Amifostine (ETHOYL) in Combination with topotecan and ARA-C for patients with poor risk myelodysplasia (MDS) and secondary acute myelogenous leukemia

Academic Article

Abstract

  • The combination of Topotecan and Ara-C is an active induction chemotherapy regimen for patients with advanced myelodysplasia (MDS) but is associated with significant toxicity and mortality, particularly in older patients. Patients treated by this regimen have prolonged myelosuppression and significant mucositis. Amifostine (Ethoyl) as a single agent potentiates hematopoiesis and significantly improves peripheral blood counts in about 30% of patients with MDS. We have conducted a study: (1) to evaluate if addition of amifostine to the combination of Topotecan and Ara-C could improve the response and decrease treatment related toxicity and mortality; (2) to evaluate the efficacy of this regimen in patients with secondary AML (AML that evolved from MDS). Eligibility criteria: patients with MDS and IPSS> 1.5 or secondary AML. No growth factors were allowed in this study. Between 6/99 and 6/2000, we have treated 14 patients (M:F=11:3, median age:60 (range 27-81). By FAB criteria: RA:1. RAEB:6, RAEBT:2 and secondary AML:5. Eleven patients had abnormal karyotype (complex:4, del(7):2, del(5):l. inv(3):l, +8:1,+21:1 and Ilq23:l). Treatment regimen consisted of Topotecan 1.25mg/nrby continuous infusion daily for 5 days, Ara C Igm/nby infusion over 2 hours daily for 5 days and Amifostine 200mg/m2every other day until ANC 1.5x10'/L or a maximum of 60 days. Six out of 7 pts (86%) with RA/RAEB achieved a morphological remission (CR). Of the seven pts with RAEBT or secondary AML, only 1 pt (15%) achieved morphological and cytogenetic remission. Among 6 √©valuable CR pts with abnormal karyotype, 4 reverted to 100% normal karyotype and 2 had greater than 90% normal metaphases. No grade 3 or 4 mucositis or diarrhoea was observed and there were no toxic death during treatment. The median time to recovery of the granulocyte count to greater than l.Oxl O'/L was 22 days (range 19-54)and of platelet count to greater than 50 x lO'/L was 25 days (range 19-54). The median duration of response was 4 months (range 1-14). Conclusion: (1) The combination of Topotecan, Ara-C and Amifostine is an effective induction regimen for patients with poor risk MDS; (2) the toxicity profile of this combination compares favorably with other published studies without Amifostine; and (3) this regimen does not appear to be effective in patients with RAEBT or secondary AML.
  • Published In

  • Blood  Journal
  • Author List

  • Fung HC; Bhatia R; O'Donnell M; Stein A; Speilberger R; Cohen S; Popplewell L; Kashyap A; Hilger J; Ivers B
  • Volume

  • 96
  • Issue

  • 11 PART II