Infusional CHOP chemotherapy (CVAD) with or without chemosensitizers offers no advantage over standard CHOP therapy in the treatment of lymphoma: A Southwest Oncology Group Study

Purpose: Two phase II studies were conducted to evaluate infusional cyclophosphamide, doxorubicin, vincristine, and dexamethasone chemotherapy, termed the CVAD regimen, alone (Southwest Oncology Group [SWOG] 9240) and with the chemosensitizers verapamil and quinine (SWOG 9125) to assess effects on response, survival and toxicity in intermediate- and high-grade advanced-stage non-Hodgkin's lymphoma (NHL). The results were compared with the historic group of patient's randomized to CHOP chemotherapy on Intergroup (INT) 0067 (SWOG 8516). Patients and Methods: All patients had biopsy-proven intermediate- or high-grade NHL (lymphoblastic histology excluded), were ambulatory and previously untreated, and had bulky stooge II, III, or IV disease. One hundred twelve patients were registered on SWOG 9240 and received cydophosphamide 750 mg/m² by intravenous bolus day 1, doxorubicin 12.5 mg/m²/d and vincristine 0.5 mg/d delivered as a continuous 96-hour infusion on days 1 through 4, and dexamethasone 40 mg/d orally on days 1 through 4 (CYAD). Cycles were repeated every 21 days for eight cycles. One hundred patients on SWOG 9125 received the same chemotherapy and the chemosensitizers verapamil 240 mg bid and quinine 40 mg tid. Chemosensitizers were begun 24 hours before chemotherapy and continued for a total of 6 days. Results: Eighty-one patients were eligible for each study. The complete response (CR) rates were 39% on SWOG 9125 and 31% on SWOG 9240, With a median follow-up of 5.8 years on SWOG 9125 and 4.5 years on SWOG 9240, the 2-year failure-free survival (FFS) rate was 42% on SWOG 9125 and 41% on SWOG 9240. Two-year overall survival (OS) rate was 64% on SWOG 9125 and 58% on SWOG 9240. These results are comparable to a 44% CR rate, a 2-year FFS of 46%, and 2-year OS of 63% observed in 225 patients treated with CHOP on INT 0067 (SWOG 8516). Conclusion: CVAD combination chemotherapy alone or with the chemosentizers verapamil and quinine is not promising therapy with respect to improved response or OS in intermediate- and high-grade advanced-stage NHL.