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Phase II study of dasatinib (BMS-354825) in patients with metastatic adenocarcinoma of the pancreas.

ABSTRACT: Src, EphA2, and platelet-derived growth factor receptors ? and ? are dysregulated in pancreatic ductal adenocarcinoma (PDAC).Dasatinib is an oral multitarget tyrosine kinase inhibitor that targets BCR-ABL, c-Src, c-KIT, platelet-derived growth factor receptor ?, and EphA2. We conducted a phase II, single-arm study of dasatinib as first-line therapy in patients with metastatic PDAC.Dasatinib (100 mg twice a day, later reduced to 70 mg twice a day because of toxicities) was orally administered continuously on a 28-day cycle. The primary endpoint was overall survival (OS). Response was measured using the Response Evaluation Criteria in Solid Tumors. Circulating tumor cells (CTCs) were also collected.Fifty-one patients enrolled in this study. The median OS was 4.7 months (95% confidence interval [CI]: 2.8-6.9 months). Median progression-free survival was 2.1 months (95% CI: 1.6-3.2 months). In 34 evaluable patients, the best response achieved was stable disease in 10 patients (29.4%). One patient had stable disease while on treatment for 20 months. The most common nonhematologic toxicities were fatigue and nausea. Edema and pleural effusions occurred in 29% and 6% of patients, respectively. The number of CTCs did not correlate with survival.Single-agent dasatinib does not have clinical activity in metastatic PDAC.

SUBMITTER: Chee CE

PROVIDER: S-EPMC3805150 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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Phase II study of dasatinib (BMS-354825) in patients with metastatic adenocarcinoma of the pancreas.

Chee Cheng Ean CE Krishnamurthi Smitha S Nock Charles J CJ Meropol Neal J NJ Gibbons Joseph J Fu Pingfu P Bokar Joseph J Teston Lois L O'Brien Timothy T Gudena Vinay V Reese Amy A Bergman Mark M Saltzman Joel J Wright John J JJ Dowlati Afshin A Brell Joanna J

The oncologist 20130926 10

<h4>Background</h4>Src, EphA2, and platelet-derived growth factor receptors α and β are dysregulated in pancreatic ductal adenocarcinoma (PDAC).<h4>Methods</h4>Dasatinib is an oral multitarget tyrosine kinase inhibitor that targets BCR-ABL, c-Src, c-KIT, platelet-derived growth factor receptor β, and EphA2. We conducted a phase II, single-arm study of dasatinib as first-line therapy in patients with metastatic PDAC.<h4>Methods</h4>Dasatinib (100 mg twice a day, later reduced to 70 mg twice a day ...[more]

PMID: 24072218

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Project description:Ixabepilone (BMS-247550), an epothilone B analog, is a microtubule stabilizing agent which has shown activity in several different tumor types and preclinical models in melanoma. In an open label, one-arm, multi-center phase II trial the efficacy and toxicity of this epothilone was investigated in two different cohorts: chemotherapy-naïve (previously untreated) and previously treated patients with metastatic melanoma.Eligible patients had histologically-confirmed stage IV melanoma, with an ECOG performance status of 0 to 2. Ixabepilone was administered at a dose of 20 mg/m(2) on days 1, 8, and 15 during each 28-day cycle. The primary endpoint was response rate (RR); secondary endpoints were time to progression (TTP) and toxicity. Twenty-four patients were enrolled and 23 were evaluable for response. Initial serum lactate dehydrogenase (LDH) levels were elevated in 6/11 (55%) of the previously treated and in 5/13 (38%) of the previously untreated patients. No complete or partial responses were seen in either cohort. One patient in the previously treated group developed neutropenia and fatal septic shock. Seventeen patients (8 in the previously untreated group and 9 in the previously treated group) progressed after 2 cycles, whereas six patients (3 in each group) had stable disease after 2-6 cycles. Median TTP was 1.74 months in the previously untreated group (95% CI = 1.51 months, upper limit not estimated) and 1.54 months in the previously treated group (95% CI = 1.15 months, 2.72 months). Grade 3 and/or 4 toxicities occurred in 5/11 (45%) of previously untreated and in 5/13 (38%) of previously treated patients and included neutropenia, peripheral neuropathy, fatigue, diarrhea, and dyspnea.Ixabepilone has no meaningful activity in either chemotherapy-naïve (previously untreated) or previously treated patients with metastatic melanoma. Further investigation with ixabepilone as single agent in the treatment of melanoma is not warranted.Clinical Trials.gov NCT00036764.

Dataset Information

Phase II study of dasatinib (BMS-354825) in patients with metastatic adenocarcinoma of the pancreas.

Publications

Phase II study of dasatinib (BMS-354825) in patients with metastatic adenocarcinoma of the pancreas.

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