Modified VAD and PSC-833 in the treatment of resistant or relapsing chronic lymphocytic leukemia (E4996): a trial of the Eastern Cooperative Oncology Group

Leuk Res. 2004 Aug;28(8):813-9. doi: 10.1016/j.leukres.2003.12.002.


Background & method: The role of multidrug resistance (MDR) was investigated in patients with relapsed chronic lymphocytic leukemia (CLL). PSC-833 was added to modified VAD (a 4-day infusion of vincristine, doxorubicin, with oral dexamethasone, every 3 weeks), in an attempt to improve the response rate (21%) in a prior study. Laboratory tests to determine MDR and apoptosis proteins were correlated with response.

Results: Two of the seven MDR-positive cases and one of the four MDR-negative patients achieved a partial response (no significant difference). No significant correlation with response was found in any of the laboratory tests for apoptosis.

Conclusion: VAD plus PSC-833 had the same (21%) partial response rate as a prior ECOG study without PSC-833. No correlation of response with MDR or apoptosis testing was found. Other drug resistance factors must play a significant role in determining the response of relapsed patients with CLL.

Publication types

  • Clinical Trial
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Cyclosporins / therapeutic use*
  • Dexamethasone / therapeutic use*
  • Doxorubicin / therapeutic use*
  • Drug Resistance, Multiple*
  • Drug Therapy, Combination
  • Female
  • Humans
  • Leukemia, Lymphocytic, Chronic, B-Cell / drug therapy*
  • Leukemia, Lymphocytic, Chronic, B-Cell / pathology
  • Male
  • Middle Aged
  • Neoplasm Recurrence, Local / drug therapy*
  • Neoplasm Recurrence, Local / pathology
  • Vincristine / therapeutic use*


  • Cyclosporins
  • Vincristine
  • Dexamethasone
  • Doxorubicin
  • valspodar

Supplementary concepts

  • VAD I protocol