Adding high-dose tamoxifen to CHOP does not influence response or survivalin aggressive non-Hodgkin's lymphoma: an interim analysis of a randomized phase III trial

Purpose: CHOP is the standard regimen currently used in the management of t he majority of patients with aggressive non-Hodgkin's lymphoma (NHL). Howev er, CHOP only produces 30-35% long-term survival. We hypothesized that addi ng high-dose tamoxifen, which is known to have multiple drug resistance-mod ulatory effects, to the CHOP regimen could increase the response rate, and consequently enhance the survival of patients with NHL. Patients and Method s: In a prospective, controlled, and randomized study, eligible adult patie nts with aggressive NHL were randomized between CHOP only (Group I), or CHO P plus high-dose tamoxifen (Group II). The primary aim was to assess the ef fect of tamoxifen on complete response (CR) rate, with the secondary evalua tion of tamoxifen potential impact on survival. The interim analysis of thi s study is presented. Results: Fifty-one and forty-seven evaluable patients were randomized to Gr oup I and Group II, respectively. The median age of all patients was 53y (r ange 18-78y). The two groups had comparable distributions of the pretreatme nt prognostic variables. The CR for patients in Group I was 80% (41 patient s) as compared with 74% (35 patients) in Group II (P=0.48). Likewise, there was no apparent difference in the partial remission rates between the two groups (6% vs 15%, respectively). Of patients who initially attained CR, 15 (37%) and 10 (29%) subsequently relapsed in Groups II and I respectively ( P = 0.45). The NHL International Prognostic Index (IPI) was the only factor that predicted attaining CR. At the time of this interim analysis, the act uarial-estimated overall survival (OS) probability (+/-S.E.) for the entire population at 5y was 58% (+/-6) with no survival difference between the tw o groups (P=0.51). Only attaining CR and the IPI predicted OS probability. The probability of remaining event-free at 5y (+/-SE) for those achieving C R was 72% (+/-9), and there was no significant difference between the two t reatment groups (P=0.68). Toxicity profile was similar in the two groups. Conclusion: Based on this interim analysis, combining high-dose tamoxifen, as used in this study, with the CHOP regimen has failed to have any favorab le effect on the outcome of patients with aggressive NHL, and therefore can not be recommended for future trials.