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

MedStar author(s):
Citation: Investigational New Drugs. 31(1):92-8, 2013 Feb.PMID: 22392508Institution: MedStar Washington Hospital Center | Washington Cancer InstituteDepartment: RadiologyForm of publication: Journal ArticleMedline article type(s): Clinical Trial, Phase I | Journal Article | Research Support, Non-U.S. Gov'tSubject headings: *Antineoplastic Combined Chemotherapy Protocols/ad [Administration & Dosage] | *Neoplasms/dt [Drug Therapy] | Adult | Aged | Aged, 80 and over | Antineoplastic Agents/ad [Administration & Dosage] | Antineoplastic Combined Chemotherapy Protocols/ae [Adverse Effects] | Antineoplastic Combined Chemotherapy Protocols/pk [Pharmacokinetics] | Epothilones/ad [Administration & Dosage] | Female | Humans | Male | Middle Aged | Protein Kinase Inhibitors/ad [Administration & Dosage] | Pyrimidines/ad [Administration & Dosage] | Thiazoles/ad [Administration & Dosage] | Tubulin Modulators/ad [Administration & Dosage]ISSN:
  • 0167-6997
Name of journal: Investigational new drugsAbstract: 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.All authors: Herbolsheimer P, Jelinek J, Kapoor R, Perry D, Smith KL, Swain SM, Verma N, Veytsman IDigital Object Identifier: Date added to catalog: 2014-04-22
Holdings
Item type Current library Collection Call number Status Date due Barcode
Journal Article MedStar Authors Catalog Article Available 22392508

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.

Powered by Koha