Phase I and pharmacokinetic study of etaracizumab (Abegrin™), a humanized monoclonal antibody against αvβ3 integrin receptor, in patients with advanced solid tumors
| Autor: | Karina Vera, Sandrine Faivre, Karen Kaucic, Luz Hammershaimb, Michel Marty, Eric Raymond, Catherine Delbaldo, Stéphanie Lozahic |
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| Rok vydání: | 2007 |
| Předmět: |
Adult
Diarrhea Male medicine.medical_specialty Vomiting Angiogenesis Inhibitors Pharmacology Antibodies Monoclonal Humanized Severity of Illness Index Gastroenterology Pharmacokinetics Etaracizumab Neoplasms Internal medicine Humans Medicine Pharmacology (medical) Infusions Intravenous Adverse effect Aged business.industry Antibodies Monoclonal Anemia Nausea Leukopenia Middle Aged Integrin alphaVbeta3 medicine.disease Anorexia Discontinuation Kinetics Treatment Outcome Oncology Vitaxin Female Chills medicine.symptom business Hyponatremia Hypophosphatemia medicine.drug |
| Zdroj: | Investigational New Drugs. 26:35-43 |
| ISSN: | 1573-0646 0167-6997 |
| Popis: | This study assessed the safety, immunogenicity, and pharmacokinetics of etaracizumab, a monoclonal antibody directed against the alphavbeta3 integrin, in patients with advanced malignancies. Four cohorts of four patients received escalating dose of etaracizumab as a 30-min intravenous infusion, first as a single test dose, followed-up 2-5 weeks later by weekly doses. Sixteen patients with advanced solid tumors received a total of 309 cycles of etaracizumab at doses ranging 1-6 mg/kg. The mean number of weekly infusions was 19 (ranging 5-53). Frequently reported adverse events were grades 1-2 asthenia (15 patients) and infusion reactions (9 patients). At 1 mg/kg, one patient experienced grade 3 chills with the first infusion. Other grade 3 toxicities included reversible hyponatremia, hypophosphatemia and hyponatremia in one patient each at 1, 4 and 6 mg/kg, respectively. No patient experienced treatment delay/discontinuation due to an adverse event. The half-life of etaracizumab ranged 49-180 h with a nonlinear increase in terminal half-life with increasing doses. There was no objective response but five patients experienced a stable disease of6-month duration. Etaracizumab was well-tolerated at doses up to 6 mg/kg with no evidence of immunogenicity. The safety profile of etaracizumab warrants further exploration in ongoing phase I/II trials. |
| Databáze: | OpenAIRE |
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