A review of the treatment options for skin rash induced by egfr-targeted therapies: Evidence from randomized clinical trials and a metaanalysis

Radiology and Oncology

Volumn 47, Issue 2, 2013, Pages 166-175

  Ocvirk, Janja ^a   Heeger, Steffen ^b   Mccloud, Philip ^c   Hofheinz, Ralf Dieter ^d  

^a INSTITUTE OF ONCOLOGY   (Slovenia)

^b MERCK KGAA   (Germany)

^c McCloud Consulting Group   (Australia)

^d UNIVERSITY OF HEIDELBERG   (Germany)

Author keywords

Acne like skin rash; Antibiotics; Cetuximab; Erlotinib; Gefitinib; Panitumumab; Vitamin k

Indexed keywords

CETUXIMAB; DOXYCYCLINE; EPIDERMAL GROWTH FACTOR RECEPTOR; ERLOTINIB; GEFITINIB; MINOCYCLINE; PANITUMUMAB; PHYTOMENADIONE; PIMECROLIMUS; PLACEBO; SUNSCREEN; TAZAROTENE; TETRACYCLINE;

ANTIBIOTIC PROPHYLAXIS; ANTIBIOTIC THERAPY; CANCER CHEMOTHERAPY; CANCER PATIENT; DRUG ERUPTION; FOLLICULITIS; HUMAN; LUNG CANCER; LUNG NON SMALL CELL CANCER; META ANALYSIS; METASTATIC COLORECTAL CANCER; RANDOMIZED CONTROLLED TRIAL (TOPIC); REVIEW; SKIN TOXICITY; SYSTEMATIC REVIEW;

EID: 84885008419     PISSN: 13182099     EISSN: 15813207     Source Type: Journal    
DOI: 10.2478/raon-2013-0014     Document Type: Review

References (67)

