title: A phase II trial of bevacizumab plus everolimus for patients with refractory metastatic colorectal cancer.
abstract: OBJECTIVE
  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.
authors.affiliation: Duke University Medical Center, Durham, North Carolina, USA.
authors.forename: Ivy
authors.initials: I
authors.lastname: Altomare
authors.forename: Johanna C
authors.initials: JC
authors.lastname: Bendell
authors.forename: Karen E
authors.initials: KE
authors.lastname: Bullock
authors.forename: Hope E
authors.initials: HE
authors.lastname: Uronis
authors.forename: Michael A
authors.initials: MA
authors.lastname: Morse
authors.forename: S David
authors.initials: SD
authors.lastname: Hsu
authors.forename: S Yousuf
authors.initials: SY
authors.lastname: Zafar
authors.forename: Gerard C
authors.initials: GC
authors.lastname: Blobe
authors.forename: Herbert
authors.initials: H
authors.lastname: Pang
authors.forename: Wanda
authors.initials: W
authors.lastname: Honeycutt
authors.forename: Linda
authors.initials: L
authors.lastname: Sutton
authors.forename: Herbert I
authors.initials: HI
authors.lastname: Hurwitz
mesh_terms: D000328:Adult; D000368:Aged; D020533:Angiogenesis Inhibitors / Q000009:adverse effects / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D000068258:Bevacizumab; D015179:Colorectal Neoplasms / Q000188:drug therapy*; D018572:Disease-Free Survival; D000068338:Everolimus; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000627:therapeutic use; D008875:Middle Aged; D020123:Sirolimus / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D020533:Angiogenesis Inhibitors; D061067:Antibodies, Monoclonal, Humanized; D007166:Immunosuppressive Agents; D000068258:Bevacizumab; D000068338:Everolimus; D020123:Sirolimus