Phase I trial of erbulozole (R55104).

Erbulozole (R55 104) is a water soluble congener of the microtubule inhibitor tubulozole, which has proven to possess anti-invasive, antitumoral and radiosensitizing capacities. A dose-finding study was performed on respectively 9 patients (every three weeks; doses ranging from 20 mg/m2 to 100 mg/m2; maximum 2 cycles per patient) and 6 patients (weekly; doses ranging from 20 mg/m2 to 50 mg/m2; maximum 60 cycles per patient). At all dosages, hematological and biochemical toxicity was very limited. Seven patients complained of pain at the tumor site (grade I to III). Dose limiting toxicity appeared at respectively 100 mg/m2 (one administration every three weeks) and 50 mg/m2 (weekly administration). At this level, 2 patients displayed a dose-limiting Wernicke's encephalopathy-like syndrome. Other secondary effects were headache, fever, exacerbation of dyspnea and moderate nausea and vomiting.