Dupont B, Fish D, McGuire D, Royal W, Singer E, Goodkin K, Graden D, Martino H, Hearn S, Ross G, Beckman R; Conference on Retroviruses and Opportunistic Infections.
Program Abstr 8th Conf Retrovir Oppor Infect Conf Retrovir Oppor Infect 8th 2001 Chic Ill. 2001 Feb 4-8; 8: 223 (abstract no. 597).
Hosp de L'Inst Pasteur, Paris, France.
Background: Topotecan, a DNA topoisomerase I inhibitor, inhibits HIV-1 and JC virus replication in vitro. Methods: We tested topotecan by 21-day continuous infusion, 0.3 mg/m2/day every 28 days, in patients with AIDS-associated PML. PML was confirmed by clinical symptoms, measurable MRI lesions, and brain biopsy or CSF JC virus PCR; HIV was confirmed by serology. Washout from and progression after prior anti-PML therapy was required, as was a stable antiretroviral regimen for 3 weeks prior to study entry. Patients received highly active antiretroviral therapy (HAART) including a protease inhibitor and had adequate bone marrow, renal, and hepatic function and an initial Karnofsky performance score of > or 50%. Dose adjustments were allowed depending on toxicity. Results: 3 of 10 patients responded by clinical (Kurtzke score) and radiologic (volumetric MRI) criteria, achieving survivals of 81.4 wks, >143 wks, and >174 wks. In the first responder, screening HIV RNA PCR was 370,000 copies/ml, which increased to 980,000 copies/ml, indicating failure of HAART. Median overall survival was 16.9 wks. Toxicities (available for 9 patients, 30 courses) included grade 4 neutropenia (6 patients, 8 courses), grade 4 thrombocytopenia (2 patients, 3 courses), and grade 3/4 anemia (5 patients, 13 courses). Non-hematologic toxicities were primarily grade 1/2. No serious toxic events occurred, with the exception of one patient who received an accidental overdose and suffered grade 4 myelosuppression, sepsis, and hemorrhagic colitis. Conclusions: Continuous infusion topotecan is feasible in AIDS patients, despite its myelosuppression, and may have clinical activity against PML. Further topotecan investigations in AIDS-related PML are warranted.
Publication Types:
Keywords:
- Acquired Immunodeficiency Syndrome
- Anti-HIV Agents
- Antiretroviral Therapy, Highly Active
- HIV
- HIV Infections
- HIV Protease Inhibitors
- HIV Seropositivity
- HIV-1
- Humans
- In Vitro
- JC Virus
- Karnofsky Performance Status
- Leukoencephalopathy, Progressive Multifocal
- Topotecan
Other ID:
UI: 102244380
From Meeting Abstracts