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Treatment of myelodysplastic syndrome with 2 schedules and doses of oral topotecan
Author(s) -
Grinblatt David L.,
Yu Daohai,
Hars Vera,
Vardiman James W.,
Powell Bayard L.,
Nattam Sreenivasa,
Silverman Lewis R.,
Castro Carlos de,
Stone Richard M.,
Bloomfield Clara D.,
Larson Richard A.
Publication year - 2008
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/cncr.23995
Subject(s) - medicine , topotecan , neutropenia , gastroenterology , cytopenia , chronic myelomonocytic leukemia , surgery , absolute neutrophil count , anemia , myelodysplastic syndromes , toxicity , chemotherapy , bone marrow
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/m 2 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.