Two Studies Clarify Optimal Treatment of Hodgkin's Disease

Laurie Barclay, MD

June 11, 2003

June 11, 2003 — Two studies reported in the June 12 issue of the New England Journal of Medicine better clarify optimal treatment of Hodgkin's disease (HD). The first shows that increased dose combination chemotherapy improves survival and reduces rates of treatment failure, while the second study shows that radiotherapy offers no benefit to those who achieve complete remission.

"Increased-dose BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone) resulted in better tumor control and overall survival than did COPP-ABVD (cyclophosphamide, vincristine, procarbazine, and prednisone alternating with doxorubicin, bleomycin, vinblastine, and dacarbazine)," write Volker Diehl, MD, and colleagues from the German Hodgkin's Lymphoma Study Group.

From 1993 to 1998, 1,201 patients, aged 15 to 65 years, with newly diagnosed, advanced HD were randomized to eight cycles of COPP-ABVD, to BEACOPP, or to increased-dose BEACOPP, each followed by local radiotherapy as needed. In 1996, enrollment in the COPP-ABVD group stopped because of inferior interim results.

Among 1,195 evaluable patients, the rate of freedom from treatment failure at five years was 69% in the COPP-ABVD group, 76% in the BEACOPP group ( P = .04), and 87% in the increased-dose BEACOPP group ( P < .001). Five-year survival was 83% in the COPP-ABVD group, 88% in the BEACOPP group, and 91% for the increased-dose BEACOPP group ( P = .06 compared with BEACOPP and P = .002 compared with COPP-ABVD).

"The occurrence of nine cases of acute leukemia after increased-dose BEACOPP seems alarming, especially as compared with the low leukemogenicity of the ABVD regimen," the authors write. "Further study is needed before a reliable assessment of the long-term risks of standard and increased-dose BEACOPP can be made."

In a separate study, patients with previously untreated stage III or IV Hodgkin's disease who were in complete remission after hybrid chemotherapy with MOPP-ABV were randomized to receive either no further treatment or involved-field radiotherapy.

Of 739 patients, 421 had a complete remission. Five-year event-free survival was 84% in the group that did not receive radiotherapy and 79% in the group that received involved-field radiotherapy ( P = .35). Five-year overall survival was 91% in the group not treated with radiotherapy and 85% in the group that did receive radiotherapy ( P = .07).

Among 250 patients in partial remission after chemotherapy, five-year event-free survival was 79% and five-year overall survival was 87%.

"There is no need for involved-field radiotherapy to maintain remission in patients with stage III or IV Hodgkin's lymphoma after six to eight cycles of MOPP-ABV chemotherapy," write Berthe M. P. Aleman, MD, and colleagues from the European Organization for Research and Treatment of Cancer Lymphoma Group. "The only patients who benefit from radiotherapy are those in partial remission after the chemotherapy."

In an accompanying editorial, Vincent T. DeVita, Jr., MD, from Yale University in New Haven, Connecticut, reviews the history of treatment for Hodgkin's disease and notes that in clinical trials, "combination chemotherapy was added to radiotherapy for early-stage disease rather than tested further as a substitute for it.... The long-term carcinogenic effect of combining chemotherapy with radiotherapy has turned out to be far too severe, however, to warrant continuing with this approach."

N Engl J Med. 2003;348:2375-2376, 2386-2395, 2396-2406

Reviewed by Gary D. Vogin, MD

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