Drugs Flashcards
Albumin-bound sirolimus (Fyarro)
Sarcoma
Perivascular epithelioid cell tumors
Dose reduce for hepatic impairment
DLT: mucositis/stomatitis
Atezolizumab (tecentriq)
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
Avapritinib (Ayvakit)
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
Dacarbazine (DTIC)
Sarcoma, HL
Alkylating agent - triazine
-renal and hepatic dose adjustment
-flu-like syndrome
-DTI: myelosuppression
Dactinomycin (actinomycin D, cosmegen)
Sarcoma
Antineoplastic ABX
-Max: 2500 mcg
-hepatic dose adjustment
-extravasation
DLT: myelosuppression
Denosumab (Xgeva)
Sarcoma
Giant cell tumor of bone: 120 mg q4weeks- first week give additional 120 mg on d8 and d15
-hypocalcemia, hypophosphatemia
Doxorubicin (adriamycin)
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
Pegylated Doxorubicin liposomal (doxil)
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
Eribulin (halaven)
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
Entrectinib (Rozlytrek)
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)
Gemcitabine (gemzar)
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
Drug induced fever can occur 3-4 days after tx (distinguish this from FN!!!)
Nadir is usually 7-10 days
Ifosfamide (ifex)
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
Imatinib (gleevec)
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)
Larotrectinib (vitrakvi)
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)
Methotrexate (MTX)
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, vitamins with folic acid!!!
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
Pazopanib (Votrient)
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)
Pembrolizumab (keytruda)
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
Pexidartinib (turalio)
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
Regorafenib (stivarga)
Sarcoma, CNS tumors, HCC, colorectal
TKI, VEGF
-dermatological toxicity
-hand foot syndrome
-hepatotoxicity
-wound healing
-photosensitivity
-HTN
-fatigue
-diarrhea
-mucositis
Ripretinib (Qinlock)
Sarcoma
KIT inhibitor, PDGFR-alpha blocker, TKI
-monitor BP
-echo or MUGA prior and during tx
-cyp3A4 interactions
Tazematostat (tazverik)
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
Temozolomide (temodar)
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
Trabectedin (yondelis)
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
Vinorelbine (navelbine)
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
Soft tissue sarcoma chemo regimen
First line: doxorubicin + ifosfamide
Second line: Gemcitabine + docetaxel
Angiosarcoma chemo regimen
Docetaxel/Paclitaxel + vinorelbine
Sunitinib (Sutent)
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
Bevacizumvab (avastin)
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
Carboplatin (paraplatin)
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
Carmustine (BiCNU)
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
Cisplatin (platinol)
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
Cyclophosphamide
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
Etoposide (Vepsid, VP-16)
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
Irinotecan (camptosar)
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
Leucovorin
MTX rescue therapy- rescues healthy cells- GIVE WITHIN 42 HOURS! But usually started 20-24 hours after start of MTX (too soon can reduce efficacy)
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)
Does not prevent nephrotoxicity but does reduce GI toxicity and myelosuppression
Lomustine
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
Procarbazine
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
Rituximab
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.
Teniposide (vumon, VP-26)
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
Vincristine (oncovin)
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
Glucarpidase
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.
Avelumab (bavencio)
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
BCG (Tice BCG)
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
Docetaxel (Taxotere)
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)
Enfortumab vedotin (Padcev)
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
Erdafitnib (Balversa)
FGFR inhibitor
Metastatic Bladder-FGFR/FGFR2 mutations and progressed on at least 1 line of platinum therapy (second line )
eye disorders
Mitomycin (mutamycin, jelmyto)
Anti tumor antibiotic
Bladder-NMIBC, MIBC if w/ 5-fu + RT
Nadofaragene firadenovec-vngc
(Adstiladrin)
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
Nivolumab (Opdivo)
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)
Penbrolizumab (Keytruda)
PD-1 inhibitor
Bladder- 1st line for platinum ineligible, or 2nd line, other indications
Sacituzumab govitecan (Trodelvy)
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
Vinblastine
Antimicrotubule
HL, bladder
-cell cycle specific
Myelosuppression
Increases cisplatin ototoxicity
Durvalumab
PD-L1 inhibitor
Bladder- second line, NSCLC, SCLC, cholangiocarcinoma, HCC
Trilaciclib
CDK 4/6 inhibitor
Myelosuppression prevention-given before platinum/etoposide containing regimens or a topotecan regimen for ES-SCLC
Defibrotide
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
Brigatinib (Alunbrig)
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
Crizotinib (Xalkori)
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
Lorlatinib (Lorbrena)
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)
Axitinib (Inlyta)
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
Belzutifan (welireg)
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!
