A phase II trial of bevacizumab plus everolimus for patients with refractory metastatic colorectal cancer.
Journal Article (Journal Article)
PURPOSE: For patients with metastatic colorectal cancer (mCRC), no standard therapy exists after progression on 5-fluorouracil, oxaliplatin, irinotecan, bevacizumab, and cetuximab or panitumumab. Preclinical data demonstrated that combined vascular endothelial growth factor and mammalian target of rapamycin inhibition has greater antiangiogenic and antitumor activity than either monotherapy. A phase I study of bevacizumab plus everolimus demonstrated that the combination is safe; activity was seen in several patients with refractory mCRC. METHODS: Fifty patients with refractory mCRC were enrolled and received bevacizumab at 10 mg/kg every 2 weeks and everolimus at 10 mg orally daily. RESULTS: Of the 50 patients enrolled, the median age was 56 years and the median number of prior regimens was four. Forty-seven patients (96%) had prior bevacizumab exposure and 42 patients (84%) had documented progression on prior bevacizumab-based therapy. Forty-nine patients were evaluable for response; eight patients had minor responses (16%) and an additional 15 patients (30%) had stable disease (SD). No complete or partial responses were seen. The median progression-free survival interval was 2.3 months; however, 26% of patients achieved prolonged SD for ≥6 months, and three patients (6%) were on study for >1 year. The median overall survival duration was 8.1 months. The most common grade 1-2 toxicities were mucositis (68%) and hyperlipidemia (64%). Clinically significant grade ≥3 toxicities included hypertension (14%), fistula/abscess/perforation (8%), mucositis (6%), and hemorrhage (2%). CONCLUSIONS: Bevacizumab plus everolimus is generally tolerable but may have risks related to mucosal damage and/or wound healing. Bevacizumab plus everolimus appears to have modest activity in refractory mCRC in patients.
Full Text
Duke Authors
- Blobe, Gerard Conrad
- Hsu, Shiao-Wen David
- Hurwitz, Herbert Ira
- Morse, Michael Aaron
- Pang, Herbert
- Sutton, Linda Marie
- Uronis, Hope Elizabeth
- Zafar, Syed Yousuf
Cited Authors
- Altomare, I; Bendell, JC; Bullock, KE; Uronis, HE; Morse, MA; Hsu, SD; Zafar, SY; Blobe, GC; Pang, H; Honeycutt, W; Sutton, L; Hurwitz, HI
Published Date
- 2011
Published In
Volume / Issue
- 16 / 8
Start / End Page
- 1131 - 1137
PubMed ID
- 21795432
Pubmed Central ID
- PMC3228156
Electronic International Standard Serial Number (EISSN)
- 1549-490X
Digital Object Identifier (DOI)
- 10.1634/theoncologist.2011-0078
Language
- eng
Conference Location
- England