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01.01.2016 | Original Article

Hedgehog pathway inhibitor in combination with radiation therapy for basal cell carcinomas of the head and neck

First clinical experience with vismodegib for locally advanced disease

verfasst von: Björn Schulze, MD, Markus Meissner, MD, Shahram Ghanaati, DMD, MD, Iris Burck, MD, Claus Rödel, MD, Panagiotis Balermpas, MD

Erschienen in: Strahlentherapie und Onkologie | Ausgabe 1/2016

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Abstract

Background

Definitive radiotherapy and vismodegib, an oral inhibitor of the hedgehog pathway, are both established treatment options for locally advanced basal cell carcinomas (BCC). Both have shown good results in local tumor control; however, the effects concerning advanced tumors are often not of a lasting nature and to date no systematic data about the combination of the two modalities are available.

Patients and methods

We retrospectively analyzed four patients who received vismodegib and radiotherapy in combination. Radiation doses varied between 50.4 Gy and 66.0 Gy. Three patients had recurrent BCC. One patient had locoregional lymph node involvement. Vismodegib was taken once a day (150 mg) during the entire time of irradiation and beyond upon instructions of the attending dermatologist.

Results

In three cases a persistent complete response was observed, in one case the tumor remained stable for approximately 6 months until further tumor progression was documented. The combined therapy was well tolerated in all cases. No exceptional side effects pointing at a drug–radiation interaction were observed.

Conclusion

The combination of vismodegib and radiation seems feasible and the initial results are promising. In our cohort, there was no increase in unexpected side effects. Further research is needed to evaluate the significance of this combined therapy.

Lear JT, Smith AG (1997) Basal cell carcinoma. Postgrad Med J 73:538–542PubMedPubMedCentralCrossRef

Nongrum HB, Bhuyan D, Royte V et al (2014) Metastatic basal cell carcinoma to the lungs: case report and review of literature. Indian Dermatol Online J 5:S26–S29CrossRef

Hernandez-Machin B, Borrego L, Gil-Garcia M et al (2007) Office-based radiation therapy for cutaneous carcinoma: evaluation of 710 treatments. Int J Dermatol 46:453–459PubMedCrossRef

Olschewski T, Bajor K, Lang B et al (n d) [Radiotherapy of basal cell carcinoma of the face and head: importance of low dose per fraction on long-term outcome]. J Dtsch Dermatol Ges 4:124–130

Schulte KW, Lippold A, Auras C et al (2005) Soft x-ray therapy for cutaneous basal cell and squamous cell carcinomas. J Am Acad Dermatol 53:993–1001PubMedCrossRef

Locke J, Karimpour S, Young G et al (2001) Radiotherapy for epithelial skin cancer. Int J Radiat Oncol Biol Phys 51:748–755PubMedCrossRef

Lovett RD, Perez CA, Shapiro SJ et al (1990) External irradiation of epithelial skin cancer. Int J Radiat Oncol Biol Phys 19:235–242PubMedCrossRef

Fitzpatrick PJ (1984) Skin cancer of the head—treatment by radiotherapy. J Otolaryngol 13:261–266PubMed

Sekulic A, Migden MR, Lewis K et al (2015) Pivotal ERIVANCE basal cell carcinoma (BCC) study: 12-month update of efficacy and safety of vismodegib in advanced BCC. J Am Acad Dermatol 72:1021–1026e8PubMedCrossRef

10.

Cirrone F, Harris CS (2012) Vismodegib and the hedgehog pathway: a new treatment for basal cell carcinoma. Clin Ther 34:2039–2050PubMedCrossRef

11.

Proctor AE, Thompson LA, O’Bryant CL (2014) Vismodegib: an inhibitor of the Hedgehog signaling pathway in the treatment of basal cell carcinoma. Ann Pharmacother 48:99–106PubMedCrossRef

12.

Yang L, Xie G, Fan Q et al (2010) Activation of the hedgehog-signaling pathway in human cancer and the clinical implications. Oncogene 29:469–481PubMedCrossRef

13.

Sims-Mourtada J, Izzo JG, Apisarnthanarax S et al (2006) Hedgehog: an attribute to tumor regrowth after chemoradiotherapy and a target to improve radiation response. Clin Cancer Res 12:6565–6572PubMedCrossRef

14.

