Clinical outcomes for modified FOLFIRINOX chemotherapy for pancreatic cancer
Authors: D. Holyoake, C. Lo, H. Stubbings, T. Roques
Journal: Annals of Oncology (2018)

Introduction: FOLFIRINOX chemotherapy improves overall survival in pancreatic ductal adenocarcinoma (PDAC) when compared to gemcitabine in clinical trials (Conroy et al., 2011). We aimed to examine the delivery and outcomes for this treatment in routine clinical practice. Methods: We identified all patients treated with a FOLFIRINOX regimen since its introduction at a university teaching hospital. Doses were modified from the published regimen to reduce toxicity (irinotecan 135 mg/m2, oxaliplatin 85 mg/m2, folinic acid 400 mg/m2, and 5-fluorouracil 2400 mg/m2 as an infusion over 48 hours). Treatment was given every 14 days, for up to 12 cycles. All patients received prophylactic supportive medications including atropine, G-CSF, antibiotics, steroids, anti-diarrhoeal and anti-emetic medications. We analysed treatment delivery and outcomes for patients with a minimum of 6-months follow-up since treatment commenced. Survival estimates (from time of commencing FOLFIRINOX) were calculated using Kaplan-Meier. Results: Thirty-eight patients with PDAC commenced treatment with FOLFIRINOX between July 2016 and February 2018. Of these, twenty-five had at least six-months duration of follow-up. Thirteen patients were male, and twelve female. Median age was sixty-seven years (range thirty-five to seventy-six). All patients were ECOG performance status 0-1. FOLFIRINOX was being used as first-line therapy for advanced disease in all but one patient. Median number of cycles administered was nine (range one to twelve). Five patients discontinued treatment early due to disease progression, after a median of five cycles (range 2 – 8), and eight due to toxicity (after a median 6 cycles, range 1 – 10). Fourteen patients had a dose reduction (including two patients starting treatment at reduced dose), with the commonest reason being symptomatic toxicity (most frequently diarrhoea, nausea/vomiting, or neuropathy). Five patients had total treatment deferrals of three weeks or more, most frequently due to deranged blood test results, symptomatic toxicity or patient choice. CTCAE grade-3 toxicities were seen in seven patients (28%) and comprised non-neutropaenic sepsis (rate 12%), nausea/vomiting (8%), and diarrhoea (8%). No febrile neutropaenia was observed, nor any grade-4 toxicity, and no patients died of treatment-related complications. One patient died within 30 days of receiving chemotherapy, and this was attributed to progressive disease. Thirteen patients (52%) had an objective disease response (complete response or partial response), and five further patients had stable appearances on imaging during treatment (20%). Median progression-free survival (PFS) was 8.4 months (95% confidence interval 6.3 – 10.6 months) and overall survival (OS) was 13.2 months (95% CI 7.6 – 18.8 months). Five patients subsequently received second-line palliative chemotherapy. Conroy et al. (2011) reported an objective response rate of 31.6%, and stable disease in 38.6% of patients, with PFS 6.4 months and OS 11.1 months. Conclusion: A modified FOLFIRINOX regimen has been implemented in routine clinical practice and observed outcomes compare favourably to published clinical trial data. This protocol may be as efficacious as the published protocol but with less toxicity, and universal administration of G CSF may have contributed to lack of febrile neutropaenia.