Have a personal or library account? Click to login
A review of the treatment options for skin rash induced by EGFR-targeted therapies: Evidence from randomized clinical trials and a metaanalysis Cover

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
Volume 47 (2013): Issue 2 (June 2013)
By: Janja Ocvirk,  Steffen Heeger,  Philip McCloud and  Ralf-Dieter Hofheinz  
Open Access
|May 2013

References

  1. 1. Bianco R, Gelardi T, Damiano V, Ciardiello F, Tortora G. Rational bases for the development of EGFR inhibitors for cancer treatment. Int J Biochem CellBiol 2007; 39: 1416-31.10.1016/j.biocel.2007.05.008
    Search in Google Scholar
  2. 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: 521-7.10.1038/307521a0
    Search in Google Scholar
  3. 3. Nicholson RI, Gee JM, Harper ME. EGFR and cancer prognosis. Eur J Cancer 2001; 37(Suppl 4): S9-15.10.1016/S0959-8049(01)00231-3
    Search in Google Scholar
  4. 4. Shelton JG, Steelman LS, 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.
    Search in Google Scholar
  5. 5. Yarden Y, Sliwkowski MX. Untangling the ErbB signalling network. Nat RevMol Cell Biol 2001; 2: 127-37.10.1038/3505207311252954
    Search in Google Scholar
  6. 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: 285-91.10.2478/v10019-011-0039-y342375722933967
    Search in Google Scholar
  7. 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.
    Search in Google Scholar
  8. 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: 610-21.10.1634/theoncologist.12-5-61017522250
    Search in Google Scholar
  9. 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. CurrOncol 2009; 16: 16-26.10.3747/co.v16i1.361264462819229368
    Search in Google Scholar
  10. 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: 345-56.10.1634/theoncologist.10-5-34515851793
    Search in Google Scholar
  11. 11. Saif MW, Kim R. Incidence and management of cutaneous toxicities associated with cetuximab. Expert Opin Drug Saf 2007; 6: 175-82.10.1517/14740338.6.2.17517367263
    Search in Google Scholar
  12. 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: 1425-33.10.1093/annonc/mdi27916012181
    Search in Google Scholar
  13. 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: 657-70.10.1016/j.jaad.2005.10.010
    Search in Google Scholar
  14. 14. Ehmann LM, Ruzicka T, Wollenberg A. Cutaneous side-effects of EGFR inhibitors and their management. Skin Therapy Lett 2011; 16: 1-3.
    Search in Google Scholar
  15. 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: 47-53.10.1093/jnci/djp439
    Search in Google Scholar
  16. 16. Lacouture ME, Mitchell EP, Piperdi B, Pillai MV, Shearer H, Iannotti 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: 1351-7.10.1200/JCO.2008.21.7828
    Search in Google Scholar
  17. 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 JDermatol 2009; 161: 515-21.10.1111/j.1365-2133.2009.09214.x
    Search in Google Scholar
  18. 18. Lacouture M. The growing importance of skin toxicity in EGFR inhibitor therapy. Oncology (Williston Park) 2009; 23: 194-6.
    Search in Google Scholar
  19. 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: 491-500.10.1016/S1470-2045(05)70243-6
    Search in Google Scholar
  20. 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.
    Search in Google Scholar
  21. 21. Perez-Soler R, Saltz L. Cutaneous adverse effects with HER1/EGFR-targeted agents: is there a silver lining? J Clin Oncol 2005; 23: 5235-46.
    Search in Google Scholar
  22. 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. ClinColorectal Cancer 2008; 7: 48-54.10.3816/CCC.2008.n.00718279577
    Search in Google Scholar
  23. 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: 1201-8.10.1200/JCO.2004.10.18214993230
    Search in Google Scholar
  24. 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. Clin Cancer Res 2007; 13: 3913-21.10.1158/1078-0432.CCR-06-261017606725
    Search in Google Scholar
  25. 25. Kovac V, Smrdel U. Meta-analyses of clinical trials in patients with non-small cell lung cancer. Minireview. Neoplasma 2004; 51: 334˝1-40.
