title: 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).
abstract: BACKGROUND
  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/microL, or had an absolute neutrophil count<1000/microL 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.
authors.affiliation: Division of Hematology, Northshore University Health System, Evanston, Illinois.
authors.forename: David L
authors.initials: DL
authors.lastname: Grinblatt
authors.forename: Daohai
authors.initials: D
authors.lastname: Yu
authors.forename: Vera
authors.initials: V
authors.lastname: Hars
authors.forename: James W
authors.initials: JW
authors.lastname: Vardiman
authors.forename: Bayard L
authors.initials: BL
authors.lastname: Powell
authors.forename: Sreenivasa
authors.initials: S
authors.lastname: Nattam
authors.forename: Lewis R
authors.initials: LR
authors.lastname: Silverman
authors.forename: Carlos
authors.initials: C
authors.lastname: de Castro
authors.forename: Richard M
authors.initials: RM
authors.lastname: Stone
authors.forename: Clara D
authors.initials: CD
authors.lastname: Bloomfield
authors.forename: Richard A
authors.initials: RA
authors.lastname: Larson
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000188:drug therapy*; D019772:Topotecan / Q000008:administration & dosage* / Q000009:adverse effects
chemical_list: D019772:Topotecan