Phase I Development Of A Weekly Dosing Schedule For The Oral Taxane Tesetaxel

2555 Background: Tesetaxel (TST) has anticancer activity in patients (pts) with metastatic breast cancer (MBC) and gastric cancer when administered orally once every 3 weeks (Q3W). This drug is not a Pgp substrate, does not cause hypersensitivity reactions, and may be associated with less neurotoxicity. The maximally tolerated dose (MTD) on the Q3W schedule is 27 mg/m2, and neutropenia is dose-limiting. Since taxane activity may be schedule-dependent, we conducted a weekly, dose-ranging, and PK evaluation of TST. Methods: Eligibility: advanced solid tumors; ECOG PS 0-2; adequate organ function. TST was given once weekly for 3 weeks in a 28-day cycle, beginning at a total flat dose of 25 mg/cycle with progressive increases in total dose up to 75 mg/cycle. Subsequently, dosing was converted to a weight-based regimen at weekly doses of 12.5, 15, and 17.5 mg/m2 (i.e., total per cycle dose up to 52.5 mg/m2). Serial plasma samples were assayed by HPLC. Results: 26 pts were treated in 8 dose cohorts. The MTD was...