Incorporating new modalities into guidelines. Topotecan for myelodysplastic syndromes

The National Comprehensive Cancer Network (NCCN) guidelines for patients with myelodysplastic syndromes (MDS) list myelosuppressive chemotherapy as an option for patients who have MDS with International Prognostic Scoring System (IPSS) scores of "intermediate" or "high." Myelodysplastic syndromes with these IPSS scores have an unfavorable natural history. Topotecan is a myelosuppressive drug that interacts with topoisomerase I and that has been used in the treatment of refractory AML. Its use in MDS has recently received considerable publicity. This paper reviews M. D. Anderson's results with topotecan and topotecan + ara-C in patients with MDS, focusing on comparisons of the results with ara-C and ara-C + fludarabine +/- idarubicin. While it is clear that the drug can produce complete responses, it is less clear that it differs from these other regimens. On average, complete response and survival rates are similar following administration of topotecan + ara-C or the other regimens. On the other hand, among patients with abnormalities of chromosomes 5 and/or 7, complete response rates are higher following topotecan + ara-C than for ara-C alone, or other ara-C combinations. The improvement in complete response rate among patients with abnormalities of chromosomes 5 and/or 7 has not resulted in an improvement in their survival (actuarial median about 6 months), largely reflecting a poor outcome following complete response. Indeed, the frequency of relapse in these patients suggests that any inherent increase in antileukemia activity in patients with abnormalities of chromosomes 5 and/or 7 is minimal. Given the overall results, topotecan +/- ara-C should not be regarded as standard therapy for MDS. The drug is nonetheless interesting and attempts to add to its efficacy are in progress.