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

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

89 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

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Fingerprint Dive into the research topics of 'Troxarcitabine, a novel dioxolane nucleoside analog, has activity in patients with advanced leukemia'. Together they form a unique fingerprint.

Cite this