Background: The purpose of this study was to look at the pharmacokinetics of docetaxel, cisplatin-derived platinum and 5-fluorouracil (5-FU), when used in combination, to exclude potential clinically relevant pharmacokinetic interactions. Methods: Fifteen patients with recurrent or metastatic solid tumors were randomized to receive docetaxel 75 mg/m2 and cisplatin 75 mg/m2 in the first treatment course on day 1 and the same combination plus 5-FU 750 mg/m2/day on days 1-5 in the second course, or the two treatment courses in reversed order. Cycles were repeated every 3 weeks. A pharmacokinetic analysis was performed during the first two cycles. Results: Full pharmacokinetic data was available for 12 of the 15 patients. Treatment was tolerated well, with frequency of toxicity consistent with the safety profile known for docetaxel, cisplatin and 5-FU. Mean clearance values for docetaxel and cisplatin showed no statistically significant difference across the "triple" and the "double" combination treatments, and the mean pharmacokinetic parameters of all agents were within the ranges for previously reported single agent treatment. Conclusion: No clinically relevant pharmacokinetic interactions between docetaxel, cisplatin and 5-FU used in combination were noticed in this study.

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Cancer Chemotherapy and Pharmacology
Erasmus MC: University Medical Center Rotterdam

Felici, A., Loos, W., Verweij, J., Cirillo, E., de Bruijn, P., Nooter, K., … de Jonge, M. (2006). A pharmacokinetic interaction study of docetaxel and cisplatin plus or minus 5-fluorouracil in the treatment of patients with recurrent or metastatic solid tumors. Cancer Chemotherapy and Pharmacology, 58(5), 673–680. doi:10.1007/s00280-006-0221-x