Phase II trial of infusional cyclophosphamide, doxorubicin, and etoposide in patients with HIV-associated non-Hodgkin's lymphoma: an Eastern Cooperative Oncology Group Trial (E1494).
OBJECTIVE
To determine the effectiveness of an infusional chemotherapy regimen in patients with HIV-associated lymphoma treated before and after the use of highly active antiretroviral therapy (HAART) in routine clinical practice.


METHODS
Ninety-eight assessable patients with HIV-associated intermediate- or high-grade non-Hodgkin's lymphoma received cyclophosphamide 200 mg/m(2)/d, doxorubicin 12.5 mg/m(2)/d, and etoposide 60 mg/m(2)/d (CDE) given by continuous intravenous infusion for 4 days (96 hours) every 4 weeks plus filgrastim. Concurrent antiretroviral treatment consisted of the nucleoside analog didanosine in the first 43 patients enrolled before December 1996 (pre-HAART group), or HAART in the remaining 55 patients enrolled after that time (HAART group).


RESULTS
Complete response occurred in 44 patients (45%; 95% CI, 35% to 55%). Failure-free survival and overall survival (OS) at 2 years was 36% (95% CI, 26% to 46%) and 43% (95% CI, 33% to 53%), respectively. At the time of the analysis, 30% in the pre-HAART group were alive compared with 47% in the HAART group; when adjusted for varying length of follow-up, patients in the HAART group had improved OS (P =.039). Patients in the HAART group experienced less grade 4 nonhematologic toxicity (22% v 42%; P =.037), thrombocytopenia (31% v 52%; P =.033), and anemia (9% v 27%; P =.021), and had fewer treatment-associated deaths (0% v 10%; P =.013).


CONCLUSIONS
Infusional CDE is an effective and potentially curative regimen for patients with HIV-associated lymphoma. Patients treated in the HAART era have less chemotherapy-associated toxicity and improved survival.
Sparano
Joseph A
JA
Albert Einstein Cancer Center and Montefiore Medical Center, Weiler Division, 1825 Eastchester Road/2 South, Rm 47-48, Bronx, NY 10461, USA. jsparano@montefiore.org
Lee
Sandra
S
Chen
Michael G
MG
Nazeer
Tipu
T
Einzig
Avi
A
Ambinder
Richard F
RF
Henry
David H
DH
Manalo
Jane
J
Li
Tianhong
T
Von Roenn
Jamie H
JH
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active; D003520:Cyclophosphamide / Q000627:therapeutic use*; D004317:Doxorubicin / Q000627:therapeutic use*; D005047:Etoposide / Q000627:therapeutic use*; D006801:Humans; D016483:Lymphoma, AIDS-Related / Q000188:drug therapy*; D008875:Middle Aged; D011379:Prognosis; D016896:Treatment Outcome
D005047:Etoposide; D004317:Doxorubicin; D003520:Cyclophosphamide