Activity of the Epipodophyllotoxin VP-16 in the Treatment of Combination Chemotherapy-Resistant Non-Hodgkin Lymphoma

Abstract

Twenty patients with several histologic subtypes of non-Hodgkin lymphoma who had become resistant to combination chemotherapy were treated with a five-day course of the epipodophyllotoxin VP-16. Of 19 evaluable patients, 8 (42%) responded to treatment with 1 complete response and 7 partial responses. The median duration of response was 5.5 months. Seven of the responders had a diffuse lymphoma and 1 had a nodular lymphoma. Of the responders who had diffuse histiocytic lymphoma (DHL), diffuse mixed lymphoma (DML), and diffuse undifferentiated lymphoma (DUL)–the more aggressive histologies in the Rappaport classification–6 of 13 (46%) evaluable patients responded to therapy. Responses were seen in node-dominant, skin-dominant, and marrow-dominant disease. Toxicity was mainly hematopoietic, 53% of patients experiencing leukopenia (<2, 000 cells per cu mm) and 68% of patients experiencing thrombocytopenia (<100, 000 platelets per cu mm). There were two deaths attributable to profound leukopenia with sepsis. The activity of VP-16 in patients who have previously been extensively treated with multiple drugs including vincristine supports its activity in the lymphomas and suggests its lack of cross-resistance with vincristine. The inclusion of VP-16 in primary treatment protocols in the diffuse lymphomas should be considered.