title: Mitoguazone therapy in patients with refractory or relapsed AIDS-related lymphoma: results from a multicenter phase II trial.
abstract: OBJECTIVE
  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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: University of Southern California School of Medicine, Los Angeles 90033, USA. hornor@hsc.usc.edu
authors.forename: A M
authors.initials: AM
authors.lastname: Levine
authors.forename: A
authors.initials: A
authors.lastname: Tulpule
authors.forename: D
authors.initials: D
authors.lastname: Tessman
authors.forename: L
authors.initials: L
authors.lastname: Kaplan
authors.forename: F
authors.initials: F
authors.lastname: Giles
authors.forename: B D
authors.initials: BD
authors.lastname: Luskey
authors.forename: D T
authors.initials: DT
authors.lastname: Scadden
authors.forename: D W
authors.initials: DW
authors.lastname: Northfelt
authors.forename: I
authors.initials: I
authors.lastname: Silverberg
authors.forename: J
authors.initials: J
authors.lastname: Wernz
authors.forename: B
authors.initials: B
authors.lastname: Espina
authors.forename: D
authors.initials: D
authors.lastname: Von Hoff
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D004334:Drug Administration Schedule; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D016483:Lymphoma, AIDS-Related / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D008935:Mitoguazone / Q000009:adverse effects / Q000627:therapeutic use*; D009503:Neutropenia / Q000139:chemically induced; D012008:Recurrence; D012074:Remission Induction; D016019:Survival Analysis; D013921:Thrombocytopenia / Q000139:chemically induced
chemical_list: D000970:Antineoplastic Agents; D008935:Mitoguazone