Doxycycline vs Isotretinoin for Acneiform Eruptions of TKI

Summary

Tyrosine Kinase inhibitors (TKIs) have become standard of care in patients with EGFR mutations in non-small cell lung cancer and other EGFR-mutated cancers. However, TKIs are well-known to cause cutaneous adverse events, including acneiform eruptions. Moderate to severe acneiform eruptions are often associated with severe pruritus and pain. Current treatment recommendations rely on expert consensus. Moderate and severe reactions requiring systemic therapy, usually tetracycline antibiotics or isotretinoin. No randomized trial has compared the relative effectiveness of tetracyclines versus isotretinoin. The objective of this unblinded, randomized trial is to compare tetracyclines to isotretinoin for treatment of moderate to severe acneiform eruptions in cancer patients on tyrosine kinase inhibitors. The primary aim of this clinical trial is to elucidate which systemic treatment is more effective in clearing acneiform eruptions caused by TKIs. The results of this study will add to the literature in this field and will aid in developing evidence based clinical guidelines.

Timeline

Start

2021-09-01

Primary completion

2022-12

Completion

2022-12

Publications

• Background Agnew T, Furber G, Leach M, Segal L. A Comprehensive Critique and Review of Published Measures of Acne Severity. J Clin Aesthet Dermatol. 2016 Jul;9(7):40-52. Epub 2016 Jul 1.
• Background Gutzmer R, Werfel T, Mao R, Kapp A, Elsner J. Successful treatment with oral isotretinoin of acneiform skin lesions associated with cetuximab therapy. Br J Dermatol. 2005 Oct;153(4):849-51. doi: 10.1111/j.1365-2133.2005.06835.x. No abstract available.
• Background Andrews ED, Garg N, Patel AB. A retrospective chart review on oral retinoids as a treatment for epidermal growth factor receptor inhibitor- and mitogen-activated protein kinase kinase inhibitor-induced acneiform eruptions. J Am Acad Dermatol. 2020 Apr;82(4):998-1000. doi: 10.1016/j.jaad.2019.10.003. Epub 2019 Oct 8. No abstract available.
• Background Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, Dancey J, Arbuck S, Gwyther S, Mooney M, Rubinstein L, Shankar L, Dodd L, Kaplan R, Lacombe D, Verweij J. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer. 2009 Jan;45(2):228-47. doi: 10.1016/j.ejca.2008.10.026.
• Background Scope A, Agero AL, Dusza SW, Myskowski PL, Lieb JA, Saltz L, Kemeny NE, Halpern AC. Randomized double-blind trial of prophylactic oral minocycline and topical tazarotene for cetuximab-associated acne-like eruption. J Clin Oncol. 2007 Dec 1;25(34):5390-6. doi: 10.1200/JCO.2007.12.6987.
• Background Gerber PA, Meller S, Eames T, Buhren BA, Schrumpf H, Hetzer S, Ehmann LM, Budach W, Bolke E, Matuschek C, Wollenberg A, Homey B. Management of EGFR-inhibitor associated rash: a retrospective study in 49 patients. Eur J Med Res. 2012 Feb 23;17(1):4. doi: 10.1186/2047-783X-17-4.
• Background Lewis V, Finlay AY. 10 years experience of the Dermatology Life Quality Index (DLQI). J Investig Dermatol Symp Proc. 2004 Mar;9(2):169-80. doi: 10.1111/j.1087-0024.2004.09113.x. No abstract available.
• Background Finlay AY, Khan GK. Dermatology Life Quality Index (DLQI)--a simple practical measure for routine clinical use. Clin Exp Dermatol. 1994 May;19(3):210-6. doi: 10.1111/j.1365-2230.1994.tb01167.x.
• Background Shikiar R, Bresnahan BW, Stone SP, Thompson C, Koo J, Revicki DA. Validity and reliability of patient reported outcomes used in psoriasis: results from two randomized clinical trials. Health Qual Life Outcomes. 2003 Oct 8;1:53. doi: 10.1186/1477-7525-1-53.
• Background Annunziata MC, Ferrillo M, Cinelli E, Panariello L, Rocco D, Fabbrocini G. Retrospective Analysis of Skin Toxicity in Patients under Anti-EGFR Tyrosine Kinase Inhibitors: Our Experience in Lung Cancer. Open Access Maced J Med Sci. 2019 Mar 27;7(6):973-977. doi: 10.3889/oamjms.2019.170. eCollection 2019 Mar 30.
• Background Lacouture ME. Mechanisms of cutaneous toxicities to EGFR inhibitors. Nat Rev Cancer. 2006 Oct;6(10):803-12. doi: 10.1038/nrc1970.
• Background Melosky B, Leighl NB, Rothenstein J, Sangha R, Stewart D, Papp K. Management of egfr tki-induced dermatologic adverse events. Curr Oncol. 2015 Apr;22(2):123-32. doi: 10.3747/co.22.2430.
• Background Giovannini M, Gregorc V, Belli C, Roca E, Lazzari C, Vigano MG, Serafico A, Villa E. Clinical Significance of Skin Toxicity due to EGFR-Targeted Therapies. J Oncol. 2009;2009:849051. doi: 10.1155/2009/849051. Epub 2009 Jun 22.
