Figitumumab in patients with refractory metastatic colorectal cancer previously treated with standard therapies: a nonrandomized, open-label, phase II trial
| Autor: | Emily K. Bergsland, Federico J. Vázquez-Mazón, Rocio Garcia-Carbonero, Carlos Becerra, Jim Cassidy, Donghua Yin, Tim Maughan, Manuel Gallén Castillo, Anne L. Thomas, Stephanie Green, Ramon Salazar, Timothy Iveson |
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| Rok vydání: | 2014 |
| Předmět: |
Adult
Male Oncology Cancer Research medicine.medical_specialty Colorectal cancer medicine.drug_class Antineoplastic Agents Toxicology Monoclonal antibody Cohort Studies chemistry.chemical_compound Refractory Internal medicine medicine Humans Pharmacology (medical) In patient Neoplasm Metastasis Survival analysis Aged Neoplasm Staging Aged 80 and over Pharmacology biology business.industry Antibodies Monoclonal Middle Aged medicine.disease Survival Analysis Clinical trial Figitumumab chemistry biology.protein Female Antibody Colorectal Neoplasms business |
| Zdroj: | Cancer Chemotherapy and Pharmacology. 73:695-702 |
| ISSN: | 1432-0843 0344-5704 |
| DOI: | 10.1007/s00280-014-2391-2 |
| Popis: | Figitumumab (CP-751,871) is a human IgG2 monoclonal antibody that binds and down-regulates insulin-like growth factor receptor-1 (IGF-1R) and inhibits activation of this receptor by IGF-1 and IGF-2. This nonrandomized, open-label, single-arm, phase II trial evaluated the antitumor activity and safety of figitumumab in patients with metastatic colorectal cancer that was refractory to ≥2 systemic therapies.Cohorts A and B received intravenous figitumumab 20 and 30 mg/kg in 3-week cycles, respectively. Both received loading doses (20 or 30 mg/kg) on days 1 and 2 of cycle 1. The primary endpoint was 6-month survival (null hypothesis for each cohort, H0: p6 mo surv = 0.45). Secondary endpoints included progression-free survival (PFS), overall survival (OS), objective response, safety, and pharmacokinetics.A total of 168 patients (Cohort A, n = 85; Cohort B, n = 83) received figitumumab. Estimated 6-month survival was 49.4 % (95 % CI 38.8-60.0) in Cohort A and 44.1 % (95 % CI 33.4-54.9) in Cohort B. Median OS was 5.8 and 5.6 months, respectively; median PFS was 1.4 months in both cohorts. No objective partial or complete responses occurred. The respective rates of treatment discontinuation due to treatment-related adverse events (AEs) were 5 and 7 %. The most common grade 3/4 nonhematologic AEs in both cohorts were hyperglycemia and asthenia. No grade 4 hematologic laboratory abnormalities occurred. Most deaths were reported as due to progressive disease; none were due to figitumumab.Six-month survival data do not support further study of figitumumab 20 or 30 mg/kg in this patient population. |
| Databáze: | OpenAIRE |
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