Safety and tolerability of phase I/II clinical trials among older and younger patients with acute myelogenous leukemia

Objectives: Remission rates and survival remain limited for the majority of elderly patients with acute myeloid leukemia. Therefore, clinical trials with novel investigational strategies could be considered for these patients. We sought to evaluate the influence of age on outcome defined by survival and toxicity of 121. patients (range 28-82 years) with high-risk, relapsed/refractory acute myelogenous leukemia [ECOG PS 0-3] who were enrolled on four consecutive phase I/II clinical trials between 1994 and 2008 conducted at two institutions. Materials and methods: 75/121 (62%) of the patients enrolled Were >= 60 years old. Treatment included phase I topotecan and etoposide (23 patients); phase I fludarabine, carboplatin, and topotecan (FCT) (27 patients); phase II FCT plus thalidomide (39 patients); and phase I ispinesib (SB 994772) (32 patients). Outcome data including CR (complete remission) rate, overall survival, and treatment related toxicities, were analyzed according to prior treatment, disease characteristics, ECOG performance status (PS), duration of first CR, and age. Results: In multivariate analysis, survival and toxicities were similar between younger and older patients. PS was the most significant determinant of overall survival (PS 0-1: 30-day survival 97.5% and 1 year survival 21% vs. PS 2-3: 79% and 9.5%, respectively) (p = 0.029). Similarly, PS was the most important factor for development of serious non-hematologic toxicities (p = 0.034). Conclusion: Our data suggest that elderly acute myeloid leukemia patients with good PS are appropriate candidates for phase I/II clinical trials. (C) 2011 Elsevier Ltd. All rights reserved.