Fumagillin analog in the treatment of Kaposi's sarcoma: a phase I AIDS Clinical Trial Group study. AIDS Clinical Trial Group No. 215 Team

• Published in: Journal of clinical oncology Vol. 16; no. 4; p. 1444
• Main Authors: Dezube, B J, Von Roenn, J H, Holden-Wiltse, J, Cheung, T W, Remick, S C, Cooley, T P, Moore, J, Sommadossi, J P, Shriver, S L, Suckow, C W, Gill, P S
• Format: Journal Article
• Language: English
• Published: United States 01.04.1998
• Subjects: Adult; AIDS-Related Opportunistic Infections - drug therapy; Antibiotics, Antineoplastic - adverse effects; Antibiotics, Antineoplastic - pharmacokinetics; Antibiotics, Antineoplastic - therapeutic use; Area Under Curve; Cyclohexanes; Dose-Response Relationship, Drug; Drug Administration Schedule; Half-Life; Humans; Male; Middle Aged; Sarcoma, Kaposi - drug therapy; Sesquiterpenes - adverse effects; Sesquiterpenes - pharmacokinetics; Sesquiterpenes - therapeutic use; Skin Neoplasms - drug therapy
• ISSN: 0732-183X
• DOI: 10.1200/JCO.1998.16.4.1444

Angiogenesis is a major component of Kaposi's sarcoma (KS) and a critical process in tumor growth. The present study was designed primarily to test the toxicity and pharmacokinetics (PK) of the angiogenesis inhibitor TNP-470 and secondarily to evaluate tumor response in patients with early AIDS-related KS. Patients with AIDS-related KS were required to have cutaneous disease with > or = 5 measurable lesions and no evidence of pulmonary, symptomatic gastrointestinal, or acutely life-threatening KS. Thirty-eight patients received TNP-470 by weekly intravenous infusion over 1 hour at one of six dose levels for up to 24 weeks. The dose levels tested included 10, 20, 30, 40, 50 and 70 mg/m2. Median CD4 count was 24 cells/microl (range, 0 to 460). Fourteen patients (36%) had > or = 50 cutaneous lesions and 19 (49%) had oral lesions. Adverse events included neutropenia (n = 2), hemorrhage (n = 3), and urticaria (n = 1). PK studies showed wide interpatient and intrapatient variability. Elimination half-life values were short (range, 0.01 to 0.61 hours). Seven patients (18%) achieved a partial response. The median time to partial response was 4 weeks (range, 2 to 25), and the median duration of response was 11 weeks (range, 3 to 26+). TNP-470, administered as a weekly, 1-hour infusion to patients with early AIDS-KS is well-tolerated at doses up to and including the highest dose tested. Tumor responses were observed in a substantial number of cases and occurred at various dose levels. TNP-470 should be evaluated further in patients with AIDS-KS as a single agent and in combination with other biologic response modifiers in early disease or after initial response to cytotoxic chemotherapy.