Troxarcitabine, a novel dioxolane nucleoside analog, has activity in patients with advanced leukemia

F. J. Giles, J. E. Cortes, S. D. Baker, D. A. Thomas, S. O'Brien, T. L. Smith, M. Beran, C. Bivins, J. Jolivet, H. M. Kantarjian

Research output: Contribution to journalArticlepeer-review

93 Scopus citations


Purpose: To investigate the toxicity profile, activity, and pharmacokinetics of a novel L-nucleoside analog, troxacitabine (BCH-4556), in patients with advanced leukemia. Patients and Methods: Patients with refractory or relapsed acute myeloid (AML) or lymphocytic (ALL) leukemia, myelodysplastic syndromes (MDS), or chronic myelogenous leukemia in blastic phase (CML-BP). Troxacitabine was given as an intravenous infusion over 30 minutes daily for 5 days. The starting dose was 0.72 mg/m2/d (3.6 mg/m2/course). Courses were given every 3 to 4 weeks according to toxicity and antileukemic efficacy. The dose was escalated by 50% until grade 2 toxicity was observed, and then by 30% to 35% until the dose-limiting toxicity (DLT) was defined. Results: Forty-two patients (AML: 31 patients; MDS: six patients [five MDS + one CMML]; ALL: four patients; CML-BP: one patient.) were treated. Median age was 61 years (range, 23 to 79 years), and 9.9 patients were males. Stomatitis and hand-foot syndrome were the DLTs. The MTD was defined as 8 mg/m2/d. The pharmacokinetlc behavior of troxacitabine is linear over the dose range of 0.72. to 10.0 m/m2. Approximately 69% of troxacitabine was excreted as unchanged drug in the urine. Marrow hypoplasia occurred between days 14 and 28 in 73% of AML patients. Three complete remissions and one partial remission were observed in 30 assessable AML patients. One MDS patient achieved a hematologic improvement. A patient with CML-BP achieved a return to chronic phase disease. Conclusion: Troxacitabine has a unique metabolic and pharmacokinetic profile and significant antileukemic activity DLTs were stomatitis and hand-foot syndrome. Troxacitabine merits further study in hematologic malignancies.

Original languageEnglish (US)
Pages (from-to)762-771
Number of pages10
JournalJournal of Clinical Oncology
Issue number3
StatePublished - Feb 1 2001
Externally publishedYes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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