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Series GSE37180 Query DataSets for GSE37180
Status Public on Apr 12, 2012
Title Gene expression profiles of ovarian tumor biopsies from Phase I dasatinib trial
Organism Homo sapiens
Experiment type Expression profiling by array
Summary A phase I trial of a SRC kinase Inhibitor, dasatinib, in combination with paclitaxel and carboplatin in patients with advanced or recurrent ovarian cancer. Background: We conducted a phase I study of dasatinib, an oral SRC tyrosine kinase inhibitor, in combination with paclitaxel and carboplatin in advanced and recurrent epithelial ovarian cancer (EOC). Methods: The primary objective was to determine the maximum tolerated dose (MTD). Secondary objectives included toxicity, response rate (RR), pharmacokinetics and pharmacodynamics. Based on the 3+3 design, cohorts of 3-6 pts received paclitaxel 175 mg/m2 and carboplatin AUC 6 every three weeks with escalating doses of dasatinib (100, 120, 150 mg daily), followed by an 8 patient expansion cohort. Results: Twenty patients were enrolled between 06/07 and 12/09. The median age was 61 yrs (42-82) with a median of 2 prior regimens (0-6), and 71% had platinum-sensitive disease. There were 3-6 pts in each cohort, and 8 in the expansion cohort. Pharmacokinetics were observed over the first 2 cycles of therapy. One DLT was observed in the 100 mg dasatinib cohort (grade 3 myalgia. Other toxicities in all cycles included neutropenia (95% grade 3-4), thrombocytopenia (35% grade 3-4), and fatigue (10% grade 3). The RR was 45% (complete responses, 3/18(17%); partial responses, 5/18(28%)) and 56% (10/18) had stable disease. The PFS6-month actuarial estimate was 86%. The median PFS and OS were 7.8 and 16.2 months, respectively. Conclusions: Due to the high incidence of myelosuppression with subsequent cycles the recommended phase II dose is 150 mg daily of dasatinib in combination with paclitaxel and carboplatin. The combination was safe with evidence of clinical activity in advanced EOC.
 
Overall design Global profiles of expression were characterized using unsupervised clustering methods and gene- and pathway-analyses of differential expression.
 
Contributor(s) Secord AA, Barry WT
Citation(s) 22837181
Submission date Apr 11, 2012
Last update date Dec 06, 2018
Contact name Miao yu
E-mail(s) miao.yu@duke.edu
Organization name Duke
Street address Laselle drive
City durham
ZIP/Postal code 27710
Country USA
 
Platforms (1)
GPL571 [HG-U133A_2] Affymetrix Human Genome U133A 2.0 Array
Samples (11)
GSM913211 001-011
GSM913213 002-005
GSM913215 D101
Relations
BioProject PRJNA158977

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE37180_RAW.tar 20.8 Mb (http)(custom) TAR (of CEL)
Processed data included within Sample table

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