Leukemia Research
Volume 24, Issue 7 , Pages 567-574 , July 2000

A phase I study of induction chemotherapy for older patients with newly diagnosed acute myeloid leukemia (AML) using mitoxantrone, etoposide, and the MDR modulator PSC 833: a Southwest Oncology Group study 9617

  • Thomas R Chauncey

      Affiliations

    • University of Washington School of Medicine, Seattle, WA, USA
    • Puget Sound Oncology Consortium, Seattle, WA, USA
    • VA Puget Sound Health Care System, (5-111-MTU), 1660 South Columbian Way Seattle, WA, 98108 USA
    • Corresponding Author InformationCorresponding author. At VA Puget Sound Health Care System, (5-111-MTU), 1660 South Columbian Way Seattle, WA, 98108 USA. Tel.: +1-206-7642709; fax: +1-206-7642851
    • ,
  • Cathryn Rankin

      Affiliations

    • The Southwest Oncology Group Statistical Center, Seattle, WA, USA
    • ,
  • Jeanne E Anderson

      Affiliations

    • University of Texas Health Science Center, San Antonio, TX, USA
    • ,
  • I-Ming Chen

      Affiliations

    • The University of New Mexico, Albuquerque, NM, USA
    • ,
  • Kenneth J Kopecky

      Affiliations

    • The Southwest Oncology Group Statistical Center, Seattle, WA, USA
    • ,
  • John E Godwin

      Affiliations

    • Loyola University Medical Center, Maywood, IL, USA
    • ,
  • Matt E Kalaycio

      Affiliations

    • Cleveland Clinic Foundation, Cleveland, OH, USA
    • ,
  • Dennis F Moore Jr

      Affiliations

    • The Wichita CCOP, Wichita KS, USA
    • ,
  • Muhammad S Shurafa

      Affiliations

    • Henry Ford Hospital, Detroit, MI, USA
    • ,
  • Stephen H Petersdorf

      Affiliations

    • University of Washington School of Medicine, Seattle, WA, USA
    • Puget Sound Oncology Consortium, Seattle, WA, USA
    • ,
  • Eric H Kraut

      Affiliations

    • The Ohio State University Health Center, Columbus, OH, USA
    • ,
  • Catherine P Leith

      Affiliations

    • The University of New Mexico, Albuquerque, NM, USA
    • ,
  • David R Head

      Affiliations

    • St Jude Children’s Research Hospital, Memphis, TN, USA
    • ,
  • Frederick W Luthardt

      Affiliations

    • Puget Sound Oncology Consortium, Seattle, WA, USA
    • ,
  • Cheryl L Willman

      Affiliations

    • The University of New Mexico, Albuquerque, NM, USA
    • ,
  • Frederick R Appelbaum

      Affiliations

    • University of Washington School of Medicine, Seattle, WA, USA
    • Puget Sound Oncology Consortium, Seattle, WA, USA

Received 6 September 1999 ,Accepted 28 January 2000.

