NEOADJUVANT CHEMORADIATION IN PANCREATIC AND DUODENAL CARCINOMA - A PHASE-II STUDY

Background. Low resectability rate and high locoregional recurrence ar e major factors contributing to the failure of surgical treatment for localized pancreatic adenocarcinoma. A Phase II study involving preope rative 5-fluorouracil (5-FU) and mitomycin C and radiation therapy was evaluated. Methods. Thirty-one patients with biopsy-proven carcinoma (24, head of pancreas; 2, body; 5 duodenum) were treated with preopera tive radiation therapy, 5040 cGy (180 cGy/fraction, 5 days/week), conc urrent with 5-FU, 1000 mg/m2/day continuous infusion (days 2-5, 28-32) and mitomycin C 10 mg/m2 bolus (day 2). Ten patients had previous lap arotomy or bypass surgery and were deemed unresectable; 21 had percuta neous, endoscopic retrograde choleangiopancreatic, or transhepatic ste nt biopsies. Results. Toxicity included neutropenic fever (2 patients) , biliary sepsis (2 patients), and nausea and vomiting requiring total parenteral nutrition. One patient died of biliary sepsis before compl etion of chemoradiation and 11 patients showed evidence of metastatic disease (clinical or occult). Resectability rate was 38% (10/26) for p ancreatic carcinoma and 80% (4/5) for duodenal carcinoma. Pathology of the resected specimens revealed extensive necrosis and hyalinization with clear margins in all cases. Lymph node metastases were found in o ne case of pancreatic carcinoma. The four resected duodenal carcinomas contained no residual tumor in the specimens. At a median follow-up o f 29 months, the median survival time for those with pancreatic carcin oma was not yet reached in the resection group and was 8 months in the nonresection group. The corresponding actuarial 5-year survival rates were 58% and 0%, respectively. Conclusions. Neoadjuvant chemoradiatio n therapy was given safely to patients with pancreatic and duodenal ca rcinoma. It facilitated complete resection in 38% of patients with pan creatic carcinoma and 80% of those with duodenal carcinoma. A signific ant downstaging of positive margins and regional lymph nodes occurs as a result of preoperative chemoradiation.