A Phase I Study of Weekly R1507, A Human Monoclonal Antibody Insulin-like Growth Factor-I Receptor Antagonist, in Patients with Advanced Solid Tumors
| العنوان: | A Phase I Study of Weekly R1507, A Human Monoclonal Antibody Insulin-like Growth Factor-I Receptor Antagonist, in Patients with Advanced Solid Tumors |
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| المؤلفون: | Lia Gore, Terri Warren, Cinara D. McCarthy, Joseph Aisner, Amita Patnaik, S. Gail Eckhardt, Robert S. Benjamin, Razelle Kurzrock, Stephen Leong, Joseph E. Eid, Gerard Greig, Kai Habben |
| المصدر: | Clinical Cancer Research. 16:2458-2465 |
| بيانات النشر: | American Association for Cancer Research (AACR), 2010. |
| سنة النشر: | 2010 |
| مصطلحات موضوعية: | Adult, Male, Cancer Research, medicine.medical_specialty, Adolescent, Maximum Tolerated Dose, Administration, Oral, Antibodies, Monoclonal, Humanized, Gastroenterology, Receptor, IGF Type 1, Young Adult, Pharmacokinetics, Neoplasms, Internal medicine, Humans, Medicine, Tissue Distribution, Survival rate, Aged, Volume of distribution, business.industry, Antibodies, Monoclonal, Middle Aged, medicine.disease, Survival Rate, Treatment Outcome, Endocrinology, Oncology, Tolerability, Response Evaluation Criteria in Solid Tumors, Pharmacodynamics, Monoclonal, Female, business, Progressive disease |
| الوصف: | Purpose: A phase I study was conducted to evaluate the pharmacokinetics, pharmacodynamics, safety, and tolerability of R1507—a fully human IgG1 type monoclonal antibody directed against the human insulin-like growth factor-I receptor. Experimental design: Patients with advanced solid tumors were assigned to receive i.v. R1507 weekly (qW), starting with 1 mg/kg. Subsequent cohorts were dosed at 3 and then 9 mg/kg. An additional 12 patients received 9 mg/kg R1507 qW. Patients remained on the study until the development of a dose-limiting toxicity or progressive disease. Results: In total, 37 patients were treated with R1507 qW. No dose-limiting toxicities were identified and the maximum tolerated dose was not reached. The pharmacokinetics of R1507 were characterized by a slow clearance and limited volume of distribution, with an estimated elimination half-life justifying weekly administration. Serum IGF-I ligand levels increased proportionally to dose during the first 72 hours in all cohorts. R1507 was well tolerated. Two patients diagnosed with Ewing's sarcoma had partial responses of 11.5 and >26 months (ongoing at time of submission); 13 patients had stable disease; and 16 had progressive disease as best response by the Response Evaluation Criteria in Solid Tumors. Conclusion: R1507 is well tolerated and shows antitumor activity in patients with solid neoplasms, in particular Ewing's sarcoma. The recommended dose for the weekly schedule is 9 mg/kg qW. Clin Cancer Res; 16(8); 2458–65. ©2010 AACR. |
| تدمد: | 1557-3265 1078-0432 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::4cc4a9972d6870f7f3c49fb184b5ca15Test https://doi.org/10.1158/1078-0432.ccr-09-3220Test |
| رقم الانضمام: | edsair.doi.dedup.....4cc4a9972d6870f7f3c49fb184b5ca15 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15573265 10780432 |
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