716 EUS Guided Intra-Tumoral Gemcitabine Therapy for Locally Advanced and Metastatic Pancreatic Cancer

Abstract

One of the biggest hurdles to progress in chemoradiotherapy of pancreatic cancer (PC) is the lack of penetration of therapeutic agents into the cancer due to tumor desmoplasia. Despite great optimism for new regimens, outcomes have not meaningfully changed and new therapies are needed to improve local control. We hypothesized that direct intratumoral injection of chemotherapy would enhance the direct drug specific effects as well as boost local radiation effect within the tumor bed. In patients with biopsy proven PC and performance status of 0-1 we sought to determine the toxicity and efficacy of EUS guided intratumoral fine needle injection (FNI) of gemcitabine when administered as one time induction therapy given prior to conventional multimodality therapy. 36 patients with locally advanced or metastatic PC underwent EUS FNI with gemcitabine (40mg/ml) after being deemed unresectable (n=34), a poor operative candidate (n=1), or after patient refusal of resection (n=1). At 4-14 days following EUS FNI, and prior to initiating standard chemoradiotherapy, a helical CT, hematology labs, hepatic and renal chemistries, and clinical follow-up were obtained to assess initial toxicity. The primary endpoint was toxicity. Secondary endpoints included time to progression, ability to downstage, and survival (6 and 12 month). We enrolled 36 PC patients (mean age 65; range 42-86 years; 19M/17F), 33 of whom had stage III/IV disease. A mean of 2.7 needle passes (range 1-4) and mean total volume of 2.5 ml (range 0.7-7.0) was injected per patient, corresponding to an intratumoral injection of 90 mg (range 28-280 mg) of gemcitabine. There were no EUS FNI procedure-related complications or grade 3 or higher adverse events associated with intratumoral therapy. Currently 16 patients are deceased with a mean survival of 6.4 mo (range 2.8-14.6). The remaining 20 patients are alive at a mean of 11.8 mo (range 4.8-18.2) following treatment initiation. Survival at 6 months and 1 year is 76% and 46% for 34 and 28 evaluable patients, respectively. Three patients initially deemed unresectable have been downstaged and undergone R0 resection. They include patients staged T3N1M0, T4N0M0, and T3N1M1 who underwent pancreatoduodenectomy, distal pancreatectomy, and pancreatoduodenectomy, respectively. In these patients, there is no evidence of disease recurrence at 10.2, 14.6, and 6.0mo, respectively. Our study suggests the feasibility and safety of intratumoral EUS FNI of gemcitabine for pancreatic cancer. These data offer promise in terms of tumor downstaging and impact on survival. Continued follow-up of current patients and additional study are needed to verify these findings and to address other key radiographic and clinical endpoints, and to refine the technique and clarify the potential role relative to standard therapy.Tabled 1StagePtsExpected Overall Survival (mo) Without Surgery based on National Cancer DatabaseStudy Patients-Deceased (n=16); Time and Death; Mean (Range)Study Patients-Alive (n=20), Duration in months: Mean (Range)IA06.8n=0n=0IB16.1n=05.2 (n=1)IIA16.2n=016.6 (n=1)IIB16.79.8 (n=1)n=0III227.26.7 (3.4-14.6) (n=12)12.2 (n=10)IV112.55.0 (n=3)10.7 (n=8) Open table in a new tab