Mitoxantrone, etoposide, and cytarabine plus cyclosporine for patients with relapsed or refractory acute myeloid leukemia

An Eastern Cooperative Oncology group pilot study

Martin S. Tallman, Sandra Lee, Branimir I. Sikic, Elisabeth M. Paietta, Peter H. Wiernik, John M. Bennett, Jacob M. Rowe

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)358-367
Number of pages10
JournalCancer
Volume85
Issue number2
DOIs
StatePublished - 1999

Fingerprint

Mitoxantrone
Cytarabine
Etoposide
Acute Myeloid Leukemia
Cyclosporine
P-Glycoprotein
Recurrence
MDR Genes
Drug Therapy
Survival
Autologous Transplantation
Multiple Drug Resistance
Bone Marrow Transplantation
Drug Resistance

Keywords

  • Acute myeloid leukemia
  • Cyclosporine
  • Multidrug resistance
  • P-glycoprotein expression

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Mitoxantrone, etoposide, and cytarabine plus cyclosporine for patients with relapsed or refractory acute myeloid leukemia : An Eastern Cooperative Oncology group pilot study. / Tallman, Martin S.; Lee, Sandra; Sikic, Branimir I.; Paietta, Elisabeth M.; Wiernik, Peter H.; Bennett, John M.; Rowe, Jacob M.

In: Cancer, Vol. 85, No. 2, 1999, p. 358-367.

Research output: Contribution to journalArticle

Tallman, Martin S. ; Lee, Sandra ; Sikic, Branimir I. ; Paietta, Elisabeth M. ; Wiernik, Peter H. ; Bennett, John M. ; Rowe, Jacob M. / Mitoxantrone, etoposide, and cytarabine plus cyclosporine for patients with relapsed or refractory acute myeloid leukemia : An Eastern Cooperative Oncology group pilot study. In: Cancer. 1999 ; Vol. 85, No. 2. pp. 358-367.
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abstract = "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.",
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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 M.

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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