TY - JOUR
T1 - Mitoxantrone, etoposide, and cytarabine plus cyclosporine for patients with relapsed or refractory acute myeloid leukemia
T2 - An Eastern Cooperative Oncology group pilot study
AU - Tallman, Martin S.
AU - Lee, Sandra
AU - Sikic, Branimir I.
AU - Paietta, Elisabeth
AU - Wiernik, Peter H.
AU - Bennett, John M.
AU - Rowe, Jacob M.
PY - 1999
Y1 - 1999
N2 - 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.
AB - 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.
KW - Acute myeloid leukemia
KW - Cyclosporine
KW - Multidrug resistance
KW - P-glycoprotein expression
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U2 - 10.1002/(SICI)1097-0142(19990115)85:2<358::AID-CNCR13>3.0.CO;2-0
DO - 10.1002/(SICI)1097-0142(19990115)85:2<358::AID-CNCR13>3.0.CO;2-0
M3 - Article
C2 - 10023703
AN - SCOPUS:0032942270
SN - 0008-543X
VL - 85
SP - 358
EP - 367
JO - cancer
JF - cancer
IS - 2
ER -