Phase I and pharmacokinetic study of CI-980 in recurrent pediatric solid tumor cases: A pediatric oncology group study

Mark L. Bernstein, Sylvain Baruchel, Susan Devine, Nektaria Markoglou, Irving W. Wainer, Marion Williams, Susan Blaney, Albert Moghrabi, Naomi Winick, Teresa Vietti

Research output: Contribution to journalArticle

6 Scopus citations

Abstract

To establish the maximum tolerated dosage (MTD), the dose-limiting toxicities (DLTs), and pharmacokinetic parameters of CI-980, a novel tubulin binder, in children with solid tumors refractory to standard therapy. Patients 21 years of age or younger with adequate nutritional, hematopoietic, renal, and hepatic function were eligible. The patient must not have been pregnant. Patients with brain tumors were not eligible for any dosage level until it was demonstrated the level did not produce DLT in patients with extracranial solid tumors. The starting dosage level was 3.5 mg/m2/day, for 3 days, administered as a continuous intravenous infusion (80% of the adult MTD). If a dosage level was associated with dose-limiting myelotoxicity, growth factors were to be added. Thirty-three patients received CI-980. Twenty-four had solid tumor; 9 had brain tumor. The MTD achieved without granulocyte colony stimulating factor (G-CSF) was 3.5 mg/m2/day (DLT: neutropenia) and with G-CSF, it was as follows: patients with brain tumor, 4.2 mg/m2/day (DLT: myelosupression); and patients with solid tumor, 5 mg/m2/day (DLT: cortical toxicity). Several responses were seen, most notably prolonged stable disease in two of five patients with medulloblastoma. Pharmacokinetic data showed a mean steady state level of 1.74 ng/mL for two patients treated with the 5 mg/m2/day regimen, with rapid decay after the termination of the infusion. CI-980 showed preliminary evidence of activity in recurrent pediatric malignancies, with tolerable, reversible toxicities.

Original languageEnglish (US)
Pages (from-to)494-500
Number of pages7
JournalJournal of Pediatric Hematology/Oncology
Volume21
Issue number6
DOIs
StatePublished - Jan 1 1999

Keywords

  • CI-980
  • Granulocyte colony stimulating factor (G-CSF)
  • Phase I trial

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Hematology
  • Oncology

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    Bernstein, M. L., Baruchel, S., Devine, S., Markoglou, N., Wainer, I. W., Williams, M., Blaney, S., Moghrabi, A., Winick, N., & Vietti, T. (1999). Phase I and pharmacokinetic study of CI-980 in recurrent pediatric solid tumor cases: A pediatric oncology group study. Journal of Pediatric Hematology/Oncology, 21(6), 494-500. https://doi.org/10.1097/00043426-199911000-00009