Phase I trial of taxol given as a 24-hour infusion every 21 days: Responses observed in metastatic melanoma

P. H. Wiernik, Edward L. Schwartz, Avi Israel Einzig, J. J. Strauman, Richard B. Lipton, J. P. Dutcher

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259 Citations (Scopus)

Abstract

Taxol, a plant product, has significant activity against certain rodent and human xenograft tumors. It promotes microtubule assembly in vitro, in contrast to vinca alkaloids, which inhibit assembly. In this phase I study, taxol was administered as a 24-hour continuous intravenous (IV) infusion in 65 courses to 26 patients. A premedication regimen of dexamethasone, cimetidine, and diphenhydramine was used to prevent the acute hypersensitivity reactions observed in previous studies of taxol. Only one episode of mild stridor occurred in this study. Peripheral neuropathy was the dose-limiting toxicity and was observed in 40% of patients treated at a dose of 250 mg/m2. Significant neutropenia of brief duration was also common. Pharmacokinetic studies by a high-performance liquid chromatography (HPLC) method demonstrated that drug plasma concentrations increased during the 24-hour infusion and then declined rapidly. Peak plasma concentrations correlated with dose, and <5% of taxol was excreted in the urine. Most of the drug was bound to serum components. Partial responses of more than 3 months' duration were observed in four of 12 melanoma patients treated. The recommended phase II dose of taxol on this schedule is 250 mg/m2. Priority should be given to the study of taxol in melanoma.

Original languageEnglish (US)
Pages (from-to)1232-1239
Number of pages8
JournalJournal of Clinical Oncology
Volume5
Issue number8
StatePublished - 1987

Fingerprint

Paclitaxel
Melanoma
Vinca Alkaloids
Diphenhydramine
Premedication
Cimetidine
Respiratory Sounds
Peripheral Nervous System Diseases
Neutropenia
Heterografts
Intravenous Infusions
Microtubules
Pharmaceutical Preparations
Dexamethasone
Rodentia
Appointments and Schedules
Hypersensitivity
Pharmacokinetics
High Pressure Liquid Chromatography
Urine

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Phase I trial of taxol given as a 24-hour infusion every 21 days : Responses observed in metastatic melanoma. / Wiernik, P. H.; Schwartz, Edward L.; Einzig, Avi Israel; Strauman, J. J.; Lipton, Richard B.; Dutcher, J. P.

In: Journal of Clinical Oncology, Vol. 5, No. 8, 1987, p. 1232-1239.

Research output: Contribution to journalArticle

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