Cytotoxic Drugs

  1. Two antimetabolites cause myeolosuppression that can be staved off with the administration of other agents. Which antimetabolites? What other agents? When admin?
    • 1. Methotrexate: give leucovorin AFTER mtx to rescue bone marrow and GI mucosa cells
    • 2. Pemetrexed: give folic acid & B12 as prophylaxis. Add'l, give steroid to min rash.
  2. Which cytotoxic drugs are vesicants?
    • Mechlorethamine (maybe bendamustine, its deriv?): nitr must alk agent
    • ALL anthracyc antitum antibios: doxorubicin, daunorubicin, epirubicin, idarubicin, mitoxantrone
    • Dactinomycin, mitomycin: some nonanthr antitum antibios
    • ALL vinca alk mitotic inhibs: vincristine, vinblastine, vinorelbine
  3. Which cytotoxic drugs are explicitly NON-vesicants?
    • Cyclophosphamide, chloreambucil ("safe!"), melphalan: some nitr must alk agents
    • Carmustine: nitrosurea alk agent
    • Bleomycin: nonanthr antitumor antibio
  4. What drug is the safest nitrogen mustard (alk agent)?
    Chlorambucil [leukeran]: a nitr must alk agent
  5. Two purine analog antimetabolites are very similar. What are they, and how do they differ?
    • Mercaptopurine and Thioguanine
    • Mercaptopurine: extensive hepatic metab by xanthine oxidase, SO decr dose mercapto if taking xanthine oxidase inhibs (allopurinol, fubuxostat). May cause HEPATIC DYSFUNCTION, as (cholestatic jaundice) in 30% pts.
    • Thioguanine: DON'T need to decr dose if taking xanth ox inhibs!
  6. Special considerations with Fludarabine [Fludara]?
    • = purine analog antimetab
    • DON'T give with pentostatin!!
    • May cause life-threat hemolytic anemia & SEVERE NEUROLOGIC FX: blind, coma, DEATH
  7. What to worry about with Ifosfamide [Ifex]?
    • A nitr must alk agent
    • Can cause HEMORRHAGIC CYSTITIS: min w/ concurrent Mesna [Mesnex] therap + extensive hydration.
    • Watch out for DEHYDRATION
    • DO urinalysis before Qdose: if microscopic hematuria, must postpone dose.
  8. What can happen with a high dose of Cladribine [Leustatin]?
    • = purine analog antimetab
    • Acute & delayed onset nephrotoxicity
  9. Special considerations with anthracycline antitumor antibiotics? What can be done?
    • ALL have potential for acute or delayed cardiotoxicity - Qagent has lifetime cum max
    • Vesicants
    • Can admin IV Dexrazoxane: to decr extravasation rxn; prophylaxis for doxorubicin-assoc cardiomyopathy in pts being treated for breast cancer
  10. What makes Streptozocin [Zanosar] unique?
    • A nitrosurea alk agent
    • Unique MoA: contains glucose moiety that => selective uptake by pancreatic islet cells, thus
    • Unique Use: for metastatic islet cell tumors
    • Unique D-L tox: renal damage - assess pre-therap & monitor
  11. How is estramustin [emcyt] different?
    • A nit must alk agent
    • Chem struct similar to estrogen
    • PALLIATIVE (not curative) for metastatic or progressive carcinoma of the prostate
    • Can cause thrombosis
  12. There are two purine analog antimetabs that CANNOT be combined. What are they and why not?
    • Pentostatin and Fludarabine.
    • This combo is CONTRAINDICATED.
    • Combo => incr risk of fatal pulmonary toxicity.
  13. There is something special about Cladribine. What is it?
    • = a purine analog antimetab.
    • Has a unique MoA: inhibits both synthesis & REPAIR of DNA, thus works against both active AND RESTING cells
  14. There are 3 agents that cause very little myelosuppression, making them good candidates for combo therapy. What are they?
