Phase I trial of bevacizumab plus escalated doses of sunitinib in patients with metastatic renal cell carcinoma Journal Article


Authors: Motzer, R. J.; Feldman, D. R.; Baum, M. S.; Ginsberg, M. S.; Hassoun, H.; Flombaum, C. D.; Velasco, S.; Fischer, P.; Ronnen, E.; Ishill, N.; Patil, S.
Article Title: Phase I trial of bevacizumab plus escalated doses of sunitinib in patients with metastatic renal cell carcinoma
Abstract: 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. © 2009 by American Society of Clinical Oncology.
Keywords: adult; treatment response; aged; middle aged; vascular endothelial growth factor a; major clinical study; clinical trial; constipation; fatigue; neutropenia; case report; bevacizumab; sunitinib; advanced cancer; cancer combination chemotherapy; diarrhea; dose response; drug dose reduction; drug efficacy; drug safety; drug withdrawal; hypertension; hypophosphatemia; side effect; hand foot skin reaction; cancer patient; antineoplastic agent; anorexia; multiple cycle treatment; pain; sensory neuropathy; cohort studies; anemia; blood toxicity; leukopenia; mucosa inflammation; nausea; thrombocytopenia; vomiting; antineoplastic combined chemotherapy protocols; cohort analysis; weight reduction; creatinine; creatinine blood level; deep vein thrombosis; dose-response relationship, drug; kidney carcinoma; kidney neoplasms; monoclonal antibody; abdominal pain; alanine aminotransferase blood level; aspartate aminotransferase blood level; backache; coughing; drug dose escalation; drug hypersensitivity; dyspnea; fever; hyperglycemia; rash; alkaline phosphatase; aspartate aminotransferase; hyperkalemia; hypoalbuminemia; hyponatremia; blood; antibodies, monoclonal; kidney tumor; carcinoma, renal cell; vasculotropin a; peripheral edema; taste disorder; xerostomia; hypoglycemia; colitis; alkaline phosphatase blood level; heartburn; headache; maximum tolerated dose; phase 1 clinical trial; hypercholesterolemia; hyperthyroidism; hypothyroidism; indoles; pyrroles; amylase blood level; dyspepsia; triacylglycerol lipase blood level; dry skin; hematoma; indole derivative; epistaxis; proteinuria; thrombotic thrombocytopenic purpura; hypertriglyceridemia; vascular disease; low molecular weight heparin; pyrrole derivative; chronic drug administration; hemorrhoid; hypernatremia; mouth pain; oral bleeding; partial thromboplastin time
Journal Title: Journal of Clinical Oncology
Volume: 27
Issue: 9
ISSN: 0732-183X
Publisher: American Society of Clinical Oncology  
Date Published: 2009-03-20
Start Page: 1432
End Page: 1439
Language: English
DOI: 10.1200/jco.2008.19.0108
PUBMED: 19224847
PROVIDER: scopus
PMCID: PMC3655420
DOI/URL:
Notes: --- - "Cited By (since 1996): 44" - "Export Date: 30 November 2010" - "CODEN: JCOND" - "Source: Scopus"
Altmetric Score
MSK Authors
  1. Sujata Patil
    383 Patil
  2. Ellen Arielle Ronnen
    11 Ronnen
  3. Robert Motzer
    744 Motzer
  4. Michael S Baum
    20 Baum
  5. Michelle S Ginsberg
    158 Ginsberg
  6. Darren Richard Feldman
    171 Feldman
  7. Hani Hassoun
    146 Hassoun
  8. Patricia Marie Russ Fischer
    19 Fischer
  9. Nicole Marie Leoce
    86 Leoce