Cabozantinib (cabometyx- tablets) ( cometriq- capsules)
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
Everolimus
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
IL-2
Kidney Ca
Rarely used d/t AE and better therapies available
*need excellent PFS and good renal function
Ipilimumab (Yervoy)
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
Lenvatinib (Lenvima)
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)
Sorafenib (Nexavar)
-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
Temsirolimus (Torisel)
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,
Tivozanib (Fotivda)
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
abiraterone (Zytiga, Yonsa)
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
Apalutamide (Erleada)
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!!!
Bicalutamide (Casodex)
Prostate
Antiandrogen
No monotherapy- use with LHRH agonist or antagonist to prevent tumor flare
ADR:
-class effect- crosses BBB: falls, seizures, diarrhea
Cabazitaxel (Jevtana)
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
Darolutamide (Nubeqa)
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
Degarelix (Firmagon)
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
Enzalutamide (Xtandi)
Prostate
Anti-Androgen
m0CSPC, m0CRPC, m1CRPC, m1CSPC
CNS ADRs: falls, seizures, HTN, fractures
Drug interactions! Inducer!
160 mg daily
Goserelin (Zoladex)
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
Histrelin (Vantas)
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
Leuprolide (lupron, eligard, viadur)
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
Lutetium Lu 177 vipivotide tetraxetan (Pulvicto)
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
Mitoxantrone
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
Olaparib (Lynparza)
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
Radium-223 (Xofigo)
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
Relugolix (Orgovyx)
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!!
Rucaparib (Rubraca)
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
Sipuleucel-T (Provenge)
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
Talazoparib (Talzenna)
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
Triptorelin (Trelstar)
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
Dinutuximab
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
Bleomycin (Blenoxane)
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
Etoposide phosphate (etopophos)
May be substituted for etoposide in patients with etoposide allergy
Equivalent doses
Oxaliplatin
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
Paclitaxel (Taxol)
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
Vinblastine (velban, Alkaban-AQ)
Vinca alkaloid- antimicrotubule
Testicular CA
Mesna
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
Dexrazoxane
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
Amifostine
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
Palifermin
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
Ivosidenib (Tibsovo)
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)
Valrubicin
Bladder Tis in pts who received x2 prior courses of BCG
-800 mg intravesical weekly x6
Anastrazole (arimidex)
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
Dostarlimab-gxly (Jemperli)
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)
Letrozole (Femara)
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
Megestrol (Megace)
Anti-neoplastic progestin w/ anti estrogenic properties
Low grade endometrial cancer
Mirvetuximab soravtansine-gynx (Elahere)
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
Nab-paclitaxel (Abraxane)
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
Niraparib (Zejula)
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
Pemetrexed (Alimta)
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
Tamoxifen (Nolvadex, Soltamox)
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
Tisotumab vedotin (Tivdak)
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
Topotecan (Hycamptin)
Topo-I inhibitor
Gyn- recurrent dx, SCLC
Trastuzumab (Herceptin)
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
Sodium thiosulfate
-prevents cisplatin ototoxicity in kids with non-metastatic hepatoblastoma and other non-metastatic cancers
-meclorethamine extravasation
don’t use is metastatic dx
Hyaluronidase
Vinca alkaloid extravasation
Irinotecan
Topoisomerase I inhibitor
Purine analogs
Azathioprine, mercaptopurine, thioguanine, cladrabine, clofarabine, Fludarabine, nelarabine, pentostatin
Tisagenlecleucel (Kymriah)
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
Blinatumomab (Blincyto)
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
I-MIBG (metaiodobenzylguanidine)
Radioconjugate for patients with relapsed or refractory Neuroblastoma
