Predictive and prognostic value of magnesium serum level in FOLFIRI plus cetuximab or bevacizumab treated patients with stage IV colorectal cancer: results from the FIRE-3 (AIO KRK-0306) study.
Aged
Antineoplastic Combined Chemotherapy Protocols
/ adverse effects
Bevacizumab
/ administration & dosage
Camptothecin
/ administration & dosage
Cetuximab
/ administration & dosage
Colorectal Neoplasms
/ drug therapy
Female
Fluorouracil
/ administration & dosage
Follow-Up Studies
Humans
Hypercalciuria
/ blood
Irinotecan
/ administration & dosage
Leucovorin
/ administration & dosage
Magnesium
/ blood
Male
Nephrocalcinosis
/ blood
Prognosis
Renal Tubular Transport, Inborn Errors
/ blood
Retrospective Studies
Survival Rate
Journal
Anti-cancer drugs
ISSN: 1473-5741
Titre abrégé: Anticancer Drugs
Pays: England
ID NLM: 9100823
Informations de publication
Date de publication:
09 2020
09 2020
Historique:
pubmed:
9
7
2020
medline:
16
6
2021
entrez:
9
7
2020
Statut:
ppublish
Résumé
Magnesium wasting is a frequent side effect of epidermal growth factor receptor (EGFR)-antibody treatment as magnesium-absorption mechanisms are dependent on EGFR signaling. EGFR-inhibition results in decreased renal reabsorption. There is evidence that hypomagnesemia during cetuximab treatment correlates with response. The prognostic role of hypomagnesemia during bevacizumab treatment has not been studied yet. Here, we evaluate the prognostic value of hypomagnesemia in patients with metastatic colorectal cancer treated with FOLFIRI plus cetuximab or bevacizumab as first-line therapy. A total of 391 of 752 patients of the firstline irinotecan study population had magnesium levels measured at baseline and for the first three cycles (6 weeks) of treatment. Of those, 240 had Rat Sarkoma wildtype tumors. Overall hypomagnesemia was more common in the cetuximab compared to the bevacizumab arm (80 vs. 43%, P < 0.005). During therapy, magnesium showed a time-dependent decrease to 80% of baseline in the cetuximab and to 89% in the bevacizumab arm. Whereas magnesium continued to decrease over time in the cetuximab-treated patients, it remained stable in the bevacizumab-treated. Overall response rate (ORR) was associated with higher magnesium at week 6 (20.9 vs. 79.1%, P = 0.041). Bevacizumab-treated patients with magnesium levels below the median value at week 6 had a significantly longer progression-free survival (PFS; 11.7 vs. 9.9 months, P = 0.034; hazard ratio 0.73) and a trend towards longer overall survival (OS) (29.6 vs. 23.2 months, P = 0.089; hazard ratio 0.77). Hypomagnesemia at predefined time points and magnesium nadir had no significant effect on ORR, OS and PFS in the cetuximab arm. Our data show different magnesium kinetics in patients with metastatic colorectal cancer treated with cetuximab or bevacizumab. For patients treated with cetuximab, hypomagnesemia did not have an impact on response and survival. Hypomagnesemia might have a prognostic value in bevacizumab treatment.
Identifiants
pubmed: 32639280
doi: 10.1097/CAD.0000000000000965
pii: 00001813-202009000-00011
doi:
Substances chimiques
Bevacizumab
2S9ZZM9Q9V
Irinotecan
7673326042
Magnesium
I38ZP9992A
Cetuximab
PQX0D8J21J
Leucovorin
Q573I9DVLP
Fluorouracil
U3P01618RT
Camptothecin
XT3Z54Z28A
Types de publication
Clinical Trial, Phase III
Journal Article
Randomized Controlled Trial
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
856-865Références
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