PMID: 9166454May 1, 1995Paper

Thymidylate synthase protein expression: Association with response to neoadjuvant chemotherapy and resection for locally advanced gastric and gastroesophageal adenocarcinoma

The Cancer Journal From Scientific American
H R AlexanderPatrick G Johnston

Abstract

A phase II study of neoadjuvant fluorouracil, leucovorin, and interferon alpha-2a was conducted to determine the feasibility of this regimen's use and the response rates in patients undergoing resection for locally advanced gastric or gastroesophageal adenocarcinoma. Also, tumor protein expression of free, total, or bound thymidylate synthase before and after initial exposure to fluorouracil was quantitated to determine if thymidylate synthase expression is associated with response in this treatment setting. Twenty-two patients with T3-4N0-2M0 gastric or gastroesophageal adenocarcinoma were treated with three cycles of neoadjuvant fluorouracil (370 mg/m2 intravenously on days 2 through 6), leucovorin (500 mg/m2 intravenously on days 2 through 6), and interferon alpha-2a (5x106 U/m2 subcutaneously days 1 through 7), followed by resection and three cycles of consolidation therapy. Endoscopic tumor biopsies were done in 13 patients before therapy and during cycle 2 of the 5-fluorouracil/leucovorin/interferon regimen, and total thymidylate synthase, free thymidylate synthase, bound thymidylate synthase, and percent complexed thymidylate synthase were quantitated by Western blot. Tumor protein expression was evaluated for its associ...Continue Reading

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