A phase I and pharmacokinetic study of LAF389 administered to patients with advanced cancer.
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| Abstract |
LAF389 is a synthetic analogue of bengamide B, a natural product isolated from Jaspidae sponges. LAF389 has both antiproliferative and antiangiogenetic properties, and preclinical investigations showed a broad antitumour activity. This clinical trial aimed to determine the safety and pharmacokinetic profile of LAF389 administered as a slow intravenous injection for 3 consecutive days every 3 weeks in patients with advanced solid tumours. Eight dose levels were tested: 1, 2.5, 5, 10, 15, 30, 25 and 20 mg/day. A total of 33 patients, median age 52 years (range 33-72), with refractory solid tumours were enroled, 19 men and 14 women with a median World Health Organization performance status of 1 (0-4). Seventy-eight cycles of treatment have been administered (mean 2.5, range 1-10). Four cardiovascular dose-limiting toxicities were reported at 30 mg (2/2 patients) and 25 mg (2/9 patients), eight additional patients at various dose levels had (cardio)vascular toxicity, probably drug related, and one patient died owing to pulmonary embolism at the 5 mg dose. No objective responses were recorded. Pharmacokinetic parameters were variable, although linear and without obvious accumulation from cycle I to cycle II. LAF389 dose escalation was terminated owing to occurrence of unpredictable cardiovascular events. This, associated with the lack of clinical activity, did not warrant further investigation of this agent.
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| Authors | Herlinde Dumez, Helen Gall, Renaud Capdeville, Catherine Dutreix, Allan T van Oosterom, Giuseppe Giaccone |
| Journal | Anti-cancer drugs (Anticancer Drugs) Vol. 18 Issue 2 Pg. 219-25 (Feb 2007) ISSN: 0959-4973 [Print] England |
| PMID | 17159608 (Publication Type: Clinical Trial, Phase I, Journal Article, Multicenter Study) |
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