Phase I/II trial of nonpegylated liposomal doxorubicin, cyclophosphamide, vincristine, and prednisone in the treatment of newly diagnosed aggressive non-Hodgkin's lymphoma.
BACKGROUND
The toxicity and efficacy of nonpegylated liposomal doxorubicin (TLC D-99) when substituted for conventional doxorubicin in the CHOP (doxorubicin/cyclophosphamide/vincristine/prednisone) regimen were evaluated in the treatment of newly diagnosed patients with aggressive non-Hodgkin's lymphoma. Liposomal doxorubicin at doses of 40 mg/m2, 50 mg/m2, 60 mg/m2, and 80 mg/m2 was given with fixed doses of cyclophosphamide, vincristine, and prednisone. Chemotherapy cycles were repeated every 21 days.


METHODS
Forty-seven patients with a median age of 55 years (range, 25-83 years) were studied.


RESULTS
No dose-limiting toxicities were observed at any level. Reversible grade 3/4 neutropenia was the most common toxicity (95.8%). Most nonhematologic side effects were grade 1/2 in severity. Complete remissions were documented in 31 of 46 evaluable patients (67.4%) and partial remissions in 7 (15.2%), for an overall major response rate of 82.6%. The median duration of complete remission is > or = 27.7 months (range, 2.4 months to > or = 59.8 months). An exploratory objective was to correlate multidrug resistance-1 (MDR-1) expression with outcome. Immunohistochemistry for MDR-1-related p-glycoprotein was assessed in lymphoma tissues from 27 patients. Of the 27 lymphoma tissues studied, 8 (30%) were MDR-1 positive at diagnosis. The complete response rate was 63% in MDR-1-positive lymphomas and 74% in the MDR-1-negative cases (P = 0.66).


CONCLUSIONS
Nonpegylated liposomal doxorubicin in combination with cyclophosphamide, vincristine, and prednisone is an active regimen for patients with newly diagnosed, aggressive non-Hodgkin's lymphoma. The regimen is relatively well tolerated, with hematologic suppression as the major toxicity. Liposomal encapsulation might evade resistance caused by MDR-1 expression.
Tulpule
Anil
A
Division of Hematology, Department of Medicine, Keck School of Medicine of the University of Southern California, Los Angeles, CA, USA. tulpule@usc.edu
Espina
Byron M
BM
Berman
Nancy
N
Buchanan
Laura H
LH
Smith
D Lynne
DL
Sherrod
Andy
A
Dharmapala
Dharshika
D
Gee
Conway
C
Boswell
William D
WD
Nathwani
Bharat N
BN
Welles
Lauri
L
Levine
Alexandra M
AM
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D003520:Cyclophosphamide / Q000008:administration & dosage*; D004317:Doxorubicin / Q000008:administration & dosage*; D005260:Female; D006801:Humans; D008228:Lymphoma, Non-Hodgkin / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D011241:Prednisone / Q000008:administration & dosage*; D012074:Remission Induction; D013997:Time Factors; D016896:Treatment Outcome; D014750:Vincristine / Q000008:administration & dosage*
D014750:Vincristine; D004317:Doxorubicin; D003520:Cyclophosphamide; D011241:Prednisone