Journal of Clinical Oncology, Vol 15, 1094-1103, Copyright © 1997 by American Society of Clinical Oncology
Mitoguazone therapy in patients with refractory or relapsed AIDS- related lymphoma: results from a multicenter phase II trial
AM Levine, A Tulpule, D Tessman, L Kaplan, F Giles, BD Luskey, DT Scadden, DW Northfelt, I Silverberg, J Wernz, B Espina and D Von Hoff
University of Southern California School of Medicine, Los Angeles 90033, USA. hornor@hsc.usc.edu
PURPOSE: Patients with AIDS-related lymphoma usually have extensive
lymphomatous disease, with relatively frequent involvement of the CNS.
Approximately half may achieve complete remission after chemotherapy.
Mitoguazone, an inhibitor of polyamine biosynthesis, has demonstrated
efficacy in patients with de novo recurrent lymphoma. The drug is
relatively nonmyelotoxic and may cross the blood-brain barrier. The current
study was designed to assess the safety and potential efficacy of
mitoguazone in patients with relapsed or refractory AIDS-lymphoma. PATIENTS
AND METHODS: Thirty-five patients were accrued, all of whom had failed one
(51%) or multiple (two to six) prior regimens. Mitoguazone (600 mg/m2) was
given intravenously on days 1 and 8, and then every 2 weeks, until best
response, progression, or toxicity. RESULTS: The median age was 39 years.
High-grade lymphoma was diagnosed in 29 patients (83%). Extranodal disease
was present in 30 patients (86%), with multiple 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 patients were assessable for response. The
objective response rate was 23% (95% confidence interval [CI], 6.9 to
39.3), with complete remission in three patients (11.5%), and partial
remission (PR) in three patients (11.5%). Six patients experienced stable
disease. Median survival from study entry was 2.6 months for the group as a
whole; 21.5 months (range, 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 and 16 (46%) vomiting (grade 3 in one). Ten patients
(29%) developed stomatitis, including grade 3 in two and grade 4 in one.
Seven patients (20%) developed neutropenia, with grade 4 in one.
Thrombocytopenia occurred 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
patients with multiply relapsed or refractory AIDS- related lymphoma, with
acceptable toxicity. Further study in patients with newly diagnosed disease
is warranted.
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