A phase I biodistribution and pharmacokinetic trial of humanized monoclonal antibody Hu3s193 in patients with advanced epithelial cancers that express the Lewis-Y antigen.
Clin Cancer Res
; 13(11): 3286-92, 2007 Jun 01.
Article
em En
| MEDLINE
| ID: mdl-17545534
ABSTRACT
PURPOSE:
We report a first-in-man trial of a humanized antibody (hu3S193) against the Le(y) antigen. EXPERIMENTALDESIGN:
Patients with advanced Le(y)-positive cancers received four infusions of hu3S193 at weekly intervals, with four dose levels (5, 10, 20, and 40 mg/m(2)). The first infusion of hu3S193 was trace labeled with Indium-111, and biodistribution, pharmacokinetics, tumor uptake, and immune response were evaluated in all patients.RESULTS:
A total of 15 patients (7 male/8 female; age range, 42-76 years; 6 breast, 8 colorectal cancer, and 1 non-small-cell lung cancer) were entered into the study. Transient grade 1 to 2 nausea and vomiting was observed following infusion of hu3S193 at the 40 mg/m(2) dose level only. There was one episode of dose-limiting toxicity with self-limiting Common Toxicity Criteria grade 3 elevated alkaline phosphatase observed in one patient with extensive liver metastases. The biodistribution of (111)In-hu3S193 showed no evidence of any consistent normal tissue uptake, and (111)In-hu3S193 uptake was observed in cutaneous, lymph node, and hepatic metastases. Hu3S193 displayed a long serum half-life (T(1/2)beta = 189.63 +/- 62.17 h). Clinical responses consisted of 4 patients with stable disease and 11 patients with progressive disease, although one patient experienced a 89% decrease in a lymph node mass, and one patient experienced inflammatory symptoms in cutaneous metastases, suggestive of a biological effect of hu3S193. No immune responses (human anti-human antibody) to hu3S193 were observed.CONCLUSION:
Hu3S193 is well tolerated and selectively targets tumors, and the long half-life and biological function in vivo of this antibody makes it an attractive potential therapy for patients with Le(y)-expressing cancers.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias Cutâneas
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Imunoterapia
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Antígenos do Grupo Sanguíneo de Lewis
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Anticorpos Monoclonais
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Neoplasias
Limite:
Adult
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Aged
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Clin Cancer Res
Ano de publicação:
2007
Tipo de documento:
Article