Considerations regarding the less-than-expected thrombocytopenia encountered with combination paclitaxel/carboplatin chemotherapy.
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.
Kearns
C M
CM
Division of Developmental Therapeutics, University of Maryland Cancer Center, Baltimore 21201, USA.
Egorin
M J
MJ
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects* / Q000493:pharmacokinetics; D019540:Area Under Curve; D016190:Carboplatin / Q000009:adverse effects / Q000493:pharmacokinetics; D006801:Humans; D017239:Paclitaxel / Q000009:adverse effects / Q000493:pharmacokinetics; D013921:Thrombocytopenia / Q000139:chemically induced*
D016190:Carboplatin; D017239:Paclitaxel