TY  - BOOK
AU  - Herbolsheimer, Pia M
AU  - Jelinek, James S
AU  - Kapoor, R
AU  - Perry, David J
AU  - Smith, Karen L
AU  - Swain, Sandra M
AU  - Verma, Nitin
AU  - Veytsman, Irina
TI  - Phase I trial of dasatinib and ixabepilone in patients with solid tumors
SN  - 0167-6997
KW  - *Antineoplastic Combined Chemotherapy Protocols/ad [Administration & Dosage]
KW  - *Neoplasms/dt [Drug Therapy]
KW  - Adult
KW  - Aged
KW  - Aged, 80 and over
KW  - Antineoplastic Agents/ad [Administration & Dosage]
KW  - Antineoplastic Combined Chemotherapy Protocols/ae [Adverse Effects]
KW  - Antineoplastic Combined Chemotherapy Protocols/pk [Pharmacokinetics]
KW  - Epothilones/ad [Administration & Dosage]
KW  - Female
KW  - Humans
KW  - Male
KW  - Middle Aged
KW  - Protein Kinase Inhibitors/ad [Administration & Dosage]
KW  - Pyrimidines/ad [Administration & Dosage]
KW  - Thiazoles/ad [Administration & Dosage]
KW  - Tubulin Modulators/ad [Administration & Dosage]
KW  - MedStar Washington Hospital Center
KW  - Washington Cancer Institute
KW  - Radiology
KW  - Clinical Trial, Phase I
KW  - Journal Article
KW  - Research Support, Non-U.S. Gov't
N2  - CONCLUSION: The combination of dasatinib and ixabepilone showed modest clinical activity with doses 100 mg orally daily and 40 mg/m(2) IV every 3 weeks, respectively. Treatment related toxicities were seen frequently; 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; PURPOSE: 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; RESULTS: Nineteen patients were enrolled. No DLTs were observed at dose level (DL) 1 (dasatinib 100 mg and ixabepilone 30 mg/m(2)). At DL 2 (dasatinib 100 mg and ixabepilone 40 mg/m(2)), one patient had multiple DLTs. At DL 3 (dasatinib 150 mg and ixabepilone 40 mg/m(2)), 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/m(2) (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
UR  - http://dx.doi.org/10.1007/s10637-012-9805-y
ER  -