Phase I Trial of Bevacizumab Plus Escalated Doses of Sunitinib in Patients With Metastatic Renal Cell Carcinoma
| Autor: | Michelle S. Ginsberg, Carlos D. Flombaum, Hani Hassoun, Patricia Fischer, Sujata Patil, Susanne Velasco, Michael Baum, Ellen A. Ronnen, Robert J. Motzer, Darren R. Feldman, Nicole Ishill |
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| Rok vydání: | 2009 |
| Předmět: |
Adult
Male Vascular Endothelial Growth Factor A Cancer Research medicine.medical_specialty Indoles Bevacizumab medicine.drug_class Urology Antibodies Monoclonal Humanized Tyrosine-kinase inhibitor Cohort Studies chemistry.chemical_compound Renal cell carcinoma Antineoplastic Combined Chemotherapy Protocols Sunitinib medicine Carcinoma Humans Pyrroles Carcinoma Renal Cell Aged Dose-Response Relationship Drug business.industry Antibodies Monoclonal Middle Aged medicine.disease Kidney Neoplasms Surgery Vascular endothelial growth factor Oncology chemistry Female business Kidney cancer medicine.drug Kidney disease |
| Zdroj: | Journal of Clinical Oncology. 27:1432-1439 |
| ISSN: | 1527-7755 0732-183X |
| DOI: | 10.1200/jco.2008.19.0108 |
| Popis: | Purpose Both bevacizumab and sunitinib target the vascular endothelial growth factor pathway and demonstrate activity against advanced renal cell carcinoma (RCC). In this phase I study, the maximum-tolerated dose (MTD) and safety of sunitinib in combination with bevacizumab were examined in patients with advanced RCC. Patients and Methods Three cohorts of three to six patients were treated with escalated doses of daily oral sunitinib (ie, 25 mg, 37.5 mg, 50 mg) for 4 weeks followed by a 2-week break and with fixed doses of bevacizumab (10 mg/kg) intravenously once every 2 weeks. Dose-limiting toxicities (DLTs) were assessed during the first cycle to determine the MTD, and an expanded cohort was treated to obtain additional safety information. Results Of 26 study participants, 25 received treatment at one of three dose levels. Grade 4 hemorrhage, identified as a DLT, occurred in one patient in each of cohorts 2 and 3. The MTD was determined to be sunitinib 50 mg/bevacizumab 10 mg/kg, but chronic therapy at this dose level frequently resulted in grades 3 to 4 hypertension and hematologic and vascular toxicities. Overall, 48% of patients discontinued treatment because of adverse events. One complete and 12 partial responses were observed, which provided an objective response rate of 52%. Conclusion In this phase I trial of patients with metastatic RCC, the combination of sunitinib and bevacizumab caused a high degree of hypertension and vascular and hematologic toxicities at the highest dose level. We do not plan to pursue additional study of this regimen at these doses in patients with RCC. |
| Databáze: | OpenAIRE |
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