRAS G12C mutation after 1 prior line of therapy
-biliary tract and pancreatic cancers (KRAS G12C mutated)
-colorectal (KRAS G12C, usually with EGFR-I)

ADRs: significant nausea, diarrhea, QTc prolongation
Others: edema, hepatotoxicity, fatigue, decreased appetite, dyspnea, MSK pain, ILD

Penetrates CNS

3A4 substrate (like sotorasib)- VERY POTENT!!

Also cyp inhibitor!

Answer 268

A

EGFR inhibitor

NSCLC-advanced/metastatic- preferred first line if EGFR S768I, L861Q, or G719x

ADRs: rash, diarrhea,, alopecia, dry skin, conjunctivitis, paronchymia, pneumonitis, hepatotoxicity, GI perforation, ocular disorders, ILD

-empty stomach
-renal dose adjustment

Answer 269

A

ALK inhibitor

NSCLC- ALK

ADRs: fatigue, constipation, edema, myalgia, visual disturbance, pneumonitis, GI toxicity, hepatotoxicity, bradycardia, QTc, ILD

-with food
-anemia
-weight gain

Answer 270

A

Bispecific antibody targeting: EGFR and MET inhibitor
This is NOT BITE therapy!

NSCLC- exon 20 insertion mutation
NCCN preferred for 1L in combo with chemo

Premeds: dex (prior to wk 1 d1-2, then optional), diphen, APAP- still everyone reacts!- can rechallenge on day 2

ADRs: Rash, paronychia, MEK pain, dyspnea, nausea, fatigue, edema, stomatitis, cough, constipatin, vomiting

Give via peripheral line for first 2 cycles (infusion rxns), then can do central after that

Answer 271

A

MET inhibitor

NSCLC- MET exon 14 skipping mutation

ADRs: edema (hallmark), photosensitivity, hematologic toxicity, inc scr, significant nausea, ILD, hepatotoxicity, elevated amylase/lipase

-bottle only good for 6 weeks after opening
-DDI: 3A4 (major substrate- tepotinib is minor), PPI (unlike tepotinib)
-BID (shorter half life)
-likely has CNS penetration

Answer 272

A

PD-1 inhibitor

-NSCLC- first line locally advanced or metastatic dx with PD-L1 50%+, also in combo with chemo for 1L (no PD-L1 requirement)
-locally advanced basal cell carcinoma after hedgehogs pathway inhibitor (sonidegib) or if hedgehog inhibitor is not appropriate
-SCC (skin cancer): locally advanced or metastatic not candidates for surgery or RT

Answer 273

A

ALk inhibitor, ROS1

ADRs: fatigue, constipation, edema, myalgia, visual disturbance, pneumonitis, GI toxicity, hepatotoxicity, bradycardia, QTc, ILD

-450 mg WITH FOOD
-moderately emetogenic
-more GI ADRs
-CNS penetration
-

Answer 274

A

EGFR inhibitor

NSCLC- EGFR

ADRs: rash, diarrhea,, alopecia, dry skin, conjunctivitis, paronchymia, pneumonitis, hepatotoxicity, GI perforation, ocular disorders, ILD

-more toxicity compared to others
-DDI: PPI/H2

Answer 275

A

BRAF inhibitor

-NSCLC- BRAFV600E (with binimetinib)
-colorectal (BRAFV600E- in combo with cetuximab or panitumumab)

Specific guidelines for dose reductions with CYP3A4 inhibitors

Answer 276

A

EGFR inhibitor

-NSCLC-EGFR- -can be combined with bevacizumab or ramucirumab (unlike others)
-pancreatic (not used in clinical practice)

ADRs: rash, diarrhea,, alopecia, dry skin, conjunctivitis, paronchymia, pneumonitis, hepatotoxicity, GI perforation, ocular disorders, ILD

-increased AC with warfarin
-DDI: PPI/H2
-inc clearance with smoking
-empty stomach

Answer 277

A

EGFR inhibitor

NSCLC- EGFR

ADRs: rash, diarrhea,, alopecia, dry skin, conjunctivitis, paronchymia, pneumonitis, hepatotoxicity, GI perforation, ocular disorders, ILD

-increases AC with warfarin
-more diarrhea
-mail changes

Answer 278

A

Alkylating agent

SCLC- subsequent lines- *IF NO BRAIN METS!!!