Nab-paclitaxel
-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
5-fluorouracil (Adracil)
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
Abemaciclib (Verzenio)
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
Ado-trastuzumab emtansine (T-DM1 Kadcyla)
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
Alpelisib (Pirqray)
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
Capecitabine (Xeloda)
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
Capivasertib (Truqap)
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
Elacestrant (Orserdu)
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
Epirubicin (Ellence)
Anthracycline
Breast cancer
Exemestane (Aromasin)
Aromatase inhibitor -steroidal
Breast- post menopausal (only premenopausal if ovarian suppression or ablation)
Fam-trastuzumab deruxtecan-nxki (Enhertu)
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
Fulvestrant (Faslodex)
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
Ixabepilone (Ixempra)
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
Lapatinib (Tykerb)
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
Iarotrectimib (
Margetuximab-cmkb (Margenza)
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
Neratinib (Nerlynx)
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
Palbociclib (Ibrance)
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
Pertuzumab (Perjeta)
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
Pertuzumab, trastuzumab, hyaluronidase-zzxf (Phesgo)
HER2
Breast-neoadjuvant and adjuvant
SubQ
Raloxifene ((Evista)
SERM
Breast cancer in post menopausal
Use over AI if poor BMD, use over tamoxifen if intact uterus
Clotting risk
Ribociclib (Kisqali)
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)
Selpercatinib (Retevmo)
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
Toremifene (Fareston)
SERM
Metastatic breast cancer- infrequently used
Triptorelin (Trelstar)
LHRH agonist
Breast: premenopausal in combination with AI or tamoxifen for ovarian suppression
IM
Tucatinib (Tukysa)
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
Bendamustine (Treanda)
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)
Melphalan
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
Chlorambucil (Leukeran)
Alkylating agent- nitrogen mustard
-Non-preferred option in chronic leukemias
-FL- historical tx
Meclorethamine
Alkylating agent- nitrogen mustard
-FDA discontinued manufacture of IV form d/t low demand
-there is a topical form for cutaneous T cell lymphoma
Busulfan
Alkylating agent- alkyl sulfonate
Mitomycin
Anti tumor antibiotic, alkylating agent-ethylene imine
Do not use if crcl<30 or scr>1.7
Thiotepa
Alkylating agent-ethylene imine
Dexamthasone
-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
Paclitaxel v docetaxel
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
Asparginase
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
Antithymocyte globulin equine (Atgam)
Immunosuppressant
MDS- Aplastic anemia
-infusion rxns
-serum sickness
Azacitadine (Vidaza, Onureg)
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%)
Cedazuridine/decitabine (Inqovi)
MDS NOT AML!!!
Cytosine deaminase inhibitor/hypomethylating agent
Oral
Cyclosporine (Gengraf, Neoral)
MDS- aplastic anemia
Calcineurin inhibitor
Decitabine (Dacogen)
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
Deferasirox (Exjade, Jadenu)
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)
Deferiprone (Ferriprox)
MDS- Second line for iron overload
Chelating agent
Oral
Can cause agranulocytosis- so use is controversial unlike others
Deferoxamine (Desferal)
MDS- for iron overload
Chelating agent
IM/SQ
Avoid in crcl<40 (like deferasirox)
Eye, ear, pulmonary toxicity
Eltrombopag (Promactra)
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
Epoetin alpha (Epogen, Procrit)
MDS
ESA
Darbepoetin (Aranesp)
MDS
ESA
Lenalidomide (Revlimid)
-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
Luspatercept (Reblozyl)
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
Filgrastim (Neupogen) and pegfilgrastim (Neulasta)
Can be used in MDS
Note: always start filgrastim within 72hs
Romiplostim (Nplate)
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
Midostaurin (Rydapt)
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
Quizartinib (Vanflyta)
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
Gilteritinib (Xospata)
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
Olutasidenib (Rezlidhia)
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
Enasidentib (Idhifa)
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
Venetoclax (Venclexta)
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
Glasdegib (Daurismo)
Hedgehog pathway inhibitor
AML- unfit for intensive therapy- give with LDAC
-need to take birth control!
