Top

Published in:

01-06-2016 | Original Article

Hypomagnesemia is a reliable predictor for efficacy of anti-EGFR monoclonal antibody used in combination with first-line chemotherapy for metastatic colorectal cancer

Authors: Hironori Fujii, Hirotoshi Iihara, Akio Suzuki, Ryo Kobayashi, Nobuhisa Matsuhashi, Takao Takahashi, Kazuhiro Yoshida, Yoshinori Itoh

Published in: Cancer Chemotherapy and Pharmacology | Issue 6/2016

Abstract

Purpose

Anti-EGFR monoclonal antibody is effective for KRAS wild-type metastatic colorectal cancer (mCRC), but frequently causes several adverse reactions, including hypomagnesemia and skin disorders. The present study was designed to investigate the relationship between the incidence of adverse reactions and therapeutic effects in mCRC patients receiving anti-EGFR monoclonal antibody in combination with first-line chemotherapy.

Methods

Forty-three mCRC patients who received cetuximab or panitumumab between April 2012 and December 2015 were the subjects of the present study. All patients were pretreated with oral minocycline in combination with skin treatment using moisturizer for prevention of skin rash. Hypomagnesemia and acneiform rash were graded according to the Common Terminology Criteria for Adverse Events, version 3.0. Overall response rate (ORR) and time to treatment failure (TTF) were compared between patients with and without these adverse events.

Results

The incidence rates of hypomagnesemia and acneiform rash were 32.6 % (grade 1: 20.9 %, grade 2: 11.6 %) and 93.0 % (grade 1: 41.9 %, grade 2: 41.9 %, grade 3: 9.3 %), respectively. ORR was significantly higher in patients with hypomagnesemia than in those without it (71.4 vs 34.5 %, P = 0.048). Median TTF tended to be longer, though not significantly, in patients with hypomagnesemia than in those without it. However, no significant difference in both ORR and median TTF was observed between patients with and without acneiform rash.

Conclusion

Hypomagnesemia may become a predicting factor for therapeutic effects of anti-EGFR monoclonal antibody in mCRC patients.

Garrett CR, Eng C (2011) Cetuximab in the treatment of patients with colorectal cancer. Expert Opin Biol Ther 11:937–949. doi:10.1517/14712598.2011.582464 CrossRefPubMed

Sobrero AF, Maurel J, Fehrenbacher L et al (2008) EPIC: phase III trial of cetuximab plus irinotecan after fluoropyrimidine and oxaliplatin failure in patients with metastatic colorectal cancer. J Clin Oncol 26:2311–2319. doi:10.1200/JCO.2007.13.1193 CrossRefPubMed

Karapetis CS, Khambata-Ford S, Jonker DJ et al (2008) K-ras mutations and benefit from cetuximab in advanced colorectal cancer. N Engl J Med 359:1757–1765. doi:10.1056/NEJMoa0804385 CrossRefPubMed

Van Cutsem E, Köhne CH, Hitre E et al (2009) Cetuximab and chemotherapy as initial treatment for metastatic colorectal cancer. N Engl J Med 360:1408–1417. doi:10.1056/NEJMoa0805019 CrossRefPubMed

Graziano F, Ruzzo A, Loupakis F et al (2008) Pharmacogenetic profiling for cetuximab plus irinotecan therapy in patients with refractory advanced colorectal cancer. J Clin Oncol 26:1427–1434. doi:10.1200/JCO.2007.12.4602 CrossRefPubMed

Douillard JY, Siena S, Cassidy J et al (2010) Randomized, phase III trial of panitumumab with infusional fluorouracil, leucovorin, and oxaliplatin (FOLFOX4) versus FOLFOX4 alone as first-line treatment in patients with previously untreated metastatic colorectal cancer: the PRIME study. J Clin Oncol 28:4697–4705. doi:10.1200/JCO.2009.27.4860 CrossRefPubMed

Peeters M, Price TJ, Cervantes A et al (2010) Randomized phase III study of panitumumab with fluorouracil, leucovorin, and irinotecan (FOLFIRI) compared with FOLFIRI alone as second-line treatment in patients with metastatic colorectal cancer. J Clin Oncol 28:4706–4713. doi:10.1200/JCO.2009.27.6055 CrossRefPubMed

Burtness B, Goldwasser MA, Flood W, Eastern Cooperative Oncology Group et al (2005) 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 23:8646–8654. doi:10.1200/JCO.2005.02.4646 CrossRefPubMed

Bonner JA, Harari PM, Giralt J et al (2006) Radiotherapy plus cetuximab for squamous-cell carcinoma of the head and neck. N Engl J Med 354:567–578CrossRefPubMed

10.

Amado RG, Wolf M, Peeters M et al (2008) Wild-type KRAS is required for panitumumab efficacy in patients with metastatic colorectal cancer. J Clin Oncol 26:1626–1634. doi:10.1200/JCO.2007.14.7116 CrossRefPubMed

11.

Muro K, Yoshino T, Doi T et al (2009) A phase 2 clinical trial of panitumumab monotherapy in Japanese patients with metastatic colorectal cancer. Jpn J Clin Oncol 39:321–326. doi:10.1093/jjco/hyp016 CrossRefPubMed

12.

Van Cutsem E, Peeters M, Siena S et al (2007) Open-label phase III trial of panitumumab plus best supportive care compared with best supportive care alone in patients with chemotherapy-refractory metastatic colorectal cancer. J Clin Oncol 25:1658–1664. doi:10.1200/JCO.2006.08.1620 CrossRefPubMed

13.

Vincenzi B, Santini D, Rabitti C et al (2006) Cetuximab and irinotecan as third-line therapy in advanced colorectal cancer patients: a single centre phase II trial. Br J Cancer 94:792–797. doi:10.1038/sj.bjc.6603018 CrossRefPubMedPubMedCentral

14.

