Management of skin toxicity associated with cetuximab treatment in combination with chemotherapy or radiotherapy

Carmine Pinto, Carlo Antonio Barone, Giampiero Girolomoni, Elvio Grazioso Russi, Marco Carlo Merlano, Daris Ferrari, Evaristo Maiello, American Society of Clinical Oncology, European Society of Medical Oncology, Carmine Pinto, Carlo Antonio Barone, Giampiero Girolomoni, Elvio Grazioso Russi, Marco Carlo Merlano, Daris Ferrari, Evaristo Maiello, American Society of Clinical Oncology, European Society of Medical Oncology

Abstract

Background: Cetuximab was demonstrated by clinical trials to improve response rate and survival of patients with metastatic and nonresectable colorectal cancer or carcinoma of the head and neck. Appropriate management of skin toxicity associated with epidermal growth factor receptor inhibitor (EGFR-i) therapy is necessary to allow adequate drug administration and to improve quality of life and outcomes.

Methods: A group of Italian Experts produced recommendations for skin toxicity management using the RAND/UCLA Appropriateness Method. Statements were generated on the basis of a systematic revision of the literature and voted twice by a panel of 40 expert physicians; the second vote was preceded by a meeting of the panelists.

Results: Skin toxicity included skin rash, skin dryness, pruritus, paronychia, hair abnormality, and mucositis. Recommendations for prophylaxis and therapeutic interventions for each type of toxicity were proposed.

Conclusions: Interventions that were considered appropriate to improve compliance and outcomes of cancer patients treated with EGFR-i were identified.

Conflict of interest statement

Disclosures: Carmine Pinto: None; Carlo Antonio Barone: Consultant/advisory role: Merck; Giampiero Girolomoni: None; Elvio Grazioso Russi: None; Marco Carlo Merlano: Consultant/advisory role: Merck; Expert testimony: Merck; Daris Ferrari: None; Evaristo Maiello: None.

The content of this article has been reviewed by independent peer reviewers to ensure that it is balanced, objective, and free from commercial bias. No financial relationships relevant to the content of this article have been disclosed by the independent peer reviewers.

Figures

Figure 1.
Figure 1.
Skin rash grades 1–4.

