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 clinical studies that have employed either systemic or local biologic response modifiers in the treatment of patients with pancreatic carcinoma. The purpose of this study was to determine the feasibility and safety of allogeneic mixed lymphocyte culture (cytoimplant) delivered by endoscopic ultrasound (EUS)-guided fine-needle injection (FNI) in patients with advanced pancreatic carcinoma.


METHODS
Eight patients with unresectable adenocarcinoma of the pancreas were enrolled: 4 patients in Stage II, 3 in Stage III, and 1 in Stage IV. Cytoimplants were delivered locally into the tumor using a novel EUS-guided FNI technique. Escalating doses of 3, 6, or 9 billion cells were implanted into the pancreatic tumor by a single EUS-guided FNI. Toxicity (modified National 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 follow-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 that 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 complications. There were 2 partial responses and 1 minor response, with a median 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.
Chang
K J
KJ
Gastrointestinal Oncology, Department of Medicine, University of California-Irvine, Chao Family Comprehensive Cancer Center, Orange, California 92868, USA.
Nguyen
P T
PT
Thompson
J A
JA
Kurosaki
T T
TT
Casey
L R
LR
Leung
E C
EC
Granger
G A
GA
D000230:Adenocarcinoma / Q000473:pathology / Q000628:therapy*; D000368:Aged; D000369:Aged, 80 and over; D019160:Endosonography; D005240:Feasibility Studies; D005260:Female; D005500:Follow-Up Studies; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects / Q000379:methods; D006801:Humans; D006932:Hyperbilirubinemia / Q000209:etiology; D007155:Immunologic Factors / Q000008:administration & dosage / Q000627:therapeutic use; D015552:Injections, Intralesional / Q000295:instrumentation; D017567:Karnofsky Performance Status; D008214:Lymphocytes; D008297:Male; D008875:Middle Aged; D009339:Needles; D009367:Neoplasm Staging; D010190:Pancreatic Neoplasms / Q000473:pathology / Q000628:therapy*; D012074:Remission Induction; D012449:Safety; D015996:Survival Rate; D014057:Tomography, X-Ray Computed; D014184:Transplantation, Homologous; D018084:Ultrasonography, Interventional
D007155:Immunologic Factors