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GYO Boards > Chemo > Flashcards

Chemo Flashcards

1
Q

Vesicant Chemos

A

Anthracyclines (Adria)
Act-D
Vincas (vincristine, vinblastine, vinorelbine)
Mitomycin-C

(Cisplatin)

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2
Q

Need dose adjustment for hepatic function

A 
Anthracyclines (adriamycin)
Act-D
Texans (taxol, taxotere)
Vinca alkaloids (vincristine, vinblastine, vinorelbine)
Irinotecan
5-FU
Gemcitabine
MTX
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3
Q

What chemos cause alopecia?

A 
Taxol (taxotere not as much)
Adriamycin/doxil not as much
Cyclophosphamide 
Etoposide
Vinca alkaloids
5-FU
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4
Q

What causes CNS toxicity with Ifosfamide?

…Hemorrhagic cystitis?

A

Chloracetaldehyde (methylene blue)

Acrolein (Mensa)

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5
Q

3 hour taxol infusion

A

More neurotoxicity

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6
Q

24 hour taxol infusion

A

More myelosuppresion

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7
Q

Taxol before cisplatin

A

Less myelosuppresion

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8
Q

Which chemos require dose reduction for kidney function?

A 
Platinums
Bleomycin
Melphalan
Topotecan
Mitomycin-C
Hydroxyurea
Capecitabine
Cytoxan
MTX
Ifosfamide
Alimta
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9
Q

Topoisomerase I Inhibitors

A

Topotecan

Irinotecan

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10
Q

Topoisomerase II inhibitors

A

Etoposide
Adriamycin
Mitoxantrone

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11
Q

Which chemos cause secondary malignancies?

A 
Etoposide
Cytoxan
Cisplatin
Melphalan
Ifosfamide
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12
Q

Calvert’s formula

AKA AUC

A

Carboplatin (4-6)

Dose = AUC * (GFR+25)

GFR is a function of weight

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13
Q

Vinca alkaloids:

  • Mechanism of action (cell cycle specificity)
  • Toxicity
  • Misc
A

Vincristine, Vinorelbine

  • Prevent microtubule polymerization (M-phase specific)
  • Constipation/ileus, alopecia, peripheral neuropathy (ataxia, foot drop, muscle wasting), leukopenia; SIADH, ARDS
  • Not much nausea, VESICANT; vincristine can cause autonomic neuropathy

*Hepatic excretion/dose adjustment

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14
Q

Taxol

  • Mechanism of action (cell cycle specificity)
  • Toxicity
  • Misc
A

Taxane

  • Stabilizes microtubules, preventing cell division (M phase specific)
  • Myelosuppresion (increased with 24 vs 3 hour infusion), neurotoxic (increased with 3 hour vs 24 hour infusion), hypersensitivity (cremphor), alopecia, asymptomatic bradycardia, cough/dyspnea/pneumonitis
  • Premed with H2 blockers, H1 blocker and dexamethasone

*Hepatic dose reduction

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15
Q

Cytoxan/Cyclophosmamide

  • Mechanism of action (cell cycle specificity)
  • Toxicity
  • Misc
A

Traditional alkylator - nitrogen mustard

  • Interstrand DNA cross links (N-7 on guanine) (cell cycle non-specific)
  • Myelosuppresion, SIADH, alopecia, secondary malignancy, hemorrhagic cystitis at high doses, cardiotoxicity (myocyte necrosis or myopericarditis), N/V, pulmonary fibrosis
  • Require activation in liver —> CANNOT USE IP

Renal dose adjustment

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16
Q

Ifosfamide

  • Mechanism of action (cell cycle specificity)
  • Toxicity
  • Misc
A

Traditional alkylator - nitrogen mustard
-Interstrand DNA crosslinks (N-7 on guanine) (cell cycle non-specific)
-Hemorrhagic cystitis, myelosuppresion, neurotoxicity (CNS), renal failure,
Fanconi syndrome, N/V, constipation, alopecia, hepatotoxicity, SIADH
-PRODRUG; CNS toxicity more likely with low albumin, older age

*Renal/hepatic dose adjustment

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17
Q

Melphalan

  • Mechanism of action (cell cycle specificity)
  • Toxicity
  • Misc
A

Traditional alkylator - nitrogen mustard

  • DNA Interstrand crosslinks (N-7 on guanine)
  • myelosuppresion, alopecia, mucositis, diarrhea, interstitial pneumonitis/pulmonary fibrosis
  • Renal dose adjustment, secondary malignancies
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18
Q