Zeng J, Aziz K, Chettiar ST et al (2013) Hedgehog pathway inhibition radiosensitizes non-small cell lung cancers. Int J Radiat Oncol Biol Phys 86:143–149PubMedPubMedCentralCrossRef

15.

Chung CH, Dignam JJ, Hammond ME et al (2011) Glioma-associated oncogene family zinc finger 1 expression and metastasis in patients with head and neck squamous cell carcinoma treated with radiation therapy (RTOG 9003). J Clin Oncol 29:1326–1334PubMedPubMedCentralCrossRef

16.

Chaudary N, Pintilie M, Hedley D et al (2012) Hedgehog pathway signaling in cervical carcinoma and outcome after chemoradiation. Cancer 118:3105–3115PubMedCrossRef

17.

Yoshikawa R, Tsujimura T, Tao L et al (2012) The oncoprotein and stem cell renewal factor BMI1 associates with poor clinical outcome in oesophageal cancer patients undergoing preoperative chemoradiotherapy. BMC Cancer 12:461PubMedPubMedCentralCrossRef

18.

Pollom EL, Bui TT, Chang AL et al (2015) Concurrent vismodegib and radiotherapy for recurrent, advanced basal cell carcinoma. JAMA Dermatol. doi:10.1001/jamadermatol.2015.0326

19.

Raleigh DR, Algazi A, Arron ST et al (2015) Induction Hedgehog pathway inhibition followed by combined modality radiotherapy for basal cell carcinoma. Br J Dermatol. doi:10.1111/bjd.13748

20.

Bonner JA, Harari PM, Giralt J et al (2006) Radiotherapy plus cetuximab for squamous-cell carcinoma of the head and neck. N Engl J Med 354:567–578PubMedCrossRef

21.

Schulze B, Meissner M, Wolter M et al (2014) Unusual acute and delayed skin reactions during and after whole-brain radiotherapy in combination with the BRAF inhibitor vemurafenib. Two case reports. Strahlenther Onkol 190:229–232PubMedCrossRef

22.

Hecht M, Zimmer L, Loquai C et al (2015) Radiosensitization by BRAF inhibitor therapy-mechanism and frequency of toxicity in melanoma patients. Ann Oncol 26:1238–1244PubMedCrossRef

23.

Lee IJ, Koom WS, Lee CG et al (2009) Risk factors and dose-effect relationship for mandibular osteoradionecrosis in oral and oropharyngeal cancer patients. Int J Radiat Oncol Biol Phys 75:1084–1091PubMedCrossRef

24.

Sekulic A, Migden MR, Oro AE et al (2012) Efficacy and safety of vismodegib in advanced basal-cell carcinoma. N Engl J Med 366:2171–2179PubMedCrossRef

25.

Tang JY, Mackay-Wiggan JM, Aszterbaum M et al (2012) Inhibiting the hedgehog pathway in patients with the basal-cell nevus syndrome. N Engl J Med 366:2180–2188PubMedPubMedCentralCrossRef

26.

Basset-Seguin N, Hauschild A, Grob JJ et al (2015) Vismodegib in patients with advanced basal cell carcinoma (STEVIE): a pre-planned interim analysis of an international, open-label trial. Lancet Oncol 16:729–736PubMedCrossRef

Titel: Hedgehog pathway inhibitor in combination with radiation therapy for basal cell carcinomas of the head and neck
First clinical experience with vismodegib for locally advanced disease
verfasst von: Björn Schulze, MD
Markus Meissner, MD
Shahram Ghanaati, DMD, MD
Iris Burck, MD
Claus Rödel, MD
Panagiotis Balermpas, MD
Publikationsdatum: 01.01.2016
Verlag: Springer Berlin Heidelberg
Erschienen in: Strahlentherapie und Onkologie / Ausgabe 1/2016
Print ISSN: 0179-7158
Elektronische ISSN: 1439-099X
DOI: https://doi.org/10.1007/s00066-015-0902-7

Springer Medizin

Hedgehog pathway inhibitor in combination with radiation therapy for basal cell carcinomas of the head and neck

First clinical experience with vismodegib for locally advanced disease