    • Bleomycin [Blenoxane]: a non-anthracycline antitumor antibiotic
    • Streptozocin [Zanosar]: a nitrosurea alk agent
    • Vincristine: "bone marrow sparing," a vinca alkaloid mitotic inhibitor
  15. What class of cytotoxic drugs is good for CNS cancers? Why?
    Nitrosurea alk agents: b/c can readily cross the BBB
  16. Anthracycline antitumor antibiotics have a unique AE. What is it, and how dose it vary among these agents?
    • Harmless coloring of sweat & urine
    • Red sweat & urine: doxorubicin, daunorubicin, epirubicin, idarubicin
    • Blue-green sweat & urine: mitoxantrone
  17. Epirubicin [Ellence] has a unique AE. What is it?
    • = anthracycline antitumor antibiotic
    • Irreversible amenorrhea and premature menopause
  18. Which agents are explicitly cell phase SPECIFIC?
    • Mitotic inhibitors: b/c act during mitosis
    • Antimetabolites: during active phases
    • Bleomycin: Nonanthracycline antitum antibios
    • Fluorouracil (5-FU): pyrimidine analog antimetab
  19. Which agents are expilicitly cell-cycle NON-specific?
    • Alkylating agents
    • Platinum Compounds
    • Anthracycline antitumor antibiotics
  20. Some agents have been shown to cause secondary cancers. What agents and which cancers?
    • Melphalan [Alkeran]: (a nitr must alk agent) leukemia, may be mutagenic
    • Teniposide [Vumon]: Type II topoisomerase inhibitors
  21. What to worry about with Cytarabine [Cytosar-U]?
    • = a pyrimidine analog antimetab
    • High dose: => pulmonary edema; central/periph neurotox
    • Liposomal form: can cause chemical arachnoiditis (N/V, HA, fever) - fatal if untreated
  22. What unique AE to worry about with Mitomycin [Mutamycin]?
    Hemolytic uremic syndrome: = microangiopathic hemolytic anemia + thrombocytopenia + IRREVERSIBLE renal failure
  23. For which cytotoxic drugs is renal damage the dose-limiting toxicity?
    Cisplatin [Platinol AQ]: also myelosuppression, and severe N/V (platinum compounds)
  24. For which cytotoxic drugs is peripheral neuropathy the dose-limiting toxicity?
    • Oxaliplatin: numb/ting fingers, toes, around mouth, throat. Warn to cover up, not to touch cold/chilled things.
    • Vincristine: by disrupting neurotubules req for axonal transport
    • Paclitaxel [Taxol, Abraxane]: with repeated dosing, also BM suppress
  25. For which cytotoxic drugs is oral & GI ulceration or mucositis the dose-limiting toxicity?
    • Fluorouracil, 5-FU: ulceration; also myelosuppression (mostly neutropenia), (pyrimidine analog antimetab); also D-L tox can be palmar-plantar (HFS)
    • Dactinomycin: mucositis; & myelosuppression (nonanthr antitum antibio)
  26. For which cytotoxic drugs is CNS suppression the dose-limiting toxicity?
    Penostatin [Nipent]: purine analog antimetab
  27. For which agents whose dose-limiting toxicity is myelosupression is the time of nadir unusual?
    • Carmustine: delayed BM suppress, nadir 4-6 wks after treatment (a nitrosurea alk agent)
    • Mitomycin [Mutamycin]: nadirs for neutroP and thrombocytoP 3-4 wks into treatment
  28. For which cytotoxic drugs are pulmonary problems the dose-limiting toxicities?
    • Busulfan: pulmonary infiltrates & fibrosis (also myelosuppression)
    • Bleomycin [Blenoxane}: lung injury (10% pts) = pulmonitis => pulm fibrosis => death
  29. Drug-resistance is common w/ this class.
    Alkylating agents
  30. Special considerations with Temozolomide [Temodar]?
    • PO admin: take on empty stomach; DO NOT crush/chew
    • Can cause convulsions
  31. What to worry about with Vinorelbine [Navelbine]?
    • Powerful vesicant
    • Interstitial pulmonary changes and adult respiratory distress syndrome: w/i 1wk starting treatment; most cases fatal; watch for new onset dyspnea, cough, hypoxia, other s/s lung injury
  32. The only TWO taxoid mitotic inhibitors each have unique and serious AEs. What are the agents and what AEs to watch for?
    • Paclitaxel [Taxol, Abraxane]: cardiac - bradycardia, 2nd & 3rd degree heart block, fatal MI; hypersens rxns
    • Docetaxel [Taxotere]: Incr risk of DEATH from sepsis w/ liver disease (monitor LFTs); fluid retention if liver dysfunction - edema, cardiac tamponade, dyspnea at rest, pleural effusion, ascites (can decr fluid retention w/ glucocorticoids). Monitor LFTs!!
  33. With which agents REALLY need to worry about neutrophil count and withold if neutrophils fall below certain #?
    • Docetaxel [Taxotere]: withold if <1500 (Taxoid mit inhib)
    • Topotecan [Hycamtin]: withold if <1500 (Type I top inhib)
    • Irinotecan [Camptosar]: withold if <500 or <1500? look up. (Type I top inhib)
  34. What DI to worry about with Capecitabine [Xeloda]?
    • = oral prodrug of 5-FU
    • Can enhance fx of warfarin - monitor INR, perhaps decr warf
Card Set
Cytotoxic Drugs
Important points about cytotoxic drugs for cancer