References

    1. Rowinsky EK, Schwartz GH, Gollob JA, et al. Safety, pharmacokinetics, and activity of ABX-EGF, a fully human anti-epidermal growth factor receptor monoclonal antibody in patients with metastatic renal cell cancer. J Clin Oncol. 2004;22:3003–3035.
    1. Saltz LB, Meropol NJ, Loehrer PJ, et al. 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.
    1. Zambruno G, Girolomoni G, Manca V, et al. Epidermal growth factor and transferrin receptor expression in human embryonic and fetal epidermal cells. Arch Dermatol Res. 1990;282:544–548.
    1. Pastore S, Mascia F, Mariani V, et al. The epidermal growth factor receptor system in skin repair and inflammation. J Invest Dermatol. 2008;128:1365–1374.
    1. Van Cutsem E, Köhne CH, Hitre E, et al. Cetuximab and chemotherapy as initial treatment for metastatic colorectal cancer. N Engl J Med. 2009;360:1408–1417.
    1. Bokemeyer C, Bondarenko I, Makhson A, et al. Fluorouracil, leucovorin, and oxaliplatin with and without cetuximab in the first-line treatment of metastatic colorectal cancer. J Clin Oncol. 2009;27:663–671.
    1. Van Cutsem E, Lang I, Folprecht G, et al. Cetuximab plus FOLFIRI in the treatment of metastatic colorectal cancer (mCRC): The influence of KRAS and BRAF biomarkers on outcome: Updated data from the CRYSTAL trial. Paper presented at: Proc 2010 Gastrointestinal Cancers Symposium; January 22–24; Orlando, Florida. abstract 281.
    1. Cunningham D, Humblet Y, Siena S, et al. Cetuximab monotherapy and cetuximab plus irinotecan in irinotecan-refractory metastatic colorectal cancer. N Engl J Med. 2004;351:337–345.
    1. Jonker DJ, O'Callaghan CJ, Karapetis CS, et al. Cetuximab for the treatment of colorectal cancer. N Engl J Med. 2007;357:2040–2048.
    1. Karapetis CS, Khambata-Ford S, Jonker DJ, et al. K-ras mutations and benefit from cetuximab in advanced colorectal cancer. N Engl J Med. 2008;359:1757–1765.
    1. Folprecht G, Gruenberger T, Bechstein WO, et al. Tumour response and secondary resectability of colorectal liver metastases following neoadjuvant chemotherapy with cetuximab: the CELIM randomised phase 2 trial. Lancet Oncol. 2010;11:38–47.
    1. Bonner JA, Harari PM, Giralt J, et al. Radiotherapy plus cetuximab for squamous-cell carcinoma of the head and neck. N Engl J Med. 2006;354:567–578.
    1. Bonner JA, Harari PM, Giralt J, et al. Radiotherapy plus cetuximab for locoregionally advanced head and neck cancer: 5-year survival data from a phase 3 randomised trial, and relation between cetuximab-induced rash and survival. Lancet Oncol. 2010;11:21–28.
    1. Vermorken JB, Mesia R, Rivera F, et al. Platinum-based chemotherapy plus cetuximab in head and neck cancer. N Engl J Med. 2008;359:1116–1127.
    1. Segaert S, Van Cutsem E. Clinical signs, pathophysiology and management of skin toxicity during therapy with epidermal growth factor receptor inhibitors. Ann Oncol. 2005;16:1425–1433.
    1. Lacouture ME. Mechanisms of cutaneous toxicities to EGFR inhibitors. Nat Rev Cancer. 2006;6:803–812.
    1. Baselga J, Trigo JM, Bourhis J, et al. Phase II multicenter study of the antiepidermal growth factor receptor monoclonal antibody cetuximab in combination with platinum-based chemotherapy in patients with platinum-refractory metastatic and/or recurrent squamous cell carcinoma of the head and neck. J Clin Oncol. 2005;23:5568–5557.
    1. Lenz HJ, Van Cutsem E, Khambata-Ford S, et al. Multicenter phase II and translational study of cetuximab in metastatic colorectal carcinoma refractory to irinotecan, oxaliplatin, and fluoropyrimidines. J Clin Oncol. 2006;24:4914–4921.
    1. Burtness B, Goldwasser MA, Flood W, et al. 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.
    1. Berlin J, Van Cutsem E, Peeters M, et al. Predictive value of skin toxicity severity for response to panitumumab in patients with metastatic colorectal cancer (mCRC): a pooled analysis of five clinical trials. J Clin Oncol. 2007;25 abstract 4134.
    1. Baselga J, Pfister D, Cooper MR, et al. Phase I study of anti-epidermal growth factor receptor chimeric antibody C225 alone and in combination with cisplatin. J Clin Oncol. 2000;18:904–914.
    1. Tejpar S, Peeters M, Humblet Y, et al. Relationship of efficacy with KRAS status (wild type versus mutant) in patients with irinotecan-refractory metastatic colorectal cancer (mCRC), treated with irinotecan (q2w) and escalating doses of cetuximab (q1w): the EVEREST experience (preliminary data) J Clin Oncol. 2008;26 abstract 4001.
    1. Lièvre A, Bacher J-B, Boige V, et al. K-ras mutations as an independnet prognostic factor in patients with advanced colorectal cancer treated with cetuximab. J Clin Oncol. 2008;26:374–379.
