ALKYLATING AGENTS
- work by cross-linking DNA strands and inhibiting protein synthesis and DNA synthesis
- PO or IV formulations
- can cause DNA mutations that lead to 2ndary malignancies (typically acute leukemias)
cyclophosphamide
Cytoxan
- alkylating agent
BOXED WARNING:
:: HEMORRHAGIC CYSTITIS ::: ensure adequate hydration & give MESNA
:: MESNA - chemoprotectant
:: give as pre-med with high doses of cylclophosphamide
:: myelosuppression
SIDE EFFECT
:: SIADH
ifosfamide
Ifex
-alkylating agent
BOXED WARNING
:: HEMORRHAGIC CYSTITIS: ensure adequate hydration and give MESNA
:: Mesna is chemoprotectant, must give prophylactically with ifosfamide
:: myelosuppression
:: neurotoxicity
dacarbazine
DTIC-Dome
- alkylating agent
- protect from light
- decomposed drug turns PINK
BOXED WARNING
:: hepatic necrosis
bendamustine
Bendeka
- alkylating agent
BOXED WARNING
:: myelosuppression
WARNINGS
:: hepatotoxicity
PLATINUM-BASED COMPOUNDS
- cross-link DNA & interfere with DNA synthesis and cell replication
- platinum content causes toxicities that resemble heavy metal poisoning
- peripheral sensory neuropathy
- ototoxicity
- nephrotoxicity
-require RENAL DOSE ADJUSTMENTS due to renal elimination
BOXED WARNINGS
:: anaphylactic-like reactions & risk increases with repeated exposure caution when >6 cycles of carboplatin
SIDE EFFECTS
:: peripheral neuropathy –> cumulative dose related
:: myelosuppression
cisplatin
Platinol
- platinum-based compound
- highest incidence of nephrotoxicity and CINV among platinums
- highly emetogenic: use 3 drug regimen
- cumulative nephrotoxicity & ototoxicity
- monitor renal function
- monitor Mg + K (levels may decrease)
- adequate IV hydration (1-2L) before each dose
BOXED WARNINGS
:: myelosuppression
:: renal & oto- toxicity –> doses >100mg/m2/cycle must be confirmed with prescriber
CONTRAINDICATIONS
:: pre-existing renal impairment or hearing impairment
:: myelosuppression
carboplatin
Paraplatin
- platinum-based compound
- AUC dosing = Calvert Formula
total dose (mg) = (target AUC) x (GFR + 25)
*AUC 2-8mg/mL
*GFR capped at 125mL/min - myelosuppression is dose-related
BOXED WARNING
:: myelosuppression
:: caution for anaphylactic-like reactions when >6 cycles carboplatin used
oxaliplatin
Eloxatin
- platinum-based compound
- acute sensory neuropathy
- occurs 1-7 days after administration
- exacerbated by cold exposure
ANTHRACYCLINES
- work via intercalation into DNA, inhibiting topoisomerase II
- CREATE OXYGEN-FREE RADICALS THAT DAMAGE CELLS
- CARDIOTOXICITY with all
- manifested as cardiomyopathy & heart failure
- risk related to total cumulative dose over lifetime
- best defined for DOXORUBICIN
- use dexrazoxane (Zinecard) for cardioprotection at higher doses
- potent VESICANTS
- not for liposomal anthracyclines
- use dexrazoxane (Totect) for accidental doxorubicin extravasation
How to reduce DOXORUBICIN cardiotoxicity:
- keep track of total lifetime cumulative dose
- lifetime max dose = 450-550mg/m2
- monitor LVEF before and after treatment
- ECHO or MUGA
- DEXRAZOXANE (Zinecard) = chemoprotectant
- consider when cumulative dose >300mg/m2
ZINECARD
dexrazoxane = chemoprotectant for prevention of doxorubicin-induced cardiotoxicity
- higher doses than TOTECT
TOTECT
dexrazoxane = antidote for accidental doxorubicin extravasation
doxorubicin
Adriamycin
- anthracycline
- potent vesicant
- red urine discoloration
- N/V give antiemetics
BOXED WARNING
:: myocardial toxicity
:: vesicant
:: myelosuppression
liposomal doxorubicin
Doxil
- not a vesicant
- red urine discoloration
BOXED WARNINGS
- myocardial toxicity
- infusion-related reactions
- myelosuppression
SIDE EFFECTS
hand-foot syndrome
mitoxantrone
Novantrone
- irritant with vesicant-like properties
- blue urine discoloration
Boxed Warnings
- myocardial toxicity
- myelosuppression
- secondary malignancy
anthracenedione = related to anthracyclines