1. Bianco R, Gelardi T, Damiano V, Ciardiello F, Tortora G. Rational bases for the development of EGFR inhibitors for cancer treatment. IntJBiochem Cell Biol 2007; 39:1416-31. (Pubitemid 47031050)
2. Downward J, Yarden Y, Mayes E, Scrace G, Totty N, Stockwell P, et al. Close similarity of epidermal growth factor receptor and v-erb-B oncogene protein sequences. Nature 1984; 307:521-7. (Pubitemid 14135812)
3. Nicholson Rl, Gee JM, Harper ME. EGFR and cancer prognosis. Eur J Cancer 2001; 37(Suppl 4):S9-15.
4. Shelton JG, Steelman IS, Abrams SL, Bertrand FE, Franklin RA, McMahon M, et al. The epidermal growth factor receptor gene family as a target for therapeutic intervention in numerous cancers: what's genetics got to do with it? Expert Opin Ther Targets 2005; 9:1009-30. (Pubitemid 41488837)
5. Yarden Y, Sliwkowski MX. Untangling the ErbB signalling network. Nat Rev Mol Cell Biol 2001; 2:127-37. (Pubitemid 33674041)
6. Rebersek M, Boc M, Cerkovnik P, Benedik J, Hlebanja Z, Volk N, Novakovic S, Ocvirk J. Efficacy of first-line systemic treatment in correlation with BRAF V600E and different KRAS mutations in metastatic colorectal cancer - A single institution retrospective analysis. Radiol Oncol 2011; 45:285-91.
7. Jia Y, Lacouture ME, Su X, Wu S. Risk of skin rash associated with erlotinib in cancer patients: a meta-analysis. J Support Oncol 2009; 7:211-7.
8. Lynch TJ Jr, Kim ES, Eaby B, Garey J, West DP, Lacouture ME. Epidermal growth factor receptor inhibitor-associated cutaneous toxicities: an evolving paradigm in clinical management. Oncologist 2007; 12:610-21. (Pubitemid 350012125)
9. Melosky B, Burkes R, Rayson D, Alcindor T, Shear N, Lacouture M. Management of skin rash during EGFR-targeted monoclonal antibody treatment for gastrointestinal malignancies: Canadian recommendations. Curr Oncol 2009; 16:16-26.
10. Perez-Soler R, Delord JP, Halpern A, Kelly K, Krueger J, Sureda BM, et al. HER1/EGFR inhibitor-associated rash: future directions for management and investigation outcomes from the HER1/EGFR inhibitor rash management forum. Oncologist 2005; 10: 345-56. (Pubitemid 40647253)
11. Saif MW, Kim R. Incidence and management of cutaneous toxicities associated with cetuximab. Expert Opin Drug Saf 2007; 6:175-82. (Pubitemid 46380811)
12. Segaert S, Van Cutsem E. Clinical signs, pathophysiology and management of skin toxicity during therapy with epidermal growth factor receptor inhibitors. Ann Oncol 2005; 16:1425-33. (Pubitemid 41222414)
13. Agero AL, Dusza SW, Benvenuto-Andrade C, Busam KJ, Myskowski P, Halpern AC. Dermatologic side effects associated with the epidermal growth factor receptor inhibitors. J Am Acad Dermatol 2006; 55:657-70. (Pubitemid 44436627)
14. Ehmann LM, Ruzicka T, Wollenberg A. Cutaneous side-effects of EGFR inhibitors and their management. Skin Therapy Lett 2011; 16:1-3.
15. Eilers RE Jr, Gandhi M, Patel JD, Mulcahy MF, Agulnik M, Hensing T, et al. Dermatologic infections in cancer patients treated with epidermal growth factor receptor inhibitor therapy. J Natl Cancer Inst 2010; 102:47-53.
16. Lacouture ME, Mitchell EP, Piperdi B, Pillai MV, Shearer H, lannotti N, et al. 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 2010; 28:1351-7.
17. Oslo A, Mateurs C, Soria JC, Smith A. Cutaneous side effects in patients on long-term treatment with epidermal growth factor receptor inhibitors. Br J Dermatol 2009; 161:515-21.
18. Lacouture M. The growing importance of skin toxicity in EGFR inhibitor therapy. Oncology (Wiliiston Park) 2009; 23:194-6.
19. Robert C, Soria JC, Spatz A, Le Cesne A, Malka D, Pautier P, et al. Cutaneous side-effects of kinase inhibitors and blocking antibodies. Lancet Oncol 2005; 6:491-500. (Pubitemid 40903630)
20. Peeters M, Price T, Van Laethem JL Anti-epidermal growth factor receptor monotherapy in the treatment of metastatic colorectal cancer: where are we today? Oncologist 2009; 14:29-39.
21. Perez-Soler R, Saltz L Cutaneous adverse effects with HERl/EGFR-targeted agents: is there a silver lining? J Clin Oncol 2005; 23:5235-46. (Pubitemid 46224035)
22. Racca P, Fanchini L, Caliendo V, Ritorto G, Evangelista W, Volpatto R, 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. (Pubitemid 351252451)
23. 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; 22:1201-8. (Pubitemid 41079832)
24. Wacker B, Nagrani T, Weinberg J, Witt K, Clark G, Cagnoni PJ. Correlation between development of rash and efficacy in patients treated with the epidermal growth factor receptor tyrosine kinase inhibitor erlotinib in two large phase III studies. din Cancer Res 2007; 13:3913-21. (Pubitemid 47037599)
