FOLFIRINOX and translational studies: Towards personalized therapy in pancreatic cancer

Table 1 Main prognostic factors reported in the MPACT and in PRODIGE 4/ACCORD 11 trials at multivariate analysis

Prognostic factors for metastatic pancreatic patients treated with
Gemcitabine-nab-paclitaxel	FOLFIRINOX
Age < 65 yr	Age > 65 yr
(HR = 0.81; P = 0.019)	(HR = 1.47; P < 0.019)
Hepatic metastases	Hepatic metastases
(HR = 1.81; P < 0.001)	(HR = 1.58; P = 0.051)
Number of metastatic sites > 3	Synchronous metastases
(HR = 1.08; P = 0.86)	(HR = 2.47; P < 0.003)
KPS score, 70-80 vs 90-100	Low baseline albumin level
(HR = 1.60; P < 0.001)	(HR = 1.85; P < 0.001)
Region - Eastern Europe
(HR = 1.22; P = 0.077)

KPS: Karnofsky performance status.

Table 2 Phase III clinical trials with new targeted anticancer agents combined with gemcitabine-based chemotherapy in metastatic pancreatic cancer patients

Ref.	Treatment arms	Patients	Results
Kindler et al[69] J Clin Oncol 2010	Gemcitabine + bevacizumab vs gemcitabine + placebo	302	OS: 5.8 mo vs 5.9 mo (P = 0.95)
			PFS: 3.8 mo vs 2.9 mo (P = 0.07)
		300	RR: 13% vs 10% (P = NR)
Van Cutsem et al[70] J Clin Oncol 2009	Erlotinib + gemcitabine + bevacizumab vs erlotinib + gemcitabine + placebo	306	OS: 7.1 mo vs 6.0 mo (P = 0.2087)
			PFS: 4.6 mo vs 3.6 mo (P = 0.0002)
		301	RR: 13.5% vs 8.6% (P = 0.0574)
Rougier et al[71] Eur J Cancer 2013	Gemcitabine + aflibercept vs gemcitabine + placebo	271	OS: 6.5 mo vs 7.8 mo (P = 0.2034)
			PFS: 3.7 mo vs 3.7 mo (P = 0.8645)
		275	RR: NR
Kindler et al[73] Lancet Oncol 2011	Gemcitabine + axitinib vs gemcitabine + placebo	316	OS: 8.5 mo vs 8.3 mo (P = 0.5436)
			PFS: 4.4 mo vs 4.4 mo (P = 0.5203)
		316	RR: 5% vs 2% (P = 0.0180)
Gonçalves et al[74] Ann Oncol 2012	Gemcitabine + sorafenib vs gemcitabine + placebo	52	OS: 8.0 mo vs 9.2 mo (P = 0.231)
			PFS: 3.8 mo vs 5.7 mo (P = 0.902)
		52	RR: 23% vs 19% (P = NR)
Philip et al[94] J Clin Oncol 2010	Gemcitabine + cetuximab vs gemcitabine	372	OS: 6.3 mo vs 5.9 mo (P = 0.19)
			PFS: 3.4 mo vs 3.0 mo (P = 0.18)
		371	RR: 14% vs 12% (P = 0.59)

OS: Overall survival; PFS: Progression free survival; RR: Response rate; NR: Not reported.

Table 3 miRNA candidates correlated to anticancer treatment resistance to the drugs in the FOLFIRINOX and nab-paclitaxel/gemcitabine regimens in tissues and cells from solid tumors

Drug	miRNA	Expression/polymorphism	Tumor type	Ref.
5-FU	miR-21	Overexpression	Pancreatic cancer	Donahue et al[126], J Surg Oncol 2014
5-FU and irinotecan	pri-miR26a-1	rs7372209 polymorphism	Colorectal cancer	Boni et al[132], Pharmacogenomics J 2011
5-FU and oxaliplatin	miR-106a, miR-484, miR-130b	Overexpression	Colorectal cancer	Kjersem et al[143], Mol Oncol 2014
5-FU, paclitaxel and oxaliplatin	miR-27a	Overexpression	Gastric cancer	Huang et al[135], J Cell Biochem 2014
5-FU, capecitabine and oxaliplatin	miR-625-3p, miR-181b, miR-27b	Overexpression	Colorectal cancer	Rasmussen et al[133], Mol Oncol 2013
Irinotecan and cetuximab	miR-345	Overexpression	Colorectal cancer	Schou et al[144], PLoS One 2014
Oxaliplatin	miR-203	Overexpression	Colorectal cancer	Zhou et al[145], Mol Oncol 2014
Carboplatin and paclitaxel ± sorafenib	miR-659-3p	Downregulation	Melanoma	Villaruz et al[136], Clin Epigenetics 2015
Paclitaxel	miR-200c	Downregulation	Ovarian and endometrial cancer	Cochrane et al[146], Mol Cancer Ther 2009
Paclitaxel	miR-145	Downregulation	Ovarian cancer	Zhu et al[147], Int J Cancer 2014
Paclitaxel	miR-17-5p	Downregulation	Lung cancer	Aggarwal et al[148], Planta Med 2008
Gemcitabine	miR-21	Overexpression	Pancreatic cancer	Hwang et al[127], PLoS One 2010
				Giovannetti et al[128], Cancer Res 2010
				Caponi et al[129], Ann Oncol 2013
Gemcitabine	miR-21, miR-23a, miR-27a	Overexpression	Pancreatic cancer	Frampton et al[131], Gastroenterology 2014