PURPOSE: The combination of radiotherapy and fluorouracil (5-FU) in patients with locally unresectable pancreatic carcinoma has led to a significant increase 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 was carried out with the aims of improving locoregional control and making lesions resectable in patients with unresectable pancreatic cancer. METHODS: 5-DFUR was given at a dose of 500 mg/m2 b.i.d. by way of mouth for 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. External 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 weeks (a total dose of 5000 cGy). The patients were restaged 4 weeks after the 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 initio unresectability was shown by laparotomy (16 cases) or computed tomography (16 cases), and was due to vascular invasion in 27 patients, massive regional nodal metastases in nine, and both in four. The median age was 63 years (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 underwent surgical exploration, and radical resection was possible in 5. Three 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. The median survival time was 9 months for the entire group, and 1-year survival 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 led to a successful surgical resection in 16% of otherwise inoperable cases. The median survival was comparable with the results obtained after 5-FU infusion plus radiotherapy. The resectability rate, and the benefit in terms of survival in the resected patients, make these results worthy of confirmation by larger studies.
PURPOSE: The combination of radiotherapy and fluorouracil (5-FU) in patients with locally unresectable pancreatic carcinoma has led to a significant increase 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 was carried out with the aims of improving locoregional control and making lesions resectable in patients with unresectable pancreatic cancer. METHODS:5-DFUR was given at a dose of 500 mg/m2 b.i.d. by way of mouth for 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. External 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 weeks (a total dose of 5000 cGy). The patients were restaged 4 weeks after the 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 initio unresectability was shown by laparotomy (16 cases) or computed tomography (16 cases), and was due to vascular invasion in 27 patients, massive regional nodal metastases in nine, and both in four. The median age was 63 years (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 underwent surgical exploration, and radical resection was possible in 5. Three 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. The median survival time was 9 months for the entire group, and 1-year survival 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 led to a successful surgical resection in 16% of otherwise inoperable cases. The median survival was comparable with the results obtained after 5-FU infusion plus radiotherapy. The resectability rate, and the benefit in terms of survival in the resected patients, make these results worthy of confirmation by larger studies.
Authors: Jonathan B Ashman; Adyr A Moss; William G Rule; Matthew G Callister; K Sudhakar Reddy; David C Mulligan; Joseph M Collins; Giovanni De Petris; Leonard L Gunderson; Mitesh Borad Journal: J Gastrointest Oncol Date: 2013-12
Authors: Eran Sadot; Alexandre Doussot; Eileen M O'Reilly; Maeve A Lowery; Karyn A Goodman; Richard Kinh Gian Do; Laura H Tang; Mithat Gönen; Michael I D'Angelica; Ronald P DeMatteo; T Peter Kingham; William R Jarnagin; Peter J Allen Journal: Ann Surg Oncol Date: 2015-06-12 Impact factor: 5.344
Authors: John B Ammori; Lisa M Colletti; Mark M Zalupski; Frederic E Eckhauser; Joel K Greenson; Justin Dimick; Theodore S Lawrence; Cornelius J McGinn Journal: J Gastrointest Surg Date: 2003 Sep-Oct Impact factor: 3.452
Authors: Eric H Jensen; Leonard Armstrong; Chung Lee; Todd M Tuttle; Selwyn M Vickers; Timothy Sielaff; Edward W Greeno Journal: HPB (Oxford) Date: 2013-03-19 Impact factor: 3.647