Very well tolerated despite PI highlighting hepatotoxicity and myelosuppression

-vesicant!!
-respiratory and GI
-rhabdo: watch scr and CPK

Answer 279

A

EGFR- inhibitor

NSCLC- squamous (in combination with gem-cis)

Removed from NCCN guidelines

Answer 280

A

EGFR inhibitor

NSCLC- EGFR exon 19 deletion or exon 21 L858R
-IB-IIIA COMPLETELY RESECTED (negative margins) who received prior adjuvant chemo
-advanced/metastatic: first line- preferred over others
-advanced/metastatic: second line if T790M and not already used

ADRs: rash, diarrhea,, alopecia, dry skin, conjunctivitis, paronchymia, pneumonitis, hepatotoxicity, GI perforation, ocular disorders, ILD

-Less ADRs than others overall
-increases QTc
-decrease LVEF
-high CNS penetration
-hematologic toxicity (transient decrease in plts)
-increased pneumonitis if given after ICI

Answer 281

A

VEGF inhibitor

-NSCLC
-HCC: AFP >400 and child Pugh A only
-gastric/esophageal- second line adeno only
-colorectal (less data than bevacizumab)

Considerations:
-high risk VTE and upper GI bleed for pts with upper GI cancers
-HTN and Diarrhea

Answer 282

A

KRAS inhibitor (RAS GTPase family inhibitor)

-NSCLC- KRAS G12C mutation- locally advanced or metastatic after 1+ line of prior therapy
-colorectal (off label, KRASG12C, give with EGFR-I if able)

ADRs: hepatotoxicity, diarrhea, inc urine protein, hematologist toxicity, MSK pain, fatigue, ILD

DDI: PPI/antacids, 3A4 substrate

Also cyp inhibitor!

Answer 283

A

CTLA4 inhibitor

-NSCLC- in combo with Durvalumab + chemo
-unresectable HCC- in combo with Durvalumab

Answer 284

A

MET inhibitor

NSCLC- MET exon 14 skipping mutation

ADRs: edema (more than capmatinib and not responsive to diuretics), hypoalbuminemia, hematologic toxicity, hepatotoxicity, interstitial lung dx, elevated amylase/lipase

-minor 3A4 substrate (capmatinib is major)
-with food! (Unlike capmatinib)
-daily (longer half life)

Answer 285

A

EGFR inhibitor

NSCLC- EGFR exon 20 insertion mutation
-oral (unlike amivantamab)

ADRs: nausea, QTC, ILD, classic EGFR ADRs, edema, HF

WITHDRAWN FROM MARKET

Answer 286

A

Crizotinib and Cabozantinib

We know capmatinib and tepotinib are

Answer 287

A

FGFR inhibitor

Cholangiocarcinoma with FGFR2 fusion or rearrangement

Hyperphosphatemia, eye disorders

Answer 288

A

Topo-I inhibitor

-Pancreatic with 5FU
-Biliary tract cancer with 5FU

Rates of diarrhea and myelosuppression are pretty similar to regular irinotecan, so no huge toxicity benefit

Not a 1:1 dose conversion with conventional

More expensive

70 mg/m2, but give 50 mg/m2 for homozygous ugt1A1*28

Answer 289

A

FGFR inhibitor

Cholangiocarcinoma with FGFR2 fusion or rearrangement

Hyperphosphatemia, eye disorders

Answer 290

A

Antidote for 5FU and capecitabine (competes for intervention into RNA)

Give within 8-96 hours

Interferes with RNA false base pair activity

Can use for catastrophic overdose (not just finishing a bit early) more for pump malfunction of capecitabine suicide attempt, or
immediately found to have DPD deficiency (severe ADR with FIRST exposure)

Q6h for 20 doses (5 days)

Answer 291

A

Somatostatic analog

Pancreatic cancer- used in PNET for symptom and tumor control

Answer 292

A

Somatostatin analog

Pancreatic cancer- used in PNET for symptom and tumor control

For chemo diarrhea
-grade III-IV or persistent despite loperamide
-100-150 mcg TID (up to 500 TID) or continuous infusion 25-50 mcg/hr
-wean off, don’t stop abruptly (biliary colic)

Answer 293

A

Antimetabolite (pyramidine analog)/thymidine phosphorylase inhibitor

-gastric/esophageal- third line adeno only
-colorectal (may use with bevacizumab)

ADR: myelosuppression, fatigue

Consider barriers to taking in a pt with upper GI cancer (crush-ability, absorption)

Dose based on trifluridine component (round down)

Need CBC on day 1 and 15 of each cycle (dose adjust based on neutrophil count)

Answer 294

A

Locally advanced or metastatic basal cell carcinoma that has recurred after surgery or is not a candidate for surgery or RT

-taste changes, weight loss, muscle spasms, fatigue, GI

Oral

Check CK and scr

Answer 295

A

Hedgehog pathway inhibitor

Locally advanced basal cell carcinoma that has recurred after surgery or is not a candidate for surgery or RT

