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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Chemical References |
- 3,4,5-trihydroxy-2--methoxy-8,8-dimethyl-N-(hexahydro-2-oxo-6-(cyclohexylcarbonyl)oxy-2H-azepin-3-yl)non-6-enamide
- Angiogenesis Inhibitors
- Azepines
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Topics |
- Adult
- Aged
- Angiogenesis Inhibitors
(adverse effects, pharmacokinetics, therapeutic use)
- Area Under Curve
- Azepines
(adverse effects, pharmacokinetics, therapeutic use)
- Cardiovascular Diseases
(chemically induced, epidemiology)
- Dose-Response Relationship, Drug
- Female
- Humans
- Infusions, Intravenous
- Male
- Middle Aged
- Neoplasms
(drug therapy)
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