EUS-FNI of AdV-TK Gene Transfer Therapy in Combination with Chemoradiation Therapy for Locally Advanced Pancreatic Cancer: A Case Report

Background:

Adenovirus-mediated delivery of the herpes simplex virus thymidine kinase (AdV-TK) into tumor cells with the administration of an antiherpetic prodrug has shown in vitro and in vivo efficacy in different animal models, and has been applied to various malignancies (prostate, brain, ovarian, hepatocellular) in Phase I/II trials. After injection of the AdV-TK into tumor cells, the thymidine kinase is replicated and converts prodrug (valacyclovir) into toxic nucleotide analogues which are incorporated into DNA during cell division, terminating cell division and leading to cell death. A potential secondary benefit is the ‘by-stander’ effect by which the AdV-TK may induce the induction of the host antitumor immune response.

Aim:

To evaluate the feasibility and safety in the delivery of AdV-TK by endoscopic ultrasound with fine needle injection (EUS-FNI) into patients with locally advanced pancreatic cancer.

Methods:

This study was approved by the City of Hope Institutional Review Board. The patient is a 62 year old female with a 2.8cm head of the pancreas cancer with encasement of the superior mesenteric artery. The head of the pancreas cancer was divided into four quadrants. EUS-FNI was performed using a 22 gauge needle with AdV-TK (1×1012 vector particle/ml) a total of 0.5ml was injected into each quadrant for a total of 2ml. A second injection using the same protocol was performed two weeks later. Valacyclovir caplets at a dose of 2 grams orally three times per day was administered for 14 days after each AdV-tk injection. The patient commenced with radiation treatment with 4500 cGy in 25 equal treatment fractions applied over 35 days using helical tomotherapy with concurrent continuous infusion of 5-fluorouracil at 200mg/m² per day throughout the course of radiation treatement.

Results:

The initial CT-abdomen pelvis revealed a 2.8cm pancreatic head cancer with encasement of the superior mesenteric artery. After treatment, a followup CT two months later showed a slight decrease in size to a diameter of 2.5mm. There was still encasement of the superior mesenteric artery and patient was not deemed a surgical candidate. There were no immediate or post procedural related complications from the EUS-FNI of the AdV-TK.

Conclusion:

In this patient with locally advanced pancreatic cancer, EUS-FNI of AdV-TK was safe and feasible. Further studies are needed to validate the safety and efficacy of EUS-FNI of AdV-TK in patients with locally advanced pancreatic cancer in combination with chemoradiation.