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.


CONCLUSIONS
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.
Sultana
Asma
A
Division of Surgery and Oncology, University of Liverpool, Liverpool, UK. asmasul@liv.ac.uk
Shore
Susannah
S
Raraty
Michael Gt
MG
Vinjamuri
Sobhan
S
Evans
Jonathan E
JE
Smith
Catrin Tudur
CT
Lane
Steven
S
Chauhan
Seema
S
Bosonnet
Lorraine
L
Garvey
Conall
C
Sutton
Robert
R
Neoptolemos
John P
JP
Ghaneh
Paula
P
D000230:Adenocarcinoma / Q000000981:diagnostic imaging* / Q000276:immunology; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology / Q000493:pharmacokinetics; D000912:Antibodies, Neoplasm / Q000096:biosynthesis / Q000276:immunology; D002272:Carcinoembryonic Antigen / Q000008:administration & dosage* / Q000009:adverse effects / Q000276:immunology; D006801:Humans; D000922:Immunotoxins / Q000008:administration & dosage* / Q000009:adverse effects / Q000276:immunology / Q000493:pharmacokinetics; D007261:Infusions, Intra-Arterial; D007262:Infusions, Intravenous; D007457:Iodine Radioisotopes / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000276:immunology / Q000532:radiotherapy*; D011859:Radiography; D016499:Radioimmunotherapy / Q000009:adverse effects / Q000379:methods*; D015996:Survival Rate
D000911:Antibodies, Monoclonal; D000912:Antibodies, Neoplasm; D002272:Carcinoembryonic Antigen; D000922:Immunotoxins; D007457:Iodine Radioisotopes