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Vol. 56, No. 6, 2010
Issue release date: December 2010

Meta-Analysis of Incidence and Risk of Hypomagnesemia with Cetuximab for Advanced Cancer

Cao Y. · Liao C. · Tan A. · Liu L. · Gao F.
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Abstract

Background: Cetuximab is often used in patients with colorectal cancer, head and neck cancer, and other cancers. Hypomagnesemia is a major adverse event that was often ignored in studies. The aim of this meta-analysis is to gain a better understanding of the overall incidence and risk of hypomagnesemia in patients who received cetuximab-based therapy. Methods: Databases, including Pubmed, EMBASE, The Cochrane Library, American Society of Clinical Oncology (2000–2008), and Web of Science, were searched to identify relevant studies. Eligible studies were prospective phase II/III clinical trials of patients with cancer assigned cetuximab at a dose of 400 mg/m2 i.v. on day 1 and 250 mg/m2 weekly thereafter. The primary endpoint was incidence of hypomagnesemia. Results: Nineteen clinical reports were identified which included a total of 4,559 patients available for analysis, with 3,081 patients assigned cetuximab-based treatment. This result showed a high incidence of grade 3 and 4 hypomagnesemia (5.6%; 95% CI = 3.0–10.2) and a high incidence of all-grade hypomagnesemia associated with cetuximab-based therapy for advanced cancer (36.7%; 95% CI = 22–54.4). Compared with non-cetuximab therapy, cetuximab-based therapy has a higher risk of grade 3 and 4 hypomagnesemia (4.75; 95% CI = 3.661–6.18) and all-grade hypomagnesemia (4.75; 95% CI = 3.661–6.18). Conclusion: Cetuximab-based therapy is associated with a significant risk of hypomagnesemia. Early monitoring and effective management of hypomagnesemia are important for patients that received cetuximab-based therapy.