    Search in Google Scholar
  26. 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: 524-35.10.1093/annonc/mdq38720709812
    Search in Google Scholar
  27. 27. Wollenberg A, Moosmann N, Klein E, Katzer K. A tool for scoring of acneiform skin eruptions induced by EGF receptor inhibition. Exp Dermatol 2008; 17: 790-2.10.1111/j.1600-0625.2008.00715.x18503553
    Search in Google Scholar
  28. 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: 509-22.10.1007/s00520-009-0744-x20145956
    Search in Google Scholar
  29. 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: 94-8.10.1159/00027765620215799
    Search in Google Scholar
  30. 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: 142-9.10.1093/annonc/mdm40017785763
    Search in Google Scholar
  31. 31. Lacouture ME. Insights into the pathophysiology and management of dermatologic toxicities to EGFR-targeted therapies in colorectal cancer. CancerNurs 2007; 30(4 Suppl 1): S17-26.10.1097/01.NCC.0000281758.85704.9b17666987
    Search in Google Scholar
  32. 32. Segaert S, Van Cutsem E. Clinical management of EGFRI dermatologic toxicities: the European perspective. Oncology (Williston Park) 2007; 21: 22-6.
    Search in Google Scholar
  33. 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: 845-51.10.1016/j.ejca.2006.11.01617289377
    Search in Google Scholar
  34. 34. Segaert S, Tabernero J, Chosidow O, Dirschka T, Elsner 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: 599-606.10.1111/j.1610-0387.2005.05058.x16033478
    Search in Google Scholar
  35. 35. Bernier J, Russi EG, Homey B, Merlano 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: 2191-200.10.1093/annonc/mdr13921606209
    Search in Google Scholar
  36. 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: 317-26.10.1016/j.jaad.2006.09.00517141360
    Search in Google Scholar
  37. 37. Tsimboukis S, Merikas I, Karapanagiotou EM, Saif MW, Syrigos KN. Erlotinibinduced skin rash in patients with non-small-cell lung cancer: pathogenesis, clinical significance, and management. Clin Lung Cancer 2009; 10: 106-11.10.3816/CLC.2009.n.01319362953
    Search in Google Scholar
  38. 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: 343-51.10.1097/CCO.0b013e328347406321537180
    Search in Google Scholar
  39. 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: 198-202.10.3816/SCT.2007.n.01518632517
    Search in Google Scholar
  40. 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: 1016-22.10.1634/theoncologist.2010-0082322804320798191
    Search in Google Scholar
  41. 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: 847-53.10.1002/cncr.23621391816618543329
    Search in Google Scholar
  42. 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). SupportCare Cancer 2011; 19: 1601-7.10.1007/s00520-010-0988-5393579720820817
    Search in Google Scholar
  43. 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: 5390-6.10.1200/JCO.2007.12.698718048820
    Search in Google Scholar
  44. 44. Deplanque G, Chavaillon J, Vergnenegre A, Falchero L. CYTAR: A randomized clinical trial evaluating the preventive effect of doxycycline on erlotinibinduced folliculitis in non-small cell lung cancer patients [Abstract]. J ClinOncol 2010; 28: Abstract 9019.10.1200/jco.2010.28.15_suppl.9019
    Search in Google Scholar
  45. 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: 614-20.10.1016/j.jaad.2009.03.04619646778
    Search in Google Scholar
  46. 46. Fernandez-Guarino M, Perez Garcia B, Aldanondo Fernandez de la Mora I, Garcia-Millan C, Garrido Lopez P, Jaen Olasolo P. [Treatment of acneiform rash by epidermal growth factor inhibitors with oral tetracyclines]. [Spanish]. Actas Dermosifiliogr 2006; 97: 503-8.
    Search in Google Scholar
  47. 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: 1173-4.10.1001/archderm.141.9.117316172328
    Search in Google Scholar
  48. 48. Molinari E, De Quatrebarbes J, Andre T, Aractingi S. Cetuximab-induced acne. Dermatology 2005; 211: 330-3.10.1159/00008850216286741