-taste changes, muscle spasms, inc CK, weight loss, fatigue, GI

Oral

Check CK and scr

Answer 296

A

VEGF- TKI

Colorectal cancer second line metastatic dx after fluoropyrimidine, Oxaliplatin, and irinotecan based chemo, and anti-VEGF therapy and and EGFR therapy (if RAS/RAFwildtype)

-VEGF toxicities
-increased triglycerides/cholesterol, thrombocytopenia, infections
-more selective than regorafenib (and probably less toxicities)

Answer 297

A

EGFR inhibitor

Colorectal cancer (only if KRAS wildtype)

-Skin/hair/nail toxicities are most common especially acniform rash (less than with cetuximab- don’t need Benadryl)
-diarrhea
-hypomagnesemia!!
-paronychia, mucositis: both of these more than cetuximab

Answer 298

A

VEGF inhibitor

Colorectal cancer- only given with irinotecan based regimen

Most people use bevacizumab for the VEGF, this is an option but is more expensive and there is less data)

Answer 299

A

Cutaneous T-cell lymphoma

His tone deacetylase inhibitor

-GI (n/v/d), anemia, thrombocytopenia

Answer 300

A

Cutaneous T-cell lymphoma and peripheral T-cell lymphoma

Histone deacetlyase inhibitor

QTc prolongation, -GI (n/v/d), anemia, thrombocytopenia

Withdrawn from US market for PTCL but still somehow available for CTCL and listed in NCCN

Answer 301

A

Antimetabolite

Peripheral T cell lymphoma and cutaneous T cell lymphoma

Need b12 supplementation like pemtrexed

For drug interactions think of one’s similar to MTX

Answer 302

A

Peripheral T cell lymphoma

Histone deacetylase inhibitor

Reduce dose if homozygous ugt1A1*28

Answer 303

A

“Other” regimen for subsequent line follicular lymphoma

Answer 304

A

Single dose G-CSF

There should be at least 14 days between dose and next chemo cycle (unlike pegfilgrastim which is 12 days)

Answer 305

A

Reversal agent for ifosphamide neurotoxicity

Adrs: seratonin syndrome, hemolysis

Answer 306

A

Reversal agent for ifosphamide neurotoxicity

Adrs: seratonin syndrome, hemolysis

Answer 307

A

NSCLC- ROS-1 positive

With or without food

Good activity against G2032R and D2033N mutations in ROS1

Dizziness, dysgeusia, peripheral neuropathy, constipation, dyspnea, ataxia, fatigue, cognitive d/o, MSK weakness

Warnings: CNS effects (like lorlatinib), interstitial lung dx, hepatotoxicity, myalgia and CK elevation, hyperuricemia, fractures, embryo fetal tox

3A4 substrate AND inducer
Pgp substrate

Answer 308

A

PD-L1

Second line: esophageal squamous cell

Answer 309

A

Vedotin- MMAE, antimicrotubule
Govetecan- SN38, topo-1 inhibitor
Tesirine- SG3199, alkylating
Ozogamicin- calichimichin, Dna breaks
Deruxtecan- dxd/dx8951 (MAAA-1181a), topo-1 inhibitor
Emtansine- DM1, antimicrotubule
Soravtansine- DM4, antimicrotubule

Answer 310

A

Synovial sarcoma

Answer 311

A

Synovial sarcoma

Answer 312

A

Telomerase inhibitor

Low risk MDS in pts who have lost response to or are ineligible for epo

Answer 313

A

VegF

R/R colorectal

Answer 314

A

-Dara-VRD
-Dara-KRD
-Dara-VTD
-Dara-CyBorD

Answer 315

A

Type-1: activity against ITD and TKD

Type-2: Generally only activity against ITD

Answer 316

A

Type-1: activity against ITD and TKD

Type-2: Generally only activity against ITD

Answer 317

A

Topo inhibitors: G2 and S
Antimetabolites: S
Antimicrotubules: M
Bleomycin: G2
Hormonal drugs: G1
Asparaginase: G1
Dactinomycin: G1

Answer 318

A

Peptide receptor radioneucleotide therapy

Kinda like antibody drug conjugate except payload is radiation

Combines synthetic somatastatin dotatate with lutetium lu177

Don’t give with long acting somatostatin analog (octreotide LAR) since it has somatastatin analog- separate long acting by 4 weeks

Can use short acting octreotide but stop 24 hrs before dose

It’s for NET

Note NET found anywhere in body but most often pancreas, GIT, appendix, and lungs

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