Can carboplatin be substituted for cisplatin

Cisplatin is the cornerstone of chemotherapy regimens for advanced GCT. This agent is associated with nausea, nephrotoxicity, ototoxicity, and neurotoxicity. Carboplatin is a newer platinum analog with a better toxicity profile than cisplatin and is easier to administer. Several randomized trials have addressed the issue of whether the better tolerated carboplatin can be routinely substituted for cisplatin in combination regimens for GCT.

Investigators at MSKCC have studied the role of carboplatin in good-risk GCT as defined by the MSKCC criteria [14]. Patients were randomized to receive four cycles of standard EP versus four cycles of EC (etoposide 100 mg/m2 IV daily for 5 days plus carboplatin 500 mg/m2 IV on day 1 every 28 days). In 265 evaluable patients, the complete response rate was 90% for the EP arm versus 88% for the EC arm (P = .32). In the EC arm, 12% of patients relapsed compared with only 3% on the EP arm. The patients treated with EC had inferior event-free and relapse-free survival (P = .02 and P = .005, respectively). Overall survival was not significantly different between the two arms. The authors concluded that the EC regimen was inferior to EP.

The EORTC/MRC performed a randomized phase III trial in patients who had good-risk NSGCT that also addressed the issue of cisplatin versus carboplatin [15]. A total of 528 evaluable patients were randomized to receive four cycles of BEP (using the European regimen of etoposide 120 mg/m2 on days 1, 2, 3; bleomycin 30 units day 2; cisplatin 100 mg/m2 total over 2 or 5 days every 21 days) versus four cycles of BEC (same dose of etoposide and bleomycin, but using carboplatin AUC 5 mg/mL x min.). Complete response was 94.4% in the BEP arm and 87.3% in the BEC arm (P = .009). Failure-free survival at 1 year was 91% and 77%, respectively (P!.001). Three-year survival rate was superior for patients in the BEP arm (97% versus 90%, respectively; P = .003).

Together, these trials have demonstrated that in the treatment of patients who have good-risk metastatic GCT, carboplatin is inferior to cisplatin and should not be used.

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