Methotrexate

  • Mechanism of action (cell cycle specificity)
  • Toxicity
  • Misc
A

Antimetabolite - folate antagonist

  • Inhibits dihydrofolate reductase (DHFR) (S phase specific)
  • leukopenia, interstitial pneumonitis, alopecia (at high doses), stomatitis/mucositis, hepatotoxicity and renal toxicity
  • High dose crosses BBB; leukovorin rescue

*Hepatic and renal dose adjustment

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19
Q

Pemetrexed

  • Mechanism of action (cell cycle specificity)
  • Toxicity
  • Misc
A

AKA Alimta
Antimetabolite - folate antagonist
-Inhibits three enzymes in folate metabolism (thymidylate synthase, DHFR, glycinamide ribonucleotide formyltransferase)
-Fatigue, myelosuppression, rash, ocular toxicity
-Give with folate and B12

*renal and hepatic dose adjustment

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20
Q

Fluorouracil (5-FU)

  • Mechanism of action (cell cycle specificity)
  • Toxicity
  • Misc
A

Antimetabolite - pyrimidine analog

  • Inhibits thymidylate synthase (S phase specific)
  • Myelosuppresion, mucositis, hand-foot, diarrhea, skin discoloration, nail changes, cerebellar ataxia, cardiac ischemia
  • Give following HD; Efudex cream for vulvar; crosses blood-brain barrier

*Hepatic dose adjustment

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21
Q

Capecitabine (Xeloda)

  • Mechanism of action (cell cycle specificity)
  • Toxicity
  • Misc
A

Antimetabolite - pyrimidine analog

  • Prodrug of 5-FU —> inhibits thymidylate synthase (S phase specific)
  • hand-foot, diarrhea, N/V, rash, mucositis
  • Renal dose adjustment

ORAL form of 5-FU - converted intracellularly more efficiently in tumor cells than normal

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22
Q

Gemcitabine

  • Mechanism of action (cell cycle specificity)
  • Toxicity
  • Misc
A

Antimetabolite

  • Inhibits DNA replication (but not S phase specific)
  • Leukopenia, thrombocytopenia, N/V, mucositis, flu-like syndrome, edema; radiation recall, rare ARDS/pulmonary toxicity
  • Prodrug

*Hepatic dose adjustment

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23
Q

Cisplatin

  • Mechanism of action (cell cycle specificity)
  • Toxicity
  • Misc
A

Platinum

  • Intrastrand DNA crosslinks (N-7 of guanine) (cell cycle non-specific)
  • Very emetogenic, nephrotoxic, neurotoxicity (ototoxicity), hypomag/K, myelosuppression
  • HYDRATION with Mg and K

*Renal dose adjustment

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24
Q

Carboplatin

  • Mechanism of action (cell cycle specificity)
  • Toxicity
  • Misc
A

Platinum

  • Intrastrand DNA crosslinks (N-7 of guanine) (cell cycle non-specific)
  • myelosuppression (esp thrombocytopenia), N/V
  • AUC

*Renal dose adjustment

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25
Q

Oxaliplatin

  • Mechanism of action (cell cycle specificity)
  • Toxicity
  • Misc
A

Platinum

  • Intrastrand DNA crosslinks (N-7 of guanine)
  • Neuropathy (cold), hepatotoxicity
  • Colon cancer

*Renal dose adjustment

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26
Q

Bleomycin

  • Mechanism of action (cell cycle specificity)
  • Toxicity
  • Misc
A

Antitumor antibiotic

  • Inhibits DNA synthesis/repair (G2 specific)
  • Pulmonary fibrosis, hyperpigmentation, NOT myelosuppresive or emetogenic
  • Requires metal ion cofactor - primarily copper, but also nickel, manganese and cobalt

*Check DLCO; max dose 400U

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27
Q

Dactinomycin/Act-D

  • Mechanism of action (cell cycle specificity)
  • Toxicity
  • Misc
A

Antitumor antibiotic

  • Intercalates into DNA and inhibits transcription of RNA (cell cycle non-specific but most active in G1)
  • Nausea, diarrhea, alopecia, hyperpigmentation, mucositis/stomatitis, myelosuppresion, hepatotoxicity, radiation recall dermatitis
  • Vesicant

