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Carboplatin: Mechanism of Action, Adverse Effects, Contraindications, and Dosing

Mechanism of Action of Carboplatin

Carboplatin exhibits pharmacologic properties similar to cisplatin. It forms covalent DNA adducts that produce intra- and interstrand crosslinks, thereby inhibiting DNA replication and transcription, inducing DNA strand breaks, and ultimately triggering programmed cell death (apoptosis).

Urologic Indications for Carboplatin Chemotherapy

• Adjuvant chemotherapy for stage I seminoma after orchiectomy as an alternative to active surveillance or (less commonly) adjuvant radiotherapy. Chemotherapy may be considered in patients with a higher risk of relapse, such as a primary tumor >4 cm and rete testis invasion.
• Chemotherapy for metastatic urothelial carcinoma in patients not eligible for cisplatin in combination with gemcitabine.

Pharmacokinetics

Carboplatin is administered intravenously. Renal excretion predominates, with most of the dose eliminated unchanged; in patients with normal kidney function, approximately 70% is excreted in the urine within 24 hours. Protein-bound platinum displays a substantially longer terminal half-life of several days.

Adverse Effects of Carboplatin

Bone marrow suppression is the dose-limiting toxicity. The nadir in platelet and white blood cell counts typically occurs 2–3 weeks after administration, with recovery over approximately 5–6 weeks.

Nausea and vomiting are common, though generally less frequent than with cisplatin. Additional toxicities include nephrotoxicity and neurotoxicity (both less frequent than with cisplatin), anaphylaxis or hypersensitivity reactions, genotoxic effects (effective contraception is recommended), and, less commonly, ototoxicity.

Carboplatin and Drug Interactions

Avoid nephrotoxic and ototoxic medications (for example, aminoglycosides or high-dose loop diuretics). Do not administer live vaccines during or shortly after chemotherapy.

Contraindications to Carboplatin

Hypersensitivity to platinum compounds, marked bone marrow suppression, active clinically relevant bleeding, severe thrombocytopenia, pregnancy and lactation, and severe renal insufficiency (GFR < 20 ml/min).

Dosing of Carboplatin

Clinicians calculate the carboplatin dose using the Calvert formula, which uses the glomerular filtration rate (GFR) in ml/min and a target area under the curve (AUC).

Carboplatin [mg] = Target AUC × (GFR + 25)

One may determine GFR using a 24-hour urine collection for creatinine clearance, or estimate it with the Cockcroft–Gault equation (less accurate). Administer the calculated dose as a 60-minute intravenous infusion.

• For stage I seminoma, a target area under the curve (AUC) of 7 is used
• For metastatic urothelial carcinoma in combination with gemcitabine, a target AUC of 4–5 is commonly used.

Antiemetic Premedication:

For target AUC ≥ 4 (highly emetogenic): Day 1: a 5-HT₃ receptor antagonist + dexamethasone + an NK1 receptor antagonist (e.g., aprepitant or fosaprepitant); consider olanzapine. Days 2–3: dexamethasone (± olanzapine) per guidelines.

References

R. S. Go and A. A. Adjei, “Review of the comparative pharmacology and clinical activity of cisplatin and carboplatin,” J Clin Oncol, vol. 17, no. 1, pp. 409–22, 1999.

R. T. D. Oliver et al., “Randomized trial of carboplatin versus radiotherapy for stage I seminoma: mature results on relapse and contralateral testis cancer rates in MRC TE19/EORTC 30982 study (ISRCTN27163214).,” J Clin Oncol, vol. 29, no. 8, pp. 957–962, 2011.

T. Tandstad et al., “Treatment of stage I seminoma, with one course of adjuvant carboplatin or surveillance, risk-adapted recommendations implementing patient autonomy: a report from the Swedish and Norwegian Testicular Cancer Group (SWENOTECA).,” Ann Oncol, vol. 27, no. 7, pp. 1299–1304, 2016, doi: 10.1093/annonc/mdw164.

  Deutsche Version: Nebenwirkungen und Kontraindikationen von Cisplatin

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