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In Esophageal Cancer, Promising Trimodality Approach Increases 5-FU Exposure

In Esophageal Cancer, Promising Trimodality Approach Increases 5-FU Exposure

LEBANON, New Hampshire- Increased exposure to fluorouracil (5- FU) during radiotherapy, as part of a "trimodality" approach to esophageal cancer, has yielded high resection rates, promising survival, and minimal toxicity, reported Jeffrey A. Bubis, DO, Clinical Instructor in Medicine, Norris Cotton Cancer Center, Dartmouth- Hitchcock Medical Center (abstract 4049). Currently, there is no clear standard of care in esophageal cancer. The trimodality approach under investigation at Dartmouth involves 25 patients with stage II/III esophageal carcinoma treated with neoadjuvant chemotherapy, followed by concomitant chemoradiation, and then restaging that includes surgical resection, if indicated. Almost 90% of patients had com- plete resection following neoadjuvant chemotherapy followed by concomitant chemoradiotherapy with docetaxel (Taxotere) and capecitabine (Xeloda), Dr. Bubis told ONI. With a follow-up period of 48.8 months, median survival time was 30.42 months, with an overall survival rate of 36.5%, achieved with minimal toxicity in this capecitabine dose-ranging trial. "For patients, minimal toxicity is really the best part about this regimen," he said. "We only had three patients who required feeding tubes and two patients who had dysphagia-there were no other dose-limiting toxicities. It was tolerated quite well." Building on Phase I
In 2003, at the International Congress of Anti-Cancer Treatment, in Paris, France, Dr. Bubis and colleagues reported promising phase I data from a study using a neoadjuvant regimen including weekly docetaxel and 5-FU with thoracic irradiation, followed by surgery in patients with locally advanced esophageal cancer. That phase I trial served as the foundation for the current trimodality trial. The current trimodality approach is a modification of the original strat- egy, Dr. Bubis said; it represents an attempt to improve the pathologic complete response rate (pCR), by increasing 5-FU exposure via oral capecitabine during thoracic radiation. The 25 patients studied (21 male, mean age 64 years) had clinical stage II-III cancer of the esophagus and gastroesophageal junction; this included 23 cases of adenocarcinoma and 2 cases of squamous cell carcinoma. Neoadjuvant therapy included docetaxel 80 mg/m2 and carboplatin to AUC 6, given intravenously every 3 weeks for two cycles. Following that, patients received concomitant chemoradiotherapy with docetaxel 15 mg/m2 weekly for five doses, with oral capecitabine given prior to each irradiation fraction (28 doses). Capecit- abine was given in doses ranging from 300 to 2,500 mg total daily dose. Patients were then restaged using CT scans and endoscopic ultrasound, after which they received transhiatal esophagectomy, if indicated, at 4 to 8 weeks after chemoradiation. Good Response Rate
So far, the rate of response after chemoradiation, for 21 evaluable patients, is 52.4%, Dr. Bubis reported. The pCR rate is 10.5% (2 of 19 patients), while R0 resections have been achieved in 89.5% (17 of 19 patients). The only dose-limiting toxicity encountered was grade 3 dysphagia, which was seen in two patients, and only three patients needed a feeding tube because of therapy. A total of 12 patients had weight gain over the course of therapy. While accrual into this trimodality trial continues, Dr. Bubis said the results to date for are encouraging and merit further consideration. "It certainly sets a platform on which to base further studies. That it has been well tolerated is very promising," he said. The study was funded in part by Aventis, Roche, and a grant from the National Cancer Institute.

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