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References

  1. Baselga J: The EGFR as a target for anticancer therapy – Focus on cetuximab. Eur J Cancer 2001;37(suppl 4):S16–S22.
  2. Kim ES, Khuri FR, Herbst RS: Epidermal growth factor receptor biology (IMC-C225). Curr Opin Oncol 2001;13:506–513.
  3. Xiong X, Liu H, Fu L, Li L, Li J, Luo X, Mei C: Antitumor activity of a new N-substituted thiourea derivative, an EGFR signaling-targeted inhibitor against a panel of human lung cancer cell lines. Chemotherapy 2008;54:463–474.
  4. Ciardiello F, Tortora G: Anti-epidermal growth factor receptor drugs in cancer therapy. Expert Opin Investig Drugs 2002;11:755–768.
  5. Ciardiello F: Epidermal growth factor receptor tyrosine kinase inhibitors as anticancer agents. Drugs 2000;60(suppl 1):25–42.
  6. Saltz LB, Meropol NJ, Loehrer PJ Sr, Needle MN, Kopit J, Mayer RJ: Phase II trial of cetuximab in patients with refractory colorectal cancer that expresses the epidermal growth factor receptor. J Clin Oncol 2004;22:1201–1208.
  7. Cunningham D, Humblet Y, Siena S, Khayat D, Bleiberg H, Santoro A, et al: Cetuximab monotherapy and cetuximab plus irinotecan in irinotecan-refractory metastatic colorectal cancer. N Engl J Med 2004;351:337–345.
  8. Schrag D, Chung KY, Flombaum C, Saltz L: Cetuximab therapy and symptomatic hypomagnesemia. J Natl Cancer Inst 2005;97:1221–1224.
  9. Roca JM, Alonso V, Pericay C, Escudero P, Salud A, Losa F, López LJ, Guasch I, Méndez M, Quintero-Aldana G, Grande C, Vicente P, Arrivi A, Martin C, Moreno I, García P, Antón I, Constenla M, Yubero A, Cirera L, ACROSS Cooperative Group: Cetuximab given every 2 weeks plus irinotecan is an active and safe option for previously treated patients with metastatic colorectal cancer. Chemotherapy 2010;56:142–146.
  10. Lu CY, Tan PH, Lin SH, Tsai SK, Lin SM, Mao CC, Yang LC: Body weight-related ionized hypomagnesemia in pediatric patients undergoing cardiopulmonary bypass for surgical repair of congenital cardiac defects. J Clin Anesth 2003;15:189–193.
  11. Fiset C, Kargacin ME, Kondo CS, Lester WM, Duff HJ: Hypomagnesemia: characterization of a model of sudden cardiac death. J Am Coll Cardiol 1996;27:1771–1776.
  12. US National Cancer Institute: Common Terminology Criteria for Adverse Events v3.0 (CTCAE). http://ctep.cancer.gov/protocol Development/electronic_applications/docs/ctcaev3.pdf.
  13. Burtness B, Goldwasser MA, Flood W, Mattar B, Forastiere AA, Eastern Cooperative Oncology Group: Phase III randomized trial of cisplatin plus placebo compared with cisplatin plus cetuximab in metastatic/recurrent head and neck cancer: an Eastern Cooperative Oncology Group study. J Clin Oncol 2005;23:8646–8654.
  14. Wilke H, Glynne-Jones R, Thaler J, Adenis A, Preusser P, Aranda Aguilar E, Aapro M, Van Den Berg N, Eggleton S, Siena S: MABEL – A large multinational study of cetuximab plus irinotecan in irinotecan resistant metastatic colorectal cancer. J Clin Oncol 2006;24(18S):3549.
  15. Birnbaum E, Johnson TT, Rathore R, Khurshid H, Puthawala M, Radie Keane K, Ruhl C, Wanebo H, Kennedy T, Ready N: BrUOG. Induction cetuximab (C) followed by C, paclitaxel (P), carboplatin (CP) and concurrent radiation (RT) for locoregionally advanced squamous cell carcinoma of the head and neck (SCCHN). J Clin Oncol 2007;25(18S):16504.
  16. Bradford DS, Socinski MA, LaRocca RV, Hensing TA, Bordoni RE: Phase II trial of carboplatin plus cetuximab for the treatment of stage IIIB/IV non-small cell lung cancer (NSCLC). J Clin Oncol 2007;25(18S):18005.
  17. Butts CA, Bodkin D, Middleman EL, Englund CW, Ellison D, Alam Y, Kreisman H, Graze P, Maher J, Ross HJ, Ellis PM, Mc Nulty W, Kaplan E, Pautret V, Weber MR, Shepherd FA: Randomized phase II study of gemcitabine plus cisplatin or carboplatin [corrected], with or without cetuximab, as first-line therapy for patients with advanced or metastatic non small-cell lung cancer. J Clin Oncol 2007;25:5777–5784.
  18. Pinto C, Di Fabio F, Siena S, Cascinu S, Rojas Llimpe FL, Ceccarelli C, Mutri V, Giannetta L, Giaquinta S, Funaioli C, Berardi R, Longobardi C, Piana E, Martoni AA: Phase II study of cetuximab in combination with FOLFIRI in patients with untreated advanced gastric or gastroesophageal junction adenocarcinoma (FOLCETUX study). Ann Oncol 2007;18:510–517.
  19. Jonker DJ, O’Callaghan CJ, Karapetis CS, Zalcberg JR, Tu D, Au HJ, Berry SR, Krahn M, Price T, Simes RJ, Tebbutt NC, van Hazel G, Wierzbicki R, Langer C, Moore MJ: Cetuximab for the treatment of colorectal cancer. N Engl J Med 2007;357:2040–2048.
  20. Zhu AX, Stuart K, Blaszkowsky LS, Muzikansky A, Reitberg DP, Clark JW, Enzinger PC, Bhargava P, Meyerhardt JA, Horgan K, Fuchs CS, Ryan DP: Phase 2 study of cetuximab in patients with advanced hepatocellular carcinoma. Cancer 2007;110:581–589.
