Efficacy and safety of FOLFIRINOX in patients with metastatic pancreatic cancer.

Abstract

305 Background: FOLFIRINOX, one of the gold standard in metastatic pancreatic cancer as first-line therapy for patients under 76 years with PS 0-1, good haematological and renal function and a subnormal bilirubin level (Prodige 4 criteria), was analysed in Brittany (B) and Pays de la Loire (PL) in routine clinical practice. Methods: Our aim is to evaluate the use of Folfirinox between July 2010 and December 2012 in B/PL. Results: Data of 340 patients have been studied (198 men, median age 63 years [29-81]). 208 patients were metastatic at diagnosis (liver 67%). 62 primary tumors were resected and 51 patients had received previous adjuvant chemotherapy (gemcitabine, n=48). The median progression free survival PFS and overall survival OS were respectively 6.80 months IC95% [6.18-7.43] and 10.97 months IC 95% [9.56-11.83]. Patients could be divided into 4 groups : Group 1 composed of patients treated according to Prodige 4 trial (n=242), Group 2 1st line metastatic patients with at least one Prodige 4 non-eligibility criterion (n=25), Group 3 locally advanced patients (n=59) and Group 4 by Folfirinox in 2ndline (n=14). The median number of cycles was 9 [1-27] in Group 1 and 6 [1-12] in Group 2. Clinical benefit was 65% (group 1) vs 56% (group 2). During treatment, 81% of patients had a dose adjustment (Group 1) vs 72% (Group 2) and 32% vs 40% presented grade III/IV toxicity (mostly neuro- or haematotoxicity). Median PFS were respectively in Group 1 vs Group 2 : 6.54 months IC95% [5.98-7.29] vs 4.14 [1.68-6.21] (p=0.0107) and median OS :10.91 months IC 95% [8.94-12.02] vs 7.0 IC95% [4.01-11.20] (p=0.0166). For Group 3 and 4, median OS were respectively 11.24 months [10.0-15.01] vs 11.50 [4.83-14.09]. Others results will be shown at the meeting. For Group 1, stopping treatment before progression induced significatively better median PFS and OS than going on treatment until progression : PFS : 8.25 IC95[7.52-8.74] vs 3.48. IC95 [3.09-4.44] (p<0.0001) and OS : 12.78 months IC95 [11.60-15.54] vs 7.62 IC95 [6.44-9.49] (p<0.0001). Conclusions: Our results for Group 1 are relatively consistent with those of Prodige 4: objective response rate (39% vs 32%), PFS (6.5 vs 6.4 months) and OS (10.9 vs 11.1 months). Non eligibity for Prodige 4’s criteria decreases PFS and OS significantly.

Early tumor shrinkage as a predictor of favorable outcomes in patients with advanced pancreatic cancer treated with FOLFIRINOX

“…However, it cannot be applied to all patients with pancreatic cancer due to severe toxicity of the FOLFIRINOX, such as neutropenia, leucopenia, febrile neutropenia, anorexia, and diarrhea. The study by Metges et al who are the original investigators in the PRODIGE 4/ACCORD 11 trial, based on their established criteria, showed that 81% of 242 patients required a dose reduction (median dose intensity; 5-FU bolus 82%, oxaliplatin 78%, irinotecan 81%), but that this result did not affect treatment efficacy compared to the PRODIGE 4/ACCORD 11 trial: RR 39% vs. 32%, median PFS 6.5 vs. 6.4 months, and median OS 10.9 vs. 11.1 months [ 10 ]. A Japanese phase II trial of the FOLFIRINOX showed that grade 3 or 4 neutropenia and febrile neutropenia were more frequently observed compared to those in the global phase III trial (77.8% vs. 45.7%, 22.2% vs. 5.4%, respectively) [ 11 ].…”

Pancreatic cancer and FOLFIRINOX: a new era and new questions

“…Grade 3/4 toxicities were reported in 10 patients: nausea/vomiting in one, diarrhea in one, fatigue in three, neutropenia in four, thrombocytopenia in one, and febrile neutropenia in three—all manageable. A follow-up study by the original investigators in the PRODIGE 4/ACCORD 11 study, based on their established criteria, showed that 81% of 242 patients required a dose reduction, but that this did not affect results (response rate 39% vs. 32%, PFS 6.5 vs. 6.4 months and OS 10.9 vs. 11.1 months) 27 .…”

Locally advanced pancreatic cancer — new therapeutic challenges

“…In spite of such intensity of treatment and much larger toxicity in grade 3 and 4, no deterioration of quality of life was observed among the patients treated with FFX [13]. Irrespective of the initial doubts related to the large toxicity of FFX, this regimen was quickly introduced into clinical practice and until today it has been undergoing numerous modifications -these are mFOLFIRINOX (mFFX) which reflect the attempts to reduce toxicity accompanied with the preservation of the treatment efficacy [14][15][16][17][18][19].…”