title: Phase I/II clinical study of topotecan and cytarabine in patients with myelodysplastic syndrome, chronic myelomonocytic leukemia and acute myeloid leukemia.
abstract: Topotecan, a topoisomerase-I inhibitor is an active drug in the treatment of AML and MDS. To evaluate its toxicity and efficacy in a combination regimen with cytarabine, we conducted a clinical phase I/II trial in patients with relapsed acute myeloid leukemia (AML) or relapsed or newly diagnosed MDS RAEB, RAEB-t or CMML. Twenty-one patients (11 AML, 10 MDS/CMML) entered the study and were treated with 1.25 mg/m2 topotecan as continuous intravenous infusion daily for 5 days and cytarabine 1.0 g/m2 by infusion over 2 h daily for 5 days (TA). Cycles were repeated on day 28. The median observation time was 131 weeks (range: 36-196 weeks). A total of 37 cycles of TA were administered. In 1 patient, the dose of TA had to be reduced and in 1 patient, there was a treatment delay for the second cycle, both because of hematologic toxicity. The most frequent non-hematologic side-effect of TA was fever, which occurred in 17 patients (89%) with temperatures over 38 degrees C. None of the patients died due to any treatment-related toxicities, but 2 patients (10%) died within 1 month due to disease progression. A CR was achieved in 7 patients (33%), 3 of whom were MDS and 4 AML. A partial remission was reported in 8 patients (38%), no change of disease in 2 patients (10%) and progressive disease in 4 patients (19%). The median remission duration was 18 weeks (range 2-161 weeks) for MDS patients and 11 weeks (range 2-49 weeks) for AML patients. The time to progression for patients of 60 years and older (n = 10) was 16 weeks (range 2-49 weeks) and the survival was 32 weeks (range 2-119 weeks). TA is a feasible and efficacious chemotherapeutic combination for the treatment of MDS RAEB, RAEB-t, CMML and AML. For patients of 60 years and older, this regimen is also a safe option.
authors.affiliation: Department of Internal Medicine I, University of Cologne, Germany. martin.weihrauch@uni-koeln.de
authors.forename: Martin R
authors.initials: MR
authors.lastname: Weihrauch
authors.forename: Peter
authors.initials: P
authors.lastname: Staib
authors.forename: Bettina
authors.initials: B
authors.lastname: Seiberlich
authors.forename: Martin
authors.initials: M
authors.lastname: Hoffmann
authors.forename: Volker
authors.initials: V
authors.lastname: Diehl
authors.forename: Hans
authors.initials: H
authors.lastname: Tesch
mesh_terms: D000208:Acute Disease; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000633:toxicity; D001772:Blood Cell Count; D003561:Cytarabine / Q000008:administration & dosage*; D018572:Disease-Free Survival; D005260:Female; D006452:Hemoglobinometry; D006801:Humans; D007951:Leukemia, Myeloid / Q000150:complications / Q000188:drug therapy* / Q000401:mortality; D015477:Leukemia, Myelomonocytic, Chronic / Q000150:complications / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000150:complications / Q000188:drug therapy* / Q000401:mortality; D012074:Remission Induction / Q000379:methods; D016019:Survival Analysis; D019772:Topotecan / Q000008:administration & dosage*; D016896:Treatment Outcome
chemical_list: D003561:Cytarabine; D019772:Topotecan