nach oben

Erschienen in:

01.06.2013 | Original Article

Pre-emptive skin toxicity treatment for anti-EGFR drugs: evaluation of efficacy of skin moisturizers and lymecycline. A phase II study

verfasst von: Roberta Grande, Filomena Narducci, Sara Bianchetti, Giovanni Mansueto, Donatello Gemma, Isabella Sperduti, Giorgio Trombetta, Franco Angelini, Teresa Gamucci

Erschienen in: Supportive Care in Cancer | Ausgabe 6/2013

Einloggen, um Zugang zu erhalten

Abstract

Background

Anti-epidermal growth factor receptor (EGFR) target therapies like erlotinib for metastatic lung cancer and cetuximab or panitumumab for metastatic colorectal cancer (mCRC) cause skin reaction that seems to be related to treatment efficacy. Skin toxicity evaluation protocol with panitumumab study has shown that preemptive treatment reduces the incidence of ≥Grade 2 (G2) skin toxicity in mCRC treated with panitumumab. Aim of this study is to evaluate if preemptive skin toxicity treatment with different drugs has good efficacy in patients receiving anti-EGFR therapies, such as cetuximab, panitumumab, and erlotinib, for mCRC and metastatic lung cancer.

Methods

Treatment included skin moisturizers with sunscreen and lymecycline 300 mg/daily. Primary objective is to reduce the incidence of ≥G2 skin toxicity during the first 3 months of therapy. Toxicities are reported with confidence interval at 95 %. Quality of life was assessed with Dermatology Life Quality Index every 2 weeks and evaluated with repeated measure ANOVA.

Results

Fifty-one patients with mCRC (60.8 %) and metastatic lung cancer (39.2 %) were enrolled. Anticancer drugs were erlotinib/cetuximab/panitumumab 20:30:1. At 3-month evaluation, 27.4 % patients had =G2 skin toxicity. Skin toxicity was not related with age (p = 0.67), sex (p = 0.65), previous chemotherapy regimens (p = 0.41), and current anti-EGFR treatment (p = 0.22). No gastrointestinal or hematological toxicities related to lymecycline were observed. Only six patients required further drugs. Quality of life analysis did not show a significant difference from the beginning and the end of treatment.

Conclusions

Data show efficacy of preemptive treatment with a well-tolerated profile. A reduction of severe skin toxicities is shown with an increase of grade 1 toxicities, not leading to anti-EGFR dose reduction and with better quality of life for patients.

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. JCO Mar 10:1351–1357CrossRef

Cunningham D, Humblet Y, Siena S et al (2004) Cetuximab monotherapy and cetuximab plus irinotecan in irinotecan-refractory metastatic colorectal cancer. N Engl J Med 351:337–345PubMedCrossRef

Saltz L, Meropol NJ, Loehrer PJ et al (2004) Phase II trial of cetuximab in patients with refractory colorectal cancer that expresses the epidermal growth factor receptor. J Clin Oncol 22:1201–1208PubMedCrossRef

Foon KA, Yang X-D, Weiner LM et al (2004) Preclinical and clinical evaluations of ABX-EGF, a fully human anti-epidermal growth factor receptor antibody. Int J Radiat Oncol Biol Phys 58:984–990PubMedCrossRef

Vanhoefer U, Twes M, Rojo F et al (2004) Phase I study of the humanized antiepidermal growth factor receptor monoclonal antibody EMD72000 in patients with advanced solid tumors that express the epidermal growth factor receptor. J Clin Oncol 22:175–184PubMedCrossRef

Seymour L, Goss G, Stewart D (2002) A translational research study of ZD1839 at a dose of 750 mg in patients with pretreated advanced or metastatic colorectal cancer: NCIC CTG IND.122. Ann Oncol 13: S5 (Abstr 264PD)

Oza AM, Townsley CA, Siu LL et al (2003) Phase II study of erlotinib (OSI-774) in patients with metastatic colorectal cancer. Proc Am Soc Clin Oncol 22: 196 (Abstr 785)

Kris MG, Natale RB, Herbst RS et al (2003) Efficacy of gefitinib, an inhibitor of the epidermal growth factor receptor tyrosine kinase, in symptomatic patients with non-small cell lung cancer. JAMA 290:2149–2158PubMedCrossRef

Hidalgo M, Siu LL, Nemunaitis J et al (2001) Phase I and pharmacologic study of OSI-774, an epidermal growth factor receptor tyrosine kinase inhibitor, in patients with advanced solid malignancies. J Clin Oncol 19:3267–3279PubMed

10.