    1. Peeters M, Siena S, Van Cutsem E, et al. Association of progression-free survival, overall survival, and patients-reported outcomes by skin toxicity and Kras status in patients receiving panitumumab monotherapy. Cancer. 2009;115:1544–1554.
    1. Orditura M, De Vita F, Galizia G, et al. Correlation between efficacy and skin rash occurrence following treatment with the epidermal growth factor receptor inhibitor cetuximab: a single institution retrospective analysis. Oncol Rep. 2009;21:1023–1028.
    1. Vermorken JB, Trigo J, Hitt R, et al. Open-label, uncontrolled, multicenter phase II study to evaluate the efficacy and toxicity of cetuximab as a single agent in patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck who failed to respond to platinum-based therapy. J Clin Oncol. 2007;25:2171–2177.
    1. Herbst RS, Arquette M, Shin DM, et al. Phase II multicenter study of the epidermal growth factor receptor antibody cetuximab and cisplatin for recurrent and refractory squamous cell carcinoma of the head and neck. J Clin Oncol. 2005;23:5578–5587.
    1. Duffour J, Thézenas S, Dereure O, et al. Interobserver agreement between dermatologists and oncologists in assessing dermatological toxicities in patients with metastatic colorectal cancer treated by cetuximab-based chemotherapies: a pilot comparative study. Eur J Cancer. 2010 Published April 21, 2010;doi: .
    1. Brook RH, Gompert DC. Rockville (MD): Public Health Service, AHCR; 1994. The RAND/UCLA Appropriateness Method, “Clinical practice guideline development: methodology perspectives.
    1. Bernier J, Bonner J, Vermorken JB, et al. Consensus guidelines for the management of radiation dermatitis and coexisting acne-like rash in patients receiving radiotherapy plus EGFR inhibitors for the treatment of squamous cell carcinoma of the head and neck. Ann Oncol. 2008;19:142–149.
    1. Giro C, Berger B, Bolke E, et al. High rate of severe radiation dermatitis during radiation therapy with concurrent cetuximab in head and neck cancer: Results of a survey in EORTC institutes. Radiother Oncol. 2009;90:166–171.
    1. Pryor DI, Porceddu SV, Burmeister BH, et al. Enhanced toxicity with concurrent cetuximab and radiotherapy in head and neck cancer. Radiother Oncol. 2009;90:172–176.
    1. Russi EG, Merlano MC, Comino A, et al. Ultrathin hydrocolloid dressing in skin damaged from alternating radiotherapy and chemotherapy plus cetuximab in advanced head and neck cancer (G.O.N.O. AlteRCC Italian Trial) Int J Radiat Oncol Biol Phys. 2007;69:638–639.
    1. Skvortsova I. Oxidative damage and cutaneous reactions during radiotherapy in combination with cetuximab. Radiother Oncol. 2009;90:281–282.
    1. Li T, Perez-Soler R. Skin toxicities associated with epidermal growth factor receptor inhibitors. Target Oncol. 2009;4:107–119.
    1. Osio A, Mateus C, Soria JC, et al. Cutaneous side-effects in patients on long-term treatment with epidermal growth factor receptor inhibitors. Br J Dermatol. 2009;161:515–521.
    1. Su X, Lacouture ME, Jia Y, et al. Risk of high-grade skin rash in cancer patients treated with cetuximab—an antibody against epidermal growth factor receptor: systemic review and meta-analysis. Oncology. 2009;77:124–133.
    1. Melosky B, Burkes R, Rayson D, et al. Management of skin rash during EGFR-targeted monoclonal antibody treatment for gastrointestinal malignancies: Canadian recommendations. Curr Oncol. 2009;16:16–26.
    1. Racca P, Fanchini L, Caliendo V, et al. Efficacy and Skin Toxicity Management with Cetuximab in Metastatic Colorectal Cancer: Outcomes from an Oncologic/Dermatologic Cooperation. Clin Colorectal Cancer. 2008;7:48–54.
    1. Segaert S, Tabernero J, Chosidow O, et al. The management of skin reaction in cancer patients receiving epidermal growth factor receptor targeted therapies. J Dtsch Dermatol Ges. 2005;3:599–606.
    1. Scope A, Liza A, Agero C, et al. Randomized double-blind trial of prophylactic oral minocycline and topical tazarotene for cetuximab-associated acne-like eruption. J Clin Oncol. 2007;25:5390–5396.
    1. Ocvirk J, Rebersek M. Management of cutaneous side effects of cetuximab therapy with vitamin K1 crème. Radiol Oncol. 2008;42:215–224.
    1. Jatoi A, Green EM, Rowland KM, et al. Clinical predictors of severe cetuximab-induced rash: observations from 933 patients enrolled in north central cancer treatment group study N0147. Oncology. 2009;77:120–123.
    1. Agero AL, Dusza SW, Andrade CB, et al. Dermatologic side effects associated with the epidermal growth factor receptor inhibitor. J Am Acad Dermatol. 2006;55:657–670.