*Hepatic dose adjustment

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28
Q

Mitomycin-C

  • Mechanism of action (cell cycle specificity)
  • Toxicity
  • Misc
A

Antitumor antibiotic

  • Inhibits DNA synthesis
  • CHF (doses > 30 mg/m2), fever, alopecia, N/V, myelosuppresion, nail changes, HUS

*Renal dose adjustment

29
Q

Etoposide/VP-16

  • Mechanism of action (cell cycle specificity)
  • Toxicity
  • Misc
A

Epidophyllotoxin (from the Mandrake plant)

  • Topoisomerase II inhibitor (S-G2 specific); also binds tubulin
  • Myelosuppression, mucositis, N/V, alopecia, secondary malignancy (MLL 11q23 leukemia 1-3 years), vasospastic angina
  • Hypotension 2/2 polysorbate 80; irritant
  • Renal and hepatic dose adjustment*
  • Risk of leukemia increases after cumulative dose of > 2000
30
Q

Irinotecan

  • Mechanism of action (cell cycle specificity)
  • Toxicity
  • Misc
A
  • Topoisomerase I inhibitor
  • Diarrhea (severe), neutropenia, N/V, cholinergic rxn (rhinitis, salivation, diaphoresis, flushing), alopecia, hepatotoxicity
  • Prodrug?

*Hepatic dose adjustment

31
Q

Topotecan

  • Mechanism of action (cell cycle specificity)
  • Toxicity
  • Misc
A

Camptothecin

  • Topoisomerase I inhibitor (M phase specific)
  • leukopenia/thrombocytopenia, N/V (mild), alopecia, mucositis, myalgia/arthralgia, rash, increased LFTs

*Renal dose adjustment

32
Q

Adriamycin/Doxorubicin

  • Mechanism of action (cell cycle specificity)
  • Toxicity
  • Misc
A

Anthracyclines

  • Inhibit topoisomerase II, inhibits RNA/DNA synthesis (cell cycle non-specific)
  • Myelosuppresion, cardiac toxicity - CHF at doses > 450/550 mg (get pre-treatment MUGA), radiation recall, secondary malignancies (1-3 years), N/V, red urine/tears, mucositis, VESICANT
  • Requires IRON; dexrazoxane chelates iron and reduces cardiomyopathy risk; also use for extravisation; DOES NOT CROSS PLACENTA

*Hepatic dose adjustment

33
Q

Doxil/liposomal doxorubicin

  • Mechanism of action (cell cycle specificity)
  • Toxicity
  • Misc
A

Anthracyclines

  • Inhibits topo II, DNA/RNA synthesis (cell cycle non-specific)
  • Less alopecia, myelosuppresion, nausea/vomiting, cardiotoxicity BUT MORE hand-foot syndrome (PPE), mucositis and infusion rxns; radiation recall dermatitis
  • Irritant rather than vesicant

*Hepatic dose adjustment

34
Q

Chemos effected by drug efflux pump

A

Doxorubicin, etoposide, vinca alkaloids, taxanes, topotecan, MTX

35
Q

Skipper-Schabel-Wilcox Model (AKA Log-Kill Model)

A

Constant exponential rate of tumor cell growth (constant doubling time) therefore, cell should be killed at a constant exponential rate

36
Q

Gompertzian Model

A

Cell growth is not constant —> initial tumor growth is first order, however later growth is much slower as tumor enlarges; therefore, log-kill greater for smaller tumors than larger ones

37
Q

Norton-Simon Hypothesis

A

Smaller tumors regrow at a higher growth fraction

**idea of increased intensity or sequential therapy/dose-dense schedule

38
Q

Goldie Coldman Hypothesis

A

Populations of cells within a tumor are capable of randomly mutation and becoming resistant to chemotherapy —> occur at 1 in 10^6 (tumor is not yet detectable)

**To avoid resistance, use non-cross-resistant chemotherapy or alternating

39
Q

Hexalan (Altretamine)

  • Mechanism of action (cell cycle specificity)
  • Toxicity
  • Misc
A

Alkylator

  • DNA crosslinker or anti-metabolite (cell-cycle non-specific)
  • myelosuppresion, N/V, neuropathy, renal toxicity, ataxia/seizures/mood disorder
  • Prodrug requires metabolism in liver
40
Q

Taxotere (docetaxel)

