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, orrefractory 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. Copyright (c) 2008 American Cancer Society.
RCT Entities:
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. Copyright (c) 2008 American Cancer Society.
Authors: F Zorat; V Shetty; D Dutt; L Lisak; F Nascimben; K Allampallam; S Dar; A York; S Gezer; P Venugopal; A Raza Journal: Br J Haematol Date: 2001-12 Impact factor: 6.998
Authors: Lewis R Silverman; Erin P Demakos; Bercedis L Peterson; Alice B Kornblith; Jimmie C Holland; Rosalie Odchimar-Reissig; Richard M Stone; Douglas Nelson; Bayard L Powell; Carlos M DeCastro; John Ellerton; Richard A Larson; Charles A Schiffer; James F Holland Journal: J Clin Oncol Date: 2002-05-15 Impact factor: 44.544
Authors: Alice B Kornblith; James E Herndon; Lewis R Silverman; Erin P Demakos; Rosalie Odchimar-Reissig; James F Holland; Bayard L Powell; Carlos DeCastro; John Ellerton; Richard A Larson; Charles A Schiffer; Jimmie C Holland Journal: J Clin Oncol Date: 2002-05-15 Impact factor: 44.544
Authors: Eva Hellström-Lindberg; Nina Gulbrandsen; Greger Lindberg; Tomas Ahlgren; Inger Marie S Dahl; Ingunn Dybedal; Gunnar Grimfors; Eva Hesse-Sundin; Martin Hjorth; Lena Kanter-Lewensohn; Olle Linder; Michaela Luthman; Eva Löfvenberg; Gunnar Oberg; Anja Porwit-MacDonald; Anders Rådlund; Jan Samuelsson; Jon Magnus Tangen; Ingemar Winquist; Finn Wisloff Journal: Br J Haematol Date: 2003-03 Impact factor: 6.998
Authors: Azra Raza; James A Reeves; Eric J Feldman; Gordon W Dewald; John M Bennett; H Joachim Deeg; Luke Dreisbach; Charles A Schiffer; Richard M Stone; Peter L Greenberg; Peter T Curtin; Virginia M Klimek; Jamile M Shammo; Deborah Thomas; Robert D Knight; Michele Schmidt; Kenton Wride; Jerome B Zeldis; Alan F List Journal: Blood Date: 2007-09-24 Impact factor: 22.113
Authors: S Vadhan-Raj; M Keating; A LeMaistre; W N Hittelman; K McCredie; J M Trujillo; H E Broxmeyer; C Henney; J U Gutterman Journal: N Engl J Med Date: 1987-12-17 Impact factor: 91.245