Endoscopic ultrasound-guided injectable therapy for pancreatic cancer: A systematic review

Table 1 Characteristics of published clinical studies using endoscopic ultrasound-guided fine-needle injection for pancreatic ductal adenocarcinoma

Ref.	Disease	Country	No. of subjects, No. of groups	Study type	EUS-FNI injectable agent	Type of therapy	Aes	Tumor response	Median survival
Chang et al[17], 2000	Unresectable PDAC	United States	8, single arm	Phase I	Allogeneic mixed lymphocyte culture	Immunotherapy	DLT-0	Partial remission 25%, minor response 12.5%	13.2 mo (OS)
Irisawa et al[21], 2007	Unresectable PDAC refractory to gemcitabine	Japan	7, single arm	Pilot clinical study	Dcs	Immunotherapy	Aes-0	Mixed response 28.6%, stable disease 28.6%	9.9 mo (OS)
Hirooka et al[22], 2009	LAPC	Japan	5, single arm	Phase I	OK-432-pulsed dcs	Immunotherapy	Grade 3 or 4 aes-0	Effective response 60% (partial remission 20%, stable disease 40%)	15.9 mo (OS)
Endo et al[24], 2012	Resectable PDAC	Japan	24, two arms	Phase I	Idcs and OK-432	Immunotherapy	Grade 3 aes-1	NA	No difference
Hirooka et al[25], 2017	LAPC	Japan	15, single arm	Phase I/II	Zoledronate-pulsed dcs	Immunotherapy	DLT-0 (grade 3 aes-4)	Stable disease 46.7%	11.5 mo (OS)
Levy et al[27], 2017	Unresectable PDAC	United States	36, single arm	Prospective non-randomized	Gemcitabine	Chemotherapy	Aes-0	Partial response 25%, stable disease 57%	10.4 mo (OS)
Hecht et al[31], 2003	Unresectable PDAC without liver metastasis	United States	21, single arm	Phase I/II	ONYX-015	Viral therapy	Aes-8 (four related to the virus and four to the injection technique)	Partial response 10%, stable disease 38%	7.5 mo (OS)
Hecht et al[9], 2012	LAPC	United States	50, single arm	Phase I/II	Tnferade Biologic	Viral therapy	DLT-3	Complete response 2%, partial response 6%, minor response 8%, stable disease 24%	297 d (OS)
Herman et al[33], 2013	LAPC	United States	304, two arms	Randomized phase III	Tnferade Biologic	Viral therapy	No difference in grade 3 to 4 aes	No difference	10.0 mo (OS) for both arms
Hirooka et al[35], 2018	LAPC	Japan	12, single arm	Phase I	HF-10	Viral therapy	DLT-0, Serious aes-2, Grade 3 aes-5	Effective response 78%	5.5 mo (OS)
Lee et al[36], 2020	LAPC	South Korea	9, single arm	Phase I	Ad5-DS	Viral therapy	DLT-0	Overall response 11%, disease control rate 100%	11.4 mo (PFS)
Nishimura et al[40], 2018	Unresectable PDAC	Japan	6, single arm	Prospective non-randomized	STNM01	RNA oligonucleotide	Aes-0	NA	5.8 mo (OS)
Hanna et al[42], 2012	Unresectable PDAC	United States, Israel	6, single arm	Phase I/IIA	BC-819	DNA plasmid	DLT-1	Overall response 33.3% and 66.7% in the two dose cohorts respectively	100% and 66.7% (six-month survival) in the two dose cohorts

AEs: Adverse events; NA: Not available; PDAC: Pancreatic ductal adenocarcinoma; LAPC: Locally advanced pancreatic cancer; iDC: Immature dendritic cell; DLT: Dose-limiting toxicity; OS: Overall survival; PFS: Progression-free survival.