CONTEXT: Gemcitabine and 5-fluorouracil (5-FU) sensitize tumor cells to radiation. Furthermore, 5-FU enhances the cytotoxic effect of gemcitabine. OBJECTIVE: We report the efficacy and the toxicity of concurrent chemoradiation with gemcitabine and 5-FU in the treatment of patients with locally advanced, unresectable pancreatic cancer. PATIENTS: Thirty-two patients (20 men, 12 women; median age 69.9 years) with histologically proven advanced pancreatic carcinoma were included in the study. INTERVENTIONS: The patients received chemotherapy with gemcitabine 300 mg/m2 on days 1, 15, 29 and 5-FU as continuous infusion 350 mg/m2/day of radiation while concurrent radiation (45-50 Gy) was given to the tumor and regional lymph nodes (1.8-2.0 Gy/fraction on 5 days/week). Subsequent to chemoradiotherapy, the treatment was continued with an additional two cycles of gemcitabine (1,000 mg/m2) and cisplatin (50 mg/m2) applied on days 1 and 15 of a four-week cycle. MAIN OUTCOME MEASURES: Patient survival, time to progression, and toxicity of chemoradiation. Tumor responses (complete resolution; partial response; stable disease, and progressive disease) were also evaluated. RESULTS: After the completion of chemoradiotherapy, 2 patients (6.3%) achieved complete resolution and 18 patients (56.3%) a partial response, for an overall response rate of 62.5%. Twelve patients (37.5%) were considered resectable and 9 underwent laparotomy, 7 of whom had definitive pancreatic resection. Four patients had negative surgical margins. With a median follow-up of 49.7 months (95% CI: 48.6-60.8 months) after the completion of chemoradiation, distant metastasis occurred in 25 patients (78.1%) while local recurrence was seen only in 4 of 32 patients (12.5%). Median time to progression was 9.2 months (95% CI: 8.2-10.2 months). Median survival amounted to 13.6 months (95% CI: 12.7-14.6 months) for all patients while it was prolonged to 16.4 months (95% CI: 13.4-19.4 months) for those undergoing secondary resection. In addition, performance status proved to be another prognostic factor for overall survival. The main toxicity of chemoradiation included grade 3-4 leukopenia in 18 patients (56.3%) and thrombocytopenia in 8 patients (25.0%). Episodes of cholangitis were observed in 7 patients (21.9%). CONCLUSION: Gemcitabine and 5-FU can safely be combined with external beam radiation. This preoperative treatment approach is highly effective and appears to improve survival in patients with good performance status and in those who are eligible for a secondary resection.
CONTEXT: Gemcitabine and 5-fluorouracil (5-FU) sensitize tumor cells to radiation. Furthermore, 5-FU enhances the cytotoxic effect of gemcitabine. OBJECTIVE: We report the efficacy and the toxicity of concurrent chemoradiation with gemcitabine and 5-FU in the treatment of patients with locally advanced, unresectable pancreatic cancer. PATIENTS: Thirty-two patients (20 men, 12 women; median age 69.9 years) with histologically proven advanced pancreatic carcinoma were included in the study. INTERVENTIONS: The patients received chemotherapy with gemcitabine 300 mg/m2 on days 1, 15, 29 and 5-FU as continuous infusion 350 mg/m2/day of radiation while concurrent radiation (45-50 Gy) was given to the tumor and regional lymph nodes (1.8-2.0 Gy/fraction on 5 days/week). Subsequent to chemoradiotherapy, the treatment was continued with an additional two cycles of gemcitabine (1,000 mg/m2) and cisplatin (50 mg/m2) applied on days 1 and 15 of a four-week cycle. MAIN OUTCOME MEASURES: Patient survival, time to progression, and toxicity of chemoradiation. Tumor responses (complete resolution; partial response; stable disease, and progressive disease) were also evaluated. RESULTS: After the completion of chemoradiotherapy, 2 patients (6.3%) achieved complete resolution and 18 patients (56.3%) a partial response, for an overall response rate of 62.5%. Twelve patients (37.5%) were considered resectable and 9 underwent laparotomy, 7 of whom had definitive pancreatic resection. Four patients had negative surgical margins. With a median follow-up of 49.7 months (95% CI: 48.6-60.8 months) after the completion of chemoradiation, distant metastasis occurred in 25 patients (78.1%) while local recurrence was seen only in 4 of 32 patients (12.5%). Median time to progression was 9.2 months (95% CI: 8.2-10.2 months). Median survival amounted to 13.6 months (95% CI: 12.7-14.6 months) for all patients while it was prolonged to 16.4 months (95% CI: 13.4-19.4 months) for those undergoing secondary resection. In addition, performance status proved to be another prognostic factor for overall survival. The main toxicity of chemoradiation included grade 3-4 leukopenia in 18 patients (56.3%) and thrombocytopenia in 8 patients (25.0%). Episodes of cholangitis were observed in 7 patients (21.9%). CONCLUSION:Gemcitabine and 5-FU can safely be combined with external beam radiation. This preoperative treatment approach is highly effective and appears to improve survival in patients with good performance status and in those who are eligible for a secondary resection.
Authors: Harvey J Mamon; Donna Niedzwiecki; Donna Hollis; Benjamin R Tan; Robert J Mayer; Joel E Tepper; Richard M Goldberg; A William Blackstock; Charles S Fuchs Journal: Cancer Date: 2010-12-23 Impact factor: 6.860
Authors: Milly Buwenge; Francesco Cellini; Nicola Silvestris; Savino Cilla; Francesco Deodato; Gabriella Macchia; Gian C Mattiucci; Vincenzo Valentini; Alessio G Morganti Journal: World J Gastroenterol Date: 2015-08-21 Impact factor: 5.742
Authors: Meredith A Morgan; Amichay Meirovitz; Mary A Davis; Laura E Kollar; Maria C Hassan; Theodore S Lawrence Journal: Transl Oncol Date: 2008-03 Impact factor: 4.243