Official reprint from UpToDate®
www.uptodate.com ©2017 UpToDate®

Systemic treatment of advanced cutaneous squamous and basal cell carcinomas

Renato G Martins, MD, MPH
Section Editors
Robert S Stern, MD
June K Robinson, MD
Deputy Editor
Michael E Ross, MD


Basal cell carcinoma and squamous cell carcinoma of the skin, together referred to as nonmelanoma skin cancer (NMSC), are the most commonly diagnosed malignant neoplasms in the Caucasian population of the United States. Because many patients are treated as outpatients in an office setting, reliable statistics are difficult to obtain. Nonetheless, the National Cancer Institute estimates that approximately two million new cases occurred in 2012 [1].

The vast majority of patients can be successfully managed with a variety of simple procedures, such as cryotherapy, curettage and electrodesiccation, topical treatments (fluorouracil, imiquimod), or simple surgical excision. When lesions are more advanced, Mohs micrographic surgery, more extensive surgical resection, or radiation therapy are generally sufficient to control locoregional disease.

Despite their high prevalence, these NMSCs are rarely fatal. It is estimated that in 2012 [1], approximately 1000 patients died of the disease. Squamous cell carcinomas are biologically more aggressive, and neglected lesions can be life-threatening due to local extension or metastasis. By contrast, basal cell carcinoma is only very rarely life-threatening.

The use of systemic therapy is limited to patients with distant metastases or locally advanced disease that cannot be adequately managed with surgical or radiotherapeutic techniques.

Systemic chemotherapy for basal cell and squamous cancers of the skin is discussed here. The treatment of localized basal cell and squamous cell carcinomas is discussed elsewhere. (See "Treatment and prognosis of basal cell carcinoma at low risk of recurrence" and "Treatment of basal cell carcinomas at high risk for recurrence" and "Treatment and prognosis of cutaneous squamous cell carcinoma".)


