Kamal K S Abbi1, Witold Rybka2, W Christopher Ehmann2, David F Claxton3. 1. Memorial Sloan Kettering Cancer Center, New York, NY. 2. Penn State College of Medicine, Hershey, PA. 3. Penn State College of Medicine, Hershey, PA. Electronic address: dclaxton@hmc.psu.edu.
Abstract
BACKGROUND: Clofarabine, a second-generation nucleoside analogue, was studied in combination with etoposide and mitoxantrone in acute leukemia. PATIENTS AND METHODS: In the phase I portion of this study clofarabine was given 20 or 25 mg/m(2) daily for 5 days (Days 2-6) with etoposide 100 mg/m(2) from day 1 to 5 and mitoxantrone 8 mg/m(2) from day 1 to 3. The dose-limiting toxicity was myelosuppression, and dose level 1, with clofarabine 20 mg/m(2) daily for 5 days was identified as the phase 2 dose. In total, 22 patients with relapsed or refractory acute myeloid leukemia (n = 18) and acute lymphocytic leukemia (n = 4) were treated. RESULTS: Five of 22 patients (23%) achieved complete response (CR), and 3 (13%) achieved CR with incomplete platelet recovery; an overall response rate of 36%. Median overall survival was 167 days (range, 22-1327 days). For 2 patients this regimen represented an effective bridge to allogeneic stem cell transplantation. CONCLUSION: Clofarabine in combination with etoposide and mitoxantrone is tolerable and shows significant activity in relapsed and refractory acute leukemia in adults.
BACKGROUND:Clofarabine, a second-generation nucleoside analogue, was studied in combination with etoposide and mitoxantrone in acute leukemia. PATIENTS AND METHODS: In the phase I portion of this study clofarabine was given 20 or 25 mg/m(2) daily for 5 days (Days 2-6) with etoposide 100 mg/m(2) from day 1 to 5 and mitoxantrone 8 mg/m(2) from day 1 to 3. The dose-limiting toxicity was myelosuppression, and dose level 1, with clofarabine 20 mg/m(2) daily for 5 days was identified as the phase 2 dose. In total, 22 patients with relapsed or refractory acute myeloid leukemia (n = 18) and acute lymphocytic leukemia (n = 4) were treated. RESULTS: Five of 22 patients (23%) achieved complete response (CR), and 3 (13%) achieved CR with incomplete platelet recovery; an overall response rate of 36%. Median overall survival was 167 days (range, 22-1327 days). For 2 patients this regimen represented an effective bridge to allogeneic stem cell transplantation. CONCLUSION:Clofarabine in combination with etoposide and mitoxantrone is tolerable and shows significant activity in relapsed and refractory acute leukemia in adults.
Authors: Harinder Gill; Rita Yim; Herbert H Pang; Paul Lee; Thomas S Y Chan; Yu-Yan Hwang; Garret M K Leung; Ho-Wan Ip; Rock Y Y Leung; Sze-Fai Yip; Bonnie Kho; Harold K K Lee; Vivien Mak; Chi-Chung Chan; June S M Lau; Chi-Kuen Lau; Shek-Yin Lin; Raymond S M Wong; Wa Li; Edmond S K Ma; Jun Li; Gianni Panagiotou; Joycelyn P Y Sim; Albert K W Lie; Yok-Lam Kwong Journal: Cancer Med Date: 2020-03-18 Impact factor: 4.452