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Phase II Study of Anti–Gastrin-17 Antibodies, Raised to G17DT, in Advanced Pancreatic Cancer

From the Department of Medicine, Royal Free Hospital National Health Service Trust; Department of Oncology, Royal Free and University College Medical School; Department of Surgery, The Middlesex Hospital; and Chase Farm Hospital, London, United Kingdom; and Aphton Corporation, Woodland, CA.

Address reprint requests to Martyn Caplin, MD, Centre for Gastroenterology, Royal Free Hospital National Health Service Trust, Hampstead, London NW3 2QG, United Kingdom; email: m.caplin{at}rfc.ucl.ac.uk

PURPOSE: The prognosis for advanced pancreatic cancer remains poor. Gastrin acts as a growth factor for pancreatic cancer. We describe the first study of the antigastrin immunogen G17DT in pancreatic cancer. Our aims were to determine the antibody response, safety, tolerability, and preliminary evidence of efficacy of G17DT in advanced pancreatic cancer.

PATIENTS AND METHODS: Thirty patients with advanced pancreatic cancer were immunized with three doses of either 100 µg or 250 µg of G17DT.

RESULTS: In the whole group, 20 (67%) of 30 patients produced an antibody response. The 250-µg dose resulted in a significantly greater response rate of 82% compared with 46% for the 100-µg group (P = .018). The most significant side effects, seen in three patients, were local abscess and/or fever. The median survival for the whole group from the date of the first immunization was 187 days; median survival was 217 days for the antibody responders and 121 days for the antibody nonresponders. The difference in survival between the antibody responders and nonresponders was significant (P = .0023).

CONCLUSION: Patients with advanced pancreatic cancer are able to mount an adequate antibody response to G17DT. The 250-µg dose is superior to the 100-µg dose, and it appears to be generally well tolerated. Antibody responders demonstrate significantly greater survival than antibody nonresponders. Phase III studies are currently underway in order to determine efficacy.

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