FOLFIRINOX for locally advanced and metastatic pancreatic cancer: single institution retrospective review of efficacy and toxicity

Abstract

Although FOLFIRINOX significantly increases survival in metastatic pancreatic cancer (MPC) compared to gemcitabine (Conroy et al. N Engl J Med 364:1817-1825, 2011), toxicities have tempered enthusiasm for its use in full doses. To assess the impact of dose attenuations on toxicity and efficacy, we reviewed our institution's experience with FOLFIRINOX in locally advanced pancreatic cancer (LAPC) and MPC. We performed a retrospective review of dose, toxicity, and efficacy of FOLFIRINOX in all patients with LAPC and MPC treated between June 2010 and July 2011 at Yale. Toxicities in all patients and response rate (RR) and survival in previously untreated MPC were compared to data reported by Conroy. Overall survival (OS) and progression-free survival were estimated by Kaplan-Meier method. Thirty-five patients were treated (16 LAPC; 19 MPC). Twenty-nine patients received dose attenuations with the first cycle. Median relative doses of irinotecan and bolus fluorouracil were less than those reported by Conroy (64 vs. 81 % and 66 vs. 82 %, respectively). RR was 50 % in LAPC and 47 % in MPC, and the latter did not differ significantly from the RR reported by Conroy (p = 0.19). OS at 6 and 12 months in MPC was comparable to OS reported by Conroy. Grade 3/4 toxicities were less than reported by Conroy, including fatigue (p = 0.009) and neutropenia (p < 0.0001). Nine patients experienced transient dysarthria during irinotecan administration. Our findings validate the efficacy and tolerability of FOLFIRINOX in LAPC and MPC and suggest that dose attenuations of irinotecan and bolus fluorouracil improve tolerability without compromising efficacy.

A patient-level meta-analysis of FOLFIRINOX for locally advanced pancreatic cancer.

“…After screening of the abstracts, 30 studies were selected for full text assessment, of which 13 studies fulfilled the inclusion criteria. (12,(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30) The excluded studies are presented in the webappendix, pages 2 and 3. Figure 1 presents the flowchart.…”

“…(19)(20)(21)(22)(23)(24)(25)(27)(28)(29)(30) Three studies used the NCCN criteria (22,29,30), and three studies used the AHPBA/SSO/SSAT criteria (23,24,28) to define LAPC. The other seven studies determined LAPC based on multidisciplinary review board or retrospective evaluation of pretreatment imaging.…”

“…The other seven studies determined LAPC based on multidisciplinary review board or retrospective evaluation of pretreatment imaging. (12,(19)(20)(21)(25)(26)(27) Only three studies presented a patient cohort including only LAPC patients. (22,26,30) None of the studies described a staging laparoscopy as part of the diagnostic work-up.…”

“…(12,(20)(21)(22)(24)(25)(26)(27) Of those 368 patients, 269 (73·1%) received G-CSF. Four studies gave G-CSF as primary prophylaxis.…”

“…Four studies gave G-CSF as primary prophylaxis. (20,22,25,26) one study as secondary prophylaxis (12), and three studies left it to the discretion of the treating physician. (21,24,27) …”