A phase I/II study of the MDR modulator Valspodar (PSC 833) combined with daunorubicin and cytarabine in patients with relapsed and primary refractory acute myeloid leukemia

Leuk Res. 2003 Apr;27(4):323-8. doi: 10.1016/s0145-2126(02)00181-9.


The cyclosporine analog Valspodar (PSC 833, Novartis Pharma) is a strong inhibitor of the mdr1 gene product p-glycoprotein (pgp). A phase I/II study was conducted in order to evaluate if addition of Valspodar to treatment with daunorubicin and cytarabine, given to patients with primary refractory or relapsed acute myeloid leukemia, could increase the complete remission rate.Fifty-three patients were treated in cohorts of three to six patients. Twelve patients reached a complete remission in bone marrow, five of whom also normalized their peripheral blood values. Three patients experienced treatment-related deaths from pneumonia, liver failure and cerebral hemorrhage, respectively. It is concluded that Valspodar 10 mg/kg per 24 h in combination with daunorubicin 45 mg/m(2) for 3 days and cytarabine 1 g/m(2) twice daily for 4 days is tolerable in this heavily pre-treated group of patients. Due to the moderate treatment results, the phase II part of the study was ended prematurely. The modulation of only pgp did not give an obvious improvement of the treatment results in this group of patients.

Publication types

  • Clinical Trial
  • Clinical Trial, Phase I
  • Clinical Trial, Phase II
  • Multicenter Study

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / antagonists & inhibitors
  • Acute Disease
  • Adolescent
  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage*
  • Antineoplastic Combined Chemotherapy Protocols / toxicity
  • Area Under Curve
  • Cause of Death
  • Cyclosporins / administration & dosage*
  • Cyclosporins / blood
  • Cyclosporins / pharmacokinetics
  • Cytarabine / administration & dosage
  • Daunorubicin / administration & dosage
  • Dose-Response Relationship, Drug
  • Drug Resistance, Multiple
  • Humans
  • Leukemia, Myeloid / complications
  • Leukemia, Myeloid / drug therapy*
  • Leukemia, Myeloid / mortality
  • Middle Aged
  • Remission Induction / methods
  • Salvage Therapy
  • Treatment Outcome


  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Cyclosporins
  • Cytarabine
  • valspodar
  • Daunorubicin