Please use this identifier to cite or link to this item: http://ahro.austin.org.au/austinjspui/handle/1/9493
Title: A Phase I dose-escalation study of sibrotuzumab in patients with advanced or metastatic fibroblast activation protein-positive cancer.
Authors: Scott, Andrew M;Wiseman, Greg;Welt, Sydney;Adjei, Alex;Lee, Fook-Thean;Hopkins, Wendie;Divgi, Chaitan R;Hanson, Lorelei H;Mitchell, Paul L R;Gansen, Denise N;Larson, Steven M;Ingle, James N;Hoffman, Eric W;Tanswell, Paul;Ritter, Gerd;Cohen, Leonard S;Bette, Peter;Arvay, Lisa;Amelsberg, Andree;Vlock, Dan;Rettig, Wolfgang J;Old, Lloyd J
Affiliation: Ludwig Institute for Cancer Research, Melbourne Tumour Biology, Austin, and Repatriation Medical Centre, 3084 Australia. ams@austin.unimelb.edu.au
Issue Date: 1-May-2003
Citation: Clinical Cancer Research : An Official Journal of the American Association For Cancer Research; 9(5): 1639-47
Abstract: The purpose of this research was to determine the safety, immunogenicity, pharmacokinetics, biodistribution, and tumor uptake of repeat infusions of a complementarity-determining region grafted humanized antibody (sibrotuzumab) directed against human fibroblast activation protein (FAP).A Phase I open-label dose escalation study was conducted in patients with cancers epidemiologically known to be FAP positive. Patients were entered into one of four dosage tiers of 5, 10, 25, or 50 mg/m(2) sibrotuzumab, administered weekly for 12 weeks, with trace labeling with 8-10 mCi of (131)I in weeks 1, 5, and 9.A total of 26 patients were entered into the trial (15 males and 11 females; mean age, 59.9 years; age range, 41-81 years). Twenty patients had colorectal carcinoma, and 6 patients had non-small cell lung cancer. A total of 218 infusions of sibrotuzumab were administered during the first 12 weeks of the study, with 24 patients being evaluable. One patient received an additional 96 infusions on continued-use phase for a total of 108 infusions over a 2-year period, and 1 patient received an additional 6 infusions on continued use. There were no objective tumor responses. Only one episode of dose-limiting toxicity was observed. Therefore, a maximum tolerated dose was not reached. Treatment-related adverse events were observed in 6 patients during the infusional monitoring period. Four of the 6 patients, 3 of whom had associated positive serum human antihuman antibody, were removed from the study because of clinical immune responses. Gamma camera images of [(131)I]sibrotuzumab demonstrated no normal organ uptake of sibrotuzumab, with tumor uptake evident within 24-48 h after infusion. Analysis of pharmacokinetics demonstrated a similar mean terminal t(1/2) of 1.4-2.6 days at the 5, 10, and 25 mg/m(2) dose levels, and with a longer mean t(1/2) of 4.9 days at the 50 mg/m(2) dose level.Repeat infusions of the humanized anti-FAP antibody sibrotuzumab can be administered safely to patients with advanced FAP-positive cancer.
Internal ID Number: 12738716
URI: http://ahro.austin.org.au/austinjspui/handle/1/9493
URL: http://www.ncbi.nlm.nih.gov/pubmed/12738716
Type: Journal Article
Subjects: Adult
Aged
Aged, 80 and over
Antibodies, Monoclonal.adverse effects.pharmacokinetics.therapeutic use
Antibodies, Monoclonal, Humanized
Antigens, Neoplasm.immunology.metabolism
Carcinoma, Non-Small-Cell Lung.blood.drug therapy.secondary
Colorectal Neoplasms.blood.drug therapy.secondary
Dose-Response Relationship, Drug
Female
Follow-Up Studies
Gelatinases
Humans
Infusions, Intravenous
Iodine Radioisotopes
Lung Neoplasms.blood.drug therapy.secondary
Male
Maximum Tolerated Dose
Membrane Proteins
Middle Aged
Radioimmunotherapy
Serine Endopeptidases.immunology.metabolism
Treatment Outcome
Tumor Markers, Biological.immunology.metabolism
Appears in Collections:Journal articles

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