title: Association of hypomagnesemia with inferior survival in a phase III, randomized study of cetuximab plus best supportive care versus best supportive care alone: NCIC CTG/AGITG CO.17.
abstract: BACKGROUND
  Cetuximab-induced hypomagnesemia has been associated with improved clinical outcomes in advanced colorectal cancer (CRC). We explored this relationship from a randomized clinical trial of cetuximab plus best supportive care (BSC) versus BSC alone in patients with pretreated advanced CRC.
  
  
  METHODS
  Day 28 hypomagnesemia grade (0 versus ≥1) and percent reduction (<20% versus ≥20%) of Mg from baseline was correlated with outcome.
  
  
  RESULTS
  The median percentage Mg reduction at day 28 was 10% (-42.4% to 63.0%) for cetuximab (N = 260) versus 0% (-21.1% to 25%) for BSC (N = 251) [P < 0.0001]. Grade ≥1 hypomagnesemia and ≥20% reduction from baseline at day 28 were associated with worse overall survival (OS) [hazard ratio, HR 1.61 (95% CI 1.12-2.33), P = 0.01 and 2.08 (95% CI 1.32-3.29), P = 0.002, respectively] in multivariate analysis including grade of rash (0-1 versus 2+). Dyspnea (grade ≥3) was more common in patients with ≥20% versus < 20% Mg reduction (68% versus 45%; P = 0.02) and grade 3/4 anorexia were higher in patients with grade ≥1 hypomagnesemia (81% versus 63%; P = 0.02).
  
  
  CONCLUSIONS
  In contrast to prior reports, cetuximab-induced hypomagnesemia was associated with poor OS, even after adjustment for grade of rash.
authors.affiliation: Department of Oncology, Tom Baker Cancer Centre, Calgary, Canada.
authors.forename: M M
authors.initials: MM
authors.lastname: Vickers
authors.forename: C S
authors.initials: CS
authors.lastname: Karapetis
authors.forename: D
authors.initials: D
authors.lastname: Tu
authors.forename: C J
authors.initials: CJ
authors.lastname: O'Callaghan
authors.forename: T J
authors.initials: TJ
authors.lastname: Price
authors.forename: N C
authors.initials: NC
authors.lastname: Tebbutt
authors.forename: G
authors.initials: G
authors.lastname: Van Hazel
authors.forename: J D
authors.initials: JD
authors.lastname: Shapiro
authors.forename: N
authors.initials: N
authors.lastname: Pavlakis
authors.forename: P
authors.initials: P
authors.lastname: Gibbs
authors.forename: J
authors.initials: J
authors.lastname: Blondal
authors.forename: U
authors.initials: U
authors.lastname: Lee
authors.forename: J M
authors.initials: JM
authors.lastname: Meharchand
authors.forename: R L
authors.initials: RL
authors.lastname: Burkes
authors.forename: S H
authors.initials: SH
authors.lastname: Rubin
authors.forename: J
authors.initials: J
authors.lastname: Simes
authors.forename: J R
authors.initials: JR
authors.lastname: Zalcberg
authors.forename: M J
authors.initials: MJ
authors.lastname: Moore
authors.forename: L
authors.initials: L
authors.lastname: Zhu
authors.forename: D J
authors.initials: DJ
authors.lastname: Jonker
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage* / Q000009:adverse effects; D000068818:Cetuximab; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D018572:Disease-Free Survival; D064420:Drug-Related Side Effects and Adverse Reactions / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D066246:ErbB Receptors / Q000378:metabolism; D005260:Female; D006801:Humans; D053565:Hypercalciuria / Q000139:chemically induced; D008274:Magnesium / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D009397:Nephrocalcinosis / Q000139:chemically induced; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D016283:Proto-Oncogene Proteins p21(ras); D015499:Renal Tubular Transport, Inborn Errors / Q000139:chemically induced; D016896:Treatment Outcome; D018631:ras Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D061067:Antibodies, Monoclonal, Humanized; C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; D066246:ErbB Receptors; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins; D008274:Magnesium; D000068818:Cetuximab