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Phase Ib/II dose-escalation trial evaluating the safety and tolerability of EPO906 plus capecitabine in patients with advanced cancer.

Dumez, H; Van Oosterom, AT; Rothermel, JD; Mull, R; Calvert, AH; (2004) Phase Ib/II dose-escalation trial evaluating the safety and tolerability of EPO906 plus capecitabine in patients with advanced cancer. J Clin Oncol , 22 (14_suppl) 2093-.

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Abstract

2093 Background: EPO906, a novel epothilone, is a microtubule stabilizer that causes growth arrest in a wide variety of human tumor cell lines. EPO906 has demonstrated clinical cytotoxic activity in taxane-sensitive, -resistant, and -refractory tumors and is associated with a low incidence of hematologic toxicity. Data from a phase I study indicated that EPO906 in combination with capecitabine may be active in patients (pts) with advanced cancers. We conducted a phase Ib/II study to determine the maximum tolerated dose (MTD) of EPO906 and evaluate the safety and tolerability of EPO906 in combination with capecitabine. METHODS: Eligible pts had advanced cancer, evaluable disease, and a performance status ≤ 2. Pts received EPO906 starting at 0.5 mg/m(2) via 5-min IV infusion once weekly for 3 wks and concurrent capecitabine 1,250 mg/m(2) orally twice daily during wks 2 and 3, followed by 1 wk of rest. EPO906 doses were increased by 0.5-mg/m(2) increments to 2.5 mg/m(2) or until the MTD was reached. RESULTS: To date, 24 pts have been enrolled in 4 cohorts treated with EPO906 0.5 mg/m(2) (n = 7), 1.0 mg/m(2) (n = 8), 1.5 mg/m(2) (n = 5), and 2.0 mg/m(2) (n = 4). Median age was 54 yrs (range, 31 - 75 yrs). Dose-limiting toxicity (DLT) was experienced by only 1 of 6 evaluable pts treated at 1.0 mg/m(2) (diarrhea, stomatitis), thus the dose was increased to 2.0 mg/m(2). At this dose, 3 of 4 pts experienced DLT (diarrhea, nausea, anorexia, small bowel obstruction), indicating that 2.0 mg/m(2) exceeded the MTD. Pts were enrolled in a cohort with an intermediate dose of 1.5 mg/m(2). Two of 4 evaluable pts treated at 1.5 mg/m(2) experienced DLT; this dose is the MTD. Most common adverse events (any grade) were nausea and diarrhea (experienced by 75% and 62.5% of pts, respectively). Only 3 pts (12.5%) experienced a grade 3 or 4 hematologic event. Preliminary tumor assessment shows 10 pts with stable disease (SD), and 2 pts each with rectal and renal cancer had SD with durations of 3 or 4+ and 3+ or 14+ months, respectively. CONCLUSION: EPO906 in combination with capecitabine is generally safe and well tolerated. Preliminary data suggest that this regimen may be active in pts with advanced cancers. [Table: see text].

Type: Article
Title: Phase Ib/II dose-escalation trial evaluating the safety and tolerability of EPO906 plus capecitabine in patients with advanced cancer.
Location: United States
UCL classification: UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > Research Department of Oncology
URI: http://discovery.ucl.ac.uk/id/eprint/1550545
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