25. Kovac V, Smrdel U. Meta-analyses of clinical trials in patients with non-small cell lung cancer. Minireview. Neoplasm a 2004; 51:334"l-40.
26. Potthoff K, Hofheinz R, Hassel JC, Volkenandt M, Lordick F, Hartmann JT, et al. Interdisciplinary management of EGFR-inhibitor-induced skin reactions: a German expert opinion. Ann Oncol 2011; 22:524-35.
27. Wollenberg A, Moosmann N, Klein E, Katzer K. A tool for scoring of ac- neiform skin eruptions induced by EGF receptor inhibition. Exp Dermatol 2008; 17:790-2.
28. Lacouture ME, Maitland ML, Segaert S, Setser A, Baran R, Fox LP, et al. A proposed EGFR inhibitor dermatologic adverse event-specific grading scale from the MASCC skin toxicity study group. Support Care Cancer 2010; 18: 509-22.
29. Hassel JC, Kripp M, Al-Batran S, Hofheinz RD. Treatment of epidermal growth factor receptor antagonist-induced skin rash: results of a survey among German oncologists. Onkologie 2010; 33:94-8.
30. Bernier J, Bonner J, Vermorken JB, Bensadoun RJ, Dummer R, Giralt J, 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; 19:142-9.
31. Lacouture ME. Insights into the pathophysiology and management of dermatologic toxicities to EGFR-targeted therapies in colorectal cancer. Cancer Nurs 2007; 30(4 Suppl 1): S17-26. (Pubitemid 47196598)
32. Segaert S, Van Cutsem E. Clinical management of EGFRI dermatologic toxicities: the European perspective. Oncology (Wiliiston Park) 2007; 21:22-6.
33. Galimont-Collen AF, Vos LE, Lavrijsen AP, Ouwerkerk J, Gelderblom H. Classification and management of skin, hair, nail and mucosal side-effects of epidermal growth factor receptor (EGFR) inhibitors. Eur J Cancer 2007; 43:845-51. (Pubitemid 46366684)
34. Segaert S, Tabernero J, Chosidow O, Dirschka T, Eisner J, Mancini L, et al. The management of skin reactions in cancer patients receiving epidermal growth factor receptor targeted therapies. J Dtsch Dermatol Ges 2005; 3: 599-606. (Pubitemid 41647826)
35. Bernier J, Russi EG, Homey B, Meriano MC, Mesia R, Peyrade F, et al. Management of radiation dermatitis in patients receiving cetuximab and radiotherapy for locally advanced squamous cell carcinoma of the head and neck: proposals for a revised grading system and consensus management guidelines. Ann Oncol 2011; 22:2191-200.
36. Hu JC, Sadeghi P, Pinter-Brown LC, Yashar S, Chiu MW. Cutaneous side effects of epidermal growth factor receptor inhibitors: clinical presentation, pathogenesis, and management. J Am Acad Dermatol 2007; 56:317-26. (Pubitemid 46091817)
37. Tsimboukis S, Merikas I, Karapanagiotou EM, Saif MW, Syrigos KN. Erlotinib- induced skin rash in patients with non-small-cell lung cancer: pathogenesis, clinical significance, and management. Clin Lung Cancer 2009; 10:106-11.
38. Wu PA, Balagula Y, Lacouture ME, Anadkat MJ. Prophylaxis and treatment of dermatologic adverse events from epidermal growth factor receptor inhibitors. Curr Opin Oncol 2011; 23:343-51.
39. Jatoi A. Sunshine and rash: testing the role of sunscreen to prevent epidermal growth factor receptor inhibitor-induced rash. Support Cancer Ther 2007;4:198-202. (Pubitemid 47606345)
40. Jatoi A, Thrower A, Sloan JA, Flynn PJ, Wentworth-Hartung NL, Dakhil SR, et al. Does sunscreen prevent epidermal growth factor receptor (EGFR) inhibitor-induced rash? Results of a placebo-controlled trial from the North Central Cancer Treatment Group (N05C4). Oncologist 2010; 15:1016-22.
41. Jatoi A, Rowland K, Sloan JA, Gross HM, Fishkin PA, Kahanic SP, et al. 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 2008;113:847-53.
42. Jatoi A, Dakhil SR, Sloan JA, Kugler JW, Rowland KM Jr, Schaefer PL, et al. Prophylactic tetracycline does not diminish the severity of epidermal growth factor receptor (EGFR) inhibitor-induced rash: results from the North Central Cancer Treatment Group (Supplementary N03CB). Support Care Cancer 2011; 19:1601-7.
43. Scope A, Agero AL, Dusza SW, Myskowski PL, Lieb JA, Saltz L, et al. Randomized double-blind trial of prophylactic oral minocycline and topical tazarotene for cetuximab-associated acne-like eruption. J Clin Oncol 2007; 25:5390-6. (Pubitemid 350232214)
44. Deplanque G, Chavaillon J, Vergnenegre A, Falchero L CYTAR: A randomized clinical trial evaluating the preventive effect of doxycycline on erlotinib- induced folliculitis in non-small cell lung cancer patients [Abstract], J Clin Oncol 2010; 28: Abstract 9019.
45. Scope A, Lieb JA, Dusza SW, Phelan DL, Myskowski PL, Saltz L, et al. A prospective randomized trial of topical pimecrolimus for cetuximab-associated acnelike eruption. J Am Acad Dermatol 2009; 61:614-20.
