Cancer chemotherapy and pharmacology
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Cancer Chemother. Pharmacol. · Aug 2005
Randomized Controlled Trial Clinical TrialPhase-I dose escalation and sequencing study of docetaxel and continuous infusion topotecan in patients with advanced malignancies.
Anti-tumor activity can often be enhanced with combination therapy in managing patients with metastatic cancer. However, dose sequence and schedule of delivery can alter the pharmacokinetics, toxicity, and anti-tumor response. Therefore, attention to drug-drug interactions which may be sequence or schedule-dependent are necessary. Docetaxel and topotecan are non-cross-resistance cytotoxic agents with activity in a variety of malignancies. The goal of this study was to determine the maximum tolerated dose of docetaxel and continuous infusion topotecan using two sequences of administration. ⋯ The observed toxicity was not sequence-dependent, despite the observed change in kinetics. Docetaxel and topotecan can be administered with acceptable toxicity at the recommended phase-II dose of docetaxel 60 mg m(-2) and topotecan 0.85 mg m(-2) day(-1)x3 days.