  • Mechanism of action (cell cycle specificity)
  • Toxicity
  • Misc
A

Taxane

  • Stabilizes microtubules, preventing cell division (M phase specific)
  • Myelosuppression (more than taxol), hypersensitivity, edema/fluid retention (2/2 polysorbate 80), less alopecia
  • Premed with dexamethasone to decrease edema

*Hepatic dose reduction

41
Q

Radiation recall chemotherapy

A

Anthracyclins
Act-D
Gemcitabine
(Etoposide)

42
Q

Bevacizumab/Avastin

  • Mechanism of action (cell cycle specificity)
  • Toxicity
  • Misc
A

Humanized monoclonal antibody

  • Binds to VEGFA and prevents binding to the VEGFR - decreases angiogenesis
  • Hypertension, headache, delayed healing, thrombosis, fistulas
  • Hold for proteinuria
43
Q

Bortezomib/Velcade

  • Mechanism of action (cell cycle specificity)
  • Toxicity
  • Misc
A

Small molecule inhibitor

  • proteosome inhibitor - promotes apoptosis
  • peripheral neuropathy, thrombocytopenia, N/V/D, rash, sudden cardiac death
  • not really used in GYN
44
Q

Cetuximab (IMC-C225)

  • Mechanism of action (cell cycle specificity)
  • Toxicity
  • Misc
A

Chimeric monoclonal antibody

  • Binds to extracellular EGFR, blocking tyrosine kinase activity
  • Nausea, rash, allergy
  • Not used in GYN
45
Q

Erlotinib/Tarceva

A

Small molecule inhibitor

  • Inhibits EGFR tyrosine kinase leading to cell cycle arrest and inhibition of angiogenesis
  • Diarrhea, rash, interstitial lung disease
  • Not used in GYN
46
Q

Evrolimus/Afinitor

A

Small molecule inhibitor

  • mTOR inhibitor —> mTOR is downstream in PI3K pathway and regulates cell growth and proliferation
  • Rash, stomatitis, infections, edema, fatigue
  • Endometrial cancer trials
47
Q

Ipilimumab/Yervoy

A

Immune checkpoint inhibitor

  • Monoclonal antibody to CTLA-4, binding and preventing interaction of T cell CTLA-4 with tumor cell CD80 and CD86
  • ‘itises (dermatitis, pneumonitis, enteritis/colitis, etc), inflammatory demyelinating polyneuropathy
  • Used in cervix cancer clinic trials with PDL-1 inhibitors; approved for melanoma
48
Q

Nivolumab/Opdivo

A

Immune checkpoint inhibitor

  • monoclonal antibody to PD-1 on T cells, preventing interaction with PDL-1 on tumor cells
  • ‘itises (dermatitis, pneumonitis, GI-itises, thyroiditis, iris inflammation), fatigue, weakness, cardiac arrhythmia
  • Clinical trials in GYN; approved in melanoma, lung cancer, urothelial
49
Q

Pembrolizumab/Keytruda

A

Immune checkpoint inhibitor

  • Monoclonal antibody against PD-1 on T cells, preventing interaction with tumor PDL-1
  • itises (dermatitis, pneumonitis, GI-itises, pituitary inflammation, thyroiditis, pancreatitis, nephritis), fatigue, arthralgia
  • Approved for MSI high or MMR cancers, NSCLC, melanoma, head/neck cancers; just approved for PDL-1 high cervix cancer
50
Q

Imatinib/Gleevac

A

Small molecular inhibitor

  • Tyrosine kinase inhibitor - designed to target Bcr-Abl fusion protein formed as a result of the PHL chromosome; also inhibits PDGF, SCR (stem cell receptor) and c-kit
  • Used in GIST and CML
51
Q

MEK inhibitors

A

Selumetinib, trametinib

  • Inhibit MEK1/MEK2
  • Used in LGSOC (clinical trial), BRAF mutated melanoma and KRAS/BRAF mutated colon cancers
52
Q

Trastuzimab/Herceptin

  • Mechanism of action
  • Toxicxity
  • Misc
A

Humanized monoclonal antibody

  • Binds to extracellular Her-2 (AKA Neu, gene = ERBB2) and inhibits signaling
  • Heart failure
  • Serous HER2 expression uterine cancers
53
Q

Gefitinib/Iressa

A

Small molecule inhibitor

  • Inhibits EGFR tyrosine kinase leading to cell cycle arrest and inhibition of angiogenesis
  • Rash, diarrhea, interstitial lung disease, corneal ulcer
  • Lung mostly
54
Q

