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North American and European clinical trials have shown that stage IA or IIA Hodgkin lymphoma (HL) has a very high cure rate with current combined-modality treatments. This evidence is extended by the current report from the European Organisation for Research and Treatment of Cancer (EORTC) and the Groupe d’Études des Lymphomes de l’Adulte (GELA).
A total of 1538 HL patients with early-stage disease were enrolled at 91 European centers from 1993 through 1999. Patients (35%) with favorable risk (as defined by a prognostic scoring system that incorporated patient age and sex, disease stage and histologic subtype, and sedimentation rate) were randomized to 3 cycles of mechlorethamine, vincristine [oncovin], procarbazine, prednisone, doxorubicin [adriamycin], bleomycin, and vinblastine (MOPP-ABV) plus involved-field radiotherapy (IFRT) or subtotal nodal irradiation (STNI) alone. Patients with unfavorable risk (65%) were randomized to 6 cycles of MOPP-ABV plus IFRT, 4 cycles of MOPP-ABV plus IFRT, or 4 cycles of MOPP-ABV plus STNI. The primary study endpoint was event-free survival (EFS).
Median follow-up was 92 months. Five- and 10-year survival rates (and 95% confidence intervals) are detailed in Table 1 and Table 2. Long-term toxicities included myelodysplastic syndrome or acute myeloid leukemia (MDS/AML) in 12 patients, including 3 after salvage therapy for HL relapse. Solid tumors developed in 36 patients at 5 to 127 months postrandomization; 21 tumors were within, and 15 were outside, the radiation fields. Late cardiac and pulmonary complications also were observed.
Fermé C et al. Chemotherapy plus involved-field radiation in early-stage Hodgkin’s disease. N Engl J Med 2007 Nov 8; 357:1916.
National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: Hodgkin disease/lymphoma — v.1.2007. Apr 23, 2007. (http://www.nccn.org/professionals/physician_gls/PDF/hodgkins.pdf)
Comment
Although this study involved now-outmoded chemotherapy regimens, it provides further evidence that STNI alone is insufficient for treating any early-stage HL patients. The study also shows that, for patients with unfavorable clinical features, 4 chemotherapy cycles plus IFRT are equivalent to more-extended regimens. Current National Comprehensive Cancer Network treatment guidelines for stage IA or IIA HL patients with non–bulky disease recommend 4 cycles of ABVD (ABV with dacarbazine) plus IFRT. MOPP-based regimens are no longer used because of MDS/AML and sterility risk, among other toxicities; however, anthracycline-based regimens, such as ABVD, carry risk for myocardial dysfunction and coronary or valvular disease, especially when the heart is within the radiation field. Bleomycin pulmonary toxicity also is increased in conjunction with RT (J Clin Oncol 2005; 23:7614). Whether these risks will be lower with fewer chemotherapy cycles, lower RT doses, or both is being studied in many clinical trials. Smaller radiation fields and lower doses are important, but a key unanswered question is whether RT can be eliminated completely, at least for a subset of patients with favorable clinical features and rapid response, as assessed by [18F] fluoro-2-deoxy-d-glucose positron emission tomography (PET) scans (Journal Watch Oncology and Hematology Sep 18 2007); this too is being addressed.