A phase I trial of taxol given by a 6-hour intravenous infusion

T. Brown, K. Havlin, G. Weiss, J. Cagnola, J. Koeller, J. Kuhn, J. Rizzo, J. Craig, J. Phillips, D. Von Hoff

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    Abstract

    Taxol is a unique mitotic inhibitor that has entered phase II investigation. Phase I studies demonstrated hypersensitivity reactions that were related to the cremophor vehicle and to the rate of drug infusion. As a result, the time span of intravenous (IV) infusion of taxol was routinely prolonged to 6 hours or beyond, and premedication with diphenhydramine, dexamethasone, and cimetidine was initiated. Early studies showed antitumor activity, especially against malignant melanoma and ovarian carcinoma. This phase I trial was performed giving taxol, as a 6-hour IV infusion every 21 days, without premedication. The purpose was to study the necessity of premedication and its impact on toxicity and pharmacokinetics. Thirty-one patients received 64 assessable courses of taxol. One patient had a hypersensitivity reaction, which was easily controlled using routine measures. Myelosuppression was dose-limiting, but sporadic, with two fatalities due to sepsis. Nonhematologic toxicity was of grade 1 and 2 except for one patient with grade 3 mucositis and two patients with grade 3 neuropathy. The neuropathy consisted of reversible painful paresthesias, requiring discontinuation of drug in two patients. Four partial responses were seen (three in patients with non-small-cell lung cancer, one in a patient with adenocarcinoma of unknown primary). Pharmacokinetic values were consistent with those previously reported. The occurrence of myelosuppression or neurotoxicity appeared to be associated with the area under the concentration x time curve (AUC) of taxol. The recommended phase II starting dose on this schedule is 225 mg/m2. Taxol merits broad investigation at the phase II level.

    Original languageEnglish (US)
    Pages (from-to)1261-1267
    Number of pages7
    JournalJournal of Clinical Oncology
    Volume9
    Issue number7
    DOIs
    StatePublished - 1991

    ASJC Scopus subject areas

    • Oncology
    • Cancer Research

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    Brown, T., Havlin, K., Weiss, G., Cagnola, J., Koeller, J., Kuhn, J., Rizzo, J., Craig, J., Phillips, J., & Von Hoff, D. (1991). A phase I trial of taxol given by a 6-hour intravenous infusion. Journal of Clinical Oncology, 9(7), 1261-1267. https://doi.org/10.1200/JCO.1991.9.7.1261