Patupilone Epo906

Patupilone (EPO906) has been evaluated in the phase I setting, administered as a 5 to 10-minute bolus infusion either every three weeks or in a variety of weekly infusion schedules, including weekly for four weeks on/two weeks off, weekly for two weeks on/one week off, weekly for six weeks on/three weeks off, and weekly for three weeks on/one week off (37-40). The latter two weekly regimens have been the most extensively studied (38). Diarrhea was dose-limiting, regardless of the schedule, with a maximum tolerated dose of 6.0 mg/m2 for the every three-week schedule and 2.5 mg/m2 for the weekly schedule. Other, less common, grade-3 or -4 toxicities included nausea, vomiting, and fatigue. Serious neuropathy or mye-losuppression was uncommon. Why patupilone and ixabepilone, which are structurally very similar, have such different toxicity profiles remains unclear, though differences in tissue metabolism may play a part (9). Unlike ixabepilone, patupilone can be inactivated by esterases, making tissue esterase activity a potentially important determinant of the drug's toxicity profile (41).

Several phase II trials of patupilone are being conducted in patients with a variety of cancers, including ovarian, colorectal, non-small cell lung cancer, gastric, prostate, and renal cell tumors (42-47). A phase II trial of patupilone in patients with advanced breast cancer was suspended in January 2006.

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