PURPOSE: Metastatic pancreatic cancer (mPC) still harbors a dismal prognosis. Our previous trial (PRODIGE 4—ACCORD 11) demonstrated the superiority of 6-month chemotherapy with fluorouracil, leucovorin, irinotecan, and oxaliplatin (FOLFIRINOX) over gemcitabine for overall survival. The high limiting oxaliplatin-related neurotoxicity supports the evaluation of an oxaliplatin stop-and-go strategy and a sequential strategy in mPC. METHODS: In this phase II study, patients were randomly assigned to receive either 6 months of FOLFIRINOX (arm A), 4 months of FOLFIRINOX followed by leucovorin plus fluorouracil maintenance treatment for controlled patients (arm B), or a sequential treatment alternating gemcitabine and fluorouracil, leucovorin, and irinotecan every 2 months (arm C). The primary end point was progression-free survival at 6 months. RESULTS: Between January 2015 and November 2016, 276 patients (mean age: 63 years; range: 40-76 years) were enrolled (A: 91, B: 92, and C: 90). Grade 3 or 4 neurotoxicity occurred in 10.2% of patients in arm A and 19.8% in arm B. The median ratio of received dose/targeted dose of oxaliplatin was 83% in arm A and 92% in arm B. The 6-month progression-free survival was 47.1% in A, 42.9% in B, and 34.1% in C. The median overall survival was 10.1 months in arm A, 11.2 in arm B, and 7.3 in arm C. Median survival without deterioration in quality-of-life scores was higher in the maintenance arm (11.4 months) than in arms A and C (7.2 and 7.5 months, respectively). CONCLUSION: Maintenance with leucovorin plus fluorouracil appears to be feasible and effective in patients with mPC controlled after 4 months of induction chemotherapy with FOLFIRINOX. Severe neurotoxicity was higher in the maintenance therapy arm, probably because of the higher cumulative dose of oxaliplatin.

AIM: To provide trends in incidence, management and survival of cancer of the ampulla of Vater in a well-defined French population. METHODS: Data were obtained from the population-based digestive cancer registry of Burgundy over a 34-year period. Age-standardized incidence rates were computed using the world standard population. Average annual variations in incidence rates were estimated using a poisson regression. A univariate and multivariate relative survival analysis was performed. RESULTS: Age-standardized incidence rates were 0.46 and 0.30 per 100000 inhabitants for men and women, respectively. Incidence rate increased from 0.26 (1976-1984) to 0.58 (2003-2009) for men and remained stable for women. Resection for cure was performed in 48.3% of cases. This proportion was stable over the study period. Among cases with curative resection, pancreatico-duodenectomy was performed in 94.0% of cases and ampullectomy in 6.0% of cases. A total of 50.8% of cancers of the ampulla of Vater were diagnosed at an advanced stage. Their proportion remained stable throughout the study period. The overall 1- and 5-year relative survival rates were 60.2% and 27.7%, respectively. Relative survival did not vary over time. Treatment and stage at diagnosis were the most important determinants of survival. The 5-year relative survival rate was 41.5% after resection for cure, 9.5% after palliative surgery and 6.7% after symptomatic treatment. In multivariate analysis, only stage at diagnosis significantly influenced the risk of death. CONCLUSION: Cancer of the ampulla of Vater is still uncommon, but its incidence increased for men in Burgundy. Diagnosis is often made at an advanced stage, dramatically worsening the prognosis.