Pharmacologic Study of Paclitaxel Administered With or Without the Cytoprotective Agent Amifostine, and Given as a Single Agent or in Combination With Epirubicin and Cisplatin in Patients With Advanced Solid Tumors

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Abstract
The main purpose of this study was to investigate whether the coadministration of amifostine alters the pharmacokinetic behavior of paclitaxel. Eight patients were included in the study: six received paclitaxel in combination with epirubicin and cisplatin, and two received paclitaxel as a single agent. Doses of paclitaxel in these protocols were 135, 150, 175, and 200 mg/m2 and two patients were treated at each dose level. Pharmacokinetic sampling for paclitaxel analysis was performed in each patient during two consecutive cycles, one with and one without amifostine (750 mg/m2 as a 15-minute intravenous infusion 30 minutes before paclitaxel administration). At each dose level, the pharmacokinetic data of paclitaxel were compared per patient for a cycle without amifostine versus a cycle with amifostine. Amifostine did not seem to interact pharmacokinetically with paclitaxel, given either alone or in combination chemotherapy. This is in line with the clinical findings that amifostine has no negative effects on the antitumor activity of various antineoplastic agents. Also, amifostine may reduce toxic effects of combination chemotherapy regimens that include paclitaxel.