References 

  1. Godwin JE, Kopecky KJ, Head DR, et al.  A double-blind placebo-controlled trial of granulocyte colony-stimulating factor in elderly patients with previously untreated acute myeloid leukemia: a Southwest Oncology Group Study (9031). Blood. 1998;91:3607–3615
  2. Rowe JM, Andersen JW, Mazza JJ, et al.  A randomized placebo-controlled phase III study of granulocyte-macrophage colony-stimulating factor in adult patients (>55–70 years of age) with acute myelogenous leukemia: a study of the Eastern Cooperative Oncology Group (E1490). Blood. 1995;86:457–462
  3. Mayer RJ, Davis RB, Schiffer CA, et al.  Intensive postremission chemotherapy in adults with acute myeloid leukemia. New Engl. J. Med. 1994;331:896–903
  4. Johnson PRE, LiuYin JA. Acute myeloid leukaemia in the elderly: biology and treatment. Br. J. Haem. 1993;83:1–6
  5. Stone RM, Mayer RJ. The approach to the elderly patient with acute myeloid leukemia. Hematol. Oncol. Clin. North Am. 1993;7:65–79
  6. Ryan DH, Kopecky KJ, Head D, et al.  Analysis of treatment failure in acute nonlymphocytic leukemia patients over 50 years of age: a Southwest Oncology Group Study. Am. J. Clin. Oncol. 1992;15:69–75
  7. Leith CP, Kopecky KJ, Godwin J, et al.  Acute myeloid leukemia in the elderly: assessment of multidrug resistance (MDR1) and cytogenetics distinguishes biologic subgroups with remarkably distinct responses to standard chemotherapy: a Southwest Oncology Group Study. Blood. 1997;89:3323–3329
  8. Willman CL. The prognostic significance of the expression and function of multidrug resistance transporter proteins in acute myeloid leukemia: studies of the Southwest Oncology Group Leukemia Research Program. Sem. Hematol. 1997;34(4):25–33
  9. Head DR. Revised classification of acute myeloid leukemia. Leukemia. 1996;10:1826–1831
  10. Willman CL. Immunophenotyping and cytogenetics in older adults with acute myeloid leukemia: significance of expression of the multidrug resistance gene-1 (MDR1). Leukemia. 1996;1(10):S33–S35
  11. Leith CP, Chen IM, Kopecky KJ, et al.  Correlation of multidrug resistance (MDR1) protein expression with functional dye/drug efflux in acute myeloid leukemia by multiparameter flow cytometry: identification of discordant MDR−/efflux+ and MDR1+/efflux− cases. Blood. 1995;86:2329–2342
  12. Samdani A, Vijapurkar U, Grimm MA, et al.  Cytogenetics and P-glycoprotein (PGP) are independent predictors of treatment outcome in acute myeloid leukemia (AML). Leuk. Res. 1996;20:175–180
  13. Guerci A, Merlin HL, Missoun N, et al.  Predictive value for treatment outcome in acute myeloid leukemia of cellular daunorubicin accumulation and P-glycoprotein expression simultaneously determined by flow cytometry. Blood. 1995;85:2147–2153
  14. Campos L, Guyotat D, Archimbaud E. et al. Clinical significance of multidrug resistance P-glycoprotein expression on acute nonlymphoblastic leukemia cells at diagnosis. Blood. 1992;79:473–476
  15. Filipits M, Pohl G, Stranzl T, et al.  Expression of the lung resistance protein predicts poor outcome in de novo acute myeloid leukemia. Blood. 1998;5:1508–1513
  16. Filipits M, Suchomel RW, Zöchbauer S. Multidrug resistance-associated protein in acute myeloid leukemia: no impact on treatment outcome. Clin. Cancer Res. 1997;3:1419–1425
  17. List AF. Non-P-glycoprotein drug export mechanisms of multidrug resistance. Semin. Hematol. 1997;5(34):20–24
  18. List AF, Spier CS, Grogan TM, et al.  Overexpression of the major vault transporter protein lung-resistance protein predicts treatment outcome in acute myeloid leukemia. Blood. 1996;87:2464–2469
  19. Advani R, Saba HI, Tallman MS, et al.  Treatment of refractory and relapsed acute myelogenous leukemia with combination chemotherapy plus the multidrug resistance modulator PSC833 (valspodar). Blood. 1999;93:787–795
  20. Giaccone G, Linn SC, Welink J, et al.  A dose-finding and pharmacokinetic study of reversal of multidrug resistance with SDZ PSC 833 in combination with doxorubicin in patients with solid tumors. Clin. Cancer Res. 1997;3:2005–2015
  21. Fisher GA, Lum BL, Hausdorff J, Sikic BI. Pharmacological considerations in the modulation of multidrug resistance. Eur. J. Cancer. 1996;32A:1082–1088
  22. Sonneveld P, Marie JP, Huisman C, et al.  Reversal of multidrug resistance by SDZ PSC 833, combined with VAD (vincristine, doxorubicin, dexamethasone) in refractory multiple myeloma: a phase I study. Leukemia. 1996;10:1741–1750
  23. List AF, Spier CM, Greer J, et al.  Phase I/II trial of cyclosporine as a chemotherapy-resistance modifier in acute leukemia. J. Clin. Oncol. 1993;11:1652–1660
  24. Sikic BI. Modulation of multidrug resistance: at the threshold. J. Clin. Oncol. 1993;11:1629–1635
  25. Keller RP, Altermatt HJ, Donatsch P, et al.  Pharmacologic interactions between the resistance-modifying cyclosporine SDZ PSC 833 and etoposide (VP 16-213) enhance in vivo cytostatic activity and toxicity. Int. J. Cancer. 1992;51:433–438
