Early magnesium modifications as a surrogate marker of efficacy of cetuximab-based anticancer treatment in KRAS wild-type advanced colorectal cancer patients

Vincenzi, Bruno; Galluzzo, Sara; Santini, Daniele; Rocci, Laura; Loupakis, Fotios; Correale, Pierpaolo; Addeo, Raffaele; Zoccoli, Alice; Napolitano, Andrea; Graziano, Francesco; Ruzzo, Annamaria; Falcone, Alfredo; Francini, Guido; Dicuonzo, Giordano; Tonini, Giuseppe

doi:10.1093/annonc/mdq550

Cited by 58 publications

(38 citation statements)

References 31 publications

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“…The present data are the closest to those obtained by Vickers et al (22). Building on their research and conclusions, the huge differences in results [for example when compared with the studies by Vincenzi et al (24,28)] may be associated with different baseline serum Mg concentrations or applied types of concomitant and past systemic treatments.…”

Section: Discussionsupporting

confidence: 79%

“…There are studies claiming that early hypomagnesemia may work as an inexpensive positive predictive factor for the treatment with cetuximab (24,28). This connection has already been described for the skin-related toxicity caused by this mAb (7).…”

Section: Discussionmentioning

confidence: 74%

“…Table III (17-29) shows the results of other studies regarding hypomagnesemia as a side-effect of cetuximab. In the available results of retrospective studies, the percentage of patients with any grade of hypomagnesemia varied from 6.3-93.3% with grade 3/4 in 0 to 27% (16,(25)(26)(27)(28)(29)(30). One of the first studies of this dyselectrolytemia associated with cetuximab by Fakih et al (14) showed a high incidence of grade 3 and 4 compared with later studies (27%).…”

Section: Discussionmentioning

confidence: 98%

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Assessment of frequency and severity of hypomagnesemia in patients with metastatic colorectal cancer treated with cetuximab, with a review of the literature

et al. 2015

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Abstract. Currently, there are a few systemic treatment options for patients with metastatic colorectal cancer (mCRC). Targeted therapy used in this setting includes the use of monoclonal antibodies, such as cetuximab or panitumumab, directed against epidermal growth factor receptor. The aim of the present study was to estimate the frequency and severity of hypomagnesemia among patients with mCRC treated with cetuximab. The data from the Department of Clinical Oncology, University Hospital of Krakow (Krakow, Poland), concerning 52 patients treated between 2009 and 2013 were collected. Of these, 27 patients fulfilled the inclusion criteria to enter this retrospective study. The National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 were used to grade the level of hypomagnesemia. In total, 29.6% of all patients experienced hypomagnesemia during treatment, and the majority of cases were grade 1 (22.2%). There was no statistically significant correlation between magnesium (Mg) level and patient age, duration of treatment, localization of primary tumor or metastases, and the number of metastases. However, there was an upward trend in a logistic regression model showing that the risk of developing hypomagnesemia increases with age. Hypomagnesemia is a frequent problem among mCRC patients receiving cetuximab. It is essential to introduce guidelines regarding the monitoring of the Mg level and its supplementation in this group of patients.

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Section: Discussionsupporting

confidence: 79%

Section: Discussionmentioning

confidence: 74%

Section: Discussionmentioning

confidence: 98%

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Assessment of frequency and severity of hypomagnesemia in patients with metastatic colorectal cancer treated with cetuximab, with a review of the literature

et al. 2015

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“…Next to acneiform exanthema [11], hypomagnesemia [12] has also been described as a possible clinical predictor for outcome. However, conflicting data were reported in a recent report, indicating that hypomagnesemia induced by cetuximab monotherapy was associated with inferior survival [13].…”

Section: Introductionmentioning

confidence: 99%

Clinical relevance and utility of cetuximab-related changes in magnesium and calcium serum levels

Stintzing¹,

Fischhaber²,

Mook³

et al. 2013

Anti-Cancer Drugs

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a Hypomagnesemia and hypocalcemia are common adverse events during cetuximab treatment. The influence of the chemotherapeutic combination on serum levels is unknown and the predictive value is currently under discussion. This analysis investigated 79 patients who had received cetuximab for at least 6 weeks in the day clinic of the Comprehensive Cancer Center, University of Munich. Calcium and magnesium serum levels were analyzed weekly; tumor response and adverse events were followed. Thirty-eight patients had metastatic colorectal cancer (mCRC) and the predictive value of hypomagnesemia was tested in these patients. During therapy, calcium serum levels decreased to about 97% of the baseline levels and were maintained for the duration of treatment. Magnesium levels showed a significant time-dependent decrease. Serum levels of magnesium were lower when cetuximab was combined with a platinum derivative. After a treatment duration of 12 weeks, magnesium levels decreased to 70% in platinum-treated patients, whereas they decreased to only 90% of baseline in patients who did not receive platinum therapy. In patients treated for mCRC, a decrease of serum magnesium below 95% of the baseline levels 14 days after initiating treatment separated patients significantly in terms of survival times. Magnesium levels decrease in a time-dependent manner during cetuximab therapy. As hypomagnesemia was more prominent in patients receiving platinum agents, magnesium measurements may be advised in these patients. In mCRC patients treated with cetuximab, day-14 magnesium serum levels correlated with treatment efficacy.