Types of antiemetics

A

5-HT3 receptor antagonists (ondansetron, granisetron, palonosetron (aloxi))
NK1 receptor antagonists (aprepitant (emend))
Dopamine blockade (Reglan, Phenothiazine (compazine), haldol/zyprexa)
Benzodiazepine (anticipatory nausea)
Steroids (dexamethasone)

55
Q

Amifostine/Ethyol

  • Mechanism of action (cell cycle specificity)
  • Toxicity
  • Misc
A
  • Free radical scavenger; binds to cisplatin metabolites and is used to treat platinum-associated toxicity; can also use for xerostomia associated with head and neck radiation
  • Nausea/vomiting, hypotension, hypocalcemia, SJS
  • May make chemoRT less effective; differential effects on normal/cancer cells due to different concentrations of activating alkaline phosphates energy
56
Q

What chemos are prodrugs?

A

Capecitabine
Irinotecan
Ifosfamide

57
Q

What chemos cause hand-foot syndrome (PPE)?

A

Doxil, 5-FU and capecitabine, docetaxel, vinorelbine

58
Q

Which chemos are pulmonary toxic?

A

Checkpoint inhibitors cause pneumonitis
Bleomycin, alkylating agents (mitomycin-C), nitrosoureas can cause pulmonary fibrosis
Taxol can cause pneumonitis
Gemzar can cause an ARDS-like syndrome

59
Q

What chemos are cardiotoxic?

A

Cardiomyopathy: anthracyclines (adriamycin, daunomycin)
Arrhythmia: anthracyclines and taxol (5-FU rare)
Cardiac myocyte necrosis: Cytoxan
Vasospastic angina: Etoposide

60
Q

What chemos are GU toxic?

A

Kidney damage: cisplatin, MTX, nitrosoureas, mitomycin-C

Hemorrhagic cystitis: Ifosfamide, cytoxan

61
Q

What chemos can cause SIADH?

A

Vincas, high dose cytoxan, cisplatin

62
Q

What chemos are highly emetogenic?

A

Cisplatin (>50 mg/m2), cytoxan (>1500 mg/m2), carbo (AUC >4)

**Treat with 5-HT3 and dexamethasone and NK-1

63
Q

What chemos are moderately emetogenic?

A

Cisplatin (<50 mg/m2), cytoxan (750/1500 mg/m2), doxorubicin, MTX (>1000 mg/m2), Ifosfamide, high dose 5-FU

**Treat with 5-HT3 and dexamethasone

64
Q

AMG386/Trebananib

A

Monoclonal antibody
-Binds to soluble antiopoietin 1/2 and prevents interaction with receptor Tie2

**Acts through a non-VEGF dependent angiogenesis pathway

65
Q

Dexrazoxane

A

Cardioprotective agent used with adriamycin; can also use to treat Adria extravasation
-chelates iron

**Possible higher rate of secondary malignancies

66
Q

Parp Inhibitors

  • Mechanism of action
  • Toxicity
  • Misc
A

Niraparib, olaparib, rucaparib

  • Inhibit single stranded DNA damage repair via nucleotide excision repair —> thus cells are dependent upon homologous recombination for repair of these lesions; more highly active in BRCA patients since they have a defect in HR
  • Myelosuppression, HTN, fatigue
  • “Synthetic lethality; approved for trx of BRCA mutation OC and maintenance after response to a platinum based regimen
67
Q

What are SERMs?

  • Mechanism of action
  • Side effects
A

Tamoxifen and raloxifen

  • selective estrogen receptor modulators —> block the activity of E in the breast; tam is E agonist in the uterus
  • blood clots, stroke, leg swelling/pain/cramping, HA, vasomotor symptoms, fatigue, cataracts; Tam can lead to endometrial polyps/hyperplasia/carcinosarcoma; patients on raloxifene complain of worse sexual dysfunction
68
Q

Aromatase inhibitors

  • Mechanism of action
  • Side effects
A

Anastrozole, letrozole, exemestane

  • block the conversion of androgens into estrogen
  • AES fewer than SERMS; heart disease, more bone loss, and more fractures; most common AE is joint stiffness or pain; can also see muscle pain, vasomotor symptoms, vaginal dryness, carpal tunnel syndrome, thinning hair, mood swings

GYO Boards (7 decks)

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