title: Improved Survival with Anti-VEGF Therapy in the Treatment of Unresectable Appendiceal Epithelial Neoplasms.
abstract: BACKGROUND
  Currently, cytoreductive surgery and hyperthermic intraperitoneal chemotherapy are accepted treatments for surgically resectable appendiceal epithelial neoplasms. However, for nonsurgical candidates, systemic treatment may be considered. The purpose of this analysis was to determine the benefit of biologic therapy (anti-vascular endothelial growth factor and anti-epidermal growth factor receptor) in addition to systemic chemotherapy in this select patient population.
  
  
  METHODS
  The MD Anderson Cancer Center tumor registry was retrospectively reviewed for systemic treatment-naive appendiceal epithelial neoplasm patients registered between January 2000 to July 2007 for prior cytoreductive surgery and hyperthermic intraperitoneal chemotherapy status, histologic grade, signet ring pathology, systemic chemotherapy, biologic therapy, tumor markers (carcinoembryonic antigen, carbohydrate antigen [CA] 125, and/or CA19-9), progression-free survival (PFS), overall survival (OS), and disease control rate. Kaplan-Meier method, log-rank, and Cox proportional hazard regression models were used for statistical analysis.
  
  
  RESULTS
  A total of 353 patients were identified; 130 patients met the inclusion criteria. Fifty-nine patients received biologic therapy. The use of the anti-vascular endothelial growth factor (VEGF) agent bevacizumab improved both OS (42 months vs. 76 months, hazard ratio 0.49 [95 % confidence interval 0.25-0.94] P = 0.03) and PFS (4 months vs. 9 months, hazard ratio 0.69 [95 % confidence interval 0.47-0.995], P = 0.047) for all histologic subtypes. Moderately differentiated tumors had an improved PFS relative to well-differentiated tumors, 9 months versus 3 months (P = 0.05).
  
  
  CONCLUSIONS
  Bevacizumab in combination with chemotherapy appears to play a role in surgically unresectable appendiceal epithelial neoplasm patients, with an improvement in PFS and OS. Anti-VEGF agents should be strongly considered in the management of patients with higher-grade appendiceal epithelial neoplasms who are suboptimal candidates for surgical resection.
authors.affiliation: Department of Internal Medicine, Baylor College of Medicine, Houston, TX, USA.
authors.forename: J H
authors.initials: JH
authors.lastname: Choe
authors.forename: M J
authors.initials: MJ
authors.lastname: Overman
authors.forename: K F
authors.initials: KF
authors.lastname: Fournier
authors.forename: R E
authors.initials: RE
authors.lastname: Royal
authors.forename: A
authors.initials: A
authors.lastname: Ohinata
authors.forename: S
authors.initials: S
authors.lastname: Rafeeq
authors.forename: K
authors.initials: K
authors.lastname: Beaty
authors.forename: J K
authors.initials: JK
authors.lastname: Phillips
authors.forename: R A
authors.initials: RA
authors.lastname: Wolff
authors.forename: P F
authors.initials: PF
authors.lastname: Mansfield
authors.forename: C
authors.initials: C
authors.lastname: Eng
mesh_terms: D002288:Adenocarcinoma, Mucinous / Q000188:drug therapy* / Q000556:secondary / Q000601:surgery; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D001063:Appendiceal Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D000068258:Bevacizumab / Q000008:administration & dosage; D018395:CA-19-9 Antigen / Q000097:blood; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives; D000069287:Capecitabine / Q000008:administration & dosage; D002272:Carcinoembryonic Antigen / Q000097:blood; D018279:Carcinoma, Signet Ring Cell / Q000188:drug therapy* / Q000556:secondary / Q000601:surgery; D000068818:Cetuximab / Q000008:administration & dosage; D002945:Cisplatin / Q000008:administration & dosage; D065426:Cytoreduction Surgical Procedures; D018572:Disease-Free Survival; D066246:ErbB Receptors / Q000037:antagonists & inhibitors; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D000077146:Irinotecan; D002955:Leucovorin / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D010534:Peritoneal Neoplasms / Q000188:drug therapy* / Q000556:secondary / Q000601:surgery; D011553:Pseudomyxoma Peritonei / Q000188:drug therapy* / Q000601:surgery; D012189:Retrospective Studies; D015996:Survival Rate; D047368:Tumor Burden; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors
chemical_list: D018395:CA-19-9 Antigen; D002272:Carcinoembryonic Antigen; D009944:Organoplatinum Compounds; D042461:Vascular Endothelial Growth Factor A; D000068258:Bevacizumab; D000069287:Capecitabine; D000077146:Irinotecan; D066246:ErbB Receptors; D000068818:Cetuximab; D002945:Cisplatin; D002955:Leucovorin; D005472:Fluorouracil; D002166:Camptothecin