• Background Melosky B. Supportive care treatments for toxicities of anti-egfr and other targeted agents. Curr Oncol. 2012 Jun;19(Suppl 1):S59-63. doi: 10.3747/co.19.1054.
• Background Hirsh V. Managing treatment-related adverse events associated with egfr tyrosine kinase inhibitors in advanced non-small-cell lung cancer. Curr Oncol. 2011 Jun;18(3):126-38. doi: 10.3747/co.v18i3.877.
• Background Sc O'brien, Jb Lewis & Wj Cunliffe (1998) The Leeds revised acne grading system, Journal of Dermatological Treatment, 9:4, 215-220, DOI: 10.3109/09546639809160698
• Background Bolognia, Jean., Jorizzo, Joseph L.Schaffer, Julie V., eds. Dermatology. [Philadelphia] :: Elsevier Saunders, 2012. Print.
• Background Ettinger DS, Wood DE, Aisner DL, Akerley W, Bauman J, Chirieac LR, D'Amico TA, DeCamp MM, Dilling TJ, Dobelbower M, Doebele RC, Govindan R, Gubens MA, Hennon M, Horn L, Komaki R, Lackner RP, Lanuti M, Leal TA, Leisch LJ, Lilenbaum R, Lin J, Loo BW Jr, Martins R, Otterson GA, Reckamp K, Riely GJ, Schild SE, Shapiro TA, Stevenson J, Swanson SJ, Tauer K, Yang SC, Gregory K, Hughes M. Non-Small Cell Lung Cancer, Version 5.2017, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw. 2017 Apr;15(4):504-535. doi: 10.6004/jnccn.2017.0050.
• Background DeWitt CA, Siroy AE, Stone SP. Acneiform eruptions associated with epidermal growth factor receptor-targeted chemotherapy. J Am Acad Dermatol. 2007 Mar;56(3):500-5. doi: 10.1016/j.jaad.2006.06.046. Epub 2006 Dec 12.
• Background Bidoli P, Cortinovis DL, Colombo I, Crippa A, Cicchiello F, Villa F, Cazzaniga ME, Altomare G. Isotretinoin plus clindamycin seem highly effective against severe erlotinib-induced skin rash in advanced non-small cell lung cancer. J Thorac Oncol. 2010 Oct;5(10):1662-3. doi: 10.1097/JTO.0b013e3181ec1729.
• Background Vezzoli P, Marzano AV, Onida F, Alessi E, Galassi B, Tomirotti M, Berti E. Cetuximab-induced acneiform eruption and the response to isotretinoin. Acta Derm Venereol. 2008;88(1):84-6. doi: 10.2340/00015555-0330. No abstract available.
• Background Costello CM, Hill HE, Brumfiel CM, Yang YW, Swanson DL. Choosing between isotretinoin and acitretin for epidermal growth factor receptor inhibitor and small molecule tyrosine kinase inhibitor acneiform eruptions. J Am Acad Dermatol. 2021 Mar;84(3):840-841. doi: 10.1016/j.jaad.2020.09.090. Epub 2020 Oct 8. No abstract available.
• Background Landis MN. Optimizing Isotretinoin Treatment of Acne: Update on Current Recommendations for Monitoring, Dosing, Safety, Adverse Effects, Compliance, and Outcomes. Am J Clin Dermatol. 2020 Jun;21(3):411-419. doi: 10.1007/s40257-020-00508-0.
• Background Wolverton, S., 2020. Comprehensive Dermatologic Drug Therapy. 4th ed. Elsevier, pp.Chapters 9, 22. In.
• Background Lacouture ME, Sibaud V, Gerber PA, van den Hurk C, Fernandez-Penas P, Santini D, Jahn F, Jordan K; ESMO Guidelines Committee. Electronic address: [email protected]. Prevention and management of dermatological toxicities related to anticancer agents: ESMO Clinical Practice Guidelines☆. Ann Oncol. 2021 Feb;32(2):157-170. doi: 10.1016/j.annonc.2020.11.005. Epub 2020 Nov 25. No abstract available.
• Background Lacouture ME, Anadkat MJ, Bensadoun RJ, Bryce J, Chan A, Epstein JB, Eaby-Sandy B, Murphy BA; MASCC Skin Toxicity Study Group. Clinical practice guidelines for the prevention and treatment of EGFR inhibitor-associated dermatologic toxicities. Support Care Cancer. 2011 Aug;19(8):1079-95. doi: 10.1007/s00520-011-1197-6. Epub 2011 Jun 1.
• Background Cury-Martins J, Eris APM, Abdalla CMZ, Silva GB, Moura VPT, Sanches JA. Management of dermatologic adverse events from cancer therapies: recommendations of an expert panel. An Bras Dermatol. 2020 Mar-Apr;95(2):221-237. doi: 10.1016/j.abd.2020.01.001. Epub 2020 Feb 15.
• Background Chiang HC, Anadkat MJ. Isotretinoin for high-grade or refractory epidermal growth factor receptor inhibitor-related acneiform papulopustular eruptions. J Am Acad Dermatol. 2013 Oct;69(4):657-8. doi: 10.1016/j.jaad.2013.05.032. No abstract available.
• Background Vickers AJ, Altman DG. Statistics notes: Analysing controlled trials with baseline and follow up measurements. BMJ. 2001 Nov 10;323(7321):1123-4. doi: 10.1136/bmj.323.7321.1123. No abstract available.
• Background O'Connell NS, Dai L, Jiang Y, Speiser JL, Ward R, Wei W, Carroll R, Gebregziabher M. Methods for Analysis of Pre-Post Data in Clinical Research: A Comparison of Five Common Methods. J Biom Biostat. 2017 Feb 24;8(1):1-8. doi: 10.4172/2155-6180.1000334.

Drugs

Indications