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“…Závislost reabsorpce magnezia na EGFR (cestou TRPM6 receptorem) v distálním tubulu však vede k rozvoji různě závažné hypomagnezemie. Rychlost poklesu hladiny magnezia může být spojena s mírou odpovědi v kombinovaném chemoterapeutickém režimu s fluorouracilem a ironotekanem u pa cientů s diseminovaným CRC [22].…”

Section: Cetuximabunclassified

Cancer Treatment-induced Changes in Renal Function in Patients with Tumors – Update on Current Knowledge

Pokrivčák¹,

Poprach²

2018

Klin Onkol

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Klinika komplexní onkologické péče, Masarykův onkologický ústav, Brno SouhrnVýchodiska: Abnormality funkce ledvin spojené s přítomností malignity bývají poměrně časté. Různě vyjádřená porucha renální funkce je přítomná přibližně u cca 60 % pa cientů s nádorem. Poškození ledvin může vznikat buď v důsledku přímého nebo nepřímého působení tumoru na ledviny a močové cesty. Systémová onkologická terapie může svůj negativní vliv na renální funkce uplatnit opět dvojím způsobem -přímým toxickým působením na strukturu ledvin a nepřímo v důsledku dehydratace nebo "tumor lysis syndromu". Od roku 2004 byla Food and Drug Administration schválena do klinického užití v terapii solidních nádorů řada potenciálně nefrotoxických chemoterapeutik, cílených léků a imunoterapeutik. Cíl: V rámci tohoto souhrnného článku přinášíme přehled nejnovějších informací týkajících se nefrotoxicity u nově používaných léků. Závěr: I přes nástup nových typů léků zahrnujících cílenou terapii a imunoterapii přetrvává riziko postižení ledvin. Mechanizmus vzniku je odlišný od klasické chemoterapie a většinou se jedná o toxicitu mírného nebo středního stupně. V klinických studiích nejsou ve většině případů zastoupení pa cienti s preexistující renální insuficiencí, a proto může být její vý-skyt v rutinní praxi vzhledem k vysoké prevalenci chronického onemocnění ledvin u onkologických pa cientů vyšší. Zhoršení renálních funkcí může významným způsobem ovlivnit strategii léčby, a proto je pečlivá monitorace renálních funkcí nedílnou součástí každé klinické kontroly. Klíčová slova renální selhání -toxicita -imunoterapie -chemoterapie SummaryBackground: Renal abnormalities associated with malignancy are common with renal impairment occurr ing in about 60% of patients with tumors. Kidney dis ease may occur as a result of direct or indirect effects of tumors on kidneys and the urinary tract. Systematic oncology treatment can affect renal function in two ways, via direct toxic effects on kidney structure and indirectly via dehydration or tumor lysis syndrome. Since 2004, the Food and Drug Administration has approved a number of potentially nephrotoxic chemotherapeutics, targeted drugs, and immunotherapeutics for the treatment of solid tumors. Aim: This article provides an overview of the latest information on the nephrotoxicity associated with the use of new drugs. Conclusion: Despite the development of new drug treatments, includ ing targeted ther apy and immunother apy, the risk of kidney involvement persists. The mechanisms of action of these new drugs are different from those of classical chemother apy, and their use is usually associated with only mild to moderate side effects. In clinical trials, patients with pre-exist ing renal insufficiency are not present in most cases. Deterioration of renal function may significantly affect the treatment strategy and therefore careful renal function monitor ing should be an integral part of each clinical trial.

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Early magnesium modifications as a surrogate marker of efficacy of cetuximab-based anticancer treatment in KRAS wild-type advanced colorectal cancer patients

Abstract: 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.

Cited by 58 publications

References 31 publications

Assessment of frequency and severity of hypomagnesemia in patients with metastatic colorectal cancer treated with cetuximab, with a review of the literature

Assessment of frequency and severity of hypomagnesemia in patients with metastatic colorectal cancer treated with cetuximab, with a review of the literature

Clinical relevance and utility of cetuximab-related changes in magnesium and calcium serum levels

Cancer Treatment-induced Changes in Renal Function in Patients with Tumors – Update on Current Knowledge

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