Phase I study of oral topotecan in hematological malignancies

Miloslav Beran*, Susan O'Brien, Deborah A. Thomas, Hai T. Tran, Jorge E. Cortes-Franco, Francis Giles, Elihu Estey, Hagop M. Kantarjian

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

12 Scopus citations


Purpose: In this Phase I, dose-seeking study, we investigated the dose-limiting toxicities (DLTs) and maximal tolerated dose (MTD) of oral topotecan in patients with hematological malignancies. Experimental Design: Patients with myelodysplastic syndromes, myeloproliferative disorders, or relapsed acute myelogenous leukemia were treated with 0.6-1.9 mg/m 2/day oral topotecan for 5 consecutive days on and 2 days off, for 3 weeks (15 doses/course) followed by 2-4 weeks of rest. The DLTs occurring during the first course of treatment were considered for defining the MTD. Preliminary results of antitumor activity were assessed by examining bone marrow status and peripheral blood cell counts. Results: All 26 patients enrolled in the study were evaluable for toxicity, and 24 patients were evaluable for response. A total of 54 courses were administered. The most frequently reported nonhematological toxicities (percentage of courses) were diarrhea (57%), nausea/vomiting (50%), fatigue (24%), and mucositis (9%). DLTs included grade 3 or 4 nausea/vomiting and diarrhea at 1.9 mg/m2/day. The MTD for oral topotecan in patients with hematological malignancies was defined at 1.4 mg/m2/day. Hematological toxicity was noted in all 26 patients and with all courses but was not considered dose-limiting. Four (17%) patients achieved a complete response, and six (25%) patients experienced hematological improvement. Conclusions: Protracted administration of oral topotecan is safe and well tolerated in patients with hematological malignancies. At the dose-schedule used, single-agent oral topotecan has a definite activity in patients with myelodysplastic syndrome and acute myelogenous leukemia and warrants further investigation alone or in combination with other agents.

Original languageEnglish (US)
Pages (from-to)4084-4091
Number of pages8
JournalClinical Cancer Research
Issue number11
StatePublished - Nov 1 2003

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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