title: Topotecan in the treatment of acquired immunodeficiency syndrome-related progressive multifocal leukoencephalopathy.
abstract: Progressive multifocal leukoencephalopathy (PML) affects about 1 in 20 individuals with the acquired immunodeficiency syndrome (AIDS) and has been associated with poor survival. This report describes the results of a phase II clinical trial using the drug topotecan, a semisynthetic analogue of camptothecan, administered to a cohort of subjects with AIDS-related PML. Data were evaluated on 11 of 12 subjects enrolled in the study. Three responded to therapy. Additionally, one patient was treated off-protocol and showed a response to treatment. Progression occurred after the first course; however, a partial response was noted after five courses. One study patient died from accidental overdose of topotecan. Overall, responders had higher pretreatment Karnofsky and lower Kurtzke expanded disability status scale scores than nonresponders. The most frequent toxicities were hematologic (anemia, neutropenia, and thrombocytopenia). Five patients had dose delays; all delays were due to hematologic adverse events. This study demonstrates that topotecan treatment may be associated with decreased lesion size and prolonged survival from the infection. Because of the small number of subjects in the study, further studies are required to evaluate the efficacy of topotecan in treating this disease.
authors.affiliation: Neuroscience Institute, Morehouse School of Medicine, Atlanta, Georgia 30310-1495, USA. wroyal@msm.edu
authors.forename: W
authors.initials: W
authors.lastname: Royal
authors.forename: B
authors.initials: B
authors.lastname: Dupont
authors.forename: D
authors.initials: D
authors.lastname: McGuire
authors.forename: L
authors.initials: L
authors.lastname: Chang
authors.forename: K
authors.initials: K
authors.lastname: Goodkin
authors.forename: T
authors.initials: T
authors.lastname: Ernst
authors.forename: M J
authors.initials: MJ
authors.lastname: Post
authors.forename: D
authors.initials: D
authors.lastname: Fish
authors.forename: G
authors.initials: G
authors.lastname: Pailloux
authors.forename: H
authors.initials: H
authors.lastname: Poncelet
authors.forename: M
authors.initials: M
authors.lastname: Concha
authors.forename: L
authors.initials: L
authors.lastname: Apuzzo
authors.forename: E
authors.initials: E
authors.lastname: Singer
mesh_terms: D000163:Acquired Immunodeficiency Syndrome / Q000150:complications* / Q000188:drug therapy / Q000821:virology; D000328:Adult; D023241:Antiretroviral Therapy, Highly Active; D001921:Brain / Q000473:pathology; D018791:CD4 Lymphocyte Count; D015331:Cohort Studies; D004334:Drug Administration Schedule; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D005260:Female; D015497:HIV-1; D006402:Hematologic Diseases / Q000139:chemically induced; D006801:Humans; D017567:Karnofsky Performance Status; D007968:Leukoencephalopathy, Progressive Multifocal / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D012367:RNA, Viral / Q000097:blood; D059004:Topoisomerase I Inhibitors; D019772:Topotecan / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome; D019562:Viral Load
chemical_list: D004791:Enzyme Inhibitors; D012367:RNA, Viral; D059004:Topoisomerase I Inhibitors; D019772:Topotecan