R-CHOP Schedules for Older Patients with NHL
R-CHOP Schedules for Older Patients with NHL
Abstract & Commentary
By William B. Ershler, MD, Editor
Synopsis: In this large, multi-site randomized clinical trial in older patients with non-Hodgkin lymphoma (NHL), R-CHOP-14 proved superior to CHOP-14 and 8 cycles offered no advantage compared with 6.
Source: Pfreundschuh M, et al, for the German High-Grade Non-Hodgkin Lymphoma Study Group (DSHNHL). Lancet Oncol. 2008;9:105-116.
The combination of cyclophosphamide, dox-orubicin, vincristine, and prednisone (CHOP) is commonly used to treat patients with non-Hodgkin lymphoma (NHL). Recent alterations from the standard 3 week regimen (CHOP-21) include a more dose intense 2 week regimen (CHOP-14)1 and the addition of rituximab (R-CHOP).2 The current study from German High-Grade Non-Hodgkin Lymphoma Study Group (DSHNHL) randomized older patients with NHL to six or eight cycles of CHOP-14 with or without rituximab.
In all, 1222 older patients (aged 61-80 years) were randomly assigned to six or eight cycles of CHOP-14 with or without rituximab. The CHOP regimen consisted of cyclophosphamide (750 mg/ m2 intravenously), doxorubicin (50 mg/ m2 intravenously), vincristine (2 mg intravenously) and prednisone 100 mg orally on days 1-5. All patients received granulocyte colony stimulating factor on day 6 until white count recovery. Rituximab (375 mg/ m2) was administered bi-weekly to one half of the patients. Radiotherapy was planned to sites of initial bulky disease with or without extranodal involvement. The primary endpoint was event-free survival; secondary endpoints
The three-year event-free survival was 47·2% after six cycles of CHOP-14 (95% CI 41·2-53·3), 53·0% (47·0-59·1) after eight cycles of CHOP-14, 66·5% (60·9-72·0) after six cycles of R-CHOP-14, and 63·1% (57·4-68·8) after eight cycles of R-CHOP-14. Compared with six cycles of CHOP-14, the improvement in 3-year event-free survival was 5·8% (-2·8-14·4) for eight cycles of CHOP-14, 19·3% (11·1-27·5) for six cycles of R-CHOP-14, and 15·9% (7·6-24·2) for eight cycles of R-CHOP-14. 3-year overall survival was 67·7% (62·0-73·5) for six cycles of CHOP-14, 66·0% (60·1-71·9) for eight cycles of CHOP-14, 78·1% (73·2-83·0) for six cycles of R-CHOP-14, and 72·5% (67·1-77·9) for eight cycles of R-CHOP-14. Similarly, overall survival was not enhanced by the additional two cycles, of therapy, either for CHOP alone or for R-CHOP. In a multivariate analysis that used six cycles of CHOP-14 without rituximab as the reference, and adjusting for known prognostic factors, all three intensified regimens improved 3-year event-free survival. Progression-free survival improved after six cycles of R-CHOP-14 (RR 0·50 [0·38-0·67], p <0·0001), and eight cycles of R-CHOP-14 (RR 0·59 [0·45-0·77], p = 0·0001) but overall survival improved only after six cycles of R-CHOP-14. In patients with a partial response after four cycles of chemotherapy, eight cycles were not better than six cycles.
Commentary
Thus, six cycles of R-CHOP-14 significantly improved event-free, progression-free, and overall survival compared with six or eight cycles of CHOP-14. Response-adapted addition of chemotherapy beyond six cycles, though widely practiced, is not justified. Thus, of the four regimens tested in this study, six cycles of R-CHOP-14 is the preferred treatment for elderly patients with aggressive NHL.
While this trial showed that R-CHOP-14 was better than CHOP-14 alone, the efficacy of R-CHOP-14 over R-CHOP-21 remains to be shown. The Groupe d'Etude des Lymphomes de l'Adulte (GELA) is currently assessing this question in the NHL-03-6B trial, in which eight cycles of R-CHOP-21 is being compared with eight (but not six) cycles of R-CHOP-14 treatment in elderly patients. Also, the National Cancer Research Institute (London) is comparing eight cycles of R-CHOP-21 with six cycles of R-CHOP-14 in patients with diffuse large B cell lymphoma (DLBCL) of any age and risk group. Although not completely analogous, these trials are similar enough to expect their results will be comparable. Even if these ongoing trials were to show equal efficacy for R-CHOP-14 and R-CHOP-21, it would seem that six cycles of R-CHOP-14 has a distinct advantage because it affords cessation of chemotherapy in significantly less time.
References
1. Pfreundschuh M, et al. Two-weekly or 3-weekly CHOP chemotherapy with or without etoposide for the treatment of elderly patients with aggressive lymphomas: results of the NHL-B2 trial of the DSHNHL. Blood. 2004;104(3):634-641.
2. Coiffier B, et al. CHOP chemotherapy plus rituximab compared with CHOP alone in elderly patients with diffuse large-B-cell lymphoma. N Engl J Med. 2002;346(4):235-242.
In this large, multi-site randomized clinical trial in older patients with non-Hodgkin lymphoma (NHL), R-CHOP-14 proved superior to CHOP-14 and 8 cycles offered no advantage compared with 6.Subscribe Now for Access
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