Combined therapy in advanced stages (III and IV) of follicular lymphoma increases the possibility of cure:: results of a large controlled clinical trial

Objectives: We evaluate the long-term results of a randomized clinical trial in patients with advanced stages (III and IV) of follicular lymphoma using chemotherapy or combined therapy (chemotherapy following by adjuvant radiotherapy in patients with nodal bulky disease). Material and methods: Between 1981 and 1995, patients with follicular lymphoma were treated with combined chemotherapy, mostly anthracycline-based regimens; patients who achieved complete response were randomly assigned either to receive adjuvant radiotherapy to sites or to nodal bulky disease or not control group). Results: Four hundred and sixty-nine patients were randomized; in an intent-to-treat analysis all were evaluable for efficacy and toxicity. Actuarial curves at 20 yr showed that event-free survival (EFS) and overall survival (OS) in the control group were 41% [95% confidence interval (CI) 36-56%) and 71% (95% CI 65-78%), respectively; these were statistically different from results for the patients who received adjuvant radiotherapy: 68% (95% CI 62-72%) and 89% (95% CI 79-96%), respectively (P<0.01). Acute and late toxicity were minimal; only four patients (<1%) developed myelodysplastic syndrome/acute leukemia. Cardiac toxicity was 2%, but one case was lethal. Thirty-six patients (8%) died secondary to unrelated causes, in complete remission. Conclusions: The use of adjuvant radiotherapy in patients with poor-prognosis follicular lymphoma increases EFS and OS with minimal toxicity. We feel that follicular lymphoma should be treated curatively because <80% of patients will be in first complete response at <20 yr. The use of adjuvant radiotherapy will be considered in the first line of treatment in this set of patients.