The results of a large European clinical trial show that de-escalating therapy for early-stage (stage I or II) Hodgkin lymphoma (HL) in patients with a favorable prognosis reduced short-term treatment complications while retaining high remission rates.  However, the follow-up period was relatively short and it is not possible to predict the effect of the reduced-dose protocol on late complications.

Many groups advocate 4 cycles of a doxorubicin, bleomycin, vinblastine, and dacarbazine combination (ABVD) followed by 30 Gy of involved-field radiation therapy (RT) as standard care for HL. However, this produces treatment complications in many patients—including increased risk for second malignancy, recurrent lymphoma, and cardiovascular events.  Women under 30 years of age are considered at particular risk for treatment complications, as 30% to 40% of them are likely to develop breast cancer in the 25 years after treatment. Therefore, there is much interest in alternate regimens that might reduce the exposure to and intensity of chemotherapy and RT.

This was a multicenter randomized trial of 1370 patients with newly diagnosed stage I or II HL and no clinical risk factors for poor prognosis, defined as the absence of extra-nodal disease, large mediastinal mass, and elevated erythrocyte sedimentation rate. The median age of the study population was 36 years (range 16 to 75). A total of 1190 patients were included in the final analysis. Patients were assigned to 1 of 4 treatment groups: (1) 4 cycles ABVD/30 Gy; (2) 4 cycles ABVD/20 Gy; (3) 2 cycles ABVD/30 Gy; (4) 2 cycles ABVD/20 Gy. The primary endpoint was freedom from treatment failure; secondary endpoints included overall survival (OS), progression-free survival, complete response, and assessments toxicity. The median follow-up time was 6.6 years. After 8 years, 95% of the patients were still alive.   

Five-year rates of freedom from treatment failure did not differ significantly between patients treated with 4 (93%) versus 2 cycles of ABVD (91%) (P=0.39). As well, the radiation dose did not significantly affect the primary outcome. Among patients in Groups 1 and 2, 5-year freedom from treatment failure was 92.8% in Group 1 and 93.1% in Group 2. Patients treated with 2 cycles of chemotherapy had 90.9% freedom from treatment failure in Group 3 and 91.2% in Group 4.  

In an additional comparison, no significant difference was noted in the primary outcome measure among patients who received the most intense therapy (Group 1) and those who received the least intense therapy (Group 4)  (-1.6 percentage points; P=0.79). However, wide confidence intervals (95% CI, -6.3 to 3.1) leave open the possibility that the difference could have been as large as 6.3%. Patients who received 4 cycles of ABVD had significantly more adverse events and acute treatment-related toxicity than those who had 2 cycles (grade 3 or 4 toxicity: 51.7% versus 33.2%; P<0.001). Severe toxicity (grade 3 or 4) was observed more often among the patients treated with 30 Gy of involved-field radiation therapy than among those who received 20 Gy (8.7% versus 2.9%; P<0.001).   

The authors emphasize that while current care for early-stage HL has produced excellent survival rates, it may be possible to achieve the same good results in some patients without the associated toxicities. They call for continued refinement of the existing regimen to identify patients that might not require RT, including the use of positron emission tomography (PET) imaging after chemotherapy to risk-stratify patients.

1. Engert A, Plutschow A, Eich HT, et al. Reduced treatment intensity in patients with early-stage Hodgkin’s lymphoma. N Engl J Med. 2010;363:653-662. Abstract available at: http://www.nejm.org/doi/full/10.1056/NEJMoa1000067. Accessed September 2, 2010.

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This entry was posted on Thursday, September 2nd, 2010 at 12:00 pm.