Randomised Phase I/II trial assessing the safety and efficacy of radiolabelled anti-carcinoembryonic antigen I(131) KAb201 antibodies given intra-arterially or intravenously in patients with unresectable pancreatic adenocarcinoma.

BACKGROUND: Advanced pancreatic cancer has a poor prognosis, and the current standard of care (gemcitabine based chemotherapy) provides a small survival advantage. However the drawback is the accompanying systemic toxicity, which targeted treatments may overcome. This study aimed to evaluate the safety and tolerability of KAb201, an anti-carcinoembryonic antigen monoclonal antibody, labelled with I(131) in pancreatic cancer (ISRCTN 16857581). METHODS: Patients with histological/cytological proven inoperable adenocarcinoma of the head of pancreas were randomised to receive KAb 201 via either the intra-arterial or intravenous delivery route. The dose limiting toxicities within each group were determined. Patients were assessed for safety and efficacy and followed up until death. RESULTS: Between February 2003 and July 2005, 25 patients were enrolled. Nineteen patients were randomised, 9 to the intravenous and 10 to the intra-arterial arms. In the intra-arterial arm, dose limiting toxicity was seen in 2/6 (33%) patients at 50 mCi whereas in the intravenous arm, dose limiting toxicity was noted in 1/6 patients at 50 mCi, but did not occur at 75 mCi (0/3).The overall response rate was 6% (1/18). Median overall survival was 5.2 months (95% confidence interval = 3.3 to 9 months), with no significant difference between the intravenous and intra-arterial arms (log rank test p = 0.79). One patient was still alive at the time of this analysis. CONCLUSION: Dose limiting toxicity for KAb201 with I(131) by the intra-arterial route was 50 mCi, while dose limiting toxicity was not reached in the intravenous arm.

CT and pathologic assessment of prospective nodal staging in patients with ductal adenocarcinoma of the head of the pancreas.

OBJECTIVE: The aim of our study was to compare the assessment of peripancreatic lymph nodes using CT with the gold standard of detailed histopathologic assessment of resected specimens in patients with pancreatic ductal adenocarcinoma. SUBJECTS AND METHODS: Sixty-two patients with presumed pancreatic carcinoma were prospectively studied with dual-phase contrast-enhanced helical CT, and images were interpreted in consensus by three radiologists. Complete surgical resection was performed in 28 patients. A detailed nodal classification system was used for radiologic, surgical, and pathologic staging in the nine patients whose final diagnosis at histology was pancreatic ductal adenocarcinoma. RESULTS: Forty lymph nodes were prospectively identified on CT in these nine patients. Two of 23 nodes (9%) measuring less than 5 mm in the short-axis diameter were malignant, four of 11 nodes (36%) measuring 5-10 mm were malignant, and one of six nodes (17%) larger than 10 mm was malignant. Using a short-axis diameter of greater than 10 mm as the criterion for nodal involvement, we found a sensitivity of 14% (1/7) and a specificity of 85% (28/33), with a positive predictive value of 17% (1/6), a negative predictive value of 82% (28/34), and an overall accuracy of 73% (29/40). Ovoid nodal shape, clustering of nodes, and the absence of a fatty hilum were not useful predictors of malignancy on CT. CONCLUSION: In resectable pancreatic ductal adenocarcinoma, CT is not accurate overall for the prediction of nodal involvement. In a patient with presumed pancreatic carcinoma that is considered to be resectable, the depiction on CT of peripancreatic nodes should not prevent attempted curative resection.