title: Improved time to treatment failure with an intermittent oxaliplatin strategy: results of CONcePT.
abstract: BACKGROUND
  Oxaliplatin is an integral component of colorectal cancer treatment, but its use is limited by neurotoxicity. The Combined Oxaliplatin Neurotoxicity Prevention Trial (CONcePT) tested intermittent oxaliplatin (IO) administration and the use of concurrent calcium and magnesium salts (Ca/Mg), two modifications intended to reduce neurotoxicity and extend the duration of treatment.
  
  
  METHODS
  In this trial involving double randomization, 140 patients were randomized to receive modified FOLFOX7 plus bevacizumab with IO (eight-cycle blocks of oxaliplatin treatment) versus continuous oxaliplatin (CO); and Ca/Mg versus placebo (pre- and postoxaliplatin infusion). The primary end point was time-to-treatment failure (TTF).
  
  
  RESULTS
  One hundred thirty-nine patients were entered and treated up to the point of early study termination due to concerns by the data-monitoring committee (DMC) that Ca/Mg adversely affected tumor response. Tumor response was not a study end point. Given DMC concerns, an additional independent, blinded radiology review of all images showed no adverse effect of treatment schedule or Ca/Mg on response by Response Evaluation Criteria In Solid Tumors. The IO schedule was superior to CO [hazard ratio (HR) = 0.581, P = 0.0026] for both TTF and time-to-tumor progression (TTP) (HR = 0.533, P = 0.047).
  
  
  CONCLUSIONS
  An IO dosing schedule had a significant benefit on both TTF and TTP versus CO dosing in this trial despite the very attenuated sample. There was no effect of Ca/Mg on response.
authors.affiliation: Yale Cancer Center, Yale School of Medicine, New Haven.
authors.forename: H S
authors.initials: HS
authors.lastname: Hochster
authors.affiliation: Department of Medical Oncology, Mayo Clinic Rochester, Rochester.
authors.forename: A
authors.initials: A
authors.lastname: Grothey
authors.affiliation: Drug Development Program, Florida Cancer Specialists, Ft. Myers.
authors.forename: L
authors.initials: L
authors.lastname: Hart
authors.affiliation: Cancer center, Carle Cancer Center, Urbana.
authors.forename: K
authors.initials: K
authors.lastname: Rowland
authors.affiliation: Department of Medical Oncology, Michiana Hematology Oncology, South Bend.
authors.forename: R
authors.initials: R
authors.lastname: Ansari
authors.affiliation: Division of Medical Oncology, Mayo Clinic, Rochester.
authors.forename: S
authors.initials: S
authors.lastname: Alberts
authors.affiliation: Department of Medical Oncology, Floyd Memorial Cancer Center of Indiana, New Albany.
authors.forename: N
authors.initials: N
authors.lastname: Chowhan
authors.affiliation: Clinical Trials Program, Scottsdale Healthcare Research Institute at The Virginia B. Piper Cancer Center, Scottsdale.
authors.forename: R K
authors.initials: RK
authors.lastname: Ramanathan
authors.affiliation: Department of Hematology and Oncology, Augusta Oncology Associates, Augusta.
authors.forename: M
authors.initials: M
authors.lastname: Keaton
authors.affiliation: Department of Oncology, Sarah Cannon Research Institute, Nashville.
authors.forename: J D
authors.initials: JD
authors.lastname: Hainsworth
authors.affiliation: Department of Oncology, Sanofi US, Bridgewater, USA howard.hochster@yale.edu.
authors.forename: B H
authors.initials: BH
authors.lastname: Childs
mesh_terms: D000328:Adult; D000368:Aged; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D000068258:Bevacizumab; D002125:Calcium Gluconate / Q000008:administration & dosage*; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000401:mortality; D004311:Double-Blind Method; D005260:Female; D005472:Fluorouracil; D006801:Humans; D053208:Kaplan-Meier Estimate; D002955:Leucovorin; D008278:Magnesium Sulfate / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D009944:Organoplatinum Compounds / Q000008:administration & dosage* / Q000009:adverse effects; D000077150:Oxaliplatin; D016016:Proportional Hazards Models
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D000068258:Bevacizumab; D008278:Magnesium Sulfate; D002955:Leucovorin; D002125:Calcium Gluconate; D005472:Fluorouracil
keywords: FOLFOX; bevacizumab; calcium and magnesium salts; colorectal cancer; drug-induced neurotoxicity; intermittent