Patient-tailored FOLFIRINOX as first line treatment of patients with advanced pancreatic adenocarcinoma

Abstract

FOLFIRINOX is one of the most effective reference regimens in the 1st line treatment of locally advanced (LA) and metastatic pancreatic cancer (mPC), despite its high toxicity. We evaluated our real-life experience with “patient-tailored intent to treat FOLFIRINOX” in patients with LA or mPC compared to other reports along with the pivotal phase III trial. We analyzed data from all consecutive patients with pancreatic ductal adenocarcinoma treated with dose-modified FOLFIRINOX in 2016 at Paul Brousse University Hospital. Irinotecan was administered whenever initial serum bilirubin was <1.5 × upper limit of normal. Oxaliplatin was stopped for severe sensory neuropathy. Initial dose reductions were made according to patient profile (eg, age, comorbidities) and later due to toxicity. The treatment was continued until surgery or disease progression. Endpoints were time to progression (TTP), overall survival (OS), objective response rate (ORR), and secondary complete resection (R0R1). Thirty-seven patients with unresectable LA or mPC received patient-tailored FOLFIRINOX as 1st line chemotherapy. There were 22 male (59%) and 15 female patients (41%) aged 44 to 81 years with LA (18 patients, 49%) and mPC (19 patients, 51%). They had World Health Organization-performance status of 0 (59%) or 1 (41%). A total of 384 cycles were administered. Median dose intensities (mg/m 2 /w) were 28.9 for oxaliplatin, 56.8 for irinotecan, and 886.2 for 5-fluorouracil. Thirty-four patients were assessed for response; ORR and disease control rates were 47% and 85%, respectively. R0R1 rate was 30%. Median TTP and OS were 9.6 and 14.6 months. LA disease was associated with significantly longer TTP and OS ( P < .001). FOLFIRINOX with patient-tailored dose adaptations seems to offer better results in patients with advanced PC. This approach in the neoadjuvant setting results in a macroscopic R0R1 in 61% of patients with initially unresectable disease. It deserves prospective evaluation to further improve outcomes in the management of advanced PC.

FOLFIRINOX De-Escalation in Advanced Pancreatic Cancer: A Multicenter Real-Life Study

“…The major limitation was the exclusion of early progressing patients, who were not able to receive a de‐escalation regimen. Furthermore, our study included patients with both locally advanced and metastatic aPC (vs. only patients with metastatic aPC in PRODIGE4/ACCORD11 and PRODIGE35‐PANOPTIMOX), whereas the OS of locally advanced pancreatic cancer was expected to be more favorable (even if this was not observed in our study), which introduces a new bias for the interpretation of OS [21].…”

A retrospective study of patient-tailored FOLFIRINOX as a first-line chemotherapy for patients with advanced biliary tract cancer

“…FOLFIRINOX regimen consisted in the intravenous administration of irinotecan (180 mg/m 2 ), oxaliplatin (85 mg/m 2 ), leucovorin (400 mg/m 2 ) and 5FU (2800 mg/m 2 , including the bolus injection and the 46-h constant infusion) [11]. The dosing was individualized according to patient profile as per our experience in the treatment of advanced pancreatic adenocarcinoma, with a "patient-tailored" approach [13]. Consequently, chemotherapy could have been started with or without irinotecan and/or with dose reductions of the cytotoxics in selected instances.…”

“…Patient-tailored FOLFIRINOX was discontinued in case of secondary surgery, disease progression or occurrence of an unacceptable toxicity. Recommended supportive care drugs were administered to all patients to prevent or treat chemotherapy-related toxicities as described [13,20].…”

“…Historically, BTC and pancreatic cancers were treated similarly with gemcitabine alone or combined with a platinum compound. Previous studies have shown that the combination of 5-Fluorouracil, leucovorin, oxaliplatin and irinotecan (FOLFIRINOX) or the combination of gemcitabine and nab-paclitaxel are associated with improved survival compared with gemcitabine alone in patients with metastatic pancreatic ductal adenocarcinoma [11][12][13]. Thus, both regimens are the standard of care of locally advanced or metastatic pancreatic cancer.…”

Marigold Supercritical Extract as Potential Co-adjuvant in Pancreatic Cancer: The Energetic Catastrophe Induced via BMP8B Ends Up With Autophagy-Induced Cell Death

“…The use of phytochemicals and dietary-derived compounds in cancer prevention and/or treatment is well-demonstrated (Mouhid et al, 2017;Pan et al, 2017;Kumar et al, 2018;Imran et al, 2019;Tarasiuk and Fichna, 2019), such as taxol and camptothecin, which are extensively used in the clinics (Denda et al, 2019;Sanoff et al, 2019;Ulusakarya et al, 2019). Metabolic reprogramming in cancer not only supports the proliferation but also promotes malignancy and dissemination of cancer cells.…”