Topotecan in Treating Patients With Myelodysplastic Syndrome
Topotecan in Treating Patients With Myelodysplastic Syndrome
RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing
 so they stop growing or die.

 PURPOSE: Randomized phase II trial to study the effectiveness of topotecan in treating
 patients who have myelodysplastic syndrome.
OBJECTIVES: I. Estimate complete or partial remission, hematologic improvement, and cytogenic
 response rate when oral topotecan is given twice a day for 5 days versus once a day for 10
 days to patients with myelodysplastic syndromes. II. Evaluate the safety and toxicity of oral
 topotecan in these patients. III. Evaluate whether there are morphologic and/or cytogenetic
 subsets of the myelodysplastic syndromes that will respond optimally to this regimen. IV.
 Evaluate the change in the percentage of bone marrow blast cells in these patients during
 treatment. V. Evaluate the time to transformation to acute myeloid leukemia (AML) or death in
 this patient population.

 OUTLINE: This is a randomized, multicenter study. Patients are stratified according to FAB
 subtype: 1. Refractory anemia with excess blasts 2. Refractory anemia with excess blasts in
 transformation 3. Chronic myelomonocytic leukemia 4. Refractory anemia, refractory anemia
 with ringed sideroblasts, and refractory cytopenia with multilineage dysplasia Patients are
 randomized to receive oral topotecan either twice daily for 5 days or once daily for 10 days.
 Courses are repeated every 21 days. Patients are evaluated for hematologic response after the
 initial 2 courses, and then every 4 courses. If a partial response or hematologic improvement
 is observed, treatment continues until disease progression to acute myeloid leukemia,
 relapse, death, or irreversible toxicity. Patients who achieve a complete response receive an
 additional 2 courses of therapy before discontinuation of protocol treatment. Patients are
 followed every 3 months for 2 years, then every year for an additional 3 years, and at time
 of progression.

 PROJECTED ACCRUAL: A total of 90 patients (45 per arm) will be accrued for this study within
 13 months.
DISEASE CHARACTERISTICS: Primary or therapy-related myelodysplastic syndrome: Refractory
 anemia with excess blasts Refractory anemia with excess blasts in transformation Chronic
 myelomonocytic leukemia Refractory anemia, refractory anemia with ringed sideroblasts, or
 refractory cytopenia with multilineage dysplasia These patients must also have one of the
 following criteria: Greater than 4 units of RBCs transfused within the past 3 months OR
 Platelet count less than 50,000/mm3 OR Neutrophil count less than 1,000/mm3 AND a recent
 infection requiring antibiotics

 PATIENT CHARACTERISTICS: Age: Over 15 Performance status: 0-2 Life expectancy: Not
 specified Hematopoietic: See Disease Characteristics Hepatic: Bilirubin no greater than 1.5
 mg/dL SGOT no greater than 2 times upper limit of normal Renal: Creatinine no greater than
 1.5 mg/dL Other: Not pregnant or nursing Fertile patients must use effective contraception
 Free of any evidence of prior cancer for at least 12 months

 PRIOR CONCURRENT THERAPY: Biologic therapy: At least 1 month since prior interferon No
 prior hematopoietic growth factors or cytokines except epoetin alfa No concurrent epoetin
 alfa Chemotherapy: No prior topotecan No prior chemotherapy for this disease At least 12
 months since prior chemotherapy for another disease No other concurrent chemotherapy
 Endocrine therapy: At least 1 month since prior corticosteroids No concurrent hormonal
 therapy for disease-related conditions Concurrent steroids for adrenal failure allowed No
 concurrent dexamethasone and other steroidal antiemetics Radiotherapy: No prior
 radiotherapy for this disease At least 12 months since prior radiotherapy for another
 disease Surgery: Not specified Other: No prior cytotoxic therapy (including low-dose
 antimetabolites) for this disease At least 1 month since prior retinoids