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Combination of cladribine plus topotecan for recurrent or refractory pediatric acute myeloid leukemia

  1. Hiroto Inaba MD, PhD1,2,†,*,
  2. Clinton F. Stewart Pharm D3,4,
  3. Kristine R. Crews Pharm D3,4,
  4. Shengping Yang MS5,
  5. Stanley Pounds PhD5,
  6. Ching-Hon Pui MD1,2,
  7. Jeffrey E. Rubnitz MD, PhD1,2,
  8. Bassem I. Razzouk MD1,2,6,
  9. Raul C. Ribeiro MD1,2

Article first published online: 2 NOV 2009

DOI: 10.1002/cncr.24712

Issue

Cancer

Cancer

Volume 116, Issue 1, pages 98–105, 1 January 2010

Additional Information

How to Cite

Inaba, H., Stewart, C. F., Crews, K. R., Yang, S., Pounds, S., Pui, C.-H., Rubnitz, J. E., Razzouk, B. I. and Ribeiro, R. C. (2010), Combination of cladribine plus topotecan for recurrent or refractory pediatric acute myeloid leukemia. Cancer, 116: 98–105. doi: 10.1002/cncr.24712

Author Information

  1. 1

    Department of Oncology, St. Jude Children's Research Hospital, Memphis, Tennessee

  2. 2

    Department of Pediatrics, University of Tennessee Health Science Center, Memphis, Tennessee

  3. 3

    Department of Pharmaceutical Sciences, St. Jude Children's Research Hospital, Memphis, Tennessee

  4. 4

    Department of Pharmacy, University of Tennessee Health Science Center, Memphis, Tennessee

  5. 5

    Department of Biostatistics, St. Jude Children's Research Hospital, Memphis, Tennessee

  6. 6

    Children's Center for Cancer and Blood Diseases, St. Vincent Children's Hospital, Indianapolis, Indiana

  1. †

    Fax: (901) 521-9005

*Department of Oncology, St. Jude Children's Research Hospital, 262 Danny Thomas Place, Memphis, TN 38105

Publication History

  1. Issue published online: 11 JAN 2010
  2. Article first published online: 2 NOV 2009
  3. Manuscript Accepted: 21 APR 2009
  4. Manuscript Received: 31 MAR 2009

Funded by

  • Cancer Center Core Grant. Grant Number: CA 21765
  • National Cancer Institute and by the American Lebanese Syrian Associated Charities

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Keywords:

  • acute myeloid leukemia;
  • cladribine;
  • pediatric;
  • recurrence;
  • topotecan

The authors evaluated the maximum tolerated dose and dose-limiting toxicities of a 5-day course of cladribine followed by topotecan in pediatric patients with recurrent/refractory acute myeloid leukemia. This regimen offers a treatment alternative for patients, especially those who have received anthracycline-containing chemotherapy.

Abstract

BACKGROUND:

The prognosis after recurrence of pediatric acute myeloid leukemia (AML) is poor, and effective salvage regimens are urgently needed.

METHODS:

In phase 1 and pilot studies, the authors evaluated the maximum tolerated dose (MTD) and dose-limiting toxicities (DLTs) of a 5-day course of cladribine followed by topotecan in pediatric patients with recurrent/refractory AML. The cladribine dose was escalated as follows: 9.1, 13.6, 16.3, and 19.5 mg/m2 per day (8.9 mg/m2 per day in the pilot study). Outcome was analyzed according to the absence (Stratum 1) versus presence (Stratum 2) of previous allogeneic hematopoietic stem cell transplantation. Twenty-six patients (20 in Stratum 1 and 6 in Stratum 2) were treated.

RESULTS:

The MTD was not reached in Stratum 1, but a DLT occurred at the lowest cladribine dosage (9.1 mg/m2 per day) in Stratum 2. Febrile neutropenia was common in both strata. Nine (34.6%) of 26 patients experienced a complete response, and 7 (30.4%) achieved a partial response; 5 (19.2%) were long-term survivors at the time of last follow‒up. Clinical outcome was not associated with cladribine or topotecan systemic exposure.

CONCLUSIONS:

The combination was well tolerated in Sratum 1, and the response rate was encouraging. This regimen offers a postrecurrence treatment alternative for patients, especially those who have received anthracycline-containing chemotherapy. Cancer 2010. © 2010 American Cancer Society.

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