We found a match
Your institution may have rights to this item. Sign in to continue.
- Title
Phase I/II Trial of Imatinib and Bevacizumab in Patients With Advanced Melanoma and Other Advanced Cancers.
- Authors
Flaherty, Keith T.; Hamilton, Betty K.; Rosen, Mark A.; Amaravadi, Ravi K.; Schuchter, Lynn M.; Gallagher, Maryann; Chen, Helen; Sehgal, Chandra; O'Dwyer, Peter J.
- Abstract
Background. Vascular endothelial growth factor and platelet-derived growth factor signaling in the tumor microenviron-ment appear to cooperate in promoting tumor angiogenesis. Patients and Methods. We conducted a phase I trial combining bevacizumab (i.v. every 2 weeks) and imatinib (oral daily). Once a recommended phase II dose combination was established, a phase II trial was initiated in patients with metastatic melanoma. A Simon 2-stage design was used with 23 patients required in the first stage and 41 patients in total should the criteria to proceed be met. We required that 50% of the patients be progression-free at 16 weeks. Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and power Doppler ultrasonography were performed in patients with metastatic tumors amenable to imaging with these methods at baseline and after 4 weeks. Results. A total of 17 patients were accrued to 4 dose and combination levels. Bevacizumab 10 mg/kg every 2 weeks could be safely combined with imatinib 800 mg daily. Common toxicities included fatigue, nausea, vomiting, edema, protein-uria, and anemia, but were not commonly severe. A total of 23 patients with metastatic melanoma (48% with American Joint Commission on Cancer stage M1c; median age, 63 years) were enrolled in the first stage of phase II. The 16-week progression-free survival rate was 35%, leading to termination of phase II after the first stage. In the small subset of patients who remained on study with lesions evaluable by DCE-MRI, significant decreases in tumor vascular permeability were noted, despite early disease progression using the Response Evaluation Criteria In Solid Tumors. Conclusion. Bevacizumab and imatinib can be safely combined at the maximum doses used for each agent. We did not observe significant clinical activity with this regimen in melanoma patients.
- Subjects
COMBINATION drug therapy; CLINICAL trials; COMPUTED tomography; CONFIDENCE intervals; STATISTICAL correlation; MAGNETIC resonance imaging; MELANOMA; RESEARCH funding; TUMORS; ULTRASONIC imaging; IMATINIB; BEVACIZUMAB; CONTRAST media; DATA analysis software; DESCRIPTIVE statistics; KAPLAN-Meier estimator; PHARMACODYNAMICS
- Publication
Oncologist, 2015, Vol 20, Issue 8, p952
- ISSN
1083-7159
- Publication type
Article
- DOI
10.1634/theoncologist.2015-0108