PMID: 8996593Dec 1, 1996Paper

Combinations of paclitaxel and etoposide in the treatment of lung cancer

Seminars in Oncology
E A PerezJ P Reid

Abstract

Paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) and etoposide are two chemotherapy agents with broad cytotoxic activity but different mechanisms of action and resistance. Previous in vitro studies of their combined cytotoxicity have yielded conflicting results. We evaluated the effects of drug scheduling in cell growth inhibition in lung and breast human cancer cell lines. A clonogenic assay with either simultaneous or sequential 24-hour incubation of paclitaxel and etoposide was used to assess growth inhibition, and the combination index was used to evaluate drug interactions. In these studies, including the A549 human lung cancer cell line, mild antagonism (combination index, > 1) was observed with concurrent exposure of paclitaxel and etoposide, but synergism (combination index, < 1) was observed when the drugs were incubated sequentially. In view of the wide range of antitumor activity of both paclitaxel and etoposide, and the potential importance and clinical impact of optimizing drug doses and schedules, we recently completed a phase I study with the following objectives: (1) to determine the maximum tolerated dose of paclitaxel given intravenously on day 10 after 10 days of oral etoposide and (2) to inves...Continue Reading

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