Preview

Head and Neck Tumors (HNT)

Advanced search

Use of the Hedgehog signaling pathway inhibitor in the treatment of recurrent locally advanced and metastatic basal cell skin cancer

https://doi.org/10.17650/2222-1468-2019-9-4-38-42

Abstract

The study objective is to provide data on the use of the Hedgehog signaling pathway inhibitor (vismodegib) in the treatment of recurrent locally advanced and metastatic basal cell skin cancer at the N. N. Petrov National Medical Research Center of Oncology.

Materials and methods. Clinical data of 10 patients who participated in a multicenter, non-randomized clinical trial of phase II ERIVANCE BBC (ClinicalTrials. gov NCT833417). Patients took the daily studied drug vismodegib orally at a dose of 150 mg daily until disease progression or intolerance due to side effects. Efficiency and safety assessment was carried out once every 4 weeks.

Results. Complete regression was achieved in 7 patients, while the average duration of use of the drug was 240 ± 65 days. Stabilization was observed in 2 patients, the minimum duration of the drug was 336 days. One patient showed progression after 728 days of taking the drug. Side effects of the 1 grade according to CTCAE (Common Terminology Criteria for Adverse Events), v. 3.0 were observed in all patients, in 9 they were expressed in muscle cramps, alopecia and changes in taste sensitivity, and in 1 patient isolated in the form of muscle cramps.

Conclusion. The results show a good safety profile of vismodegib, which allows it to be used in elderly patients with concomitant pathology. The frequency of response to treatment, including the achievement of complete regression in 70 % of patients, makes vismodegib an acceptable treatment option for metastatic form of basal cell skin cancer and relapse of locally advanced forms.

About the Authors

Z. A.-G. Radzhabova
N.N. Petrov National Medical Research Center of Oncology, Ministry of Health of Russia
Russian Federation
68 Leningradskaya St., Pesochny Settlement, Saint Petersburg 197758


M. A. Kotov
N.N. Petrov National Medical Research Center of Oncology, Ministry of Health of Russia
Russian Federation
68 Leningradskaya St., Pesochny Settlement, Saint Petersburg 197758


Z. S. Bekyasheva
N.N. Petrov National Medical Research Center of Oncology, Ministry of Health of Russia
Russian Federation
68 Leningradskaya St., Pesochny Settlement, Saint Petersburg 197758


M. A. Radzhabova
S.M. Kirov Military Medical Academy, Ministry of Defense of Russia
Russian Federation
6 Akademika Lebedeva St., Saint Petersburg 194044


E. V. Levchenko
N.N. Petrov National Medical Research Center of Oncology, Ministry of Health of Russia
Russian Federation
68 Leningradskaya St., Pesochny Settlement, Saint Petersburg 197758


References

1. Macha M.A., Batra S.K., Ganti A.K. Profile of vismodegib and its potential in the treatment of advanced basal cell carcinoma. Cancer Manag Res 2013;5:197–203. DOI: 10.2147/CMAR.S45976.

2. Wu S., Han J., Li W.-Q. et al. Basal-cell carcinoma incidence and associated risk factors in U.S. women and men. Am J Epidemiol 2013;178(6):890–7. DOI: 10.1093/aje/kwt073.

3. Lucas R., McMichael T., Smith W., Armstrong B. Solar ultraviolet radiation: global burden of disease from solar ultraviolet radiation. Environmental Burden of Disease Series, No. 13. Geneva: World Health Organization, 2006. 250 p. Available at: http://www.who.int/uv/health/solaruvradfull_180706.pdf.

4. Sekulic A., Mangold A.R., Northfelt D.W., LoRusso P.M. Advanced basal cell carcinoma of the skin: targeting the hedgehog pathway. Curr Opin Oncol 2013;25(3):218–23. DOI: 10.1097/CCO.0b013e32835ff438.

5. Varga E., Korom I., Raskó Z. et al. Neglected basal cell carcinomas in the 21 st century. J Skin Cancer. 2011;2011: 392151. DOI: 10.1155/2011/392151.

6. Wadhera A., Fazio M., Bricca G., Stanton O. Metastatic basal cell carcinoma: a case report and literature review. How accurate is our incidence data? Dermatol Online J 2006;12(5):7.

7. Lo J.S., Snow S.N., Reizner G.T. et al. Metastatic basal cell carcinoma: report of twelve cases with a review of the literature. J Am Acad Dermatol 1991;24(5 Pt 1):715–9. DOI: 10.1016/0190-9622(91)70108-E.

8. Snow S.N., Sahl W., Lo J.S. et al. Metastatic basal cell carcinoma: report of five cases. Cancer 1994;73(2):328–35. DOI: 10.1002/1097-0142(19940115)73: 2 < 328 :: AID-CNCR2820730216 > 3.0. CO; 2-U.

9. Reifenberger J., Wolter M., Weber R.G. et al. Missense mutations in SMOH in sporadic basal cell carcinomas of the skin and primitive neuroectodermal tumors of the central nervous system. Cancer Res 1998;58(9):1798–803.

10. Xie J., Murone M., Luoh S.-M. et al. Activating Smoothened mutations in sporadic basal-cell carcinoma. Nature 1998;391(6662):90–2. DOI: 10.1038/34201.

11. Göppner D., Leverkus M. Basal cell carcinoma: from the molecular understanding of the pathogenesis to targeted therapy of progressive disease. J Skin Cancer 2011;2011:650258. DOI: 10.1155/2011/650258.

12. Daya-Grosjean L., Couvé-Privat S. Sonic hedgehog signaling in basal cell carcinomas. Cancer Lett 2005;225(2):181–92. DOI: 10.1016/j.canlet.2004.10.003.

13. LoRusso P.M., Rudin C.M., Reddy J.C. 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(8): 2502–11. DOI: 10.1158/1078-0432. CCR-10-2745.

14. Food and Drug Administration. Skin cancer patients have more treatment options. Available at: https://www.fda.gov/consumers/consumer-updates/skincancer-patients-have-more-treatmentoptions.

15. European Medicines Agency. European Public Assessment Report: Erivedge. Available at: https://www.ema.europa.eu/en/medicines/human/EPAR/erivedge.

16. Migden M.R., 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(6):716–28. DOI: 10.1016/S1470-2045(15)70100-2.

17. Sekulic A., Migden M.R., Oro A.E. et al. Efficacy and safety of vismodegib in advanced basal-cell carcinoma. N Engl J Med 2012;366(23):2171–9. DOI: 10.1056/NEJMoa1113713.

18. Therasse P., Arbuck S.G., Eisenhauer E.A. et al. New guidelines to evaluate the response to treatment in solid tumors. J Natl Cancer Inst 2000;92(3):205–16. DOI: 10.1093/jnci/92.3.205.

19. National Cancer Institute: Cancer Therapy Evaluation Program: Common Terminology Criteria for Adverse Events v3.0(CTCAE). Available at: http://ctep.cancer.gov/protocolDevelopment/electronic_applications/docs/ctcaev3.pdf.


Review

For citations:


Radzhabova Z.A., Kotov M.A., Bekyasheva Z.S., Radzhabova M.A., Levchenko E.V. Use of the Hedgehog signaling pathway inhibitor in the treatment of recurrent locally advanced and metastatic basal cell skin cancer. Head and Neck Tumors (HNT). 2019;9(4):38-42. (In Russ.) https://doi.org/10.17650/2222-1468-2019-9-4-38-42

Views: 1139


Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.


ISSN 2222-1468 (Print)
ISSN 2411-4634 (Online)