Multi-institutional experience using 5-fluorouracil, leucovorin, irinotecan, and oxaliplatin (FOLFIRINOX) in patients with pancreatic cancer (PCA).

Abstract

e14519 Background: FOLFIRINOX resulted in significant improvement in survival in a recent phase III trial. However, the toxicity associated with its use may be significant. Theobjectives of this study were to determine the tolerability and outcome in patients with advanced PCA treated with FOLFIRINOX in 3 cancer centers in the USA. Methods: This was a retrospective analysis in pts with PCA treated with FOLFIRINOX at Karmanos Cancer Center (Detroit, MI), University of Michigan (Ann Arbor, MI) and Moffitt Cancer Center (Tampa, FL) from 2010 to 2012. Results: 54 patients with advanced PCA (61%males, median age 57.5 years [range 34-73], 72 % Caucasians) were evaluable. 67% of the primary tumors were in the head of the pancreas and 48% of patients had biliary stents prior to treatment. ECOG performance status (PS) was 0-1 in 91%. 91% of the patients had stage IV disease mostly with liver metastases. The median number of cycles received per patient was 5 (1-24). At the outset of treatment, bolus 5FU was omitted in 15% of pts and granulocyte growth factor was given in 89% of the cases. 80% of patients experienced at least one grade 1 or 2 toxicity (fatigue in 44%). Grade 3 toxicities occurred in 26 (48%) pts (fatigue [9]; neutropenia [7]; vomiting [7]; diarrhea [5]; neuropathy [4]; anemia [4]; thrombocytopenia [2] and infection [2]). 13% of patients (7) experienced grade 4 toxicities (vomiting [3]; febrile neutropenia [2] and neutropenia [2]). There was no grade 5 toxicity. Dose reduction was necessary in 87% of pts. 17% of pts required hospitalization during treatment. Partial responses were documented in 39% and stable disease in 29%. Side effects were the reason for treatment discontinuation in 35% of this population. Median PFS and OS were 3.8 (0.9 – 13.6) and 7.2 (0.5 – 17.8) months, respectively. Conclusions: In this multi-institutional experience in pts with PCA, significant grade 3 and 4 toxicities were associated with the FOLFIRINOX regimen leading to treatment discontinuation in a third of the population. PFS and OS represented a modest improvement over what would be expected from using single agent gemcitabine despite the relatively high objective response rate.

A Phase II Study of Biweekly Cisplatin, Fixed-Dose-Rate Gemcitabine and Infusional 5-Fluorouracil in Patients With Metastatic Pancreatic and Biliary Cancers

“…Despite these advances, there is concern regarding the toxicity of therapy. With the introduction of FOLFIRINOX, we performed a retrospective study to evaluate efficacy and tolerance in an initial 54 patient cohort treated in 3 institutions (10). While a 39% partial response rate and 29% stable disease rate were observed, median PFS and OS of 3.8 and 7.2 months were not particularly impressive.…”

Recent Treatment Advances and Novel Therapies in Pancreas Cancer: A Review

“…The second issue relates to the tolerability of this regimen outside of the highly controlled environment of a clinical trial. “Tolerability” of FOLFIRINOX remains controversial with some reports showing easily manageable side effects [ 7 , 8 ], while others demonstrate significant toxicity with 32 % hospitalization [ 9 ] and treatment discontinuation in one third of the patients [ 10 ]. Conscious of these limitations, Mahaseth and colleagues proposed a modified FOLFIRINOX in which the 5-FU bolus was removed and growth factor prophylaxis was used routinely.…”