nach oben

Erschienen in:

01.02.2016 | Original Article

Prophylactic versus reactive treatment of acneiform skin rashes from epidermal growth factor receptor inhibitors in metastatic colorectal cancer

verfasst von: Bogdan Dascalu, Hagen F. Kennecke, Howard J. Lim, Daniel J. Renouf, Jenny Y. Ruan, Jennifer T. Chang, Winson Y. Cheung

Erschienen in: Supportive Care in Cancer | Ausgabe 2/2016

Einloggen, um Zugang zu erhalten

Abstract

Purpose

There are concerns regarding potential negative effects of prophylactic treatment of epidermal growth factor receptor (EGFR)-inhibitor-related rashes on metastatic colorectal cancer (mCRC) outcomes. We aimed to characterize treatment patterns of EGFR-inhibitor-induced rashes and evaluate prophylactic versus reactive approaches to rash management in relation to overall survival (OS).

Methods

Patients diagnosed with KRAS wild-type mCRC from July 2010 to June 2012 in British Columbia and prescribed cetuximab or panitumumab were reviewed to describe patterns of use of oral antibiotics and steroid creams. Using Cox regression, the relationship between prophylactic versus reactive rash management and OS was characterized.

Results

A total 119 patients were analyzed: median age was 63 years, 61 % were male, 34 % received cetuximab, 66 % received panitumumab, and median number of EGFR inhibitor treatment was nine cycles. Rash occurred in >90 % of patients, and reactive was favored over prophylactic treatment (66 vs. 34 %). Older patients and those with Eastern Cooperative Oncology Group (ECOG) performance status 0/1 were more likely to receive prophylactic creams (44 vs. 20 % for age <60, p = 0.01) and oral antibiotics (62 vs. 12 % for ECOG ≥2, p = 0.01), respectively. Median OS was 7.0 months. The number of treatment cycles and OS were similar in both prophylactic and reactive groups (both p > 0.05). In Cox regression, ECOG >2 correlated with worse survival (hazard ratio (HR) 22.01, 95 % confidence interval (CI) 5.25–92.30, p < 0.01). However, survival outcomes were similar between patients prescribed antibiotics prophylactically versus reactively (HR = 1.10, 95 % CI 0.43–2.80, p = 0.85), and steroid creams prophylactically versus reactively (HR = 2.00, 95 % CI 0.58–6.92, p = 0.27).

Conclusion

Prophylactic treatment of EGFR-inhibitor-related rashes is associated with similar outcomes compared to reactive rash treatment in mCRC.

Li T, Perez-Soler R (2009) Skin toxicities associated with epidermal growth factor receptor inhibitors. Target Oncol 4:107PubMedCrossRef

Jatoi A, Green EM, Rowland KM Jr et al (2009) Clinical predictors of severe cetuximab-induced rash: observations from 933 patients enrolled in north central cancer treatment group study N0147. Oncology 77:120PubMedPubMedCentralCrossRef

Jacot W, Bessis D, Jorda E et al (2004) Acneiform eruption induced by epidermal growth factor receptor inhibitors in patients with solid tumours. Br J Dermatol 151:238PubMedCrossRef

Busam KJ, Capodieci P, Motzer R et al (2001) Cutaneous side-effects in cancer patients treated with the antiepidermal growth factor receptor antibody C225. Br J Dermatol 144:1169PubMedCrossRef

Wierzbicki R, Jonker DJ, Moore MJ et al (2011) A phase II, multicenter study of cetuximab monotherapy in patients with refractory, metastatic colorectal carcinoma with absent epidermal growth factor receptor immunostaining. Invest New Drugs 29:170CrossRef

Jatoi A, Nguyen PL (2008) Do patients die from rashes from epidermal growth factor receptor inhibitors? A systematic review to help counsel patients about holding therapy. Oncologist 13:1201–1204PubMedCrossRef

Wagner LL, 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 21(suppl 5):34–36PubMed

Peréz-Soler R, Saltz L (2005) Cutaneous adverse effects with HER1/EGFR-targeted agents: is there a silver lining? J Clin Oncol 23:5235–5246PubMedCrossRef

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 351:341CrossRef

10.

Agero AL, Dusza SW, Benvenuto-Andrade C et al (2006) Dermatologic side effects associated with the epidermal growth factor receptor inhibitors. J Am Acad Dermatol 55:657PubMedCrossRef

11.

Perez-Soler R (2006) Rash as a surrogate marker for efficacy of epidermal growth factor receptor inhibitors in lung cancer. Clin Lung Cancer 8(suppl 1):S7PubMedCrossRef

12.

Kris M, 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: A randomized trial. JAMA 290:2149–2158PubMedCrossRef

13.

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 28:1351–1352PubMedCrossRef

14.

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 25:5390PubMedCrossRef

15.

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 113:847PubMedPubMedCentralCrossRef

16.

Saltz L, Kjes MS, Abbruzzese J et al (2003) The presence and intensity of the cetuximab-induced acne-like rash predicts increased survival in studies across multiple malignancies. Proc Am Soc Clin Oncol 22:204 (abstr 817)CrossRef

17.

Melosky B, Burkes R, Rayson D et al (2009) Management of skin rash during EGFR-targeted monoclonal antibody treatment for gastrointestinal malignancies: Canadian recommendations. Curr Oncol 16:16–26PubMedPubMedCentralCrossRef

18.

Oken MM, Creech RH, Tormey DC et al (1982) Toxicity and response criteria of the eastern cooperative oncology group. Am J Clin Oncol 5:649–655PubMedCrossRef

19.

Peeters M, Siena S, Van Cutsem E et al (2009) Association of progression-free survival, overall survival, and patient-reported outcomes by skin toxicity and KRAS status in patients receiving Panitumumab monotherapy. Cancer 115:1544PubMedCrossRef

20.

Van Cutsem E, Peeters M, Siena S et al (2007) Open-label, phase 3 clinical trial of panitumumab plus best supportive care compared with best supportive care alone in patients with chemotherapy-refractory metastatic colorectal cancer. J Clin Oncol 25:1658–1664PubMedCrossRef

21.

Saltz LB, Meropol NJ, Loehrer PJ Sr 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

22.

Perez-Soler R, Chachoua A, Hammond LA et al (2004) Determinants of tumor response and survival with erlotinib in patients with non-small-cell lung cancer. J Clin Oncol 22:3238–3247PubMedCrossRef

Titel: Prophylactic versus reactive treatment of acneiform skin rashes from epidermal growth factor receptor inhibitors in metastatic colorectal cancer
verfasst von: Bogdan Dascalu
Hagen F. Kennecke
Howard J. Lim
Daniel J. Renouf
Jenny Y. Ruan
Jennifer T. Chang
Winson Y. Cheung
Publikationsdatum: 01.02.2016
Verlag: Springer Berlin Heidelberg
Erschienen in: Supportive Care in Cancer / Ausgabe 2/2016
Print ISSN: 0941-4355
Elektronische ISSN: 1433-7339
DOI: https://doi.org/10.1007/s00520-015-2846-y

Springer Medizin

Prophylactic versus reactive treatment of acneiform skin rashes from epidermal growth factor receptor inhibitors in metastatic colorectal cancer