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

September 1, 2004

The 30 reports in this special supplement to Oncology News International represent highlights of ongoing major clinical trials and new research presented at ASCO 2004 regarding state-of-the-art chemotherapeutic management of gastrointestinal and other cancers. Important developments in capecitabine as adjuvant therapy, novel targeted agents, and new combinations are discussed.

LEBANON, New Hampshire-Increased exposure to fluorouracil (5-FU) during radiotherapy, as part of a"trimodality" approach to esophagealcancer, has yielded high resection rates,promising survival, and minimal toxicity,reported Jeffrey A. Bubis, DO,Clinical Instructor in Medicine, NorrisCotton Cancer Center, Dartmouth-Hitchcock Medical Center (abstract4049).Currently, there is no clear standardof care in esophageal cancer. Thetrimodality approach under investigationat Dartmouth involves 25 patientswith stage II/III esophageal carcinomatreated with neoadjuvantchemotherapy, followed by concomitantchemoradiation, and then restagingthat includes surgical resection, ifindicated.Almost 90% of patients had com-plete resection following neoadjuvantchemotherapy followed by concomitantchemoradiotherapy with docetaxel(Taxotere) and capecitabine (Xeloda),Dr. Bubis told ONI. With afollow-up period of 48.8 months, mediansurvival time was 30.42 months,with an overall survival rate of 36.5%,achieved with minimal toxicity in thiscapecitabine dose-ranging trial. "Forpatients, minimal toxicity is really thebest part about this regimen," he said."We only had three patients who requiredfeeding tubes and two patientswho had dysphagia-there were noother dose-limiting toxicities. It wastolerated quite well."Building on Phase I
In 2003, at the International Congressof Anti-Cancer Treatment, inParis, France, Dr. Bubis and colleaguesreported promising phase I data froma study using a neoadjuvant regimenincluding weekly docetaxel and 5-FUwith thoracic irradiation, followed bysurgery in patients with locally advancedesophageal cancer. That phaseI trial served as the foundation for thecurrent trimodality trial.The current trimodality approachis a modification of the original strat-egy, Dr. Bubis said; it represents anattempt to improve the pathologiccomplete response rate (pCR), by increasing5-FU exposure via oralcapecitabine during thoracic radiation.The 25 patients studied (21 male, meanage 64 years) had clinical stage II-IIIcancer of the esophagus and gastroesophagealjunction; this included 23cases of adenocarcinoma and 2 casesof squamous cell carcinoma.Neoadjuvant therapy included docetaxel80 mg/m2 and carboplatinto AUC 6, given intravenously every3 weeks for two cycles. Following that,patients received concomitant chemoradiotherapywith docetaxel 15mg/m2 weekly for five doses, with oralcapecitabine given prior to each irradiationfraction (28 doses). Capecit-abine was given in doses ranging from300 to 2,500 mg total daily dose. Patientswere then restaged using CTscans and endoscopic ultrasound, afterwhich they received transhiatalesophagectomy, if indicated, at 4 to 8weeks after chemoradiation.Good Response Rate
So far, the rate of response afterchemoradiation, for 21 evaluable patients,is 52.4%, Dr. Bubis reported.The pCR rate is 10.5% (2 of 19 patients),while R0 resections have beenachieved in 89.5% (17 of 19 patients).The only dose-limiting toxicity encounteredwas grade 3 dysphagia,which was seen in two patients, andonly three patients needed a feedingtube because of therapy. A total of 12patients had weight gain over thecourse of therapy.While accrual into this trimodalitytrial continues, Dr. Bubis said the resultsto date for are encouraging andmerit further consideration. "It certainlysets a platform on which to basefurther studies. That it has been welltolerated is very promising," he said.The study was funded in part by Aventis,Roche, and a grant from theNational Cancer Institute.