Neoadjuvant Modified (m) FOLFIRINOX for Locally Advanced Unresectable (LAPC) and Borderline Resectable (BRPC) Adenocarcinoma of the Pancreas

Abstract

Background For patients with metastatic pancreatic cancer, FOLFIRINOX (fluorouracil [5-FU], leucovorin [LV], irinotecan [IRI], and oxaliplatin) has shown improved survival rates compared with gemcitabine but with significant toxicity, particularly in patients with a high tumor burden. Because of reported response rates exceeding 30 %, the authors began to use a modified (m) FOLFIRINOX regimen for patients with advanced nonmetastatic disease aimed at downstaging for resection. This report describes their experience with mFOLFIRINOX and aggressive surgical resection. Methods Between January 2011 and August of 2013, 43 patients with borderline resectable pancreatic cancer (BRPC, n = 18) or locally advanced pancreatic cancer (LAPC, n = 25) were treated with mFOLFIRINOX (no bolus 5-FU, no LV, and decreased IRI). Radiation was used based on response and intended surgery. Charts were retrospectively reviewed to assess response, toxicities, and extent of resection when possible. Results The most common grade 3/4 toxicity was diarrhea in six patients (14 %) with no grade 3/4 neutropenia or thrombocytopenia. Resection was attempted in 31 cases (72 %) and accomplished in 22 cases (51.1 %) including 11 of 25 LAPC cases (44 %). Vascular resection was required in 4 cases (18 %), with R0 resection in 86.4 %of the resections. Complications occurred in 6 cases (27 %), with no perioperative deaths. The median progression-free survival period was 18 months if the resection was achieved compared with 8 months if no resection was performed (p < 0.001). Conclusion Neoadjuvant mFOLFIRINOX is an effective, well-tolerated regimen for patients with advanced nonmetastatic pancreatic cancer. When mFOLFIRINOX is coupled with aggressive surgery, high resection rates are possible even when the initial imaging shows locally advanced disease. Although data are still maturing, resection appears to offer at least a progression-free survival advantage.

Combination therapy with gemcitabine and nab-paclitaxel for locally advanced unresectable pancreatic cancer

“…In addition, Faris et al evaluated the FOLFIRINOX regimen for the treatment of LURPC and found an RR of 27%, as well as favorable treatment outcomes (median disease-free survival: 11.3 months); however, the median survival time was not reported (3). Moreover, Nanda and Blazer et al also reported favorable outcomes when they compared FOLFIRINOX with CRT for the treatment of LURPC, with median survival times of 18.6 and 12.2 months, respectively (16,17). During the present study, the RR was 71%, and although the median survival time was not calculated, the mean survival time was 13.3 months.…”

Contemporary Management of Borderline Resectable and Locally Advanced Unresectable Pancreatic Cancer

“…Resection was attempted in 72% of cases, including 11 of 25 LAPC cases (44%). R0 resection was obtained in 86.4%, or 19 of 22, with an 18-month median PFS for patients undergoing resection compared with 8 months for patients who did not undergo resection [6]. At Memorial Sloan-Kettering Cancer Center, LAPC patients (101) received FOLFIRINOX followed by CRT.…”

“…LAPC is treated with combination chemotherapy or combined chemoradiation therapy (CRT). These approaches have not shown any improvement in survival [6,7]. In this review, we highlight the evidence that defines the treatment approach for BRPC and LAPC.…”

“…Median overall survival (mOS) ranges from 5.5 to 22 months for BRPC and LAPC patients; LAPC survival reaches an mOS of approximately 16 months, whereas that of BRPC rarely reaches 2 years [2, [4][5][6][7][8]. The objective of treatment in BRPC is to achieve downstaging of the tumor to facilitate marginnegative (R0) resection.…”

Iontophoretic device delivery for the localized treatment of pancreatic ductal adenocarcinoma

“…FOLFIRINOX, a promising mixture of cytotoxic agents including folinic acid (leucovorin), fluorouracil, irinotecan, and oxaliplatin, has limited use in many patients because of its high systemic toxicity (16,17). Modified FOLFIRINOX regimens have been created to improve tolerability (5,18). Given the ability of the iontophoretic device to deliver drugs locally with minimal systemic exposure, the iontophoretic delivery of FOLFIRINOX Significance Drug delivery to pancreatic tumors is impaired by a unique desmoplastic response and poor tumor vascularization.…”