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)

Purpose: 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. Patients and Methods: Ninety-eight assessable patients with HIV-associated intermediate- or high-grade non-Hodgkin's lymphoma received cyclophosphamide 200 mg/m²/d, doxorubicin 12.5 mg/m²/d, and etoposide 60 mg/m²/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% v27%; P = .021), and had fewer treatment-associated deaths (0% v 10%; P = .013). Conclusion: 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.