Laetitia Dahan1, Nicolas Williet2, Karine Le Malicot3, Jean-Marc Phelip2, Jérôme Desrame4, Olivier Bouché5, Caroline Petorin6, David Malka7, Christine Rebischung8, Thomas Aparicio9, Cédric Lecaille10, Yves Rinaldi11, Anthony Turpin12, Anne-Laure Bignon13, Jean-Baptiste Bachet14, Jean-François Seitz1, Come Lepage15,16, Eric François17. 1. Department of Digestive Oncology, La Timone, Aix Marseille Université, Marseille, France. 2. Hepatogastroenterology Department, University Hospital of Saint-Etienne, Saint-Etienne, France. 3. Biostatistics Department, Fédération Francphone de Cancérologie Digestive, EPICAD INSERM LNC-UMR 1231 University of Burgundy and Franche Comté, Dijon, France. 4. Cancerology Institute, Jean-Mermoz Private Hospital, Lyon, France. 5. Department of Digestive Oncology, CHU Reims, Reims, France. 6. Hepatogastroenterology Department, Estaing University Hospital, Clermont Ferrand, France. 7. Cancerology Department, Gustave Roussy Institute, Villejuif, France. 8. Cancerology Department, Daniel Hollard Institute, Grenoble, France. 9. Department of Gastroenterology and Digestive Oncology, Saint Louis Hospital, APHP, Paris, France. 10. Cancerology Department, Bordeaux Nord Polyclinic, Bordeaux, France. 11. Hepatogastroenterology Department, European Hospital of Marseille, Marseille, France. 12. Department of Medical Oncology, University Lille, CNRS UMR9020, Inserm UMR-S 1277-Canther-Cancer Heterogeneity, Plasticity and Resistance to Therapies, CHU Lille, Lille, France. 13. Hepatogastroenterology Department, University Hospital of Caen, Caen, France. 14. Sorbonne University, UPMC, IUC, Paris 6, Hepato-Gastroenterology and Digestive Oncology Department, Pitié Salpêtrière Hospital, Paris, France. 15. Hepatogastroenterology and Cancerology Department, Dijon Bourgogne Hospital, Dijon, France. 16. Fédération Francophone de Cancérologie Digestive, EPICAD INSERM LNC-UMR 1231 University of Burgundy and Franche Comté, Dijon, France. 17. Cancerology Department, Antoine Lacassagne Centre, Nice, France.
Abstract
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.
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.
Authors: Kim A Reiss; Rosemarie Mick; Ursina Teitelbaum; Mark O'Hara; Charles Schneider; Ryan Massa; Thomas Karasic; Rashmi Tondon; Chioma Onyiah; Mary Kate Gosselin; Alyssa Donze; Susan M Domchek; Robert H Vonderheide Journal: Lancet Oncol Date: 2022-07-07 Impact factor: 54.433