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.
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
Which cytotoxic drugs are explicitly NON-vesicants?
- Cyclophosphamide, chloreambucil ("safe!"), melphalan: some nitr must alk agents
- Carmustine: nitrosurea alk agent
- Bleomycin: nonanthr antitumor antibio
What drug is the safest nitrogen mustard (alk agent)?
Chlorambucil [leukeran]: a nitr must alk agent
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!
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
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.
What can happen with a high dose of Cladribine [Leustatin]?
- = purine analog antimetab
- Acute & delayed onset nephrotoxicity
Special considerations with anthracycline antitumor antibiotics? What can be done?
- ALL have potential for acute or delayed cardiotoxicity - Qagent has lifetime cum max
- Can admin IV Dexrazoxane: to decr extravasation rxn; prophylaxis for doxorubicin-assoc cardiomyopathy in pts being treated for breast cancer
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
- MINIMAL BONE MARROW SUPPRESSION: woot!
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
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.
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
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
What class of cytotoxic drugs is good for CNS cancers? Why?
Nitrosurea alk agents: b/c can readily cross the BBB
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
Epirubicin [Ellence] has a unique AE. What is it?
- = anthracycline antitumor antibiotic
- Irreversible amenorrhea and premature menopause
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
Which agents are expilicitly cell-cycle NON-specific?
- Alkylating agents
- Platinum Compounds
- Anthracycline antitumor antibiotics
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
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
What unique AE to worry about with Mitomycin [Mutamycin]?
Hemolytic uremic syndrome: = microangiopathic hemolytic anemia + thrombocytopenia + IRREVERSIBLE renal failure
For which cytotoxic drugs is renal damage the dose-limiting toxicity?
Cisplatin [Platinol AQ]: also myelosuppression, and severe N/V (platinum compounds)
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
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)
For which cytotoxic drugs is CNS suppression the dose-limiting toxicity?
Penostatin [Nipent]: purine analog antimetab
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
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
Drug-resistance is common w/ this class.
Special considerations with Temozolomide [Temodar]?
- PO admin: take on empty stomach; DO NOT crush/chew
- Can cause convulsions
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
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!!
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)
What DI to worry about with Capecitabine [Xeloda]?
- = oral prodrug of 5-FU
- Can enhance fx of warfarin - monitor INR, perhaps decr warf