RANDOMISED PHASE I/II TRIAL ASSESSING THE SAFETY AND EFFICACY OF RADIO LABELLED ANTI-CARCINOEMBRYONIC ANTIGEN ANTIBODIES IN UNRESECTABLE PANCREATIC CANCER

Background: Advanced pancreatic cancer has a very poor prognosis and novel treatments may improve the outlook. Objectives: This study aimed to evaluate the safety and tolerability of KAb 201, an iodine 131 (I131) labelled anti-carcinoembryonic antigen (CEA) monoclonal antibody. Pharmacokinetics, antigenicity and efficacy of KAb 201 were also assessed. Patients and Methods: Patients with histologically/cytologically proven, advanced adenocarcinoma of the head of pancreas were randomised to either the intra-arterial (i.a.) or intravenous (i.v.) arms. Following a positive dosimetry scan, a therapeutic dose of Kab 201 was given. Patients were assessed for safety and efficacy and followed up until death. Results: Between February 2003 and July 2005, 24 patients were enrolled. Nineteen patients (median age 60 years, range 47-67 years; median Karnofsky Performance Status [KPS] 80, range 70-100; stage IVa = 8; stage IV b = 11) were randomised, 9 to the i.v and 10 to the i.a. arm. Eighteen patients received the treatment dose (one patient had a negative dosimetry scan). In the i.a. arm, dose limiting toxicity (DLT) was seen at in 2/6 (33%) patients at 50 mCi whereas in the i.v. arm, DLT was noted in 1/6 (17%) patients at 50mCi, but did not occur at 75 mCi (0/3). Median overall survival was 5.6 months (95% confidence intervals = 3.7 - 9 months) from study entry, with no significant difference between the i.v and i.a arms on Kaplan Meier analysis (log rank p = 0.81). One patient is alive at the time of this analysis, at 15 months. Patients with KPS scores of 90/100 survived longer than those with KPS of 70/80 (log rank p = 0.067). Conclusions: Dose limiting toxicity for KAb 201 by the i.a. route was 50 mCi, while DLT was not reached in the i.v. arm. A good performance status was associated with a survival advantage.