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Phase 3 study of the multidrug resistance modulator PSC-833 in previously untreated patients 60 years of age and older with acute myeloid leukemia: Cancer and Leukemia Group B Study 9720.

Publication ,  Journal Article
Baer, MR; George, SL; Dodge, RK; O'Loughlin, KL; Minderman, H; Caligiuri, MA; Anastasi, J; Powell, BL; Kolitz, JE; Schiffer, CA; Bloomfield, CD ...
Published in: Blood
August 15, 2002

The Cancer and Leukemia Group B conducted a phase 3 trial of the P-glycoprotein modulator PSC-833 in untreated acute myeloid leukemia patients aged 60 years and older. Patients were randomized to 1 of 2 regimens, with doses determined in a prior phase 1 study, consisting of cytarabine 100 mg/m(2)/d by 7-day infusion, with daunorubicin 60 mg/m(2) and etoposide 100 mg/m(2) daily for 3 days (ADE), or daunorubicin 40 mg/m(2) and etoposide 60 mg/m(2) for 3 days with PSC-833, 2.8 mg/kg over 2 hours, and then 10 mg/kg/d by 3-day infusion (ADEP). The ADEP arm was closed after randomization of 120 patients (61 to ADE and 59 to ADEP) because of excessive early mortality. Rates of complete remission, nonresponse, and death were 46%, 34%, and 20% for ADE, versus 39%, 17%, and 44% for ADEP (P =.008). Nevertheless, disease-free survival (median 7 vs 8 months; P =.38) and overall survival (approximately 33% alive at 1 year) did not differ and were similar to historical results. Although the number of patients was limited, ADE patients whose pretreatment cells exhibited PSC-833-modulated dye efflux in vitro (n = 22) had worse outcomes than those without efflux (n = 11) (complete remission, nonresponse, and death rates of 41%, 41%, and 18%, compared with 91%, 9%, and 0%; P =.03), but with ADEP outcomes were nearly identical. Moreover, for patients with PSC-833-modulated efflux, median disease-free survival was 5 months with ADE and 14 months with ADEP (P =.07). Further modulation trials in older patients must await the design of less-toxic regimens.

Duke Scholars

Published In

Blood

ISSN

0006-4971

Publication Date

August 15, 2002

Volume

100

Issue

4

Start / End Page

1224 / 1232

Location

United States

Related Subject Headings

  • Remission Induction
  • Middle Aged
  • Male
  • Logistic Models
  • Leukemia, Myeloid, Acute
  • Immunology
  • Humans
  • Female
  • Etoposide
  • Drug Resistance, Multiple
 

Citation

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Baer, M. R., George, S. L., Dodge, R. K., O’Loughlin, K. L., Minderman, H., Caligiuri, M. A., … Larson, R. A. (2002). Phase 3 study of the multidrug resistance modulator PSC-833 in previously untreated patients 60 years of age and older with acute myeloid leukemia: Cancer and Leukemia Group B Study 9720. Blood, 100(4), 1224–1232.
Baer, Maria R., Stephen L. George, Richard K. Dodge, Kieran L. O’Loughlin, Hans Minderman, Michael A. Caligiuri, John Anastasi, et al. “Phase 3 study of the multidrug resistance modulator PSC-833 in previously untreated patients 60 years of age and older with acute myeloid leukemia: Cancer and Leukemia Group B Study 9720.Blood 100, no. 4 (August 15, 2002): 1224–32.
Baer MR, George SL, Dodge RK, O’Loughlin KL, Minderman H, Caligiuri MA, Anastasi J, Powell BL, Kolitz JE, Schiffer CA, Bloomfield CD, Larson RA. Phase 3 study of the multidrug resistance modulator PSC-833 in previously untreated patients 60 years of age and older with acute myeloid leukemia: Cancer and Leukemia Group B Study 9720. Blood. 2002 Aug 15;100(4):1224–1232.

Published In

Blood

ISSN

0006-4971

Publication Date

August 15, 2002

Volume

100

Issue

4

Start / End Page

1224 / 1232

Location

United States

Related Subject Headings

  • Remission Induction
  • Middle Aged
  • Male
  • Logistic Models
  • Leukemia, Myeloid, Acute
  • Immunology
  • Humans
  • Female
  • Etoposide
  • Drug Resistance, Multiple