title: Modified VAD and PSC-833 in the treatment of resistant or relapsing chronic lymphocytic leukemia (E4996): a trial of the Eastern Cooperative Oncology Group.
abstract: METHODS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Hematology/Oncology, Guthrie Clinic, One Guthrie Square, Sayre, PA 18840, USA. wfriedenberg@clinic.guthrie.org
authors.forename: William R
authors.initials: WR
authors.lastname: Friedenberg
authors.forename: Martin S
authors.initials: MS
authors.lastname: Tallman
authors.forename: Isadore
authors.initials: I
authors.lastname: Brodsky
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Paietta
authors.forename: Jacob M
authors.initials: JM
authors.lastname: Rowe
authors.forename: Sandra J
authors.initials: SJ
authors.lastname: Lee
authors.forename: Kendrith M
authors.initials: KM
authors.lastname: Rowland
authors.forename: George W
authors.initials: GW
authors.lastname: Schnetzer
authors.forename: John C
authors.initials: JC
authors.lastname: Reed
mesh_terms: D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D003524:Cyclosporins / Q000627:therapeutic use*; D003907:Dexamethasone / Q000627:therapeutic use*; D004317:Doxorubicin / Q000627:therapeutic use*; D018432:Drug Resistance, Multiple; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy* / Q000473:pathology; D014750:Vincristine / Q000627:therapeutic use*
chemical_list: D003524:Cyclosporins; D014750:Vincristine; D003907:Dexamethasone; D004317:Doxorubicin; C070272:valspodar