Combination trial of subcutaneous interferon alfa-2b and oral cyclophosphamide in favorable histology, non-Hodgkin's lymphoma

Patients with follicular non-Hodgkin's lymphoma (NHL) respond well to chemotherapy but frequently relapse and progress with conversion to more aggressive histology lymphomas. In a prior Cancer and Leukemia Group B (CALGB) trial, oral cyclophosphamide, given as a single agent, was found to be equivalent to a five-drug regimen in remission induction in patients with follicular NHL who had not received prior chemotherapy. Recently, interferon alfa-2b (Intron A; Schering Plough) has been demonstrated to elicit complete or partial responses in up to 50% of patients with nodular NHL who had received prior chemotherapy. In the current CALGB pilot trial, oral cyclophosphamide (100 mg/m² daily) combined with interferon alfa-2b (2 × 10⁶ IU/m² s.c. on alternate days) is being evaluated, both in previously treated and untreated patients with stage III or IV follicular NHL, for toxicity, safety and efficacy in remission induction. A total of 68 patients have been entered into this study. Four patients are ineligible on pathology review, and 60 have on-study data currently available. Forty-one (60%) had not received prior chemotherapy and 19 (32%) had previously received some form of chemotherapy. Leukopenia was found to be the single, most common toxicity experienced by all patients. Previously untreated patients experienced leukopenia of <2,000 WBC/μl at a significantly higher rate (53% versus 14%) than a similar patient population receiving oral cyclophosphamide as a single agent in the prior CALGB trial. Leukopenia was found to be promptly reversible, however, by dose suspension or adjustment, and other toxicities were demonstrated to be mild and tolerable. In patients who had received prior chemotherapy, severe or life-threatening leukopenia (63%), thrombocytopenia (23%) and anemia (15%) were more common and frequently dose limiting. The combined partial and complete response rate was found to be 84%, with a median follow up of only three months in patients not previously receiving chemotherapy, and was equivalent to the early response rate to oral cyclophosphamide alone in the prior CALGB trial. Despite the higher incidence of leukopenia in previously untreated patients, the combination of oral cyclophosphamide and subcutaneous interferon alfa-2b appears warranted to test the hypothesis that interferon may prevent the conversion to higher grade histology, or improve survival in previously untreated patients with nodular NHL.