Cyclophosphamide, ara-C and topotecan (CAT) for patients with refractory or relapsed acute leukemia

Jorge Cortes, Elihu Estey, Miloslav Beran, Susan O'Brien, Francis Giles, Charles Koller, Michael Keating, Hagop Kantarjian

Research output: Contribution to journalArticle

34 Scopus citations

Abstract

Topotecan is a topoisomerase I inhibitor with significant activity in patients with myelodysplastic syndrome and chronic myelomonocytic leukemia. Pre-clinical data suggest a synergistic activity with DNA damaging agents such as cyclophosphamide, where topotecan might prevent the repair of cyclophosphamide-induced DNA damage. We thus designed a combination including cyclophosphamide 500 mg/m2 every 12 hours given on days 1 to 3; topotecan 1.25 mg/m2/day by continuous infusion on days 2 to 6, and cytosine arabinoside (ara-C) 2 g/m2 over 4 hours daily for 5 days on days 2 to 6 (CAT). Sixty six (63 evaluable) patients were treated. Fifty two patients had refractory (n = 12) or relapsed (n = 40) acute myelogenous leukemia (AML), and eleven had acute lymphocytic leukemia (ALL) (refractory n = 3, relapsed n = 8); their median age was 57 years (range, 18 to 79 years). Eleven patients (17%) achieved a complete remission (CR), and two patients (3%) had a hematologic improvement (HI; met all criteria for CR except for platelets < 100 x 109/L), for an overall response rate of 20%. Responses occurred in 12 of 52 AML patients (23%), including 10 CR (19%) and 2 HI (4%), and in 1 of 11 patients with ALL (9%). Myelosuppression was universal; there were 23 episodes of pneumonia or sepsis and 18 episodes of fever of unknown origin complicating 74 courses of CAT. Non-hematologic toxicity was mostly gastrointestinal, including nausea, vomiting, diarrhea and mucositis, but was severe in only 8%. In summary, the CAT regimen is well tolerated and has significant anti-leukemia activity which warrants further investigation.

Original languageEnglish (US)
Pages (from-to)479-484
Number of pages6
JournalLeukemia and Lymphoma
Volume36
Issue number5-6
DOIs
StatePublished - Jan 1 2000
Externally publishedYes

Keywords

  • Acute leukemia
  • Cyclophosphamide
  • Cytarabine
  • Salvage
  • Topotecan

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

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    Cortes, J., Estey, E., Beran, M., O'Brien, S., Giles, F., Koller, C., Keating, M., & Kantarjian, H. (2000). Cyclophosphamide, ara-C and topotecan (CAT) for patients with refractory or relapsed acute leukemia. Leukemia and Lymphoma, 36(5-6), 479-484. https://doi.org/10.3109/10428190009148395