Considerations regarding the less-than-expected thrombocytopenia encountered with combination paclitaxel/carboplatin...

Whenever drugs are given in combination for the treatment of a disease, the potential for synergistic, additive, or antagonistic effects exists. Evaluation of the effects of drugs in combination requires that the effect of each drug as a single agent be well described. Recently, combination chemotherapy with carboplatin and paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) has met with much clinical interest. Toxicity expectations of the combination were based on the established pharmacokinetic/pharmacodynamic relationships of each drug as a single agent. In several independent studies, investigators have noted that carboplatin-associated thrombocytopenia was less than expected in patients treated with combination carboplatin/paclitaxel. Although the mechanism underlying this observation has not been identified, carboplatin underdosing, variation in analytic or computational techniques, and pharmacokinetic interactions can be ruled out as contributing factors.