Correspondence
Rituximab plus CHOP for Diffuse Large-B-Cell Lymphoma
N Engl J Med 2002; 346:1830-1831June 6, 2002
- Article
To the Editor:
The study by Coiffier et al. (Jan. 24 issue)1 raises several issues. First, the Southwest Oncology Group had clearly established the superiority of three courses of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) followed by radiation in patients with stage I or II diffuse large-B-cell lymphoma by the time Coiffier et al. began their study.2 Nevertheless, patients with stage II disease were given eight cycles of CHOP, which thus raises the ethical question of whether the therapy these patients received was more toxic than necessary.
Second, the central review of the diagnosis revealed that 49 patients with presumed diffuse large-B-cell lymphoma (15 percent of the CHOP group and 10 percent of the group given CHOP plus rituximab) were found to have a different diagnosis after enrollment. An intention-to-treat analysis would therefore most likely show the apparent superiority of combination therapy over CHOP alone. Third, the dose of prednisone used — 40 mg per square meter of body-surface area per day for five days — is approximately 30 percent lower than the widely accepted dose.2,3 Fourth, there was no evaluation of responses during therapy; such an evaluation could have resulted in the discontinuation of unnecessary chemotherapy for patients with progression or a complete remission at the end of four cycles of chemotherapy.
3 ReferencesSaad Akhtar, M.D.
Irfan Maghfoor, M.D.
King Faisal Specialist Hospital and Research Center, Riyadh 11211, Saudi Arabia
akhtars18@hotmail.com 1
Coiffier B ,Lepage E ,Briere J , et al. CHOP chemotherapy plus rituximab compared with CHOP alone in elderly patients with diffuse large-B-cell lymphoma. N Engl J Med 2002;346:235-242
Full Text | Web of Science | Medline2
Miller TP ,Dahlberg S ,Cassady JR , et al. Chemotherapy alone compared with chemotherapy plus radiotherapy for localized intermediate- and high-grade non-Hodgkin's lymphoma. N Engl J Med 1998;339:21-26
Full Text | Web of Science | Medline3
Fisher RI ,Gaynor ER ,Dahlberg S , et al. Comparison of a standard regimen (CHOP) with three intensive chemotherapy regimens for advanced non-Hodgkin's lymphoma. N Engl J Med 1993;328:1002-1006
Full Text | Web of Science | Medline
Author/Editor Response
The authors reply:
To the Editor: Akhtar and Maghfoor question the chemotherapy regimen we used in combination with rituximab in elderly patients with diffuse large-B-cell lymphoma. We do not think that it was too intensive: elderly patients with diffuse large-B-cell lymphoma have a poor outcome, and CHOP yields the longest survival with the least toxicity. We decided to include patients with stage II disease because the long-term results of the Southwest Oncology Group trial1 and the study by Reyes et al.2 did not confirm the benefit of radiation therapy for localized lymphoma. The low rate of adverse events that we observed confirms that CHOP is not too toxic for use in elderly patients.
Our data were presented on an intention-to-treat basis to avoid biases. However, the observed benefit was identical for the patients who had confirmed diffuse large-B-cell lymphoma on pathological review and those who did not have diffuse large-B-cell lymphoma.
Numerous variations of the CHOP regimen have been used during the past 25 years, but the Southwest Oncology Group initially used a dose of 40 mg of prednisone per square meter.3 We used this smaller dose because of the susceptibility of elderly patients to the adverse effects of high doses of corticosteroids and because of the frequency of adverse events such as diabetes or infection associated with a daily dose of 100 mg for five days. We do not think that this small decrease in the dose led to results that differed from those obtained with use of a higher dose. The two groups received the same dose; thus, this decrease did not interfere with the demonstrated benefit of CHOP plus rituximab.
All studies whose findings have made CHOP the gold standard for the treatment of aggressive lymphoma have scheduled eight cycles of CHOP, regardless of the patients' early response to this chemotherapy regimen.4 We are not aware of any comparative studies that used six cycles of CHOP. The incidence of adverse events during the last two cycles was very low in our study, and most were grade 1 or 2 events. Thus, the increase in survival observed after eight cycles of CHOP plus rituximab leads us to recommend this combination for elderly patients with diffuse large-B-cell lymphoma.
4 ReferencesBertrand Coiffier, M.D.
Hospices Civils de Lyon, 69495 Pierre Benite CEDEX, France
bertrand.coiffier@chu-lyon. fr Christian Gisselbrecht, M.D.
Hôpital Saint-Louis, 75010 Paris, FranceFelix Reyes, M.D.
Hôpital Henri Mondor, 94010 Creteil, France1
Miller TP ,Leblanc M ,Spier C ,Chase E ,Fischer RI . CHOP alone compared to CHOP plus radiotherapy for early stage aggressive non-Hodgkin's lymphomas: update of the Southwest Oncology Group (SWOG) randomized trial. Blood 2001;98:724a-724a abstract.
CrossRef | Web of Science2
Reyes F ,Lepage E ,Munck JN , et al. Superiority of the ACVBP regimen over a combined treatment with three cycles of CHOP followed by involved field radiotherapy in patients (pts) with low risk localized aggressive non Hodgkin's lymphoma: results of the LNH93-1 study. Blood 2000;96:832a-832a abstract.
Web of Science3
Coltman CA, Dahlberg S, Jones SE, et al. CHOP is curative in thirty percent 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. New York: Park Row, 1986:71-7.
4
Fisher RI ,Gaynor ER ,Dahlberg S , et al. Comparison of a standard regimen (CHOP) with three intensive chemotherapy regimens for advanced non-Hodgkin's lymphoma. N Engl J Med 1993;328:1002-1006
Full Text | Web of Science | Medline
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