-cardio toxicity/QTc
-nausea, dysgeusia
All-trans-retinoic acid (ATRA)
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)
Arsenic trioxide
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
Asparginase erwinia recombinant (Rylaze)
ALL
Use only in severe hypersensitivity (grade 3) or antibody inactivation to Peg-asparginase
Brexucabtagene autoleucel (Tecartus)
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
Calasparginase (Asparlas)
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
Cladrabine (Mavenclad, Leustatin)
Antimetabolite (purine analog)
AML, hairy cell leukemia, WM
Clofarabine (Clolar)
Antimetabolite (purine analog)
AML, ALL
Cytarabine
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
Dasatinib (Sprycel)
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
Daunorubicin
Anthracycline
AML, ALL
Red urine
Cardiotoxicity seen at 550 mg/m2
Daunorubicin and Cytarabine (Vyxeos)
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
Dexamethasone/prednisone in leukemia
Steroids are part of backbone of tx in ALL- has anti leukemic activity
Fludarabine (Fludara)
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
Gemtuzumab ozogamicin (Mylotarg)
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)
Hydroxyurea (Hydrea)
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)
Idarubicin (Idamycin)
Anthracycline
AML
Many “theoretical” advantages over daunorubicin (uptake, potency, etc.) but not proven to be better
Red urine
Imatinib (Gleevec)
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)
Inotuzumab ozogamicin (Besponsa)
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
Mercaptopurine (Purixan)
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
Nelarabine (Arranon)
Antimetabolite (purine analog)
ALL- good for R/R T-cell ALL
Neurotoxicity
Peg-Asparginase (Oncaspar)
ALL
Hydrolyses asparagine (leukemic cells cannot make)
Cap at 3750 units in adults
No more than q2wks
Tagraxofusp-ezrs (Elzonris)
Biological response modulator (anti-CD123)
Indication: blastic plasmacytoid dendritic cell neoplasm (BPDCN)
Warning: capillary leak syndrome
Thioguanine (Tabloid)
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
Axicabtagene ciloleucel (Yescarta)
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
Lisocabtagene maraleucel (Breyanzi)
CAR-T cell therapy
CD19
Relapsed refractory B-cell NHL
Ciltacabtagene autoleucel (Carvykti)
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)
Acalabrutinib (Calquence)
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
Alemtuzumab(Campath)
Anti-CD52 mAb
Chronic leukemia via compassionate use program
Asciminib (Scemblix)
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
Bosutinib (Bosulif)
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
Duvelisib (Copiktra)
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
Ibrutinib (Imbruvica)
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
Idelalisib (Zydelig)
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
Nilotinib (Tasigna)
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)
Obinutuzumab (Gazyva)
Anti-CD20 mAb
-Chronic leukemias
-FL
Could split 1st dose over 2 days on CLL to decrease infusion rxn
Ofatumumab (Arzerra)
Anti-CD20 mAb
Chronic leukemias CLL?
Exclusively available via patient access Novartis oncology program (PANO)
Omacetaxine mepesuccinate (Synribo)
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
Pentostatin (Nipent)
Adenosine deaminase (ADA) inhibitor
Hairy cell leukemia- one of the preferred initial options
Pirtobrutinib (Jaypirca)
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)
Ponatinib (Iclusig)
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
Zanubrutinib (Brukinase)
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
BiTE
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
Moxetumomab Pasudotox-tdfk
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
Brentuximab vedotin (Adcetris)
Antibody drug conjugate -CD30
Hodgkin’s lymphoma
Epcoritamab (Epkinly)
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
Glofitamab (Columvi)
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
Loncastuximab tesirine (Zynlonta)
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
Polatuzumab Vedotin (Polivy)
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!!
