title: A Phase II Study of FOLFOXIRI Plus Panitumumab Followed by Evaluation for Resection in Patients With Metastatic KRAS Wild-Type Colorectal Cancer With Liver Metastases Only.
abstract: BACKGROUND
  Patients with liver-only metastatic colorectal cancer (mCRC) who are not candidates for potentially curative resection may become resectable with more aggressive chemotherapy regimens. In this nonrandomized trial, we evaluated folinic acid, 5-fluorouracil (5-FU), oxaliplatin, and irinotecan (FOLFOXIRI) plus the epidermal growth factor receptor inhibitor panitumumab as first-line treatment for KRAS wild-type mCRC with liver-only metastasis.
  
  
  METHODS
  Patients received FOLFOXIRI (5-FU, 3,200 mg/m(2), 48-hour continuous intravenous (i.v.) infusion; leucovorin, 200 mg/m(2) i.v.; irinotecan, 125 mg/m(2); oxaliplatin, 85 mg/m(2) i.v.) and panitumumab (6 mg/kg i.v.) on day 1 of 14-day cycles. Patients were restaged and evaluated for surgery every four cycles. Planned enrollment was originally 49 patients. The primary endpoint was objective response rate.
  
  
  RESULTS
  Fifteen patients (median age: 55 years; 87% male) received a median 6 cycles of treatment (range: 1-33 cycles); 10 patients (67%) were surgical candidates at baseline. Twelve patients were evaluable for clinical response; 9 (60%) achieved partial response. Ten patients underwent surgery; all were complete resections and pathologic partial response. Treatment-related grade 3 adverse events included diarrhea (33%) and rash (20%). Enrollment was halted because of emerging data on expanded KRAS/NRAS mutations beyond the region we initially examined, and the potential for negative interaction with oxaliplatin-based therapy. Eight patients underwent expanded KRAS/NRAS analysis outside exon 2; no additional mutations were found.
  
  
  CONCLUSIONS
  KRAS/NRAS mutations outside the region tested in this study were recently shown to be associated with inferior survival on similar treatment regimens. Therefore, this trial was stopped early. This regimen remains a viable option for patients with liver-only mCRC in the KRAS/NRAS wild-type population. Enrollment criteria on future studies should include testing for the newly identified mutations.
authors.affiliation: Sarah Cannon Research Institute, Nashville, Tennessee, USA Tennessee Oncology, PLLC, Nashville, Tennessee, USA jbendell@tnonc.com.
authors.forename: Johanna C
authors.initials: JC
authors.lastname: Bendell
authors.affiliation: Florida Hospital Cancer Institute, Orlando, Florida, USA.
authors.forename: Ahmed
authors.initials: A
authors.lastname: Zakari
authors.affiliation: Tennessee Oncology, PLLC, Nashville, Tennessee, USA.
authors.forename: James D
authors.initials: JD
authors.lastname: Peyton
authors.affiliation: Center for Cancer and Blood Disorders, Bethesda, Maryland, USA.
authors.forename: Ralph
authors.initials: R
authors.lastname: Boccia
authors.affiliation: Sarah Cannon Research Institute, Nashville, Tennessee, USA Florida Cancer Specialists, Ft. Myers, Florida, USA.
authors.forename: Mark
authors.initials: M
authors.lastname: Moskowitz
authors.affiliation: Tennessee Oncology, PLLC, Nashville, Tennessee, USA.
authors.forename: Victor
authors.initials: V
authors.lastname: Gian
authors.affiliation: Sarah Cannon Research Institute, Nashville, Tennessee, USA Florida Cancer Specialists, Ft. Myers, Florida, USA.
authors.forename: Andrew
authors.initials: A
authors.lastname: Lipman
authors.affiliation: Sarah Cannon Research Institute, Nashville, Tennessee, USA Oncology Hematology Care (OHC), Cincinnati, Ohio, USA.
authors.forename: David
authors.initials: D
authors.lastname: Waterhouse
authors.affiliation: Northeast Georgia Medical Center, Gainesville, Georgia, USA.
authors.forename: Richard
authors.initials: R
authors.lastname: LoCicero
authors.affiliation: Sarah Cannon Research Institute, Nashville, Tennessee, USA.
authors.forename: Chris
authors.initials: C
authors.lastname: Earwood
authors.affiliation: Sarah Cannon Research Institute, Nashville, Tennessee, USA.
authors.forename: Cassie M
authors.initials: CM
authors.lastname: Lane
authors.affiliation: Tennessee Oncology, PLLC, Nashville, Tennessee, USA.
authors.forename: Anthony
authors.initials: A
authors.lastname: Meluch
mesh_terms: D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002166:Camptothecin / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D005260:Female; D005472:Fluorouracil / Q000009:adverse effects / Q000627:therapeutic use; D006801:Humans; D002955:Leucovorin / Q000009:adverse effects / Q000627:therapeutic use; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000556:secondary / Q000601:surgery*; D008297:Male; D008875:Middle Aged; D009944:Organoplatinum Compounds / Q000009:adverse effects / Q000627:therapeutic use; D000077544:Panitumumab; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics*; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; C117307:KRAS protein, human; D009944:Organoplatinum Compounds; D000077544:Panitumumab; D016283:Proto-Oncogene Proteins p21(ras); D002955:Leucovorin; D005472:Fluorouracil; D002166:Camptothecin