Results of topotecan-based combination therapy in patients with myelodysplastic syndromes and chronic myelomonocytic leukemia.

The efficacy and safety of topotecan and high-dose cytarabine were evaluated in 59 patients with advanced myelodysplastic syndromes (MDS) (n = 38) or chronic myelomonocytic leukemia (CMML) (n = 21). Topotecan 1.25 mg/m2/d was administered by continuous Intravenous infusion daily for 5 days, and cytarabine 1.0g/m2/d by Infusion over 2 hours for 5 days. At a median follow-up duration of 7 months, 59 patients were evaluable for response and toxicity. Complete remission (CR) was achieved in a significantly larger proportion of MDS patients than CMML patients (66% v 48%, P < or = .05). CR rates for good-risk and poor-risk MDS patients were similar (79% and 58%, respectively). Treatment was particularly effective in patients with poor-prognosis karyotypes and secondary MDS, producing CR rates of 63% and 69%, respectively. Medlan duration of CR was 32 weeks (41 weeks for MDS; 33 weeks for CMML). Median survival was 60 weeks for MDS patients and 41 weeks for CMML patients. Prospective analysis of response by International Prognostic Scoring System (IPSS) risk classification showed comparable CR rates among intermediate 1 (60%), Intermediate 2 (83%), and high-risk (56%) categories. Fever of undetermined origin and Infections occurred in 72% and 59% of patients, respectively. Six patients (10%) died during Induction therapy. This regimen was well tolerated and was associated with a low mortality rate.