Prednisone
Used in DLBCL, PMBL, BL, HL, indolent lymphomas, MM
Tafasitamab (Monjuvi)
Anti-CE 19 mAb
R/R DLBCL ineligible for auto HCT; tafasitamab w/ Lenalidomide
Selinexor
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
Rituximab Hycela
SubQ
CLL, DLBCL, FL: all have different administration times and vial sizes
Must have tolerated at least one full dose of IV
Mogamulizumab-kpkc (Poteligeo)
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
90Yttrium ibritumomab tiuxetan (Zevalin)
Radiotherapy
Follicular lymphoma
Bortezomib (Velcade)
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
Carfilzomib (Kyprolis)
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
Copanlisib (Aloqopa)
P13K inhibitor
withdrawn from US market
IV
Mosunetuzumab-axgb (Lunsumio)
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
Degarelix vs relugolix
Relugolix is oral
Flutamide and nilutamide
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
Darolutamide v daratumumab v durvalumab
Darolutamide: prostate
Daratumumab: MM
Durvalumab: bladder second line
Belantamab-mafodotin-blmf (Blenrep)
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
Daratumumab (darzalex , Darzalex faspro)
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
Elotuzumab (Emplicit)
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
Elranatamab-bcmm (Elrexfio)
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
Idecabtagene vicleucel (Abecma)
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)
Isatuximab-irfc (Sarclisa)
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
Ixazomib (Ninlaro)
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
Pomalidomide (Pomalyst)
Immunomodulating agent
MM
ADR: dermatological toxicity, myelosuppression, VTE (ppx)
(Less diarrhea and rash than revlimid)
REMS- teratogen
Talquetemab-tgvs (Talvey)
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
Teclistamab (Tecvayli)
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
Thalidomide (thalomid)
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
Calcitonin
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)
Dexrazoxane (for extravasation)
-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
Aldesleukin (Proleukin)
IL-2
Melanoma
Not used much d/t toxicity and low response
Capillary leak syndrome
Binimetinib (Mektovi)
MEK inhibitor
Melanoma, NSCLC
Ocular toxicity, decrease LVEF
Cobimetinib (Cotellic)
MEK inhibitor
Melanoma (with vemurafenib)
Highest rates of ADRs of all BRAF/MEK inhibitors: rash, transaminitis, may decreased LVEF
Dabrafenib (Tafinlar)
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
Nivolumab + relatlimab (Opdualag)
PD-1 inhibitor + lymphocyte activation gene-3 (LAG3) blocking antibody
Melanoma
Relatlimab only available in this combination
Talimogene laherparepvec (Imlygic)
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
Tebentafusp (Kimmtrak)
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
Vemurafenib (Zelboraf)
BRAF inhibitor
Highest rate of AES of all BRAF/MEK combos: rash, transaminitis, QTc
Melanoma (with Cobimetinib)
Trametinib (Mekinst)
MEK inhibitor
Ovarian, Melanoma, thyroid, NSCLC-MEK, HCC
ADR: may decrease LVEF, dermatological toxicity (rash), fevers, ocular toxicity, anemia
-empty stomach
-Refrigerate
Rolapitant
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
Sargramostim
GM-CSF
Stimulates granulocytes and macrophages
-Primarily for HCT
-also indicated in AML
Eflapegrastim
Long acting G-CSF
Cetuximab (Erbitux)
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! (this is a true anaphylactic rxn!!)
-hypomagnesemia!!!
-rare aseptic meningitis
Toripalimab-tpzi (Loqtorzi)
PD-1 inhibitor
Metastatic/recurrent nasopharyngeal carcinoma (with cisplatin/Gemcitabine)- or single agent if progression on platinum
Pralsetinib (Gavreto)
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
Vandetanib (Caprelsa)
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
Benzydamine
Mucositis prevention in RT
Not approved in United States
RAI
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
Memantine
Give in BC concurrently with WBRT and x6 months after to delay cognitive decline
Adagrasib (Krazati)
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!
