FOLFOX as second-line chemotherapy in patients with pretreated metastatic pancreatic cancer from the FIRGEM study

Abstract

BackgroundFOLFOX second-line treatment seems to be a validated option for patients with pancreatic cancer (PC) progressing after gemcitabine chemotherapy. However, other therapeutics strategy has developed in first-line therapy, as the FIRGEM phase II study that evaluated gemcitabine alone versus FOLFIRI.3 alternating with gemcitabine every two months. The present study assessed the efficacy and safety of FOLFOX after failure of the first-line therapy used in the FIRGEM study.MethodsIn this prospective observational cohort study, we analysed all consecutive patients who received second-line chemotherapy with FOLFOX among 98 patients with metastatic PC included in the FIRGEM study. Progression-free survival (PFS) and overall survival (OS) were estimated from the start of second-line chemotherapy using the Kaplan-Meier method.ResultsAmong 46 patients who received second-line chemotherapy, 27 patients (male, 55%; median age, 61 years; performance status (PS) 0–1, 44%) were treated with FOLFOX after progression to first-line gemcitabine alone (n = 20) or FOLFIRI.3 alternating with gemcitabine (n = 7). Grade 3 toxicity was observed in 33% of patients (no grade 4 toxicity). At the end of follow-up, all patients had progressed and 25 had died. No objective response was observed, and disease control rate was 36%. Median PFS and OS were 1.7 and 4.3 months, respectively. In multivariate analysis, PS was the only independent prognostic factor. For patients PS 0–1 versus 2–3, median PFS was 3.0 versus 1.2 months (log rank, p = 0.002), and median OS was 5.9 versus 2.6 months (log rank, p = 0.001).ConclusionsThis study suggests that FOLFOX second-line therapy offered interesting efficacy results with an acceptable toxicity profile in metastatic PC patients with a good PS.

Analysis of second-line chemotherapies for ductal pancreatic adenocarcinoma in a German single-center cohort

“…In the subsequent multivariate analysis (ECOG ‡1, CA 19-9 >1000, presence of metastasis), we found that higher ECOG performance status grade had a significantly negative effect on OS. However, due to the retrospective design of our study, the limited number of patients, and the single center setting, we obviously have limitations to compare our findings statistically to other published second-line chemotherapy trials [12][13][14][15][16][17][18][19][20][21]. It should also be noted that our study took place in the pre-FOLFIRINOX and pre-nab-paclitaxel era.…”

A phase II study of sorafenib, oxaliplatin, and 2 days of high-dose capecitabine in advanced pancreas cancer

“…However, how to optimally sequence in oxaliplatin regimens after gemcitabine/nab-paclitaxel is unknown. Some studies have shown relatively poor activity of FOLFOX in pretreated metastatic pancreatic cancer patients [20]. However, other studies have shown modest response rates for FOLFOX-like regimens [17,21].…”

State of the art and future directions of pancreatic ductal adenocarcinoma therapy

“…Median time to progression was 2.3 months and OS from the beginning of the second line was 4.7 months. Combinations of 5FU with platinum salts (oxaliplatin or cisplatin) or with irinotecan (standard or nanoliposomal form) have shown interesting activity after progression under gemcitabine (Chen et al, 2015;Dahan et al, 2010;Neuzillet et al, 2012;Oettle et al, 2014;Yoo et al, 2009;Zaanan et al, 2014). Noticeably, only patients remaining in good performance status (ECOG 0-1) seem to benefit from second or further line of treatment.…”