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Open Access 01-08-2012 | Clinical Trial

Phase 1b dose-finding study of motesanib with docetaxel or paclitaxel in patients with metastatic breast cancer

Authors: Richard H. De Boer, Dusan Kotasek, Shane White, Bogda Koczwara, Paul Mainwaring, Arlene Chan, Rebeca Melara, Yining Ye, Adeboye H. Adewoye, Robert Sikorski, Peter A. Kaufman

Published in: Breast Cancer Research and Treatment | Issue 1/2012

Abstract

The purpose of this study was to investigate the safety, tolerability, and pharmacokinetics of motesanib when combined with docetaxel or paclitaxel in patients with metastatic breast cancer. In this open-label, dose-finding, phase 1b study, patients received motesanib 50 or 125-mg orally once daily (QD), beginning day 3 of cycle 1 of chemotherapy, continuously in combination with either paclitaxel 90 mg/m² on days 1, 8, and 15 every 28-day cycle (Arm A) or docetaxel 100 mg/m² on day 1 every 21-day cycle (Arm B). Dose escalation to motesanib 125 mg QD occurred if the incidence of dose-limiting toxicities (DLTs, primary endpoint) was ≤33 %. If the maximum tolerated dose (MTD) of motesanib was established in Arm B, additional patients could receive motesanib at the MTD plus docetaxel 75 mg/m². Forty-six patients were enrolled and 45 received ≥1 dose of motesanib. The incidence of DLTs was <33 % in all cohorts; thus, motesanib 125 mg QD was established as the MTD. Seven patients (16 %) had grade 3 motesanib-related adverse events including cholecystitis (2 patients) and hypertension (2 patients). Pharmacokinetic parameters of motesanib were similar to those reported in previous studies. The objective response rate was 56 % among patients with measurable disease at baseline who received motesanib in combination with taxane-based chemotherapy. The addition of motesanib to either paclitaxel or docetaxel was generally tolerable up to the 125-mg QD dose of motesanib. The objective response rate of 56 % suggests a potential benefit of motesanib in combination with taxane-based chemotherapy.

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Title: Phase 1b dose-finding study of motesanib with docetaxel or paclitaxel in patients with metastatic breast cancer
Authors: Richard H. De Boer
Dusan Kotasek
Shane White
Bogda Koczwara
Paul Mainwaring
Arlene Chan
Rebeca Melara
Yining Ye
Adeboye H. Adewoye
Robert Sikorski
Peter A. Kaufman
Publication date: 01-08-2012
Publisher: Springer US
Published in: Breast Cancer Research and Treatment / Issue 1/2012
Print ISSN: 0167-6806
Electronic ISSN: 1573-7217
DOI: https://doi.org/10.1007/s10549-012-2135-0

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