LONG-TERM RESULTS OF A MULTICENTER RANDOMIZED, COMPARATIVE PHASE-III TRIAL OF CHOP VERSUS CNOP REGIMENS IN PATIENTS WITH INTERMEDIATE AND HIGH-GRADE NON-HODGKINS-LYMPHOMAS

59 previously untreated patients with intermediate- or high-grade, sta ge II-IV non-Hodgkin's lymphoma (NHL) were entered into an open-label, randomised, multicentre study to compare the efficacy and safety of C HOP (cyclophosphamide, doxorubicin, vincristine and prednisolone) with that of CNOP (cyclophosphamide, mitoxantrone, vincristine and prednis olone). 10 patients refused treatment following randomisation. The rem aining 349 patients received either the CHOP or CNOP regimen every 3 w eeks for a maximum of six to eight cycles. The randomisation procedure was violated for 34 patients treated at two study centres. Data from these 34 patients were analysed separately for efficacy and survival. Data from the remaining 325 patients, 164 assigned to CHOP and 161 to CNOP, were used in the major efficacy and survival analyses. Of these 325 patients, 263 (81%) met the eligibility criteria of the protocol. Supplementary analyses of data from these 263 patients, 132 assigned t o CHOP and 131 to CNOP, were conducted for efficacy and survival. Data from all 349 treated patients were analysed for safety. In the 325 ra ndomised patients, the overall objective response rate was not signifi cantly different between the two groups (chi(2), test, P = 0.35). The CHOP regimen had a 51% (83/164) complete remission (CR) rate compared with 40% (64/161) for the CNOP regimen (P = 0.05). Among those with CR , the median time to response was 104 days with the CHOP regimen and 7 7 days with the CNOP regimen, and the median duration of CR was 667 an d 1833 days, respectively. The median time to progression was 449 days for CHOP patients and 564 days for CNOP patients. The median survival time was 932 days for CHOP patients and 1801 days for CNOP patients, with a risk of death on CNOP relative to CHOP of 0.93 (95% confidence interval 0.68-1.27). After 5 years, 50% of patients in the CNOP arm an d 40% of patients in the CHOP arm were still alive; these differences between treatment groups were not statistically significant. The media n time to treatment failure (TTF) was 285 days for patients on the CHO P arm and 282 days for patients on the CNOP arm. Separate analyses of 263 eligible randomised patients, and 34 patients in whom the randomis ation procedure was not followed, yielded similar results far remissio n rate, TTF, duration of CR and estimated overall survival. The incide nce of non-haematological events, such as severe nausea and vomiting ( P < 0.01), mucositis (P < 0.05) and alopecia (P < 0.001), were signifi cantly lower in patients treated with CNOP as compared with those who received the CHOP regimen. The incidence of cardiovascular toxicity of any severity was similar in the two groups. While severe and potentia lly life-threatening neutropenia occurred more frequently in patients treated with CNOP compared with CHOP (0.05 > P > 0.10), the incidence of infection of any severity was similar in both arms. We conclude tha t CHOP and CNOP regimens were both efficacious in patients with previo usly untreated aggressive NHL.