Phase I trial of 9-aminocamptothecin in children with refractory solid tumors: A pediatric oncology group study

Anne Marie Langevin, Daniel T. Casto, Paul J. Thomas, Steven D. Weitman, Cynthia Kretschmar, Holcombe Grier, Charles Pratt, Ronald Dubowy, Mark Bernstein, Susan Blaney, Teresa Vietti

Research output: Contribution to journalArticlepeer-review

16 Scopus citations


Purpose: A phase I trial of 9-aminocamptothecin (9-AC) was performed in children with solid tumors to establish the dose-limiting toxicity (DLT), maximum-tolerated dose (MTD), and the pharmacokinetic profile in children and to document any evidence of activity. Patients and Methods: A 72-hour infusion of 9-AC dimethylacetamide formulation was administered every 21 days to 23 patients younger than 21 years of age with malignant tumors refractory to conventional therapy. Doses ranged from 36 to 62 μg/m2 per hour. Pharmacokinetics were to be performed in at least three patients per dose level. The first course was used to determine the DLT and MTD. Results: Nineteen patients on four dose levels were assessable for toxicities. At 62 μg/m2 per hour, three patients experienced dose-limiting neutropenia and one patient experienced dose-limiting thrombocytopenia. Pharmacokinetics were performed on 15 patients (nine patients had complete sets of plasma sampling performed). The pharmacokinetics of both lactone and total 9-AC were highly variable. The percentage of 9-AC lactone at steady-state was 10.8% ± 3.6%. Total 9-AC and its lactone form had a terminal half-life of 8.1 ± 3.8 and 7.1 ± 3.9 hours, respectively, and a volume of distribution at steady-state (Vdss) of 21.2 ± 13.3 L/m2 and 135.3 ± 52.5 L/m2, respectively. Hepatic metabolism and biliary transport had an important role in 9-AC disposition. Conclusion: The recommended phase II dose of 9-AC administered as a 72-hour infusion every 21 days to children with solid tumors is 52 μg/m2 per hour. Neutropenia and thrombocytopenia were dose limiting.

Original languageEnglish (US)
Pages (from-to)2494-2499
Number of pages6
JournalJournal of Clinical Oncology
Issue number7
StatePublished - Jul 1998

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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