Phase I clinical trial of allogeneic mixed lymphocyte culture (cytoimplant) delivered by endoscopic ultrasound-guided fine-needle injection in patients with advanced pancreatic carcinoma

BACKGROUND, To the authors' knowledge, there are no other published clinica l studies that have employed either systemic or local biologic response mod ifiers in the treatment of patients with pancreatic carcinoma. The purpose of this study was to determine the feasibility and safety of allogeneic mix ed lymphocyte culture (cytoimplant) delivered by endoscopic ultrasound (EUS )-guided fine-needle injection (FNI) in patients with advanced pancreatic c arcinoma. METHODS, Eight patients with unresectable adenocarcinoma of the pancreas we re enrolled: 4 patients in Stage II, 3 in Stage III, and 1 in Stage TV. Cyt oimplants were delivered locally into the tumor using a novel EUS-guided FN I technique. Escalating doses of 3, 6, or 9 billion cells were implanted in to the pancreatic tumor by a single EUS-guided FNI. Toxicity (modified Nati onal Cancer Institute criteria) was assessed at Day 1, Week 1, and Months 1 and 3. Clinical endpoints included Karnofsky performance status (KPS), CA 19-9, tumor response (computed tomography and/or EUS), and survival with fo llow-up examinations and imaging tests on months 3, 6, 9, 12, and 24. RESULTS. There were no bone marrow, hemorrhagic, infectious, renal, cardiac , or pulmonary toxicities. There were 3 transient Grade 3 gastrointestinal toxicities, and 3 patients had transient episodes of hyperbilirubinemia tha t were reversed by replacement of biliary stents. Seven of 8 patients (86%) experienced low grade fever that responded to acetaminophen, and all fever was resolved within the first 4 weeks. There were no procedure-related com plications. There were 2 partial responses and 1 minor response, with a med ian survival of 13.2 months. CONCLUSIONS, A single injection of cytoimplant immunotherapy by EUS-guided FNI appears to be feasible and is not associated with substantial toxicity. Cancer 2000;88:1325-35. (C) 2000 American Cancer Society.