Topotecan and cytarabine is an active combination regimen in myelodysplastic syndromes and chronic myelomonocytic leukemia

Purpose: To evaluate the efficacy and safety of the combination of topoteca n and cytarabine in patients with myelodysplastic syndromes (MDSs) and chro nic myelomanocytic leukemia (CMML). Patients and Methods: Fifty-nine patients with MDSs and 27 with CMML were e nrolled. They were either previously untreated (66%) or had received only b iologic agents (14%) or chemotherapy with or without biologic agents (20%), Treatment consisted of topotecan 1.25 mg/m(2) by continuous intravenous in fusion daily for 5 days and cytarabine 1.0 g/m(2) by infusion over 2 hours daily for 5 days. Prophylaxis included antibacterial, antifungal, and antiv iral agents. At a median fallow-up of 7 months, all 86 patients were assess able for response and toxicity. Results: Complete remission (CR)was observed in 48 patients (56%; 61% with MDSs, 44% with CMML; P = .15). Similar CR rates were observed for patients with good-risk and poor-risk MDS (70% and 56%, respectively), The treatment effectively induced CR in patients with a poor-prognosis karyotype involvi ng chromosomes 5 and 7 (CR, 71%) and secondary MDSs (CR, 72%). Fifty-four p atients received one induction course, 25 patients received two, and the re st received more than two. The median number of continuation courses was tw o. The median overall duration of CR was 34 weeks (50 weeks for MDSs and 33 weeks far CMML), The median survival was 60 weeks for MDS and 44 weeks for CMML patients. CR and survival durations were longer in patients with refr actory anemia with excess blasts (RAEB). Grade 3 or 4 mucositis or diarrhea was observed in three patients each. Fever was observed in 63%, and infect ions in 49% of patients, Six patients (7%) died during induction therapy. Conclusion: Topotecan and cytarabine induced high CR rates in unselected pa tients with MDSs and CMML, particularly among patients with poor-prognosis cytogenetics and secondary MDSs. Topotecan-cytarabine is an active inductio n regimen in MDS and CMML patients, is well tolerated, and is associated wi th a low mortality rate. (C) 1999 by American Society of Clinical Oncology.