COMBINATION TRIAL OF SUBCUTANEOUS RECOMBINANT ALPHA-2B INTERFERON ANDORAL CYCLOPHOSPHAMIDE IN FOLLICULAR LOW-GRADE NON-HODGKINS-LYMPHOMA

The follicular non-Hodgkin's lymphomas (NHL) have been among those tum ors demonstrated to show frequent responses to alpha interferon in pha se I and II clinical trials. In addition, there are data suggesting th at alpha interferon demonstrates synergistic antitumor activity with a lkylating agents in animal models for a number of tumors. Based on the se data, Cancer and Leukemia Group B (CALGB) undertook a phase II pilo t study of the combination of interferon rIFNalpha2b (2 x 10(6) IU/M2 S.C. tiw) and cyclophosphamide (100 Mg/M2 per day orally) with the ult imate purpose of examining this combination as long-term therapy of fo llicular lymphoma in comparison to oral cyclophosphamide alone. One hu ndred five advanced stage III or IV eligible patients with pathologica lly diagnosed International Working Formulation B or C histology were entered on CALGB 8553 to determine toxicity and response rates to the combination. Both previously chemotherapy-treated patients (32) and pa tients without prior chemotherapy (73) were entered on study. For pati ents without prior chemotherapy the overall response rate to the combi nation regimen was 86% with 58% of chemotherapy-treated patients achie ving complete response. Chemotherapy-treated patients had a total resp onse rate of 62% with only 25% complete responders. Complete responses in patients without prior chemotherapy were positively correlated wit h absence of B symptoms, and good performance status and negatively co rrelated with the histological subtype of follicular mixed small-cleav ed and large cell histology (IWF C); only performance status was signi ficantly correlated with response in patients who had previously had c hemotherapy. Survival at 5 years is estimated to be 63% for those with out chemotherapy and 39% for those previously treated with chemotherap y patients. The maximum toxicities experienced during therapy with the combination regimen of cyclophosphamide and interferon alpha were pri marily related to myelosuppression. Sixty-seven percent of patients wi thout prior chemotherapy and 65% of patients receiving prior chemother apy experienced severe leukopenia while severe thrombocytopenia and an emia occurred in 6-31% of these patients. Non-myelosuppressive toxicit ies were less frequently seen. These response rates are similar to tho se achieved in a previous CALGB trial with oral cyclophosphamide as a single agent, although severe myelotoxicity was increased to approxima tely 60% of patients from less than 10% with the single-agent therapy. The combination of alpha interferon and cyclophosphamide administered in this fashion is safe when peripheral counts are carefully monitore d. Randomized studies of this regimen in comparison to oral cyclophosp hamide are currently in progress. (C) 1994 Wiley-Liss, Inc.