Lacouture ME, Mitchell EP, Piperdi B et al (2010) Skin toxicity evaluation protocol with panitumumab (STEPP), a phase II, open-label, randomized trial evaluating the impact of a pre-Emptive Skin treatment regimen on skin toxicities and quality of life in patients with metastatic colorectal cancer. J Clin Oncol 28:1351–1357. doi:10.1200/JCO.2008.21.7828 CrossRefPubMed

15.

Scope A, Agero AL, Dusza SW et al (2007) Randomized double-blind trial of prophylactic oral minocycline and topical tazarotene for cetuximab-associated acne-like eruption. J Clin Oncol 25:5390–5396. doi:10.1200/JCO.2007.12.6987 CrossRefPubMed

16.

Vincenzi B, Galluzzo S, Santini D et al (2011) 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. doi:10.1093/annonc/mdq550 CrossRefPubMed

17.

Vickers MM, Karapetis CS, Tu D et al (2013) 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. doi:10.1093/annonc/mds577 CrossRefPubMed

18.

Groenestege WM, Thébault S, van der Wijst J et al (2007) Impaired basolateral sorting of pro-EGF causes isolated recessive renal hypomagnesemia. J Clin Invest 117:2260–2267. doi:10.1172/JCI31680 CrossRefPubMedPubMedCentral

19.

Eisenhauer EA, Therasse P, Bogaerts J et al (2009) New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer 45:228–247. doi:10.1016/j.ejca.2008.10.026 CrossRefPubMed

20.

Hajian-Tilaki K (2013) Receiver operating characteristic (ROC) curve analysis for medical diagnostic test evaluation. Casp J Intern Med 4:627–635

21.

Wang Q, Qi Y, Zhang D et al (2015) Electrolyte disorders assessment in solid tumor patients treated with anti-EGFR monoclonal antibodies: a pooled analysis of 25 randomized clinical trials. Tumour Biol 36:3471–3482. doi:10.1007/s13277-014-2983-9 CrossRefPubMedPubMedCentral

22.

Cao Y, Liao C, Tan A, Liu L, Gao F (2010) Meta-analysis of incidence and risk of hypomagnesemia with cetuximab for advanced cancer. Chemotherapy 56:459–465CrossRefPubMed

23.

Balagula Y, Wu S, Su X, Lacouture ME (2011) The effect of cytotoxic chemotherapy on the risk of high-grade acneiform rash to cetuximab in cancer patients: a meta-analysis. Ann Oncol 22:2366–2374. doi:10.1093/annonc/mdr016 CrossRefPubMed

24.

Yamada M, Iihara H, Fujii H et al (2015) Prophylactic effect of oral minocycline in combination with topical steroid and skin care against panitumumab-induced acneiform rash in metastatic colorectal cancer patients. Anticancer Res 35:6175–6181PubMed

25.

Pérez-Soler R (2003) Can rash associated with HER1/EGFR inhibition be used as a marker of treatment outcome? Oncology (Williston Park) 17(11 Suppl 12):23–28

26.

Abdel-Rahman O, Fouad M (2015) Correlation of cetuximab-induced skin rash and outcomes of solid tumor patients treated with cetuximab: a systematic review and meta-analysis. Crit Rev Oncol Hematol 93:127–135. doi:10.1016/j.critrevonc.2014.07.005 CrossRefPubMed

27.

Petrelli F, Borgonovo K, Barni S (2013) The predictive role of skin rash with cetuximab and panitumumab in colorectal cancer patients: a systematic review and meta-analysis of published trials. Target Oncol 8:173–181. doi:10.1007/s11523-013-0257-x CrossRefPubMed

28.

Orditura M, De Vita F, Galizia G et al (2009) Correlation between efficacy and skin rash occurrence following treatment with the epidermal growth factor receptor inhibitor cetuximab: a single institution retrospective analysis. Oncol Rep 21:1023–1028. doi:10.3892/or_00000319 CrossRefPubMed

Title: Hypomagnesemia is a reliable predictor for efficacy of anti-EGFR monoclonal antibody used in combination with first-line chemotherapy for metastatic colorectal cancer
Authors: Hironori Fujii
Hirotoshi Iihara
Akio Suzuki
Ryo Kobayashi
Nobuhisa Matsuhashi
Takao Takahashi
Kazuhiro Yoshida
Yoshinori Itoh
Publication date: 01-06-2016
Publisher: Springer Berlin Heidelberg
Published in: Cancer Chemotherapy and Pharmacology / Issue 6/2016
Print ISSN: 0344-5704
Electronic ISSN: 1432-0843
DOI: https://doi.org/10.1007/s00280-016-3039-1

Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras

Prof. Fabrice Barlesi

Developed by: Springer Medicine

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Purpose

Methods

Results

Conclusion

Please log in to get access to this content

Other articles of this Issue 6/2016

Phase II trial of biweekly docetaxel, cisplatin, and 5-fluorouracil chemotherapy for advanced esophageal squamous cell carcinoma

A phase 0 clinical trial of novel candidate extended-release formulations of capecitabine

YSL-12, a novel microtubule-destabilizing agent, exerts potent anti-tumor activity against colon cancer in vitro and in vivo

Phase II trial of concurrent bio-chemoradiotherapy using docetaxel, cisplatin, and cetuximab for locally advanced head and neck squamous cell carcinoma

Mechanism-based modeling of the clinical effects of bevacizumab and everolimus on vestibular schwannomas of patients with neurofibromatosis type 2

Platinum-based drugs: past, present and future

Keynote webinar | Spotlight on antibody–drug conjugates in cancer