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
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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.
Patients and 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.
Fifty-one and forty-seven evaluable patients were randomized to Group I and Group II, respectively. The median age of all patients was 53y (range 18–78y). 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.
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.
Keywordsnon-Hodgkin's lymphoma CHOP tamoxifen
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- 1.Coltman Jr ACet al. CHOP is curative in thirty per cent of patients with large cell lymphoma: A twelve year Southwest Oncology Group follow-up. In: Skarin A (ed).Update on Treatment for Diffuse Large Cell Lymphoma. Park Row: New York, 1986, pp 71–77.Google Scholar
- 6.Yuen AR, Sikic BI. Multidrug resistance in lymphomas.J Clin Oncol 1994;11: 2453–2459.Google Scholar
- 8.Inaba M. Biochemical mechanism for resistance to anthracycline antibiotics.Prog Clin Bio Res 1986;223: 35–44.Google Scholar
- 9.Sorris AHet al. Cyclosporin A does not reverse clinical resistance to paclitaxel in patients with relapsed non-Hodgkin's lymphoma.J Clin Oncol 1996;14: 233–239.Google Scholar
- 10.Wilson WHet al. Reversal of Multidrug resistance (mdr-1) with R-verapamil and analysis of mdr-1 expression in patients with lymphoma refractory to EPOCH chemotherapy.Proc Am Assoc Cancer Res 1993;34: 212, (abstract).Google Scholar
- 21.The Non-Hodgkin's Lymphoma Pathologic Classification Project: National Cancer Institute sponsored study of classification of non-Hodgkin's lymphoma: Summary and description of a working formulation for clinical usage.Cancer 1982;49: 2112–2135.Google Scholar
- 25.Cox DR, Snell EJ.Analysis of Binary Data. London: Chapman & Hall, 1989.Google Scholar
- 28.Cox DR, Oakes D. Regression models and life tables (with discussion).J R Statist Soc 1972;B34: 187–220.Google Scholar
- 29.Dixon WJet al. BMDP Statistical Software. Berkeley: University of California Press, 1990.Google Scholar
- 30.The International Non-Hodgkin's Lymphoma Prognostic Factors Project: a predictive model for aggressive non-Hodgkin's lymphoma.N Engl J Med 1993;329: 987–994.Google Scholar
- 33.Feller WK. Statistical aspects of extra-sensory perception.J Parapsychol 1940;4: 271–298.Google Scholar
- 34.McPherson K. Interim analysis and stopping rules. In: Buyse ME (ed.)Cancer Clinical Trials: Methods and Practice. Oxford: Oxford University Press, 1988, pp 407–422.Google Scholar
- 35.Haioun Cet al. Comparison of autologous bone marrow transplantation with sequential chemotherapy for intermediate-grade and high-grade non-Hodgkin's lymphoma in first complete remission: a study of 464 patients. Groupe d'Etude des Lymphomes de l'Adulte.J Clin Oncol 1994;12: 2543–2551.PubMedGoogle Scholar