Chemotherapy Drugs Flashcards
Bleomycin
- B of BEP for germ cell, sometimes sex cord stromal
- MOA: G2-M phase specific antibiotic; breaks DNA bonds. Iron is necessary cofactor for free radical generation
- Clearance: renal
- Dose limiting = pulmonary fibrosis 10% (enhanced by oxygen and radiation therapy)
- Patient must have PFTs before starting each cycle, look at *DLCO (diffusing capacity), VC – must d/c if 15% decrease in either of these or if fine rales on lung exam
- Toxicity – skin reactions #1, hypersensitivity (fever/chills) in 25%, alopecia, MILD myelosuppression
- Inc sx’s w/ cumulative dose >400units
Carboplatin
- MOA: alkylating agent
- Clearance: renal
- Myelosuppression: especially thrombocytopenia (nadir day 21)
- Should be infused AFTER taxol to prevent delayed taxol excretion and toxicity (cisplatin too)
- Hypersensitivity reactions – increase from 1% to 27% after 7 doses
- Peripheral neuropathy (10%)
- Amenorrhea
- emetic but not as much as CDDP
- Alopecia uncommon
Cisplatin (CDDP)
- Cervical, germ cell – P in BEP
- MOA: alkylating agent
- Clearance: renal
- Damages distal renal tubule (Mg/K/Ca loss), hydrate, hydrate, hydrate
- Nausea/vomiting: more than carboplatin
- Ototoxicity:contraindicated in pts with preexisting hearing deficiency
- Neurotoxicity
- Myelosuppression: at 2 weeks
- hypersentivity: facial edema, wheezing, bronchospasm, hypotension
- Alopecia
Adriamycin (Doxorubicin)
-Carcinosarcoma, ovarian
-MOA: Antibiotic (anthracycline from streptomyces) inhibits topoisomerase II, directly binds DNA and generates free radicals
-Toxicities = #1 myelosuppression (leukopenia most common, nadir 10-14d)
-Mild N/V
-Radiation recall, hypersensitivity to sun
-Universal alopecia
-Extravasation necrosis
-Stomatitis
-Cardiotoxic (Cardiotoxicity. Acute: 2–3 days as arrhythmias, EKG changes, pericarditis, and/
or myocarditis. Usually transient and mostly asymptomatic and not dose related. Chronic: form a dose-dependent (cumulative doses are greater than 450 mg/m2), dilated cardiomyopathy & CHF.
-Metabolized by liver, excreted in bile (look at bili level…)
-MUGA or echo before starting..
-Pts get red-orange urine
-patients with prior mediastinal/pericardial irradiation, concomitant use of other cardiotoxic drugs, doxorubicin exposure at an early age, and advanced age
Liposomal doxorubicin (Doxil)
- Recurrent ovarian, carcinosarcoma, endometrial
- -#1 myelosuppression (leukopenia most common) increase in PPE (usually after 2-3 cycles), mild nausea
- Infusion reaction: low back pain, flushing, chest tightness, SOB, hypotension – stop infusion, restart at slower rate in 30 minutes
- Not as cardiotoxic (SCM says no MUGA)
- Mucositis
- Alopecia
- Radiation recall
- Red/orange urine
- Hepatic metabolism
Etoposide (VP 16)
- Salvage ovarian, cervical, E in BEP for germ cell, E in EMACO for trophoblastic disease
- Inhibits DNA topoisomerase II, alkaloid extracted from the podophyllum peltatum mandrake
- Hepatically metabolized, 30-50% excreted in urine
- Toxicity: myelosuppression (leukopenia), mild N/V esp w/ oral dose, alopecia (2/3), AML (2% after total dose 2000mg/m2), , hypotension if rapidly infused, anaphylaxis most common with first infusion
Gemcitabine (Gemzar)
- Recurrent ovarian cancer
- MOA: Nucleoside analog/Antimetabolite
- Clearance: renal
