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.