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 cycloph osphamide, doxarubicin, vincristine, and dexamethasone chemotherapy, termed the CVAD regimen, alone (Southwest Oncology Group [SWOG] 9240) and with th e chemosensitizers verapamil and quinine (SWOG 9125) to assess effects on r esponse, survival, and toxicity in intermediate- and high-grade advanced-st age non-Hodgkin's lymphoma (NHL). The results were compared with the histor ic group of patients randomized ta CHOP chemotherapy on Intergroup (INT) 00 67 (SWOG 8516). Patients and Methods: All patients had biopsy-proven intermediate or high-g rade NHL (lymphoblastic histology excluded), were ambulatory and previously untreated, and had bulky stage 11, III, or IV disease. One hundred twelve patients were registered on SWOG 9240 and received cyclophosphamide 750 mg/ m(2) by intravenous bolus day 1, doxorubicin 12.5 mg/m(2)/d and vincristine 0.5 mg/d delivered as a continuous 96-hour infusion on days 1 through 4, a nd dexamethasone 40 mg/d orally on days 1 through 4 (CVAD), Cycles were rep eated every 21 days for eight cycles. One hundred patients on SWOG 9125 rec eived the same chemotherapy and the chemosensitizers verapamil 240 mg bid a nd quinine 40 mg tid, Chemosensitizers were begun 24 hours before chemother apy and continued for a total of 6 days. Results: Eighty one patients were eligible for each study. The complete res ponse (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 5-year failure-free survival (885) 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 9 240. These results are comparable to a 44% CR rate, a 2-year FFS of 46%, an d 5-year OS of 63% observed in 225 patients treated with CHOP on INT 0067 ( SWOG 8516). Conclusion: CVAD combination chemotherapyalone or with the chemosensitisers verapamil and quinine is not promising therapy with respect to improved re sponse or OS in intermediate- and high grade advanced-stage NHL. (C) 2001 b y American Society of Clinical Oncology.