Chemoradiotherapy as preoperative treatment in locally advanced unresectable pancreatic cancer patients: Results of a feasibility study

Purpose: The combination of radiotherapy and fluorouracil (5-FU) in patient s with locally unresectable pancreatic carcinoma has led to a significant i ncrease in survival in comparison with radiotherapy alone. Doxifluridine (5 -DFUR) is an orally active fluoropyrimidine, and its cytotoxic metabolite ( 5-FU) may concentrate in areas of high tumor vascularization. This trial wa s carried out with the aims of improving locoregional control and making le sions resectable in patients with unresectable pancreatic cancer. Methods: 5-DFUR was given at a dose of 500 mg/m(2) b.i.d. by way of mouth f or 4 days every other week for a total of four courses, with leucovorin 25 mg b.i.d. orally being given 2 hours before each 5-DFUR administration. Ext ernal beam RT was administered at a dose of 1000 cGy per week for 3 weeks, followed by a 2-week break and then by 1000 cGy per week for a further 2 we eks (a total dose of 5000 cGy). The patients were restaged 4 weeks after th e end of treatment and explored for resection in cases of partial response (PR). Results: A total of 32 patients were treated between 1992 and 1997. Ab init io unresectability was shown by laparotomy (16 cases) or computed tomograph y (16 cases), and was due to vascular invasion in 27 patients, massive regi onal nodal metastases in nine, and both in four. The median age was 63 year s (range 36-71); performance status (PS) (ECOG): 0-1 = 28 and PS 2 = 4. All the patients had measurable disease and were evaluable for response. There were seven PR (22%), 10 SD (31%), and 15 PD (47%). All of the responders u nderwent surgical exploration, and radical resection was possible in 5. Thr ee of these patients are still disease-free with a follow-up of 18, 27, and 65 months; the other two cases relapsed 11 and 14 months after surgery. Th e median survival time was 9 months for the entire group, and I-year surviv al rate was 31%. The treatment was never stopped because of toxicity. There were no CTC-NCI grade 3 or 4 toxic events; grade 1-2 diarrhea was observed in 10 cases. Conclusions: This preoperative regimen was feasible and Igd to a successful surgical resection in 16% of otherwise inoperable cases. The median surviv al was comparable with the results obtained after 5-FU infusion plus radiot herapy. The resectability rate, and the benefit in terms of survival in the resected patients, make these results worthy of confirmation by larger stu dies. (C) 1999 Elsevier Science Inc.