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

Streb,Joanna; Püsküllüoğlu,Miroslawa; Glanowska,Izabela; Ochenduszko,Sebastian; Konopka,Kamil; Łupkowski,Radoslaw; Michalowska‑Kaczmarczyk,Anna; Bochenek‑Cibor,Justyna; Majka,Marcin; Krzemieniecki,Krzysztof

doi:10.3892/ol.2015.3800

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

Authors:
- Joanna Streb
- Miroslawa Püsküllüoğlu
- Izabela Glanowska
- Sebastian Ochenduszko
- Kamil Konopka
- Radoslaw Łupkowski
- Anna Michalowska‑Kaczmarczyk
- Justyna Bochenek‑Cibor
- Marcin Majka
- Krzysztof Krzemieniecki
View Affiliations

Affiliations: Department of Clinical Oncology, University Hospital, Jagiellonian University Medical College, Kraków 31‑008, Poland, Department of Radiation Therapy, St. Luke's Hospital, Tarnów 33‑100, Poland, Department of Transplantation, Polish‑American Institute of Pediatrics, Jagiellonian University Medical College, Kraków 31‑008, Poland
Published online on: October 12, 2015 https://doi.org/10.3892/ol.2015.3800
Pages: 3749-3755

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

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.

View Figures

View References

1	Fakih M and Vincent M: Adverse events associated with anti-EGFR therapies for the treatment of metastatic colorectal cancer. Curr Oncol. 17(Suppl 1): S18–S30. 2010.PubMed/NCBI
2	Boyle P and Langman JS: ABC of colorectal cancer: Epidemiology. BMJ. 321:805–808. 2000. View Article : Google Scholar : PubMed/NCBI
3	Saltz LB, Meropol NJ, Loehrer PJ Sr, Needle MN, Kopit J and Mayer RJ: Phase II trial of cetuximab in patients with refractory colorectal cancer that expresses the epidermal growth factor receptor. J Clin Oncol. 22:1201–1208. 2004. View Article : Google Scholar : PubMed/NCBI
4	Cunningham D, Humblet Y, Siena S, Khayat D, Bleiberg H, Santoro A, Bets D, Mueser M, Harstrick A, Verslype C, et al: Cetuximab monotherapy and cetuximab plus irinotecan in irinotecan-refractory metastatic colorectal cancer. N Engl J Med. 351:337–345. 2004. View Article : Google Scholar : PubMed/NCBI
5	Jonker DJ, O'Callaghan CJ, Karapetis CS, Zalcberg JR, Tu D, Au HJ, Berry SR, Krahn M, Price T, Simes RJ, et al: Cetuximab for the treatment of colorectal cancer. N Engl J Med. 357:2040–2048. 2007. View Article : Google Scholar : PubMed/NCBI
6	Bokemeyer C, Van Cutsem E, Rougier P, Ciardiello F, Heeger S, Schlichting M, Celik I and Köhne CH: Addition of cetuximab to chemotherapy as first-line treatment for KRAS wild-type metastatic colorectal cancer: Pooled analysis of the CRYSTAL and OPUS randomized clinical trials. Eur J Cancer. 48:1466–1475. 2012. View Article : Google Scholar : PubMed/NCBI
7	Pacek A, Kozioł M, Püsküllüoğlu M, Tomaszewski KA, Ochenduszko S, Zygulska AL and Krzemieniecki K: Assessment of skin-related toxicity in patients with metastatic colorectal cancer treated with cetuximab. Acta Dermatovenerol Croat. 22:137–144. 2014.PubMed/NCBI
8	Martin KJ, González EA and Slatopolsky E: Clinical consequences and management of hypomagnesemia. J Am Soc Nephrol. 20:2291–2295. 2009. View Article : Google Scholar : PubMed/NCBI
9	Saif MW: Management of hypomagnesemia in cancer patients receiving chemotherapy. J Support Oncol. 6:243–248. 2008.PubMed/NCBI
10	National Cancer Institute Common Toxicity Criteria. Version 4.0. May 28–2009.http://ctep.cancer.gov/protocolDevelopment/electronic_applications/ctc.htmAccessed. May 2–2014
11	Groenestege WM, Thébault S, van der Wijst J, van den Berg D, Janssen R, Tejpar S, van den Heuvel LP, van Cutsem E, Hoenderop JG, Knoers NV, et al: Impaired basolateral sorting of pro-EGF causes isolated recessive renal hypomagnesemia. J Clin Invest. 117:2260–2267. 2007. View Article : Google Scholar : PubMed/NCBI
12	Tejpar S, Piessevaux H, Claes K, Piront P, Hoenderop JG, Verslype C and Van Cutsem E: Magnesium wasting associated with epidermal-growth-factor receptor-targeting antibodies in colorectal cancer: A prospective study. Lancet Oncol. 8:387–394. 2007. View Article : Google Scholar : PubMed/NCBI
13	Yang XD, Jia C, Corvalan JR, Wang P and Davis CG: Development of ABX-EGF, a fully human anti-EGF receptor monoclonal antibody, for cancer therapy. Crit Rev Oncol Hematol. 38:17–23. 2001. View Article : Google Scholar : PubMed/NCBI
14	Fakih M: Anty-EGFR monoclonal antibody-induced hypomagnesaemia. Lancet Oncol. 8:366–367. 2007. View Article : Google Scholar : PubMed/NCBI
15	Edge S, Byrd DR, Compton CC, Fritz AG, Greene FL and Trotti A: AJCC Cancer Staging Manual. (7th). (New York, NY). Springer. 1432010.
16	Schrag D, Chung KY, Flombaum C and Saltz L: Cetuximab therapy and symptomatic hypomagnesemia. J Natl Cancer Inst. 97:1221–1224. 2005. View Article : Google Scholar : PubMed/NCBI