- Toxicity – #1 myelosuppression (leukopenia/plt), pulm fibrosis, GI, rash, diarrhea, stomatitis, mild nausea
- Flu like sx’s
Ifosfamide
- Recurrent/advanced cervical cancer, Carcinosarcoma, high grade ESS
- MOA: Alkylating agent
- Mesna & hydration protect bladder
- Hepatically metabolized, renally cleared
- Toxicity = hemorrhagic cystitis from acrolein metabolite; lethargy/confusion/seizure/coma from chloracetaldehyde metabolite (exacerbated by hypoalbuminemia) antidote is methylene blue, N/V, alopecia (80%), myelosuppression (leukopenia), infertility
Methotrexate
- Ectopic, Trophoblastic disease
- MOA: Antimetabolite: Folate antagonist, inhibits DHFR, purine analog(A/G) – inhibits DNA and RNA synthesis
- Cell cycle specific – S phase
- Clearance: renal
- Toxicity: N/V, stomatitis usually 3-7 days after tx, myelosuppression (#1), diarrhea, hepatotoxicity, pneumonitis, skin rash, radiation recall
Paclitaxel (Taxol)
-Ovarian, uterine (carcinoma and carcinosarcoma), cervix
-MOA: Stabilizes microtubules, Cell cycle specific M
-Mech of chemo resistance? MDR (multi drug resistance ) gene
-From the Pacific yew tree, Taxus brevifolia
Clearance: Hepatically metabolized, P450
-Plasma clearance is inhibited by platinum compounds, so taxol is given before Carbo/CDDP
-3 hr dosing has more neurotoxicity, 24 hour dosing has more myelosuppressive toxicity
-Acute HSR(20-40% of pts) almost always within first 10 minutes of infusion
-Toxicity: Neurotoxicity (dose dependent), alopecia, myelosuppression, bone pain, transient bradycardia, joint pain day 3
Docetaxel (Taxotere)
- Recurrent/primary ovarian
- MOA: Antimicrotubule, cell-cycle specific-M
- Hepatic metabolism, p450
- Myelosuppression(neutropenia nadir d 7-10), HSR usually with first or second treatment, fluid retention syndrome-increases with increasing total dose, rash, brown discoloration of nails, alopecia, mucositis, generalized fatigue & asthenia, vesicant
Dactinomycin
- MOA: anti-tumor antibiotic. Prevents DNA synthesis by binding G&C base pairs. makes ROS
- mainly biliary excretion 50%, renal 20%
- used with GTD
- Sig N/V alone is dose limiting, vesicant, hyperpigmentation/radiation recall, mucositis/diarrhea
Topotecan (Hycamtin)
-Recurrent ovarian, advanced / recurrent cervical
-MOA: Semisynthetic derivative of camptothecin, alkaloid extract of the camptotheca acuminata tree
Inhibits Topoisomerase I
-Renally excreted
-Toxicity: N/V, myelosuppression #1(neutropenia nadir at 7-10d) , fatigue, diarrhea, mild alopecia, mild vesicant
Cyclophosphamide (Cytoxan)
- MOA:Alkylating agent
- metabolized in liver, cleared renally
- Toxicities: Myelosuppression dose limiting
- Urinary (dysuria, hemorrhagic cystitis with high doses)
- Alopecia with high dose
- Amenorrhea with possible permanent sterility
- N/V
- increased risk of secondary malignancy (AML & bladder cancer)
- SIADH
- cardiac toxicity
5-FU (5-Flourouracil)
-Capcitabine (metabolized to 5FU)
- MOA: Nucleoside analog
- Cell cycle specific to S phase
- Metabolized hepatically, Renally excreted
- Toxicity: myelosupression, mucositis, diarrhea, PPE, Neurologic toxicity manifested by somnolence, confusion, seizures, cerebellar ataxia, and rarely encephalopathy. Cardiac symptoms of chest pain, EKG changes, and serum enzyme elevation. Blepharitis, tear-duct stenosis, acute and chronic conjunctivitis.
