Modified VAD and PSC-833 in the treatment of resistant or relapsing chronic lymphocytic leukemia (E4996): a trial of the Eastern Cooperative Oncology Group.
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.
Friedenberg
William R
WR
Hematology/Oncology, Guthrie Clinic, One Guthrie Square, Sayre, PA 18840, USA. wfriedenberg@clinic.guthrie.org
Tallman
Martin S
MS
Brodsky
Isadore
I
Paietta
Elisabeth
E
Rowe
Jacob M
JM
Lee
Sandra J
SJ
Rowland
Kendrith M
KM
Schnetzer
George W
GW
Reed
John C
JC
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*
D003524:Cyclosporins; D014750:Vincristine; D003907:Dexamethasone; D004317:Doxorubicin; C070272:valspodar