Phase I trial of paclitaxel in children with refractory solid tumors: A pediatric oncology group study

Craig A. Hurwitz, Mary V. Relling, Steven D. Weitman, Yaddanapudi Ravindranath, Teresa J. Vietti, Douglas R. Strother, Abdelsalam H. Ragab, Charles B. Pratt

Research output: Contribution to journalArticlepeer-review

86 Scopus citations


Purpose: A phase I study was performed to describe the principal toxicities and identify the maximum-tolerated dose (MTD) of Taxol (paclitaxel; Bristol-Myers Squibb Co, Wallingford, CT) in children with therapy-resistant solid tumors. Additionally, the pharmacokinetic disposition of Taxol in children was studied, and preliminary evidence of the activity of Taxol against pediatric solid tumors was assessed. Patients and Methods: Twenty-four-hour continuous infusions of Taxol were administered every 21 days to children (median age, 12 years; range, 2 to 22) with refractory solid tumors. Doses ranged from 200 to 420 mg/m2, there was no intrapatient dose escalation. Results: A total of 62 courses of Taxol were administered to 31 patients. Two patients developed acute anaphylaxis during their second infusion of taxol at doses of 200 mg/m2 and 350 mg/m2, respectively. No other allergic reactions were documented. Myelosuppression occurred at all dose levels, but was of short duration (≤ 7 days) and did not appear to increase with consecutive courses or at higher dosage levels. A stocking-and-glove peripheral neuropathy became evident at doses A 290 mg/m2. Dose-limiting neurotoxicity occurred at 420 mg/m2 and comprised a significant fine-motor and peripheral neuropathy in one patient, and a tonic-clonic seizure in another. End-of-infusion plasma concentrations ranged from 0.40 to 6.4 μmol/L, and were not found to be dose-dependent over the range of doses studied. A complete response was documented in one patient, partial response in two, and minimal response in one for an overall response rate of 13%. Conclusion: Neurotoxicity was dose-limiting when Taxol was administered by 24-hour continuous infusion to pediatric patients with relapsed solid tumors. In this population, the recommended dose for phase II trials is 350 mg/m2/d.

Original languageEnglish (US)
Pages (from-to)2324-2329
Number of pages6
JournalJournal of Clinical Oncology
Issue number12
StatePublished - 1993
Externally publishedYes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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