Early magnesium modifications as a surrogate marker of efficacy of cetuximab-based anticancer treatment in KRAS wild-type advanced colorectal cancer patients.
BACKGROUND
KRAS wild-type mutational status is necessary but not sufficient to get benefit from epidermal growth factor receptor inhibition. Predictive markers are currently being evaluated. In this study, we investigated early hypomagnesemia as a predictor of efficacy and outcome in terms of time to progression (TtP) and overall survival (OS) in a cohort of patients affected by advanced colorectal adenocarcinoma KRAS wild-type cetuximab-treated.


METHODS
One hundred and forty-three patients affected by stage IV colorectal adenocarcinoma KRAS wild type receiving cetuximab + irinotecan (CTX+IRI) as third-line anticancer treatment and resistant to oxaliplatin- and irinotecan-based chemotherapy were retrospectively included. Magnesium plasma levels were measured before the first day and 7, 14, 21 and 28 days after CTX+IRI infusion.


RESULTS
The median magnesium basal value showed a statistically significant decrease after the start of CTX+IRI treatment (at 28 days, P < 0.0001). Patients with an early decrease of magnesium levels >50% compared with the basal level had a higher tumor response rate (55.8% versus 16.7%, P < 0.0001), a longer TtP (6.3 versus 3.6, P < 0.0001) and a longer median OS (11.0 versus 8.1, P = 0.002).


CONCLUSIONS
We have shown that early hypomagnesemia could be a predictor of efficacy and outcome in those patients. Magnesium circulating level is an easy and inexpensive biomarker to routinely be detected in patients treated with cetuximab.
Department of Medical Oncology, University Campus Bio-Medico, Rome.
B
B
Vincenzi
Department of Medical Oncology, University Campus Bio-Medico, Rome. Electronic address: s.galluzzo@unicampus.it.
S
S
Galluzzo
Department of Medical Oncology, University Campus Bio-Medico, Rome.
D
D
Santini
Department of Medical Oncology, University Campus Bio-Medico, Rome.
L
L
Rocci
Unit of Medical Oncology, Azienda-Ospedaliero Universitaria Pisana, University of Pisa, Pisa.
F
F
Loupakis
Section of Medical Oncology, Department "Giorgio Segre" of Pharmacology, University of Siena, Siena.
P
P
Correale
Oncology Department, "S. Giovanni di Dio" Hospital, Frattaminore.
R
R
Addeo
Department of Medical Oncology, University Campus Bio-Medico, Rome.
A
A
Zoccoli
Department of Medical Oncology, University Campus Bio-Medico, Rome.
A
A
Napolitano
Unit of Medical Oncology, Hospital of Pesaro, Pesaro.
F
F
Graziano
Section of Biochemistry and Molecular Biology "G. Fornaini", Department of Biomolecular Sciences, University of Urbino, Urbino.
A
A
Ruzzo
Section of Medical Oncology, Department "Giorgio Segre" of Pharmacology, University of Siena, Siena.
A
A
Falcone
Oncology Department, "S. Giovanni di Dio" Hospital, Frattaminore.
G
G
Francini
Laboratory Medicine, University Campus Bio-Medico, Rome, Italy.
G
G
Dicuonzo
Department of Medical Oncology, University Campus Bio-Medico, Rome.
G
G
Tonini
D000230:Adenocarcinoma / Q000097:blood* / Q000188:drug therapy*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000097:blood*; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives; D000068818:Cetuximab; D015179:Colorectal Neoplasms / Q000097:blood / Q000188:drug therapy*; D018572:Disease-Free Survival; D005260:Female; D005838:Genotype; D006801:Humans; D000077146:Irinotecan; D053208:Kaplan-Meier Estimate; D008274:Magnesium / Q000097:blood*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009367:Neoplasm Staging; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D016283:Proto-Oncogene Proteins p21(ras); D012189:Retrospective Studies; D018631:ras Proteins / Q000235:genetics*
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D014408:Biomarkers, Tumor; C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; D000077146:Irinotecan; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins; D008274:Magnesium; D000068818:Cetuximab; D002166:Camptothecin