Van Cutsem E, Mayer R, Gold P et al (2004) Correlation of acne rash and tumor response with cetuximab monotherapy in patients with colorectal cancer refractory to both irinotecan and oxaliplatin. Eur J Cancer 2 (Suppl): 85–86 (Abstr 279)

11.

Rhee J, Oishi K, Garey J et al (2005) Management of rash and other toxicities in patients treated with epidermal growth factor receptor-targeted agents. Clin Colorectal Cancer 5(Suppl 2):S101–S106PubMedCrossRef

12.

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(11):2366–2374. doi:10.1093/annonc/mdr016 PubMedCrossRef

13.

Thatcher N, Nicolson M, Groves RW et al. (2009) Expert consensus on the management of erlotinib-associated cutaneous toxicity in the UK. Oncologist 14:840–847PubMed

14.

Wagner LI, Lacouture ME (2007) Dermatologic toxicities associated with EGFR inhibitors: the clinical psychologist’s perspective. Impact on health-related quality of life and implications for clinical management of psychological sequelae. Oncology (Williston Park) 21:34–36

15.

Eilers RE, Gandhi M, Patel JD et al (2010) Dermatologic infections in cancer patients treated with epidermal growth factor receptor inhibitor therapy. J Natl Cancer Inst 102:47–53PubMedCrossRef

16.

Boone SL, Rademaker A, Liu D et al (2007) Impact and management of skin toxicity associated with anti-epidermal growth factor receptor therapy: survey results. Oncology 72:152–159PubMedCrossRef

17.

Janne PA, Gurubhagavatula S, Yeap BY et al (2004) Outcomes of patients with advanced non-small cell lung cancer treated with gefitinib on an expanded access study. Lung Cancer 44:221–230PubMedCrossRef

18.

Forsythe B, Faulkner K (2004) Overview of the tolerability of gefitinib monotherapy: clinical experience in non-small cell lung cancer. Drug Saf 27:1081–1092PubMedCrossRef

19.

Jatoi A, Rowland K, Sloan JA et al (2008) Tetracycline to prevent epidermal growth factor receptor inhibitor-induced skin rashes: results of a placebo controlled trial from the North Central Cancer Treatment Group (N03CB). Cancer 113:847–853PubMedCrossRef

20.

Scope A, Agero A, Dusza S 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, 812, 2006PubMedCrossRef

21.

Plewig G, Kligman AM (2000) Acne and rosacea, 3rd edn. Springer, BerlinCrossRef

22.

Finlay AY, Khan GK (1994) Dermatology Life Quality Index (DLQI): a simple practical measure for routine clinical use. Clin Exp Dermatol 19:210–216PubMedCrossRef

Titel: Pre-emptive skin toxicity treatment for anti-EGFR drugs: evaluation of efficacy of skin moisturizers and lymecycline. A phase II study
verfasst von: Roberta Grande
Filomena Narducci
Sara Bianchetti
Giovanni Mansueto
Donatello Gemma
Isabella Sperduti
Giorgio Trombetta
Franco Angelini
Teresa Gamucci
Publikationsdatum: 01.06.2013
Verlag: Springer-Verlag
Erschienen in: Supportive Care in Cancer / Ausgabe 6/2013
Print ISSN: 0941-4355
Elektronische ISSN: 1433-7339
DOI: https://doi.org/10.1007/s00520-012-1715-1

Springer Medizin

Pre-emptive skin toxicity treatment for anti-EGFR drugs: evaluation of efficacy of skin moisturizers and lymecycline. A phase II study