Dose escalation and pharmacokinetic study of irinotecan in combination with paclitaxel in patients with advanced cancer.

Autor: Murren, John R., Peccerillo, Kathleen, DiStasio, Susan A., Xin Li, Leffert, Janine J., Pizzorno, Giuseppe, Burtness, Barbara A., McKeon, Anne, Yung chi Cheng, Murren, J R, Peccerillo, K, DiStasio, S A, Li, X, Leffert, J J, Pizzorno, G, Burtness, B A, McKeon, A, Cheng, Y
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Zdroj: Cancer Chemotherapy & Pharmacology; Jul2000, Vol. 46 Issue 1, p43-50, 8p
Abstrakt: Purpose: Based on preclinical data demonstrating synergy between camptothecin analogues and taxanes, we determined the maximum tolerated dose (MTD) of irinotecan that could be given in combination with a fixed dose of paclitaxel of 75 mg/m2, when both drugs were delivered on a weekly schedule. The pharmacokinetics of this combination were explored to determine whether the sequence of administration affected the elimination of irinotecan.Methods: For the first cycle patients with advanced cancer were treated with irinotecan given as a 90-min infusion followed immediately by paclitaxel given at a dose of 75 mg/m2 over 1 h. The sequence of drug administration was reversed in subsequent cycles for most patients. Chemotherapy was given weekly for 4 weeks, followed by a 2-week rest. In selected patients, plasma concentrations of irinotecan were determined by high-performance liquid chromatography during the first 24 h of cycle 1 and after the first dose of cycle 2 to determine whether the order of drug administration affected the elimination of irinotecan, or the toxicologic effects of the chemotherapy.Results: A total of 53 cycles were delivered to 21 patients. Reversible neutropenia was dose-limiting. Suppression of the other blood cell elements was modest. There was one partial response in a man with a previously treated cholangiocarcinoma that lasted 26 weeks. Prolonged stabilization of disease (6 months or more) was observed in five of the patients (24%). At the recommended dose of irinotecan (50 mg/m2), transfusions of red cells and platelets were not required. The sequence of drug administration produced no significant differences in the pharmacokinetic parameters of irinotecan or SN-38, which were similar to the values reported when irinotecan is administered alone. The most prominent nonhematologic toxicities were mild diarrhea and fatigue.Conclusions: The recommended dose of irinotecan on this schedule is 50 mg/m2. The sequence of drug administration affects neither the elimination of irinotecan nor the chemotherapy-related toxicity. This combination is well tolerated and causes minimal clinical side effects. [ABSTRACT FROM AUTHOR]
Databáze: Complementary Index
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