PREOPERATIVE CHEMORADIATION FOR ADENOCARCINOMA OF THE PANCREAS AND DUODENUM

Purpose: This study was designed to evaluate the effects of preoperati ve chemoradiation on resectability, response, local control, and survi val in patients with local or local-regional involvement from carcinom a of the pancreas or cancer of the duodenum and to assess the associat ed toxicity of such treatment. Methods and Materials: This prospective pilot study of preoperative chemoradiation was initiated in 1986 for patients with clinical evidence of adenocarcinoma of the pancreas or d uodenum without evidence of distant metastases. Radiation was given at 1.8 Gy per day to a total dose of 50.4 Gy. Two cycles of chemotherapy were given concurrent with radiation. On days 2-5 and 29-32, 5-fluoro uracil (1 gm/m(2)/24 h X 4 days) was given, while mitomycin-C (10 mg/m (2)) was given on day 2 only. Surgical resection was 4-6 weeks followi ng completion of chemoradiation. Thirty-one patients (17 male and 14 f emale) were entered on the protocol with a median potential follow-up of 4.5 years (range 6 months to 7.5 years). The median age was 64 year s (range 32-73 years). Twenty-seven patients had pancreatic cancer (25 head, two body), while four patients had carcinoma arising from the d uodenum. Twenty-one patients were initially judged to be unresectable and ten potentially resectable prior to chemoradiation. Results: Twent y-nine of 31 patients completed the entire course of radiation and bot h cycles of chemotherapy. Acute toxicity from chemoradiation consisted of nausea, vomiting, diarrhea, stomatitis, or hematologic suppression which was moderate to severe (Grade 3 or 4) in seven patients (23%). One patient died of sepsis following the first week of therapy. Sevent een patients (55%) underwent curative resection with subtotal or total pancreatectomy or Whipple resection (four duodenum, 13 pancreas) and two (2/17) had pathologic nodal involvement, while (0/17) none had inv olved margins. A complete pathologic response was seen in all four (4/ 4) patients with duodenal cancer and in none (0/13) with pancreatic ca ncer who underwent resection. The median postoperative hospitalization stay was 22 days (range 4-144 days). Of 17 patients who underwent cur ative resection, there were two postoperative mortalities (12%). Late complications have included abscess, one; and nonmalignant ascites, fi ve. Ten of the 31 patients are alive. For patients with pancreatic can cer the median survival is 9 months, while survival at 1 year and 3 ye ars are 36% and 19% overall and 60% and 43% at 1 and 3 years for those undergoing resection. Six of the 27 patients (22%) with pancreatic ca ncer are alive without recurrence. All four patients with duodenal can cer are alive without recurrence (12 months, 23 months, 35 months, 90 months). Conclusion: Preoperative chemoradiation for cancer of the pan creas and duodenal region was relatively well-tolerated and enhanced r esectability and downstaging of nodal metastases were suggested. The 3 -year survival, particularly in patients who underwent resection, was high. For these reasons the applicability of this treatment regimen fo r pancreatic cancer is presently being studied in a group-wide multi-i nstitutional Phase II trial. Chemoradiation for duodenal cancer has pr oduced a complete pathologic response in all patients and survival has been excellent, suggesting efficacy of this regimen for duodenal canc er.