Afatinib (Gilotrif)
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
Alectinib (Alecensa)
ALK inhibitor
NSCLC- ALK
ADRs: fatigue, constipation, edema, myalgia, visual disturbance, pneumonitis, GI toxicity, hepatotoxicity, bradycardia, QTc, ILD
-with food
-anemia
-weight gain
Amivantamab (Rybrevant)
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
Capmatinib (Tabrecta)
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
Cemiplimab (Libtayo)
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
Ceritinib (Zykadia)
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
-
Dacomitinib (Vizimpro)
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
Encorafenib (Braftovi)
BRAF inhibitor
-NSCLC- BRAFV600E (with binimetinib)
-colorectal (BRAFV600E- in combo with cetuximab or panitumumab)
Specific guidelines for dose reductions with CYP3A4 inhibitors
Erlotinib (Tarceva)
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
Gefitinib (Iressa)
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
Lurbinectedin (Zepzelca)
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
Necitumumab (Portrazza)
EGFR- inhibitor
NSCLC- squamous (in combination with gem-cis)
Removed from NCCN guidelines
Osimertinib (Tagrisso)
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
Ramucirumab (Cyramza)
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
Sotorasib (Lumakras)
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!
Tremelimumab (Imjudo)
CTLA4 inhibitor
-NSCLC- in combo with Durvalumab + chemo
-unresectable HCC- in combo with Durvalumab
Tepotinib (Tepmetko)
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)
Mobocertinib
EGFR inhibitor
NSCLC- EGFR exon 20 insertion mutation
-oral (unlike amivantamab)
ADRs: nausea, QTC, ILD, classic EGFR ADRs, edema, HF
WITHDRAWN FROM MARKET
Which drugs that are also MET inhibitors?
Crizotinib and Cabozantinib
We know capmatinib and tepotinib are
Futibatinib (Lytgobi)
FGFR inhibitor
Cholangiocarcinoma with FGFR2 fusion or rearrangement
Hyperphosphatemia, eye disorders
Liposomal irinotecan (Onivyde)
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
Pemigatinib (Pemzayre)
FGFR inhibitor
Cholangiocarcinoma with FGFR2 fusion or rearrangement
Hyperphosphatemia, eye disorders
Uridine triacetate
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)
Lanreotide (Somatuline depot)
Somatostatic analog
Pancreatic cancer- used in PNET for symptom and tumor control
Octreotide (Sandostatin depot)
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)
Trifluridine/tipiracil (Lonsurf)
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)
Vismodegib
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
Sonidegib
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
Fruquintinib (Fruzaqla)
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)
Panitumumab (Vectibix)
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
Ziv-aflibercept
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)
Vorinostat
Cutaneous T-cell lymphoma
His tone deacetylase inhibitor
-GI (n/v/d), anemia, thrombocytopenia
Romidepsin
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
Pralatrexate
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
Belinostat
Peripheral T cell lymphoma
Histone deacetylase inhibitor
Reduce dose if homozygous ugt1A1*28
Ibritumomab tiuxetan
“Other” regimen for subsequent line follicular lymphoma
Epflapegrastim and efbemalenograstim
Single dose G-CSF
There should be at least 14 days between dose and next chemo cycle (unlike pegfilgrastim which is 12 days)
Methylene blue
Reversal agent for ifosphamide neurotoxicity
Adrs: seratonin syndrome, hemolysis
Methylene blue
Reversal agent for ifosphamide neurotoxicity
Adrs: seratonin syndrome, hemolysis
Repotrectinib
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
Tislelizumab
PD-L1
Second line: esophageal squamous cell
Vedotin, govetecan, tesirine, ozagamicin, deruxtecan, emtansine, soravtansine
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
afamitresgene autoleucel
Synovial sarcoma
afamitresgene autoleucel
Synovial sarcoma
Imetelstat
Telomerase inhibitor
Low risk MDS in pts who have lost response to or are ineligible for epo
Afilbercept
VegF
R/R colorectal
Multiple myeloma induction quad regimens
-Dara-VRD
-Dara-KRD
-Dara-VTD
-Dara-CyBorD
Type-1 vs type-2 FLT-3 TKIs
Type-1: activity against ITD and TKD
Type-2: Generally only activity against ITD
Type-1 vs type-2 FLT-3 TKIs
Type-1: activity against ITD and TKD
Type-2: Generally only activity against ITD
Chemo classes and cell cycle phases
Topo inhibitors: G2 and S
Antimetabolites: S
Antimicrotubules: M
Bleomycin: G2
Hormonal drugs: G1
Asparaginase: G1
Dactinomycin: G1
Lutetium Lu 177 dotatate
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
