Carboplatin versus cisplatin in solid tumors: an analysis of the literature

Introduced into clinical usage in 1992 as a platinum analogue with a distinctively different toxicity profile from cisplatin, carboplatin has become a commonly preferred agent over cisplatin. The comparative therapeutic efficacy of the two agents remains controversial however, prompting an analysis of the phase III trials in ovarian cancer and other tumors in which the two were compared.

Clinical trials comparing carboplatin with cisplatin, both as single agents and in combination with other agents, were analyzed within the tumors for which platinum has become a standard or commonly employed agent. A Medline search identifying the randomized trials and references from these reports were collated for analysis.

The original clinical comparative trials as well as literature reviews and commentaries were reviewed. Five solid tumors were identified within which comparative trials had been conducted: ovary, 10 trials; lung, 2 trials; head and neck, 2 trials; germ cell tumors, 3 trials and 1 trial in bladder cancer. Depending upon the end point selected, cisplatin was superior or equivalent to carboplatin in therapeutic efficacy in all five tumors but was associated with an increased toxicity profile for gastrointestinal, renal and neurologic effects.

For some tumors, cisplatin appears to be superior to carboplatin in terms of therapeutic effectiveness (germ cell tumors, bladder cancer, head and neck cancer), while for others, effectiveness is comparable (lung cancer, ovarian cancer). Toxicity profiles are distinctly different for the two analogues however, generally favoring carboplatin. The issue of potential carboplatin underdosing related to the lack of physiologic dose calculations (utilizing the AUC [area under the curve] method) in the comparative trials of cis- versus carboplatin is probably not clinically important since a dose response effect has not been established for carboplatin or for cisplatin. The selection of the optimal platinum analogue to be employed is dependent on the type of tumor, the treatment intention (palliative vs. curative) and the other component drugs being used in combination.