title: An open-label phase II study evaluating the safety and efficacy of ramucirumab combined with mFOLFOX-6 as first-line therapy for metastatic colorectal cancer.
abstract: BACKGROUND
  Vascular endothelial growth factor (VEGF) and VEGF receptor 2 (VEGFR-2) are believed to mediate angiogenesis in colorectal cancer (CRC). Ramucirumab (RAM; IMC-1121B) is a human IgG1 monoclonal antibody that inhibits VEGF ligand binding to VEGFR-2, inhibiting VEGFR-2 activation and signaling.
  
  
  METHODS
  Patients with metastatic CRC, Eastern Cooperative Oncology Group performance status 0-1, and adequate organ function who had not received chemotherapy for metastatic disease received RAM and the modified FOLFOX-6 regimen every 2 weeks. Endpoints included progression-free survival (PFS), objective response rate, overall survival, and safety. The sample size was based on a potentially improved median PFS from 8 months to 11 months.
  
  
  RESULTS
  Forty-eight patients received therapy. Median PFS was 11.5 months (95% confidence interval [CI]: 8.6-13.1 months). The objective response rate was 58.3% (95% CI: 43.21-72.39). The disease control rate (complete or partial response plus stable disease) was 93.8% (95% CI: 82.8-98.7). Median overall survival was 20.4 months (95% CI: 18.5-25.1 months). The most frequent grade 3-4 adverse events included neutropenia (grade 3: 33.3%; grade 4: 8.3%), hypertension (grade 3: 16.7%), and neuropathy (grade 3: 12.5%). Two patients died during the study due to myocardial infarction and cardiopulmonary arrest.
  
  
  CONCLUSIONS
  RAM may enhance the efficacy of modified FOLFOX-6 chemotherapy with an acceptable safety profile in metastatic CRC.
authors.affiliation: Hospital Universitario Virgen del Rocio, Instituto de Biomedicina de Sevilla (center affiliated with the Red Temática de Investigación Cooperativa en Cancer, Instituto Carlos III, Spanish Ministry of Science and Innovation), Sevilla, Spain;
authors.forename: Rocio
authors.initials: R
authors.lastname: Garcia-Carbonero
authors.forename: Fernando
authors.initials: F
authors.lastname: Rivera
authors.forename: Joan
authors.initials: J
authors.lastname: Maurel
authors.forename: Jean-Pierre M
authors.initials: JP
authors.lastname: Ayoub
authors.forename: Malcolm J
authors.initials: MJ
authors.lastname: Moore
authors.forename: Andres
authors.initials: A
authors.lastname: Cervantes
authors.forename: Timothy R
authors.initials: TR
authors.lastname: Asmis
authors.forename: Jonathan D
authors.initials: JD
authors.lastname: Schwartz
authors.forename: Federico
authors.initials: F
authors.lastname: Nasroulah
authors.forename: Shaila
authors.initials: S
authors.lastname: Ballal
authors.forename: Josep
authors.initials: J
authors.lastname: Tabernero
mesh_terms: D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000401:mortality; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D005472:Fluorouracil / Q000009:adverse effects / Q000627:therapeutic use; D006801:Humans; D002955:Leucovorin / Q000009:adverse effects / Q000627:therapeutic use; D009362:Neoplasm Metastasis / Q000188:drug therapy*; D009944:Organoplatinum Compounds / Q000009:adverse effects / Q000627:therapeutic use; D011485:Protein Binding / Q000187:drug effects; D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A / Q000276:immunology; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000037:antagonists & inhibitors; D000096662:Ramucirumab
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D005472:Fluorouracil; D002955:Leucovorin; D009944:Organoplatinum Compounds; D042461:Vascular Endothelial Growth Factor A; D040301:Vascular Endothelial Growth Factor Receptor-2; D000096662:Ramucirumab; C467484:VEGFA protein, human; C000588866:KDR protein, human