MITOGUAZONE THERAPY IN PATIENTS WITH REFRACTORY OR RELAPSED AIDS-RELATED LYMPHOMA - RESULTS FROM A MULTICENTER PHASE-II TRIAL

Purpose: Patients with AIDS-related lymphoma usually have extensive ly mphomatous disease, with relatively frequent involvement of the CNS. A pproximately half may achieve complete remission after chemotherapy. M itoguazone, an inhibitor of polyamine biosynthesis, has demonstrated e fficacy in patients with de novo recurrent lymphoma. The drug is relat ively nonmyelotoxic and may cross the blood-brain barrier. The current study was designed to assess the safety and potential efficacy of mit oguazone in patients with relapsed or refractory AIDS-lymphoma. Patien ts and Methods: Thirty-five patients were accrued, all of whom held fa iled one (51%) or multiple (two to six) prior regimens. Mitoguazone (6 00 mg/m(2)) was given intravenously on days 1 and 8, and then every 2 weeks, until best response, progression, or toxicity. Results: The med ian age was 39 years. High-grade lymphoma was diagnosed in 29 patients (83%). Extranodal disease wets present in 30 patients (86%), with mul tiple extranodal sites (two to seven) in 18 (51%). The median CD4 cell count at study entry was 66/dL (range, zero to 549). Twenty-six patie nts were assessable for response. The objective response rate was 23% (95% confidence interval [CI], 6.9 to 39.3), with complete remission i n three patients (11.5%), and partial remission (PR) in three patients (11.5%). Six patients experienced stable disease. Median survival fro m study entry was 2.6 months for the group as a whole; 21.5 months (ra nge, 3.8 to 29.1) in complete responders, 5.6 months (range, 3.8 to 34 .8) in partial responders. The most common toxicities occurred solely during drug infusion and included vasodilation (63%), paresthesia (86% ), and somnolence (17%). Fourteen patients (40%) experienced nausea an d 16 (46%) vomiting (grade 3 in one). Ten patients (29%) developed sto matitis, including grade 3 in two and grade 4 in one. Seven patients ( 20%) developed neutropenia, with grade 4 in one. Thrombocytopenia occu rred in nine patients (26%). While on study, three patients developed sepsis, four had pneumonia, and two developed opportunistic infections . Conclusion: Mitoguazone is an effective agent in patient with multip ly relapsed or refractory AIDS-related lymphoma, with acceptable toxic ity. Further study in patients with newly diagnosed disease is warrant ed. (C) 1997 by American Society of Clinical Oncology.