  21. Argiris E, Gibson MK, Heron DE, Smith RP, Ferris RL, Lai SY, Kim SW, Branstetter BF, Johnson JT, Grandis JR: Phase II trial of neoadjuvant docetaxel (T), cisplatin (P), and cetuximab (E) followed by concurrent radiation (X), P, and E in locally advanced head and neck cancer (HNC). J Clin Oncol 2008;26(suppl 20):6002.
  22. Belani CP, Schreeder MT, Steis RG, Guidice RA, Marsland TA, Butler EH, Ramalingam SS: Cetuximab in combination with carboplatin and docetaxel for patients with metastatic or advanced-stage nonsmall cell lung cancer: a multicenter phase 2 study. Cancer 2008;113:2512–2517.
  23. Bendell JC, Uronis HE, Morse MA, Blobe G, Aklilu M, Nixon A, Niedzweicki D, Honeycutt W, Howard L, Hurwitz H: Initial results of a phase II study of oxaliplatin (OX), capecitabine (CAP), bevacizumab (BV), and cetuximab (CET) in the treatment of metastatic colorectal cancer (mCRC). J Clin Oncol 2008;26(suppl 20):4063.
  24. Borghaei H, Langer CJ, Millenson M, Tuttle H, Seldomridge J, Rovito M, Mintzer D, Treat J: Phase II trial of cetuximab (C225) in combination with monthly carboplatin (Cb) and weekly paclitaxel (Pac) in patients with advanced NSCLC: promising early results. J Clin Oncol 2008;26(suppl 20):8104.
  25. Konner J, Schilder RJ, DeRosa FA, Gerst SR, Tew WP, Sabbatini PJ, Hensley ML, Spriggs DR, Aghajanian CA: A phase II study of cetuximab /paclitaxel/carboplatin for the initial treatment of advanced-stage ovarian, primary peritoneal, or fallopian tube cancer. Gynecol Oncol 2008;110:140–145.
  26. Ku GY, Shah MA, Tang LH, Miron B, Kelsen DP, Ilson DH: Cetuximab (C225) plus irinotecan/cisplatin (CPT/Cis) for CPT/Cis-refractory esophageal cancer. J Clin Oncol 2008;26(suppl 20):15580.
  27. O’Neil H, Bernard SA, Goldberg RM, Moore DT, Garcia R, Marroquin C, Morse MA, Woods L, Sanoff HK: Phase II study of oxaliplatin, capecitabine, and cetuximab in advanced hepatocellular carcinoma. J Clin Oncol 2008;26(suppl 20):4604.
  28. Safran H, Suntharalingam M, Dipetrillo T, Ng T, Doyle LA, Krasna M, Plette A, Evans D, Wanebo H, Akerman P, Spector J, Kennedy N, Kennedy T: Cetuximab with concurrent chemoradiation for esophagogastric cancer: assessment of toxicity. Int J Radiat Oncol Biol Phys 2008;70:391–395.
  29. Sobrero AF, Maurel J, Fehrenbacher L, Scheithauer W, Abubakr YA, Lutz MP, Vega-Villegas ME, Eng C, Steinhauer EU, Prausova J, Lenz HJ, Borg C, Middleton G, Kröning H, Luppi G, Kisker O, Zubel A, Langer C, Kopit J, Burris HA 3rd: EPIC: phase III trial of cetuximab plus irinotecan after fluoropyrimidine and oxaliplatin failure in patients with metastatic colorectal cancer. J Clin Oncol 2008;26:2311–2319.
  30. Tol J, Koopman M, Rodenburg CJ, Cats A, Creemers GJ, Schrama JG, Erdkamp FL, Vos AH, Mol L, Antonini NF, Punt CJ: A randomised phase III study on capecitabine, oxaliplatin and bevacizumab with or without cetuximab in first-line advanced colorectal cancer, the CAIRO2 study of the Dutch Colorectal Cancer Group (DCCG). An interim analysis of toxicity. Ann Oncol 2008;19:734–738.
  31. Vermorken JB, Mesia R, Rivera F, Remenar E, Kawecki A, Rottey S, Erfan J, Zabolotnyy D, Kienzer HR, Cupissol D, Peyrade F, Benasso M, Vynnychenko I, De Raucourt D, Bokemeyer C, Schueler A, Amellal N, Hitt R: Platinum-based chemotherapy plus cetuximab in head and neck cancer. N Engl J Med 2008;359:1116–11127.
  32. Schrag D, Chung KY, Flombaum C, Saltz L: Cetuximab therapy and symptomatic hypomagnesemia. J Natl Cancer Inst 2005;97:1221–1224.
  33. Touyz RM: Transient receptor potential melastatin 6 and 7 channels, magnesium transport, and vascular biology: implications in hypertension. Am J Physiol Heart Circ Physiol 2008;294:H1103–H1118.
  34. Walder RY, Landau D, Meyer P, Shalev H, Tsolia M, Borochowitz Z, Boettger MB, Beck GE, Englehardt RK, Carmi R, Sheffield VC: Mutation of TRPM6 causes familial hypomagnesemia with secondary hypocalcemia. Nat Genet 2002;31:171–174.
  35. Schlingmann KP, Weber S, Peters M, Niemann Nejsum L, Vitzthum H, Klingel K, Kratz M, Haddad E, Ristoff E, Dinour D, Syrrou M, Nielsen S, Sassen M, Waldegger S, Seyberth HW, Konrad M: Hypomagnesemia with secondary hypocalcemia is caused by mutations in TRPM6, a new member of the TRPM gene family. Nat Genet 2002;31:166–170.
  36. 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, Bindels RJ: Impaired basolateral sorting of pro-EGF causes isolated recessive renal hypomagnesemia. J Clin Invest 2007;117:2260–2267.
  37. Vincenzi B, Santini D, Tonini G: Biological interaction between anti-epidermal growth factor receptor agent cetuximab and magnesium. Expert Opin Pharmacother 2008;9:1267–1269.
  38. Fakih M: Management of anti-EGFR-targeting monoclonal antibody-induced hypomagnesemia. Oncology (Williston Park) 2008;22:74–76.


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