    Search in Google Scholar
  49. 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. JCutan Med Surg 2001; 5: 105-10.10.1177/120347540100500202
    Search in Google Scholar
  50. 50. Mitchell E, Lacouture M, Shearer H, Iannotti 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 Clin Oncol 2009; 27: Abstract CRA4027.10.1200/jco.2009.27.18_suppl.cra4027
    Search in Google Scholar
  51. 51. Hedges LV, Olkin I. Statistical methods for meta-analysis. Orlando: Academic Press; 1985.
    Search in Google Scholar
  52. 52. Laird NM, Ware JH. Random-effects models for longitudinal data. Biometrics 1982; 38: 963-74.10.2307/2529876
    Search in Google Scholar
  53. 53. Luu M, Lai SE, Patel J, Guitart J, Lacouture ME. Photosensitive rash due to the epidermal growth factor receptor inhibitor erlotinib. PhotodermatolPhotoimmunol Photomed 2007; 23: 42-5.10.1111/j.1600-0781.2007.00273.x17254038
    Search in Google Scholar
  54. 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.
    Search in Google Scholar
  55. 55. Li T, Perez-Soler R. Skin toxicities associated with epidermal growth factor receptor inhibitors. Target Oncol 2009; 4: 107-19.10.1007/s11523-009-0114-019452131
    Search in Google Scholar
  56. 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 9124.10.1200/jco.2007.25.18_suppl.9124
    Search in Google Scholar
  57. 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 Clin Oncol 2006; 23: Abstract 3036.10.1200/jco.2006.24.18_suppl.3036
    Search in Google Scholar
  58. 58. Ocvirk J, Rebersek M. Management of cutaneous side effects of cetuximab therapy with vitamin K1 creme. Radiol Oncol 2008; 42: 215-24.10.2478/v10019-008-0022-4
    Search in Google Scholar
  59. 59. Ocvirk J, Rebersek M. Topical application of vitamin K1 cream for cetuximabrelated skin toxicities [Abstract]. Ann Oncol 2009; 20: Abstract PD-0021.
    Search in Google Scholar
  60. 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 monocloncal antibody (mAb) treatment in patients with metastatic cancer: first analysis of an observational Italian study [Abstract]. J Clin Oncol 2011; 29: Abstract 594.10.1200/jco.2011.29.4_suppl.594
    Search in Google Scholar
  61. 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 Clin Oncol 2010; 28: Abstract e14011.10.1200/jco.2010.28.15_suppl.e14011
    Search in Google Scholar
  62. 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: 1079-95.10.1007/s00520-011-1197-6312870021630130
    Search in Google Scholar
  63. 63. Potthoff K, Hassel JC, Wollenberg A. Therapie und prophylaxe EGFRinhibitor- induzierter hautreaktionen. Arzneimitteltherapie 2010; 28: 191-8.
    Search in Google Scholar
  64. 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 Clin Oncol 2010; 28: 4706-13.10.1200/JCO.2009.27.605520921462
    Search in Google Scholar
  65. 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 Clin Oncol 2010; 28: 4697-705.10.1200/JCO.2009.27.486020921465
    Search in Google Scholar
  66. 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 Clin Oncol 2009; 27: 663-71.10.1200/JCO.2008.20.839719114683
    Search in Google Scholar
  67. 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 Clin Oncol 2011; 29: 2011-9.10.1200/JCO.2010.33.509121502544
    Search in Google Scholar
DOI: https://doi.org/10.2478/raon-2013-0014 | Journal eISSN: 1581-3207 | Journal ISSN: 1318-2099
Journal RSS Feed
Language: English
Page range: 166 - 175
Published on: May 21, 2013
Published by: Association of Radiology and Oncology
In partnership with: Paradigm Publishing Services
Publication frequency: 4 issues per year
Keywords:
acne-like skin rash,
cetuximab,
antibiotics,
erlotinib,
gefitinib,
panitumumab,
vitamin K
Related subjects:
Medicine,
Clinical medicine,
Internal medicine,
Haematology, oncology,
Radiology

© 2013 Janja Ocvirk, Steffen Heeger, Philip McCloud, Ralf-Dieter Hofheinz, published by Association of Radiology and Oncology
This work is licensed under the Creative Commons License.

Previous articleVolume 47 (2013): Issue 2 (June 2013)Next article