46. Fernandez-Guarino M, Perez Garcia B, Aldanondo Fernandez de la Mora I, Garcia-Millan C, Garrido Lopez P, Jaen Olasolo P. [Treatment of acnei- form rash by epidermal growth factor inhibitors with oral tetracyclines]. [Spanish], Actas Dermosipliogr 2006; 97:503-8. (Pubitemid 44861913)
47. Micantonio T, Fargnoli MC, Ricevuto E, Ficorella C, Marchetti P, Peris K. Efficacy of treatment with tetracyclines to prevent acneiform eruption secondary to cetuximab therapy. Arch Dermatol 2005; 141:1173-4. (Pubitemid 41373978)
48. Molinari E, De Quatrebarbes J, Andre T, Aractingi S. Cetuximab-induced acne. Dermatology 2005; 211:330-3. (Pubitemid 41642106)
49. Chren MM, Lasek RJ, Sahay AP, Sands LP. Measurement properties of Skindex-16: a brief quality-of-life measure for patients with skin diseases. J Cutan Med Surg 2001; 5:105-10. (Pubitemid 32588315)
50. Mitchell E, Lacouture M, Shearer H, lannotti N. Final STEPP results of prophylactic versus reactive skin toxicity (ST) treatment (tx) for panitumumab (pmab)-related ST in patients (pts) with metastatic colorectal cancer (mCRC) [Abstract], J din Oncol 2009; 27: Abstract CRA4027.
51. Hedges LV, Olkin I. Statistical methods for meta-analysis. Orlando: Academic Press; 1985.
52. Laird NM, Ware JH. Random-effects models for longitudinal data. Biometrics 1982; 38:963-74.
53. Luu M, Lai SE, Patel J, Guitart J, lacouture ME. Photosensitive rash due to the epidermal growth factor receptor inhibitor erlotinib. Photodermatol Photoimmunoi Photomed 2007; 23:42-5. (Pubitemid 46189309)
54. Segaert S, Simonart T. The epidermal vitamin D system and innate immunity: some more light shed on this unique photoendocrine system? Dermatology 2008; 217:7-11. (Pubitemid 351896560)
55. Li T, Perez-Soler R. Skin toxicities associated with epidermal growth factor receptor inhibitors. Target Oncol 2009; 4:107-19.
56. Perez-Soler R, Zou Y, Li T, Ling Y. Steroids and immunosuppressive agents potentiate the cytotoxicity of the EGFR inhibitor erlotinib (E) in human skin keratinocytes whereas Vit K3 exerts a protective effect: implications for the management of the skin rash [Abstract], J Clin Oncol 2007; 25: Abstract 9124.
57. Perez-Soler R, Zou Y, Li T, Tornos C, Ling Y. Topical vitamin K3 (Vit K3, Menadione) prevents erlotinib and cetuximab-induced EGFR inhibition in the skin [Abstract]. J din Oncol 2006; 23: Abstract 3036.
58. Ocvirk J, Rebersek M. Management of cutaneous side effects of cetuximab therapy with vitamin K1 creme. Radiol Oncol 2008; 42:215-24.
59. Ocvirk J, Rebersek M. Topical application of vitamin K1 cream for cetuximab- related skin toxicities [Abstract], Ann Oncol 2009; 20: Abstract PD-0021.
60. Pinto C, Barone C, Martoni A, Di Tullio P, Di Fabio F, Cassano A. Vitamin K1 cream in the management of skin rash during anti-EGFR monodoncal antibody (mAb) treatment in patients with metastatic cancer: first analysis of an observational Italian study [Abstract]. J din Oncol 2011; 29: Abstract 594.
61. Ocvirk J, Rebersek M, Boc M, Mesti T, Ebert M. Prophylactic use of K1 cream for reducing skin toxicity during cetuximab treatment in patients with metastatic colorectal cancer (mCRC) [Abstract], J din Oncol 2010; 28: Abstract e14011.
62. Lacouture ME, Anadkat MJ, Bensadoun RJ, Bryce J, Chan A, Epstein JB, et al. Clinical practice guidelines for the prevention and treatment of EGFR inhibitor-associated dermatologic toxicities. Support Care Cancer 2011; 19:1079-95.
63. Potthoff K, Hassel JC Wollenberg A. Therapie und prophylaxe EGFR- inhibitor-induzierter hautreaktionen. Arzneimitteitherapie 2010; 28:191-8.
64. Peeters M, Price TJ, Cervantes A, Sobrero AF, Ducreux M, Hotko Y, et al. 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 din Oncol 2010; 28: 4706-13.
65. Douillard JY, Siena S, Cassidy J, Tabernero J, Burkes R, Barugel M, et al. 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 din Oncol 2010; 28:4697-705.
66. Bokemeyer C, Bondarenko I, Makhson A, Hartmann JT, Aparicio J, de Braud F, et al. Fluorouracil, leucovorin, and oxaliplatin with and without cetuximab in the first-line treatment of metastatic colorectal cancer. J din Oncol 2009; 27:663-71.
67. Van Cutsem E, Kohne CH, Lang I, Folprecht G, Nowacki MP, Cascinu S, et al. Cetuximab plus irinotecan, fluorouracil, and leucovorin as first-line treatment for metastatic colorectal cancer: updated analysis of overall survival according to tumor KRAS and BRAF mutation status. J din Oncol 2011; 29: 2011-9.