17	Erbitux-Summary of product characteristics. http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/000558/WC500029119.pdfAccessed. May 2–2014
18	Chen P, Wang L, Li H, Liu B and Zou Z: Incidence and risk of hypomagnesemia in advanced cancer patients treated with cetuximab: A meta-analysis. Oncol Lett. 5:1915–1920. 2013.PubMed/NCBI
19	Cao Y, Liao C, Tan A, Liu L and Gao F: Meta-analysis of incidence and risk of hypomagnesemia with cetuximab for advanced cancer. Chemotherapy. 56:459–465. 2010. View Article : Google Scholar : PubMed/NCBI
20	Price TJ, Peeters M, Kim TW, Li J, Cascinu S, Ruff P, Suresh AS, Thomas A, Tjulandin S, Zhang K, et al: Panitumumab versus cetuximab in patients with chemotherapy-refractory wild-type KRAS exon 2 metastatic colorectal cancer (ASPECCT): A randomised, multicentre, open-label, non-inferiority phase 3 study. Lancet Oncol. 15:569–579. 2014. View Article : Google Scholar : PubMed/NCBI
21	Lordick F, Kang YK, Chung HC, Salman P, Oh SC, Bodoky G, Kurteva G, Volovat C, Moiseyenko VM, Gorbunova V, et al: Capecitabine and cisplatin with or without cetuximab for patients with previously untreated advanced gastric cancer (EXPAND): A randomised, open-label phase 3 trial. Lancet Oncol. 14:490–499. 2013. View Article : Google Scholar : PubMed/NCBI
22	Vickers MM, Karapetis CS, Tu D, O'Callaghan CJ, Price TJ, Tebbutt NC, Van Hazel G, Shapiro JD, Pavlakis N, Gibbs P, et al: 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. Ann Oncol. 24:953–960. 2013. View Article : Google Scholar : PubMed/NCBI
23	Weickhardt AJ, Price TJ, Chong G, Gebski V, Pavlakis N, Johns TG, Azad A, Skrinos E, Fluck K, Dobrovic A, et al: Dual targeting of the epidermal growth factor receptor using the combination of cetuximab and erlotinib: Preclinical evaluation and results of the phase II DUX study in chemotherapy-refractory, advanced colorectal cancer. J Clin Oncol. 30:1505–1512. 2012. View Article : Google Scholar : PubMed/NCBI
24	Vincenzi B, Santini D, Galluzzo S, Russo A, Fulfaro F, Silletta M, Battistoni F, Rocci L, Zobel BB, Adamo V, et al: Early magnesium reduction in advanced colorectal cancer patients treated with cetuximab plus irinotecan as predictive factor of efficacy and outcome. Clin Cancer Res. 14:4219–4224. 2008. View Article : Google Scholar : PubMed/NCBI
25	Pazo-Oubiña Do F, Estefanell-Tejero A, Riu-Viladoms G, Anglada-Martínez H, Molas-Ferrer G and Creus-Baró N: Magnesium monitoring practice in monoclonal anti-epidermal growth factor receptor antibodies therapy. J Clin Pharm Ther. 38:101–103. 2013. View Article : Google Scholar : PubMed/NCBI
26	Demizu M, Ueda H, Osawa M, Chihara S, Igarashi T, Yano K, Kimura F, Tanaka N and Hiratsuka M: Effect of magnesium supplementation on early-stage hypomagnesemia in patients treated with cetuximab. Gan To Kagaku Ryoho. 40:897–900. 2013.PubMed/NCBI
27	Melichar B, Králíčková P, Hyšpler R, Kalábová H, Cerman J Jr, Holečková P, Studentová H and Malířová E: Hypomagnesaemia in patients with metastatic colorectal carcinoma treated with cetuximab. Hepatogastroenterology. 59:366–371. 2012.PubMed/NCBI
28	Vincenzi B, Galluzzo S, Santini D, Rocci L, Loupakis F, Correale P, Addeo R, Zoccoli A, Napolitano A, Graziano F, et al: Early magnesium modifications as a surrogate marker of efficacy of cetuximab-based anticancer treatment in KRAS wild-type advanced colorectal cancer patients. Ann Oncol. 22:1141–1146. 2011. View Article : Google Scholar : PubMed/NCBI
29	Maliakal P and Ledford A: Electrolyte and protein imbalance following anti-EGFR therapy in cancer patients: A comparative study. Exp Ther Med. 1:307–311. 2010. View Article : Google Scholar : PubMed/NCBI
30	Fakih MG, Wilding G and Lombardo J: Cetuximab-induced hypomagnesemia in patients with colorectal cancer. Clin Colorectal Cancer. 6:152–156. 2006. View Article : Google Scholar : PubMed/NCBI
31	Stintzing S, Fischhaber D, Mook C, Modest DP, Giessen C, Schulz C, Haas M, Boeck S, Michl M, Stemmler J, et al: Clinical relevance and utility of cetuximab-related changes in magnesium and calcium serum levels. Anticancer Drugs. 24:969–974. 2013. View Article : Google Scholar : PubMed/NCBI
32	Thomas SE, Anderson S, Gordon KL, Oyama TT, Shankland SJ and Johnson RJ: Tubulointerstitial disease in aging: Evidence for underlying peritubular capillary damage, a potential role for renal ischemia. J Am Soc Nephrol. 9:231–242. 1998.PubMed/NCBI
33	Wolf FI, Cittadini AR and Maier JA: Magnesium and tumors: Ally or foe? Cancer Treat Rev. 35:378–382. 2009. View Article : Google Scholar : PubMed/NCBI