Treatment of myelodysplastic syndrome with 2 schedules and doses of oral topotecan

A Randomized Phase 2 Trial by the Cancer and Leukemia Group B (CALGB 19803)

Authors

  • David L. Grinblatt PhD,

    Corresponding author
    1. Division of Hematology, Northshore University Health System, Evanston, Illinois
    • Division of Hematology, Evanston Northwestern Healthcare, 2650 Ridge Avenue, Room 5134, Evanston, IL 60201===

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    • Fax: (847) 570-2336

  • Daohai Yu MS,

    1. Department of Biostatistics, H. Lee Moffitt Cancer Center, Tampa, Florida
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  • Vera Hars MD,

    1. Cancer and Leukemia Group B Statistical Center, Duke University Medical Center, Durham, North Carolina
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  • James W. Vardiman MD,

    1. Section of Hematopathology, Department of Pathology, University of Chicago, Chicago, Illinois
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  • Bayard L. Powell MD,

    1. Comprehensive Cancer Center, Wake Forest University School of Medicine, Winston-Salem, North Carolina
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  • Sreenivasa Nattam MD,

    1. Fort Wayne Medical Oncology/Hematology, Ft. Wayne, Indiana
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  • Lewis R. Silverman MD,

    1. Division of Hematology/Oncology, Mount. Sinai School of Medicine, New York, New York
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  • Carlos de Castro III MD,

    1. Comprehensive Cancer Center, Duke University, Durham, North Carolina
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  • Richard M. Stone MD,

    1. Dana-Farber Cancer Institute, Boston, Massachusetts
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  • Clara D. Bloomfield MD,

    1. Comprehensive Cancer Center, Ohio State University, Columbus, Ohio
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  • Richard A. Larson MD,

    1. Department of Medicine and Cancer Research Center, University of Chicago, Chicago, Illinois
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  • for the Cancer and Leukemia Group B

    1. Department of Medicine and Cancer Research Center, University of Chicago, Chicago, Illinois
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    • The following institutions participated in this study: Dana-Farber Cancer Institute, Boston, Mass (Eric P. Winer, MD; supported by CA32291); Dartmouth Medical School-Norris Cotton Cancer Center, Lebanon, NH (Marc S. Ernstoff, MD; supported by CA04326); Duke University Medical Center, Durham, NC (Jeffrey Crawford, MD; supported by CA47577); Greenville Clinical Cooperative Oncology Program, Cancer Centers of the Carolinas, Greenville, SC (Jeffrey K. Giguere, MD; supported by CA29165); Illinois Oncology Research Association, Peoria, Ill (John W. Kugler, MD; supported by CA35113); Massachusetts General Hospital, Boston, Mass (Michael L. Grossbard, MD; supported by CA12449); Mount Sinai School of Medicine, New York, NY (Lewis R. Silverman, MD; supported by CA04457); Roswell Park Cancer Institute, Buffalo, NY (Ellis Levine, MD; supported by CA02599); State University of New York Upstate Medical University, Syracuse, NY (Stephen L. Graziano, MD; supported by CA21060); Ohio State University Medical Center, Columbus, Ohio (Clara D. Bloomfield, MD; supported by CA77658); University of California at San Diego, San Diego, Calif (Joanne Mortimer, MD; supported by CA11789); University of Chicago, Chicago, Ill (Gini Fleming, MD; supported by CA41287); University of Illinois Minority-Based Clinical Cooperative Oncology Program, Chicago, Ill (Lawrence E. Feldman, MD; supported by CA74811); University of Iowa, Iowa City, Iowa (Gerald Clamon, MD; supported by CA47642); University of Maryland Greenebaum Cancer Center, Baltimore, Md (Martin Edelman, MD; supported by CA31983); University of Minnesota, Minneapolis, Minn (Bruce A. Peterson, MD; supported by CA16450); University of Missouri/Ellis Fischel Cancer Center, Columbia, Mo (Michael C. Perry, MD; supported by CA12046); University of North Carolina at Chapel Hill, Chapel Hill, NC (Thomas C. Shea, MD; supported by CA47559); University of Tennessee Memphis, Memphis, Tenn (Harvey B. Niell, MD; supported by CA47555); Wake Forest University School of Medicine, Winston-Salem, NC (David D. Hurd, MD; supported by CA03927); and Weill Medical College of Cornell University, New York, NY (Scott Wadler, MD; supported by CA07968).


  • The content of this article is solely the responsibility of the authors and does not necessarily represent the official views of the National Cancer Institute.

Abstract

BACKGROUD:

The Cancer and Leukemia Group B evaluated oral topotecan administered at 2 schedules and doses for myelodysplastic syndrome (MDS).

METHODS:

Patients with previously untreated primary or therapy-related MDS were eligible. Patients with refractory anemia (RA), RA with ringed sideroblasts, or refractory cytopenia with multilineage dysplasia (RCMD) were eligible only if they were dependent on erythrocyte transfusion, had a platelet count <50,000/μL, or had an absolute neutrophil count <1000/μL with a recent infection that required antibiotics. Patients were randomized to receive oral topotecan either at a dose of 1.2 mg/m2 twice daily for 5 days (Arm A) or once daily for 10 days (Arm B) repeated every 21 days for at least 2 cycles. Responding patients continued until they developed disease progression or unacceptable toxicity or until they had received 2 cycles beyond a complete response.

RESULTS:

Ninety patients received treatment, including 46 patients on Arm A and 44 patients on Arm B. Partial responses with improvement in all 3 cell lines occurred in 6 patients (7%), and hematologic improvement (in 1 or 2 cell lines) was observed in 21 patients (23%), for an overall response rate of 30%. Response duration was longer on Arm A (23 months vs 14 months; P = .02). Seven of 14 patients with chronic myelomonocytic leukemia responded. There were 8 treatment-related deaths from infection (6 deaths) and bleeding (2 deaths). Diarrhea was the most frequent nonhematologic toxicity (grade 3, 11%; grade 4, 2%; grading determined according to the National Cancer Institute Comman Toxicity Criteria v.2.0).

CONCLUSIONS:

Oral topotecan in the dose and schedules evaluated in this trial demonstrated only a modest response rate with a troublesome toxicity profile in the treatment of MDS. Cancer 2009. © 2008 American Cancer Society.

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