Phase I study of rubitecan and gemcitabine in patients with advanced malignancies

P. M. Fracasso, J. S. Rader, R. Govindan, T. J. Herzog, M. A. Arquette, A. Denes, D. G. Mutch, J. Picus, B. R. Tan, C. L. Fears, S. A. Goodner, S. L. Sun

Research output: Contribution to journalArticle

7 Scopus citations

Abstract

Background: Rubitecan (9-nitrocamptothecin, 9-NC, Orathecin™) and gemcitabine have single-agent activity in pancreatic and ovarian carcinoma. We conducted a phase I trial to evaluate the maximum tolerated dose (MTD) and toxicities of this combination in advanced malignancies. Patients and methods: Twenty-one patients with refractory or recurrent malignancies were enrolled in this dose escalation trial. Dose escalation proceeded from a starting level of rubitecan at 0.75 mg/m2/day administered orally on days 1-5 and 8-12 in combination with gemcitabine Results: The MTD was defined as rubitecan 1 mg/m2 administered orally days 1-5 and 8-12, and gemcitabine 1000 mg/m2 administered intravenously over 30 min days 1 and 8, given every 21 days. Dose-limiting toxicity was myelosuppression including neutropenia and thrombocytopenia. Other side effects included diarrhea, nausea, vomiting and fatigue. Five patients with stable disease were observed among 18 evaluable patients. Conclusions: The recommended phase II dose is rubitecan 1 mg/m2 given orally on days 1-5 and 8-12 in combination with gemcitabine 1000 mg/m2 as a 30-min intravenous infusion on days 1 and 8 of a 21-day cycle.

Original languageEnglish (US)
Pages (from-to)1819-1825
Number of pages7
JournalAnnals of Oncology
Volume13
Issue number11
DOIs
StatePublished - Nov 1 2002

Keywords

  • 9-Nitrocamptothecin
  • Gemcitabine
  • Gemzar®
  • Orethecin™
  • Phase I
  • Rubitecan

ASJC Scopus subject areas

  • Hematology
  • Oncology

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    Fracasso, P. M., Rader, J. S., Govindan, R., Herzog, T. J., Arquette, M. A., Denes, A., Mutch, D. G., Picus, J., Tan, B. R., Fears, C. L., Goodner, S. A., & Sun, S. L. (2002). Phase I study of rubitecan and gemcitabine in patients with advanced malignancies. Annals of Oncology, 13(11), 1819-1825. https://doi.org/10.1093/annonc/mdf342