title: Primary mFOLFOX6 plus bevacizumab without resection of the primary tumor for patients presenting with surgically unresectable metastatic colon cancer and an intact asymptomatic colon cancer: definitive analysis of NSABP trial C-10.
abstract: OBJECTIVE
  Major concerns surround combining chemotherapy with bevacizumab in patients with colon cancer presenting with an asymptomatic intact primary tumor (IPT) and synchronous yet unresectable metastatic disease. Surgical resection of asymptomatic IPT is controversial.
  
  
  METHODS
  Eligibility for this prospective, multicenter phase II trial included Eastern Cooperative Oncology Group (ECOG) performance status 0 to 1, asymptomatic IPT, and unresectable metastases. All received infusional fluorouracil, leucovorin, and oxaliplatin (mFOLFOX6) combined with bevacizumab. The primary end point was major morbidity events, defined as surgical resection because of symptoms at or death related to the IPT. A 25% major morbidity rate was considered acceptable. Secondary end points included overall survival (OS) and minor morbidity related to IPT requiring hospitalization, transfusion, or nonsurgical intervention.
  
  
  RESULTS
  Ninety patients registered between March 2006 and June 2009: 86 were eligible with follow-up, median age was 58 years, and 52% were female. Median follow-up was 20.7 months. There were 12 patients (14%) with major morbidity related to IPT: 10 required surgery (eight, obstruction; one, perforation; and one, abdominal pain), and two patients died. The 24-month cumulative incidence of major morbidity was 16.3% (95% CI, 7.6% to 25.1%). Eleven IPTs were resected without a morbidity event: eight for attempted cure and three for other reasons. Two patients had minor morbidity events only: one hospitalization and one nonsurgical intervention. Median OS was 19.9 months (95% CI, 15.0 to 27.2 months).
  
  
  CONCLUSIONS
  This trial met its primary end point. Combining mFOLFOX6 with bevacizumab did not result in an unacceptable rate of obstruction, perforation, bleeding, or death related to IPT. Survival was not compromised. These patients can be spared initial noncurative resection of their asymptomatic IPT.
authors.affiliation: National Surgical Adjuvant Breast and Bowel Project, Pittsburgh, PA, USA. mccahill@trinity-health.org
authors.forename: Laurence E
authors.initials: LE
authors.lastname: McCahill
authors.forename: Greg
authors.initials: G
authors.lastname: Yothers
authors.forename: Saima
authors.initials: S
authors.lastname: Sharif
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Petrelli
authors.forename: Lily Lau
authors.initials: LL
authors.lastname: Lai
authors.forename: Naftali
authors.initials: N
authors.lastname: Bechar
authors.forename: Jeffrey K
authors.initials: JK
authors.lastname: Giguere
authors.forename: Shaker R
authors.initials: SR
authors.lastname: Dakhil
authors.forename: Louis
authors.initials: L
authors.lastname: Fehrenbacher
authors.forename: Samia H
authors.initials: SH
authors.lastname: Lopa
authors.forename: Lawrence D
authors.initials: LD
authors.lastname: Wagman
authors.forename: Michael J
authors.initials: MJ
authors.lastname: O'Connell
authors.forename: Norman
authors.initials: N
authors.lastname: Wolmark
mesh_terms: D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage* / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D000068258:Bevacizumab; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D005260:Female; D005472:Fluorouracil / Q000009:adverse effects / Q000627:therapeutic use; D006471:Gastrointestinal Hemorrhage / Q000453:epidemiology; D006801:Humans; D007415:Intestinal Obstruction / Q000453:epidemiology; D007416:Intestinal Perforation / Q000453:epidemiology; D002955:Leucovorin / Q000009:adverse effects / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis / Q000188:drug therapy*; D009944:Organoplatinum Compounds / Q000009:adverse effects / Q000627:therapeutic use
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D009944:Organoplatinum Compounds; D000068258:Bevacizumab; D002955:Leucovorin; D005472:Fluorouracil