Premium
Mitoxantrone, etoposide, and cytarabine plus cyclosporine for patients with relapsed or refractory acute myeloid leukemia
Author(s) -
Tallman Martin S.,
Lee Sandra,
Sikic Branimir I.,
Paietta Elisabeth,
Wiernik Peter H.,
Bennett John M.,
Rowe Jacob M.
Publication year - 1999
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/(sici)1097-0142(19990115)85:2<358::aid-cncr13>3.0.co;2-0
Subject(s) - mitoxantrone , medicine , etoposide , cytarabine , myeloid leukemia , chemotherapy , refractory (planetary science) , gastroenterology , leukemia , surgery , transplantation , physics , astrobiology
BACKGROUND One potential mechanism of drug resistance to chemotherapy is the overexpression of multidrug resistance ( MDR ) genes coding for P‐glycoprotein (P‐gp), which leads to reduced intracellular retention of chemotherapy. This study tested the efficacy and toxicity of mitoxantrone, etoposide, and intermediate dose cytarabine (MEC) with cyclosporine (CSP) as an MDR modulator in patients with recurrent and refractory acute myeloid leukemia, and also correlated P‐gp expression in leukemia cells with response. METHODS Thirty‐eight eligible patients who were in first recurrence after < 6 months of complete remission (CR) (11 patients), refractory to initial induction therapy or to one attempt at reinduction after recurrence (18 patients), in second recurrence (4 patients), or in recurrence after either allogeneic or autologous bone marrow transplantation (5 patients) received either MEC alone (13 patients) or MEC‐CSP (25 patients). CSP was given as a loading dose of 6 mg/kg for 2 hours intravenously (i.v.) starting 2 hours before the first dose of etoposide, followed by a continuous i.v. infusion of 18 mg/kg/day for 98 hours. RESULTS Three of the 13 patients (23%) who received MEC achieved CR, as did 6 of the 25 patients (24%) who received MEC‐CSP. The median remission duration for all patients who achieved CR was 149 days (range, 26–466 days), 91 days (range, 81–172 days) for the 3 patients who received MEC, and 189.5 days (range, 26–466 days) for the patients treated with MEC‐CSP. The median survival for the patients treated with MEC and MEC‐CSP was 104 and 72 days, respectively. CONCLUSIONS No significant association was found between P‐gp expression and response. No apparent benefit in the CR rate, remission duration, or survival was observed with the addition of CSP to MEC. Cancer 1999;85:358–67. © 1999 American Cancer Society.