A phase I trial of bryostatin-1 in children with refractory solid tumors: A Pediatric Oncology Group Study

Steven Weitman, Anne Marie Langevin, Roger L. Berkow, Paul J. Thomas, Craig A. Hurwitz, Andrew S. Kraft, Ronald L. Dubowy, Debra L. Smith, Mark Bernstein

Research output: Contribution to journalArticlepeer-review

33 Scopus citations


Bryostatin-1, a macrocyclic lactone, appears to elicit a wide range of biological responses including modulation of protein kinase C (PKC). PKC, one of the major elements in the signal transduction pathway, is involved in the regulation of cell growth, differentiation, gene expression, and tumor promotion. Because of the potential for a unique mechanism of interaction with tumorgenesis, a Phase I trial of bryostatin-1 was performed in children with solid tumors to: (a) establish the dose-limiting toxicity (DLT) and maximum-tolerated dose (MTD); (b) establish the pharmacokinetic profile in children; and (c) document any evidence of antitumor activity. A 1-h infusion of bryostatin-1 in a PET formulation (60% polyethylene glycol 400, 30% ethanol, and 10% Tween 80) was administered weekly for 3 weeks to 22 children (age range, 2-21 years) with malignant solid tumors refractory to conventional therapy. Doses ranged from 20 to 57 μg/m2/dose. Pharmacokinetics were performed in at least three patients per dose level. The first course was used to determine the DLT and MTD. Twenty-two patients on five dose levels were evaluable for toxicities. At the 57 μg/m2/dose level dose-limiting myalgia (grade 3) was observed in three patients; two of those patients also experienced photophobia or eye pain, and one experienced headache. Symptoms occurred in all patients within 24-72 h after the second dose of bryostatin-1 with resolution within 1 week of onset. Other observed toxicities (grades 1 and 2) included elevation in liver transaminases, thrombocytopenia, fever, and flu-like symptoms. The bryostatin-1 infusion was typically well tolerated. Although stable disease was noted in several patients, no complete or partial responses were observed. The recommended Phase II dose of bryostatin-1 administered as a 1-h infusion weekly for 3 of every 4 weeks to children with solid tumors is 44 μg/m2/dose. Myalgia, photophobia, or eye pain, as well as headache, were found to be dose limiting.

Original languageEnglish (US)
Pages (from-to)2344-2348
Number of pages5
JournalClinical Cancer Research
Issue number9
StatePublished - Sep 1999

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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