Subscribers log in here

To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information or to purchase a personal subscription, click below on the option that best describes you:
Literature review current through: Mar 2017. | This topic last updated: Feb 21, 2017.
The content on the UpToDate website is not intended nor recommended as a substitute for medical advice, diagnosis, or treatment. Always seek the advice of your own physician or other qualified health care professional regarding any medical questions or conditions. The use of this website is governed by the UpToDate Terms of Use ©2017 UpToDate, Inc.
  1. http://www.cancer.gov/cancertopics/types /skin. Accessed on May 11, 2013
  2. Califano JA, Lydiatt WM, Nehal KS, et al. Cutaneous Squamous Cell Carcinoma of the Head and Neck. In: AJCC Cancer Staging Manual, 8th, Amin MB. (Ed), Springer, New York 2017. p.171.
  3. Epstein EH. Basal cell carcinomas: attack of the hedgehog. Nat Rev Cancer 2008; 8:743.
  4. Hahn H, Wicking C, Zaphiropoulous PG, et al. Mutations of the human homolog of Drosophila patched in the nevoid basal cell carcinoma syndrome. Cell 1996; 85:841.
  5. Johnson RL, Rothman AL, Xie J, et al. Human homolog of patched, a candidate gene for the basal cell nevus syndrome. Science 1996; 272:1668.
  6. Xie J, Murone M, Luoh SM, et al. Activating Smoothened mutations in sporadic basal-cell carcinoma. Nature 1998; 391:90.
  7. Von Hoff DD, LoRusso PM, Rudin CM, et al. Inhibition of the hedgehog pathway in advanced basal-cell carcinoma. N Engl J Med 2009; 361:1164.
  8. LoRusso PM, Rudin CM, Reddy JC, et al. Phase I trial of hedgehog pathway inhibitor vismodegib (GDC-0449) in patients with refractory, locally advanced or metastatic solid tumors. Clin Cancer Res 2011; 17:2502.
  9. Basset-Seguin N, Hauschild A, Grob JJ, et al. Vismodegib in patients with advanced basal cell carcinoma (STEVIE): a pre-planned interim analysis of an international, open-label trial. Lancet Oncol 2015; 16:729.
  10. Mohan SV, Chang J, Li S, et al. Increased Risk of Cutaneous Squamous Cell Carcinoma After Vismodegib Therapy for Basal Cell Carcinoma. JAMA Dermatol 2016; 152:527.
  11. Chang AL, Oro AE. Initial assessment of tumor regrowth after vismodegib in advanced Basal cell carcinoma. Arch Dermatol 2012; 148:1324.
  12. Atwood SX, Sarin KY, Whitson RJ, et al. Smoothened variants explain the majority of drug resistance in basal cell carcinoma. Cancer Cell 2015; 27:342.
  13. Dijkgraaf GJ, Alicke B, Weinmann L, et al. Small molecule inhibition of GDC-0449 refractory smoothened mutants and downstream mechanisms of drug resistance. Cancer Res 2011; 71:435.
  14. Sekulic A, Migden MR, Oro AE, et al. Efficacy and safety of vismodegib in advanced basal-cell carcinoma. N Engl J Med 2012; 366:2171.
  15. Chang AL, Solomon JA, Hainsworth JD, et al. Expanded access study of patients with advanced basal cell carcinoma treated with the Hedgehog pathway inhibitor, vismodegib. J Am Acad Dermatol 2014; 70:60.
  16. Sekulic A, Migden MR, Lewis K, et al. Pivotal ERIVANCE basal cell carcinoma (BCC) study: 12-month update of efficacy and safety of vismodegib in advanced BCC. J Am Acad Dermatol 2015; 72:1021.
  17. Rodon J, Tawbi HA, Thomas AL, et al. A phase I, multicenter, open-label, first-in-human, dose-escalation study of the oral smoothened inhibitor Sonidegib (LDE225) in patients with advanced solid tumors. Clin Cancer Res 2014; 20:1900.
  18. Migden MR, Guminski A, Gutzmer R, et al. Treatment with two different doses of sonidegib in patients with locally advanced or metastatic basal cell carcinoma (BOLT): a multicentre, randomised, double-blind phase 2 trial. Lancet Oncol 2015; 16:716.
  19. Dummer R, Guminski A, Gutzmer R, et al. The 12-month analysis from Basal Cell Carcinoma Outcomes with LDE225 Treatment (BOLT): A phase II, randomized, double-blind study of sonidegib in patients with advanced basal cell carcinoma. J Am Acad Dermatol 2016; 75:113.
  20. Kim J, Tang JY, Gong R, et al. Itraconazole, a commonly used antifungal that inhibits Hedgehog pathway activity and cancer growth. Cancer Cell 2010; 17:388.
  21. Kim DJ, Kim J, Spaunhurst K, et al. Open-label, exploratory phase II trial of oral itraconazole for the treatment of basal cell carcinoma. J Clin Oncol 2014; 32:745.
  22. Carneiro BA, Watkin WG, Mehta UK, Brockstein BE. Metastatic basal cell carcinoma: complete response to chemotherapy and associated pure red cell aplasia. Cancer Invest 2006; 24:396.
  23. Bauman JE, Eaton KD, Martins RG. Treatment of recurrent squamous cell carcinoma of the skin with cetuximab. Arch Dermatol 2007; 143:889.
  24. Suen JK, Bressler L, Shord SS, et al. Cutaneous squamous cell carcinoma responding serially to single-agent cetuximab. Anticancer Drugs 2007; 18:827.
  25. Arnold AW, Bruckner-Tuderman L, Zuger C, Itin PH. Cetuximab therapy of metastasizing cutaneous squamous cell carcinoma in a patient with severe recessive dystrophic epidermolysis bullosa. Dermatology 2009; 219:80.
  26. Maubec E, Petrow P, Scheer-Senyarich I, et al. Phase II study of cetuximab as first-line single-drug therapy in patients with unresectable squamous cell carcinoma of the skin. J Clin Oncol 2011; 29:3419.
  27. Reigneau M, Robert C, Routier E, et al. Efficacy of neoadjuvant cetuximab alone or with platinum salt for the treatment of unresectable advanced nonmetastatic cutaneous squamous cell carcinomas. Br J Dermatol 2015; 173:527.
  28. Foote MC, McGrath M, Guminski A, et al. Phase II study of single-agent panitumumab in patients with incurable cutaneous squamous cell carcinoma. Ann Oncol 2014; 25:2047.
  29. Lewis CM, Glisson BS, Feng L, et al. A phase II study of gefitinib for aggressive cutaneous squamous cell carcinoma of the head and neck. Clin Cancer Res 2012; 18:1435.
  30. Yin VT, Pfeiffer ML, Esmaeli B. Targeted therapy for orbital and periocular basal cell carcinoma and squamous cell carcinoma. Ophthal Plast Reconstr Surg 2013; 29:87.
  31. Sadek H, Azli N, Wendling JL, et al. Treatment of advanced squamous cell carcinoma of the skin with cisplatin, 5-fluorouracil, and bleomycin. Cancer 1990; 66:1692.
  32. Jarkowski A 3rd, Hare R, Loud P, et al. Systemic Therapy in Advanced Cutaneous Squamous Cell Carcinoma (CSCC): The Roswell Park Experience and a Review of the Literature. Am J Clin Oncol 2016; 39:545.
  33. Winkler JK, Schneiderbauer R, Bender C, et al. Anti-programmed cell death-1 therapy in nonmelanoma skin cancer. Br J Dermatol 2017; 176:498.
  34. Chang AL, Kim J, Luciano R, et al. A Case Report of Unresectable Cutaneous Squamous Cell Carcinoma Responsive to Pembrolizumab, a Programmed Cell Death Protein 1 Inhibitor. JAMA Dermatol 2016; 152:106.
  35. Lipson EJ, Bagnasco SM, Moore J Jr, et al. Tumor Regression and Allograft Rejection after Administration of Anti-PD-1. N Engl J Med 2016; 374:896.
  36. Borradori L, Sutton B, Shayesteh P, Daniels GA. Rescue therapy with anti-programmed cell death protein 1 inhibitors of advanced cutaneous squamous cell carcinoma and basosquamous carcinoma: preliminary experience in five cases. Br J Dermatol 2016; 175:1382.
  37. Otley CC, Coldiron BM, Stasko T, Goldman GD. Decreased skin cancer after cessation of therapy with transplant-associated immunosuppressants. Arch Dermatol 2001; 137:459.
  38. Salgo R, Gossmann J, Schöfer H, et al. Switch to a sirolimus-based immunosuppression in long-term renal transplant recipients: reduced rate of (pre-)malignancies and nonmelanoma skin cancer in a prospective, randomized, assessor-blinded, controlled clinical trial. Am J Transplant 2010; 10:1385.