Introduction
Cisplatin is a platinum-based chemotherapy medication that has been a cornerstone of cancer treatment since its FDA approval in 1978. It belongs to the alkylating-like agent class and remains one of the most widely used antineoplastic drugs worldwide. Cisplatin is particularly notable for its curative potential in testicular cancer and its essential role in combination regimens for various solid tumors.
Mechanism of Action
Cisplatin exerts its cytotoxic effects through formation of DNA adducts. After intracellular activation by aquation, the platinum complex binds to nucleophilic sites on DNA, primarily at the N7 position of guanine and adenine bases. This results in:intrastrand and interstrand cross-links that distort the DNA helix, inhibit DNA replication and transcription, and ultimately trigger apoptotic cell death. The drug is cell cycle non-specific but demonstrates greatest activity during the S-phase.
Indications
FDA-approved indications include:
- Metastatic testicular cancer (in combination regimens)
- Metastatic ovarian cancer (in combination regimens)
- Advanced bladder cancer
- Head and neck cancer (as monotherapy or combination therapy)
- Cervical cancer (in combination with radiation therapy)
- Non-small cell lung cancer (in combination regimens)
Off-label uses include esophageal, gastric, and endometrial cancers, among others.
Dosage and Administration
Standard dosing:- Testicular cancer: 20 mg/m² IV daily for 5 days every 3 weeks
- Ovarian cancer: 75-100 mg/m² IV every 3-4 weeks
- Bladder cancer: 50-70 mg/m² IV every 3-4 weeks
- IV infusion over 1-2 hours (6-8 hours for high-dose regimens)
- Requires pre- and post-hydration with 1-2 liters of IV fluids
- Must be administered with antiemetic prophylaxis
- Renal impairment: Dose reduction required (avoid if CrCl <60 mL/min)
- Elderly: Increased risk of toxicity; consider dose reduction
- Pediatrics: Safety established for children >1 month
Pharmacokinetics
Absorption: Not orally bioavailable; administered IV only Distribution: Widely distributed throughout body tissues; high concentrations in kidney, liver, and intestine Metabolism: Undergoes non-enzymatic conversion to active aquated species Elimination: Primarily renal excretion (90%); biphasic elimination with terminal half-life of 58-73 hours Protein binding: >90% bound to plasma proteinsContraindications
- History of severe hypersensitivity to cisplatin or other platinum compounds
- Preexisting renal impairment (CrCl <60 mL/min)
- Hearing impairment
- Myelosuppression
- Pregnancy (unless benefit outweighs risk)
- Concurrent administration with live vaccines
Warnings and Precautions
Black Box Warnings:- Cumulative renal toxicity (may be severe and permanent)
- Myelosuppression
- Anaphylactic-like reactions
- Ototoxicity (may be profound and irreversible)
- Neurotoxicity (may be irreversible)
- Electrolyte disturbances (hypomagnesemia, hypokalemia, hypocalcemia)
- Embryo-fetal toxicity
- Secondary malignancies
- Extravasation risk (causes tissue necrosis)
Drug Interactions
Major interactions:- Aminoglycosides: Increased risk of nephrotoxicity and ototoxicity
- Loop diuretics: Enhanced ototoxicity
- Nephrotoxic drugs (NSAIDs, vancomycin): Additive renal damage
- Phenytoin: Reduced phenytoin levels
- Live vaccines: Reduced vaccine efficacy
Adverse Effects
Very common (>10%):- Nausea and vomiting (dose-limiting, acute and delayed)
- Nephrotoxicity (dose-related)
- Myelosuppression (neutropenia, thrombocytopenia)
- Ototoxicity (tinnitus, hearing loss)
- Neurotoxicity (peripheral neuropathy)
- Hypomagnesemia
- Anorexia
- Diarrhea
- Elevated creatinine
- Alopecia
- Anaphylaxis
- Hemolytic anemia
- Cardiac abnormalities
- Vision loss
- Secondary leukemia
Monitoring Parameters
Baseline:- Complete blood count with differential
- Comprehensive metabolic panel (electrolytes, renal function)
- Audiogram
- Neurological assessment
- Pregnancy test
- CBC weekly
- Renal function before each dose
- Magnesium, potassium, calcium levels
- Hearing assessment periodically
- Neurological evaluation
- Long-term renal function monitoring
- Annual hearing assessment
- Surveillance for secondary malignancies
Patient Education
Key points to discuss:- Report any hearing changes, ringing in ears, or dizziness immediately
- Maintain adequate hydration (2-3 L daily unless contraindicated)
- Report signs of infection (fever, chills) or unusual bleeding
- Use reliable contraception during and for months after treatment
- Nausea management strategies (multiple antiemetics will be prescribed)
- Neuropathy symptoms (tingling, numbness in hands/feet)
- Avoid pregnancy and breastfeeding during treatment
- Schedule treatments when you can rest afterward
- Arrange for transportation after infusion
- Maintain good oral hygiene to prevent mucositis
- Report any injection site pain or redness
References
1. National Comprehensive Cancer Network (NCCN) Guidelines. Various cancer sites. 2023 2. Cisplatin prescribing information. FDA label. 2022 3. Miller RP, Tadagavadi RK, Ramesh G, et al. Mechanisms of cisplatin nephrotoxicity. Toxins. 2010;2(11):2490-2518 4. Dasari S, Tchounwou PB. Cisplatin in cancer therapy: molecular mechanisms of action. Eur J Pharmacol. 2014;740:364-378 5. American Society of Clinical Oncology (ASCO) guidelines for cisplatin use 6. McWhinney SR, Goldberg RM, McLeod HL. Platinum neurotoxicity pharmacogenetics. Mol Cancer Ther. 2009;8(1):10-16 7. UpToDate: Cisplatin drug information. Wolters Kluwer. 2023
This information is intended for educational purposes only and should not replace professional medical advice. Always consult with a qualified healthcare provider for personalized medical guidance.