Faculty Collaboration Database

A phase 1 study of gemcitabine combined with dasatinib in patients with advanced solid tumors. Invest New Drugs 2013 Aug;31(4):918-26

Date

11/28/2012

Pubmed ID

23179336

Pubmed Central ID

PMC4482128

DOI

10.1007/s10637-012-9898-3

Scopus ID

2-s2.0-84880921289 (requires institutional sign-in at Scopus site)   29 Citations

Abstract

PURPOSE: Dasatinib has been shown preclinically to overcome resistance to gemcitabine. We evaluated the safety and biological activity of the combination of dasatinib and gemcitabine in patients with advanced solid tumors.

EXPERIMENTAL DESIGN: In a phase 1 study (3 + 3 design), patients received daily dasatinib with weekly gemcitabine on days 1, 8 and 15 of a 28-day cycle (except cycle 1 which was 8 weeks). Dose escalation began with dasatinib 70 mg orally (PO) daily and gemcitabine 800 mg/m(2) intravenously (IV) weekly.

RESULTS: Forty-seven patients (15 men; median age = 55 years; median number of prior systemic treatments = 4) were enrolled. Dose-limiting toxicities were grade 3 fatigue and dehydration, with the maximum tolerated dose being dasatinib 100 mg PO qd and gemcitabine 600 mg/m(2) IV weekly. The most common grade 3-4 toxicities were anemia (21.5 %), thrombocytopenia (26.2 %), leukopenia (26.2 %), and pleural effusion (10.7 %). Six of 47 patients attained stable disease (SD) ≥ 6 months or partial response including 2 of 8 patients with pancreatic cancer (SD ≥ 6 months; both gemcitabine-refractory), 2 of 3 patients with thymoma (SD for 9.8 and 15 months), 1 of 1 patient with anal squamous cancer (SD 15 months) and 1 of 5 patients with inflammatory breast cancer. No significant changes in circulating tumor cells or interleukin-8 levels were observed.

CONCLUSIONS: The combination was well tolerated at doses of dasatinib 100 mg PO daily and gemcitabine 600 mg/m(2) IV weekly. SD ≥ 6 months/ PR was observed in gemcitabine-refractory pancreatic cancer, thymoma, anal cancer and inflammatory breast cancer.

Author List

Hong DS, Choe JH, Naing A, Wheler JJ, Falchook GS, Piha-Paul S, Moulder SL, George GC, Choe JM, Strauss LC, Gallick GE, Kurzrock R

Author

Razelle Kurzrock MD Center Associate Director, Professor in the Medicine department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adult
Aged
Aged, 80 and over
Antineoplastic Combined Chemotherapy Protocols
Cell Count
Dasatinib
Demography
Deoxycytidine
Dose-Response Relationship, Drug
Female
Humans
Interleukin-8
Male
Maximum Tolerated Dose
Middle Aged
Neoplasm Staging
Neoplasms
Neoplastic Cells, Circulating
Pyrimidines
Thiazoles
Young Adult