  26. Lum BL, Kaubisch S, Yahanda AM, et al.  Alteration of etoposide pharmacokinetics and pharmacodynamics by cyclosporine in a phase I trial to modulate multidrug resistance. J. Clin. Oncol. 1992;10:1635–1642
  27. Yahanda AM, Alder KM, Fisher GA, et al.  A phase I trial of etoposide with cyclosporine as a modulator of multidrug resistance. J. Clin. Oncol. 1992;10:1624–1634
  28. Solary E, Witz B, Caillot D, et al.  Combination of quinine as a potential reversing agent with mitoxantrone and cytarabine for the treatment of acute leukemias: a randomized multicenter study. Blood. 1996;88:1198–1205
  29. Miller TP, Grogan TM, Dalton WS, et al.  P-glycoprotein expression in malignant lymphoma and reversal of clinical drug resistance with chemotherapy plus high dose verapamil. J. Clin. Oncol. 1991;9:17–24
  30. Lee EJ, George SL, Caligiuri M, et al.  Parallel phase I studies of daunomycin given with cytarabine and etoposide with or without the multidrug resistance modulator PSC-833 in previously untreated patients 60 years of age or older with acute myelogenous leukemia: results of Cancer and Leukemia Group B study 9420. J. Clin. Oncol. 1999;17:2831–2839
  31. List AF, Kopecky KJ, Willman CL, et al.  Benefit of cyclosporine (CsA) modulation of anthracycline resistance in high-risk AML: a Southwest Oncology Group (SWOG) study. Blood. 1998;92:312a
  32. Kornblau SM, Estey E, Madden T, et al.  Phase I study of mitoxantrone plus etoposide with multidrug blockade by SDZ PSC-833 in relapsed or refractory acute myelogenous leukemia. J. Clin. Oncol. 1997;15:1796–1802
  33. Sonneveld P, Lowenberg B, Vossebeld P, et al.  Dose finding study of PSC833, a novel MDR reversing agent, with daunorubicin and ara-C in untreated elderly patients with acute myeloid leukemia. Blood. 1997;90:507a
  34. Sonneveld P, Durie BGM, Lokhorst HM, et al.  Modulation of multidrug resistance multiple myeloma by cyclosporin. Lancet. 1992;340:255–259
  35. Watanabe T, Tsuge H, Oh-Hara T, et al.  Comparative study on reversal efficacy of SDZ PSC 833, cyclosporin A and verapamil on multidrug resistance in vitro and in vivo. Acta Oncol. 1995;34:235–241
  36. Investigators Brochure, PSC-833, Sandoz Pharmaceuticals Corp., December, 1993.
  37. Friche E, Jensen PB, Nissen NI. Comparison of cyclosporin A and SDZ PSC833 as multidrug-resistance modulators in a daunorubicin-resistant Ehrlich ascites tumor. Cancer Chemother. Pharmacol. 1992;30:235–237
  38. Boesch D, Gaveriaux C, Jachez B, et al.  In vivo circumvention of P-glycoprotein-mediated multidrug resistance of tumor cells with SDZ PSC 833. Cancer Res. 1991;51:4226–4233
  39. Twentyman PR, Bleehen NM. Resistance modification by PSC-833, a novel non-immunosuppressive cyclosporin A. Eur. J. Cancer. 1991;27:1639–1642
  40. Twentyman PR. Modification of cytotoxic drug resistance by non-immunosuppressive cyclosporins. Br. J. Cancer. 1988;57:254–258
  41. Bow EJ, Sutherland JA, Kilpatrick MG, et al.  Therapy of untreated acute myeloid leukemia in the elderly: remission-induction using a non-cytarabine-containing regimen of mitoxantrone plus etoposide. J. Clin. Oncol. 1996;14:1345–1352
  42. Boote DJ, Dennis IF, Twentyman PR, et al.  Phase I study of etoposide with SDZ PSC 833 as a modulator of multidrug resistance in patients with cancer. J. Clin. Oncol. 1996;14:610–618
  43. Ho AD, Lipp T, Ehninger G, et al.  Combination of mitoxantrone and etoposide in refractory acute myelogenous leukemia-an active and well-tolerated regimen. J. Clin. Oncol. 1988;6:213–217
  44. Green S, Weiss GR. Southwest Oncology Group standard response criteria, endpoint definitions, and toxicity criteria. Invest. New Drugs. 1992;10:239–253
  45. Cheson BD, Cassileth PA, Head DR, et al.  Report of the NCI-sponsored workshop on definitions of diagnosis and response in acute myeloid leukemia. J. Clin. Oncol. 1990;8:813–819
  46. Leith CP, Kopecky KJ, Chen IM, et al.  Frequency and clinical significance of the expression of the multidrug resistance proteins MDR1/P-glycoprotein, MRP1, and LRP in acute myeloid leukemia: a Southwest Oncology Group study. Blood. 1999;94:1086–1099
  47. Beck WT, Grogan TM, Willman CL, et al.  Methods to detect P-glycoprotein-associated multidrug resistance in patients’ tumors: consensus recommendations. Cancer Res. 1996;56:3010–3020
  48. Dastugue N, Payen C, Lafage-Pochitaloff M, et al.  Prognostic significance of karyotype in de novo adult acute myeloid leukemia. Leukemia. 1995;9:1491–1498
  49. Grimwade D, Walker H, Oliver F, et al.  The importance of diagnostic cytogenetics on outcome in AML: analysis of 1612 patients entered into the MRC AML 10 trial. Blood. 1998;92:2322–2333
  50. Tallman M, Lee E, Sikic BI, et al.  Mitoxantrone, etoposide and cytarabine plus cyclosporine in patients with relapsed or refractory acute myeloid leukemia: an Eastern Cooperative Oncology Group pilot study. Cancer. 1999;85:358–367
  51. Erlichman C, Moore M, Thiessen JJ, et al.  Phase I pharmacokinetic study of cyclosporin A combined with doxorubicin. Cancer Res. 1993;53:4837–4842

PII: S0145-2126(00)00024-2

Leukemia Research
Volume 24, Issue 7 , Pages 567-574 , July 2000

Article Tools