481P - Tesetaxel: analysis of two dosing schedules (once weekly vs. every 3 weeks) using a novel oral taxane

Date 01 October 2012
Event ESMO Congress 2012
Session Poster presentation III
Topics Drug Development
Presenter Muralidhar Beeram
Authors M. Beeram1, K. Papadopoulos2, A.W. Tolcher1, D. Rasco2, T. Cousin3, L. Itri3, A. Patnaik1
  • 1The START Center for Cancer Care, 78229 - San Antonio/US
  • 2Developmental Therapeutics, The START Center for Cancer Care, 78229 - San Antonio/US
  • 3Developmental Therapeutics, Genta Incorporated, 07922 - Berkeley Heights/US



Tesetaxel (TST) is a novel oral taxane that is active in taxane-resistant models, is not a substrate for p-glycoprotein, and has limited preclinical neuropathy. TST is active in breast and gastric cancers when administered orally once every 3 weeks (Q3W). Taxanes may have schedule-related activity and adverse reactions. We conducted a dose-ranging study comparing the safety, efficacy, and pharmacokinetics (PK) using two schedules.


Patients (pts) had solid tumors, ECOG PS ≤ 2, and adequate organ function. In Schedule 1, TST was given once every 3 weeks from 18 to 27 mg/m2, escalated in increments of 3 mg/m2 to determine the MTD. In Schedule 2, TST was given once weekly for 3 weeks every 28 days, beginning at a total flat dose of 25 mg/cycle with increases up to 75 mg/cycle. Dosing was then 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). 3 pts were treated at each dose level until the MTD.


27 pts were treated on Schedule 1. The MTD was 27 mg/m2 and neutropenia was dose-limiting. One pt with nasopharyngeal carcinoma had a PR and 11 pts had stable disease, including several with taxane-resistant breast cancer. Cmax and AUC increased with increasing dose; however, the differences across the dose range examined were modest. No dose-related differences were apparent for other PK parameters. On schedule 2, 26 pts were treated in 8 dose cohorts. The MTD was 15 mg/m2 (total cycle dose, 45 mg/m2). Constitutional symptoms (fatigue and anorexia) proved dose-limiting at 17.5 mg/m2/wk. Only 1 pt had Grade 3 neutropenia. One pt with MBC (who had progressed after 2 prior taxane regimens) had a PR; 1 pt with prostate cancer had prolonged PSA reduction. PK analyses showed low but progressive increases in trough TST concentrations (0.4–4.6 nmol/mL) 7 days after each succeeding dose, consistent with the prolonged T½ of this drug (∼180 hrs). There was no substantial drug accumulation over multiple cycles.


Tesetaxel administered once every 3 weeks is active in pts with advanced gastric, breast and other solid tumors, including pts who have received prior taxanes. The weekly regimen is currently being evaluated in Phase 2.


A.W. Tolcher: Corporate sponsored research.

T. Cousin: Employee of Genta Inc.

L. Itri: Employee of Genta Inc.

All other authors have declared no conflicts of interest.