    1. Hu JC, Sadeghi P, Pinter-Brown LC, et al. Cutaneous side effects of epidermal growth factor receptor inhibitors: Clinical presentation, pathogenesis, and management. J Am Acad Dermatol. 2007;56:317–326.
    1. Busam KJ, Capodieci P, Motzer R, et al. Cutaneous side-effects in cancer patients treated with the antiepidermal growth factor receptor antibody C225. Br J Dermatol. 2001;144:1169–1176.
    1. Braiteh F, Kurzrock R, Johnson FM. Trichomegaly of the eyelashes after lung cancer treatment with the epidermal growth factor receptor inhibitor erlotinib. J Clin Oncol. 2008;26:3460–3462.
    1. Schwartz G, Dutcher JP, Vogelzang NJ, et al. Phase 2 clinical trial evaluating the safety and effectiveness of ABX-EGF in renal cell cancer (RCC) Proc Am Soc Clin Oncol. 2002;21 abstract 91.
    1. Herbst RS, Giaccone G, Schiller JH, et al. Gefitinib in combination with paclitaxel and carboplatin in advanced non-small-cell lung cancer: a phase III trial—INTACT 2. J Clin Oncol. 2004;22:785–794.
    1. Herbst RS, LoRusso PM, Purdom M, et al. Dermatologic side effects associated with gefitinib therapy: clinical experience and management. Clin Lung Cancer. 2003;4:366–369.
    1. Kimyai-Asadi A, Jih MH. Follicular toxic effects of chimeric antiepidermal growth factor receptor antibody cetuximab used to treat human solid tumors. Arch Dermatol. 2002;138:129–131.
    1. Lee MW, Seo CW, Kim SW, et al. Cutaneous side effects in nonsmall cell lung cancer patients treated with Iressa (ZD1839), an inhibitor of epidermal growth factor. Acta Derm Venereol. 2004;84:23–26.
    1. Pérez-Soler R, Chachoua A, Hammond LA, et al. Determinants of tumor response and survival with erlotinib in patients with nonesmall-cell lung cancer. J Clin Oncol. 2004;22:3238–3247.
    1. Fox LP. Nail toxicity associated with epidermal growth factor receptor inhibitor therapy. J Am Acad Dermatol. 2007;56:460–465.
    1. Lai SE, Minnelly L, O'Keeffe P, et al. Influence of skin color in the development of erlotinib-induced rash: a report from the SERIES clinic. J Clin Oncol. 2007;25 abstract 9127.
    1. National Cancer Institute. Common terminology criteria for adverse event v. 2.0 1999, v. 3.0 2006, v. 4.0 2009. .
    1. Wollenberg A, Moosmann N, Klein E, et al. A tool for scoring of acneiform skin eruptions induced by EGF receptor inhibition. Exp Dermatol. 2008;17:790–792.
    1. Lacouture ME, Maithand ML, Saegart S, et al. A propsed EGFR inhibitor adverse event-specific grading scale from the MASCC skin toxicity study group. Support Care Cancer. 2010;18:509–522.
    1. Romito F, Giuliani F, Cormio C, et al. Psychological effects of cetuximab-induced cutaneous rash in advanced colorectal cancer patients. Support Care Cancer. 2010;18:329–334.
    1. Joshi SS, Ortiz S, Witherspoon JN, et al. Effects of epidermal growth factor receptor inhibitor-induced dermatologic toxicities on quality of life. Cancer. 2010;116:3916–3923.
    1. Eriksen JG, Overgaard M. Late onset of skin toxicity induced by EGFr-inhibitors. Radiother Oncol. 2009;90:280–281.
    1. Merlano MC, Russi EG. Epidermal Growth factor receptor-inhibitors and radiotherapy-induced cutaneous adverse effects: “Koebner-Phenomenon” or radio-dermatitis? Radiother Oncol. 2009;92:142–143.
    1. Mak SS, Lolassiotis A, Wan W, et al. The effects of hydrocolloid dressing and gentian violet on radiation-induced moist desquamation wound healing. Cancer Nurs. 2000;23:220–229.
    1. Bone RC. Systemic inflammatory response syndrome: a unifying concept of systemic inflammation. In: Fein A, Abraham A, et al., editors. Sepsis and Multiorgan Failure. Philadelphia, Pa: Lippincott, Williams, & Wilkins; 1997. pp. 1–10.
    1. Boone SL, Rademaker A, Liu D, et al. Impact and management of skin toxicity associated with anti-epidermal growth factor receptor therapy: survey results. Oncology. 2007;72:152–159.
    1. Ocvirk J, Rebersek M. Topical application of vitamin K1 cream for cetuximab-related skin toxicities. Ann Oncol; Paper presented at: ESMO Conference: 11th World Congress on Gastrointestinal Cancer; June 24–27, 2009; Barcelona, Spain. 2009. pp. vii22–vii23. abstract PD-0021.
    1. Ocvirk J, Rebersek M. Treatment of cetuximab-associated cutaneous side effects using topical application of vitamin K1 cream. J Clin Oncol; Paper presented at: 45th ASCO Annual Meeting; May 2009; Orlando, Florida. 2009. p. e15087. abstract e15087.
    1. Radovics N, Kornek G, Thalhammer F, et al. Analysis of the effects of vitamin K1 cream on cetuximab-induced acne-like rash. J Clin Oncol; Paper presented at: 46th ASCO Annual Meeting; June 4–8, 2010; Chicago, Illinois. 2010. p. e19671. abstract e19671.

Source: PubMed

Patrocinadores y Colaboradores

Condiciones médicas

Intervenciones de drogas

3
Suscribir