Role of Fluorouracil, Doxorubicin, and Streptozocin Therapy in the Preoperative Treatment of Localized Pancreatic Neuroendocrine Tumors

Introduction: 5-Fluorouracil, doxorubicin, and streptozocin (FAS) leads to a 39 % response rate in advanced pancreatic neuroendocrine tumors (pNETs). We sought to validate our hypothesis that preoperative FAS may facilitate resection of locoregionally advanced pNETs by reducing the anatomic extent of the primary tumor. Patients: All patients who received FAS between 2000 and 2012 as initial therapy for a localized pNET were reviewed. Tumor size and vascular relationships were compared on pretreatment and posttreatment imaging studies to quantify treatment response. Results: Twenty-nine patients received a median 4 cycles of FAS (range 2–15). Rates of RECIST progressive disease (PD), stable disease (SD), and partial response (PR) were 3, 90, and 7 %, respectively. An interface was observed between the tumor and a major mesenteric artery and/or vein in 19 (66 %) and 24 (83 %) patients, respectively; after therapy with FAS, 17 (59 %) and 22 (76 %) had persistent interface with artery and/or vein. Fourteen (48 %) patients underwent pancreatectomy, 7 (50 %) required vascular management, and 9 (64 %) operations were R0. The median overall survival of unresected and resected patients was 41 months (95 % CI, 16–66) and 112 months (95 % CI, 104–120) (P = 0.04). Conclusions: Although patients receiving FAS for locoregionally advanced pNETs are unlikely to progress during systemic therapy, significant “downstaging” appears uncommon.