Definition
Platinum compounds are alkylating-like chemotherapeutic agents that form DNA cross-links, leading to DNA damage, replication inhibition, and apoptosis. They are widely used in the treatment of solid tumors, particularly lung, ovarian, testicular, bladder, and head & neck cancers.
Common Agents
| Drug | Brand Name | Common Indications | Route |
|---|---|---|---|
| Cisplatin | Platinol | Testicular, ovarian, bladder, lung, head & neck cancers | IV |
| Carboplatin | Paraplatin | Ovarian, lung, head & neck cancers | IV |
| Oxaliplatin | Eloxatin | Colorectal cancer (FOLFOX regimen) | IV |
Mechanism of Action
- Platinum compounds form covalent bonds with DNA, causing intra- and inter-strand cross-links.
- DNA damage triggers cell cycle arrest and apoptosis.
- Effect is cell-cycle nonspecific, but rapidly dividing cells are most sensitive.
Pharmacist-Relevant Considerations
| Toxicity / Concern | Notes / Monitoring |
|---|---|
| Nephrotoxicity | Major with cisplatin; ensure hydration and electrolyte monitoring |
| Myelosuppression | Dose-limiting for carboplatin; monitor CBC |
| Neurotoxicity | Oxaliplatin: peripheral neuropathy; cold sensitivity; usually cumulative |
| Ototoxicity | Cisplatin; audiogram monitoring in high doses |
| Nausea / vomiting | Cisplatin highly emetogenic; prophylactic 5-HT3 ± NK1 ± dexamethasone recommended |
| Electrolyte disturbances | Hypomagnesemia, hypokalemia, hypocalcemia with cisplatin; monitor electrolytes |
| Drug interactions | Avoid concurrent nephrotoxic drugs; adjust dosing with renal impairment |
Dosing Highlights
- Cisplatin: IV, cycles every 3–4 weeks; pre- and post-hydration required.
- Carboplatin: IV, dosing often calculated using Calvert formula (AUC-based); less nephrotoxic.
- Oxaliplatin: IV, usually part of FOLFOX; dose adjustments in hepatic impairment.
Supportive Care
- Aggressive hydration for cisplatin
- Anti-emetics for highly emetogenic platinum agents
- Electrolyte monitoring and replacement
- Neuropathy monitoring, especially for oxaliplatin