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Phase I trial of dasatinib and ixabepilone in patients with solid tumors

Phase I trial of dasatinib and ixabepilone in patients with solid tumors SummaryPurpose. Dasatinib is an oral tyrosine kinase inhibitor (TKI) of BCR-ABL and SRC family and ixabepilone is an epothilone B analog. Synergistic activity has been reported when combining dasatinib with chemotherapy. This study was conducted to determine the dose-limiting toxicities (DLTs) and the maximum tolerated doses (MTDs) for this combination. Patients and methods. Patients with metastatic solid tumors who progressed on standard therapy received dasatinib orally daily and ixabepilone IV every 3 weeks at escalating doses using 3 + 3 design. An expansion cohort was studied after reaching the MTD. Pharmacokinetic studies were performed. Results. Nineteen patients were enrolled. No DLTs were observed at dose level (DL) 1 (dasatinib 100 mg and ixabepilone 30 mg/m2). At DL 2 (dasatinib 100 mg and ixabepilone 40 mg/m2), one patient had multiple DLTs. At DL 3 (dasatinib 150 mg and ixabepilone 40 mg/m2), the first patient developed grade 3 AE during cycle 2, the second patient had a DLT and a grade 3 AE during cycle 2. The accrual to DL 3 was halted without reaching the maximally administered dose (MAD) and MTDs were determined to be dasatinib 100 mg and ixabepilone 40 mg/m2 (DL 2). One patient had a partial response and 12 patients stable disease as their best response. Fourteen patients came off study due to toxicities. Conclusion. The combination of dasatinib and ixabepilone showed modest clinical activity with doses 100 mg orally daily and 40 mg/m2 IV every 3 weeks, respectively. Treatment related toxicities were seen frequently. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Investigational New Drugs Springer Journals

Phase I trial of dasatinib and ixabepilone in patients with solid tumors

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References (28)

Publisher
Springer Journals
Copyright
Copyright © Springer Science+Business Media, LLC 2012
Subject
Medicine & Public Health; Oncology; Pharmacology/Toxicology
ISSN
0167-6997
eISSN
1573-0646
DOI
10.1007/s10637-012-9805-y
pmid
22392508
Publisher site
See Article on Publisher Site

Abstract

SummaryPurpose. Dasatinib is an oral tyrosine kinase inhibitor (TKI) of BCR-ABL and SRC family and ixabepilone is an epothilone B analog. Synergistic activity has been reported when combining dasatinib with chemotherapy. This study was conducted to determine the dose-limiting toxicities (DLTs) and the maximum tolerated doses (MTDs) for this combination. Patients and methods. Patients with metastatic solid tumors who progressed on standard therapy received dasatinib orally daily and ixabepilone IV every 3 weeks at escalating doses using 3 + 3 design. An expansion cohort was studied after reaching the MTD. Pharmacokinetic studies were performed. Results. Nineteen patients were enrolled. No DLTs were observed at dose level (DL) 1 (dasatinib 100 mg and ixabepilone 30 mg/m2). At DL 2 (dasatinib 100 mg and ixabepilone 40 mg/m2), one patient had multiple DLTs. At DL 3 (dasatinib 150 mg and ixabepilone 40 mg/m2), the first patient developed grade 3 AE during cycle 2, the second patient had a DLT and a grade 3 AE during cycle 2. The accrual to DL 3 was halted without reaching the maximally administered dose (MAD) and MTDs were determined to be dasatinib 100 mg and ixabepilone 40 mg/m2 (DL 2). One patient had a partial response and 12 patients stable disease as their best response. Fourteen patients came off study due to toxicities. Conclusion. The combination of dasatinib and ixabepilone showed modest clinical activity with doses 100 mg orally daily and 40 mg/m2 IV every 3 weeks, respectively. Treatment related toxicities were seen frequently.

Journal

Investigational New Drugs – Springer Journals

Published: Feb 1, 2013

Keywords: Dasatinib; Ixabepilone; Phase 1

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