{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,7]],"date-time":"2026-02-07T02:51:55Z","timestamp":1770432715082,"version":"3.49.0"},"reference-count":16,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2007,3,20]],"date-time":"2007-03-20T00:00:00Z","timestamp":1174348800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancer"],"published-print":{"date-parts":[[2007,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>BACKGROUND.<\/jats:title><jats:p>In previous experimental models, because of its ability to inhibit the activity of platelet\u2010derived growth factor \u03b2 receptor, imatinib decreased the interstitial fluid pressure and improved the delivery and efficacy of anticancer drugs, including fluorouracil. The objective of this Phase I study was to define the dose\u2010limiting toxicity (DLT) and maximum tolerated dose (MTD) of imatinib in combination with fluorouracil and leucovorin in patients with chemotherapy\u2010refractory gastrointestinal cancer.<\/jats:p><\/jats:sec><jats:sec><jats:title>METHODS.<\/jats:title><jats:p>A 3\u2010patient cohort dose\u2010escalating study design was used. Patients received leucovorin 200 mg\/m<jats:sup>2<\/jats:sup> followed by fluorouracil 2000 mg\/m<jats:sup>2<\/jats:sup> as a 24\u2010hour infusion on Days 1 and 2 combined with imatinib on Days \u22124, \u22123, \u22122, \u22121, 1, 2, 3, and 4. Cycles were repeated every 2 weeks, and the imatinib dose was escalated from 300 mg daily to 700 mg daily in 100\u2010mg steps.<\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS.<\/jats:title><jats:p>Thirty patients were enrolled at 5 dose levels. Frequent and dose\u2010dependant National Cancer Institute Common Toxicity Criteria grade 1\u20134 adverse events with suspected relation to the treatment were anemia (43%), nausea (33%), fluid retention (27%), elevated serum \u03b3\u2010glutamyl\u2010transpeptidase (20%), and diarrhea. DLTs were severe neutropenia, central fluid retention, and severe nausea observed in 1 patient each, resulting in an MTD for imatinib of 600 mg per day. There were no differences in imatinib pharmacokinetics before or during chemotherapy. A minor response was observed; and signs of clinical activity, including the resolution of ascites and improvement in performance status, were noted in some patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>CONCLUSIONS.<\/jats:title><jats:p>The combination of biweekly fluorouracil\/leucovorin and imatinib 600 mg daily given in a week\u2010on\/week\u2010off schedule was feasible and safe. Nausea and fluid retention represented the DLTs. Cancer 2007. \u00a9 2007 American Cancer Society.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cncr.22622","type":"journal-article","created":{"date-parts":[[2007,3,21]],"date-time":"2007-03-21T08:09:22Z","timestamp":1174464562000},"page":"1897-1904","source":"Crossref","is-referenced-by-count":21,"title":["Imatinib mesylate for targeting the platelet\u2010derived growth factor \u03b2 receptor in combination with fluorouracil and leucovorin in patients with refractory pancreatic, bile duct, colorectal, or gastric cancer\u2014A dose\u2010escalation Phase I 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