title: Adding high-dose tamoxifen to CHOP does not influence response or survival in aggressive non-Hodgkin's lymphoma: an interim analysis of a randomized phase III trial.
abstract: OBJECTIVE
  CHOP is the standard regimen currently used in the management of the majority of patients with aggressive non-Hodgkin's lymphoma (NHL). However, CHOP only produces 30-35% long-term survival. We hypothesized that adding high-dose tamoxifen, which is known to have multiple drug resistance-modulatory effects, to the CHOP regimen could increase the response rate, and consequently enhance the survival of patients with NHL.
  
  
  METHODS
  In a prospective, controlled, and randomized study, eligible adult patients with aggressive NHL were randomized between CHOP only (Group I), or CHOP plus high-dose tamoxifen (Group II). The primary aim was to assess the effect of tamoxifen on complete response (CR) rate, with the secondary evaluation of tamoxifen potential impact on survival. The interim analysis of this study is presented.
  
  
  RESULTS
  Fifty-one and forty-seven evaluable patients were randomized to Group I and Group II, respectively. The median age of all patients was 53 y (range 18-78 y). The two groups had comparable distributions of the pretreatment prognostic variables. The CR for patients in Group I was 80% (41 patients) 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 actuarial-estimated overall survival (OS) probability (+/-S.E.) for the entire population at 5 y was 58% (+/-6) with no survival difference between the two groups (P=0.51). Only attaining CR and the IPI predicted OS probability. The probability of remaining event-free at 5 y (+/-SE) for those achieving CR was 72% (+/-9), and there was no significant difference between the two treatment groups (P=0.68). Toxicity profile was similar in the two groups.
  
  
  CONCLUSIONS
  Based on this interim analysis, combining high-dose tamoxifen, as used in this study, with the CHOP regimen has failed to have any favorable effect on the outcome of patients with aggressive NHL, and therefore cannot be recommended for future trials.
authors.affiliation: Departments of Oncology, King Faisal Specialist Hospital and Research Center, Riyadh, Kingdom of Saudi Arabia. ezzat@kfshrc.edu.sa
authors.forename: A A
authors.initials: AA
authors.lastname: Ezzat
authors.forename: E M
authors.initials: EM
authors.lastname: Ibrahim
authors.forename: R K
authors.initials: RK
authors.lastname: Stuart
authors.forename: D
authors.initials: D
authors.lastname: Ajarim
authors.forename: S
authors.initials: S
authors.lastname: Bazarbashi
authors.forename: M O
authors.initials: MO
authors.lastname: El-Foudeh
authors.forename: M
authors.initials: M
authors.lastname: Rahal
authors.forename: A
authors.initials: A
authors.lastname: Al-Sayed
authors.forename: J
authors.initials: J
authors.lastname: Berry
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D018931:Antineoplastic Agents, Hormonal / Q000008:administration & dosage*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D003131:Combined Modality Therapy; D003520:Cyclophosphamide / Q000008:administration & dosage; D018450:Disease Progression; D004317:Doxorubicin / Q000008:administration & dosage; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008228:Lymphoma, Non-Hodgkin / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011241:Prednisone / Q000008:administration & dosage; D011446:Prospective Studies; D016019:Survival Analysis; D013629:Tamoxifen / Q000008:administration & dosage*; D016896:Treatment Outcome; D014750:Vincristine / Q000008:administration & dosage
chemical_list: D018931:Antineoplastic Agents, Hormonal; D013629:Tamoxifen; D014750:Vincristine; D004317:Doxorubicin; D003520:Cyclophosphamide; D011241:Prednisone