New challenges in perioperative management of pancreatic cancer

Table 1 Comparison of American Hepatopancretobiliary Association/Society for Surgery of the Alimentary Tract/Society of Surgical Oncology, MD Anderson Cancer Center, and National Comprehensive Cancer Network definitions of borderline resectable pancreatic cancer

	AHPBA/SSO/SAT	MDACC	NCCN 2012
SMV-PV	Abutment, encasement or occlusion	Short segment occlusion	Abutment with impingement or narrowing
SMA	Abutment	Abutment	Abutment
CHA	Abutment or short segment encasement	Abutment or short segment encasement	Abutment or short segment encasement
Celiac trunk	No abutment or encasement	Abutment	No abutment or encasement

AHPBA/SSO/SSAT: American Hepatopancretobiliary Association/Society of Surgical Oncology/Society for Surgery of the Alimentary Tract; MDACC: MD Anderson Cancer Center; NCCN: National Comprehensive Cancer Network; SMV: Superior mesenteric vein; PV: Portal vein; SMA: Superior mesenteric artery; CHA: Common hepatic artery; Abutment: Tumor-vessel interface less than 180° of vascular circumference; Encasement: Tumor-vessel interface at least 180° of vascular circumference.

Table 2 Major phase III trials of adjuvant therapy for resected Pancreatic ductal adenocarcinoma

Ref.	Year	n	Treatment arms	OS (mo)	P value	5-yr OS (%)
GITSG[15]	1985	21	CRT1/5-FU then 5-FU maintenance for 2 yr	20.0	0.035	19
		22	Observation	10.9		5
EORTC[16]	1999	60	2CRT/5-FU	17.1	0.09	20
		54	Observation	12.6		10
ESPAC-1[18]	2004	145	1CRT/5-FU +/- 5-FU/FA bolus for 6 cycles	15.9	0.05	10
		144	No CRT	17.9		20
CONKO-001[14]	2007	179	Gem 6 cycles	22.8	0.005	20.7
		175	Observation	20.2		10.4
RTOG 97-04[22] (pancreatic head only)	2008	187	Gem 3 wk, CRT/5-FU, Gem 3 mo	20.5	0.09	22
		194	5-FU 3 wk, CRT/5-FU, 5-FU 3 mo	17.1		18
ESPAC-3[21]	2010	551	5-FU/FA for 6 cycles	23.0	0.53	NA
		537	Gem for 6 cycles	23.6		NA

¹CRT:20 Gy + 5-FU bolus days 1-3 x 2;

²20 Gy + 5-FU continous infusion x 2. CRT: Chemoradiotherapy; 5-FU: 5-Fluorouracil; FA: Folinic acid; Gem: Gemcitabine; OS: Overall survival; NA: Not available.

Table 3 Major phase III ongoing adjuvant/neoadjuvant trials

Sponsor/study name	Treatment arms	Primary outcome	Clinicaltrial.gov No.	EudraCT number
Unicancer	Gemcitabine vs folfirinox	DFS	NCT01526135
Celgene corporation	Nab-paclitaxel + gem vs gem	OS	NCT01964430
Radiation therapy Oncology group	Pre and post CRT 5-FU vs pre and post CRT gem	OS, DFS	NCT00003216
National cancer institute	Gem vs gem + erlotinib, followed by CT vs CRT with capecitabine or 5-FU	OS	NCT01013649
EORTC trial 40084 - 22084	Gem vs gem + erlotinib followed or not by CRT with capecitabine or 5-FU	OS		2011-000618-20
CONKO 005	Gem vs gem + erlotinib	DFS		2007-003813-15

FOLFIRINOX: 5-Fluorouracil, folinic acid, irinotecan and oxaliplatin; 5-FU: 5-Fluorouracil; FA: Folinic acid; Gem: Gemcitabine; OS: Overall survival; DFS: Disease free survival.

Table 4 Selected ongoing neoadjuvant/preoperative trials registered at clinicaltrial.gov before January 2014

Clinicaltrial.gov No.	Type of cancer	Intervention	Design	Primary outcome	Biomarker
NCT01771146	Locally advanced	FOLFIRINOX	Phase II Single arm	PFS	No
NCT01458717	Borderline resectable	Gemcitabine and CRT vs uprfont surgery	Phase II/III Randomized trial	2-yr OS	No
NCT01065870	Locally advanced	gemcitabine, capecitabine and docetaxel +/- RT with gemcitabine and capecitabine	Phase II/III Non randomized	2-yr OS	No
NCT01314027	Resectable	Neoadjuvant gemcitabine/oxaliplatin vs adjuvant CT with gemcitabine	Phase III randomized multicenter trial	PFS	No
NCT01521702	Resectable	Neoadjuvant gemcitabine/oxaliplatine vs surgery and adjuvant gemcitabine	Phase III Randomized Multicenter trial	PFS	No
NCT00536874	Resectable	Gemcitabine and oxaliplatine	Phase II Single arm	OS 18 mo	Yes (proteomic profiling, laboratory biomarker analysis)
NCT01661088	Borderline resectable	FOLFIRINOX, gemcitabine during and after radiation therapy	Phase II Single arm	R0 resection rate	No
NCT00609336	Resectable	Gemcitabine, docetaxel, capecitabine, RT and surgery	Phase II Single arm	OS	No
NCT00869258	Locally advanced	Gemcitabine, docetaxel and capecitabine followed by RT with gemcitabine	Phase II Single arm	Conversion rate	No
NCT00557492	Resectable	Bevacizumab with gemcitabine and radiation therapy	Phase II Single arm	R0 resection rate	Yes (not specified)
NCT01298011	Resectable	Gemcitabine and nab-paclitaxel	Phase II Single arm	Histological response	Yes (SPARC expression in the tumor)
NCT01359007	Borderline resectableLocally advanced	FOLFIRINOX	Phase I Single arm	R0 resection rate	No
NCT01470417	ResectableBorderline resectable	Nab-paclitaxel and gemcitabineNab-paclitaxel and gemcitabine with CT	Phase II Not randomized	Biochemical and pathologic response rateR0 resection rate	Yes (biochemical radiographic, and pathologic factors)
NCT01494155	Resectable	Capecitabine, Hydroxychloroquine and proton RT	Phase II Single arm	PFS	Yes (autophagy)
NCT00733746	Resectable	Gemcitabine and erlotinib	Phase II Single arm	OS	Yes (gene expression, polymorphism and laboratory biomarker analysis)
NCT01726582	ResectableBorderline resectable	Targeted CT prior and after surgery guided by molecular profilingCRT before surgery	Phase II Single arm	R0 resection rate	Yes (see: http://www.mcw.edu/surgery/patientinfo/pancreatic-cancer-trial.htm)
NCT01150630	Resectable	Adjuvant vs neoadjuvant Capecitabine, cisplatine, epirubicine and gemcitabine	Phase II/III Multicenter randomized trial	Event-free survival at 1 yr	No

FOLFIRINOX: 5-Fluorouracil, folinic acid, irinotecan and oxaliplatin; CRT: Chemoradiation therapy; CT: Chemotherapy; RT: Radiation therapy; PFS: Progression free survival; OS: Overall survival.