Cutaneous Premalignant and Malignant Lesions - Keratoacanthoma and Squamous Cell Carcinoma

Definition

The development of cutaneous premalignant and malignant lesions are rarely derived from Multikinase inhibitor treatment (but can occur especially with sorafenib).

Incidence

Image provided with courtesy of  Dr. V. Sibaud, Cancer University Institue, Toulouse Oncopole-France 2014. All rights reserved.

Keratoacanthoma from a patient receiving Multikinase inhibitor treatment - image provided with courtesy of  Dr. V. Sibaud, Cancer University Institue, Toulouse Oncopole-France 2014. All rights reserved.

Squamous cell carcinoma/Keratoacanthoma occurs in 0.09% and 3% of patients treated with regorafenib and sorafenib, respectively.1,2

Onset

In patients treated with sorafenib and sunitinib, the median treatment duration before the diagnosis of cutaneous malignancies, including squamous cell carcinoma and basal cell carcinoma, was 13.5 months.3 These lesions are caused by paradoxical activation of mitotic cell pathways by the multikinase inhibitor onto a genetic background of activating Mutations of the same pathway.4
Resolution

Squamous cell carcinoma

Squamous cell carcinoma from a patient receiving Multikinase inhibitor treatment - image provided with courtesy of Prof. Dr. Siegfried Segaert (University Hospital Leuven, Leuven Belgium) 2014 All rights reserved

Resolution of cutaneous malignancies with sorafenib was seen following discontinuation of therapy, with no new or persisting keratoacanthoma or squamous cell carcinomas observed.5,6 Also see management of keratoacanthoma and squamous cell carcinoma.

 

References

1Food and Drug Administration. Nexavar® (sorafenib) Prescribing Information 2013.
2European Medicines Agency. Stivarga® (regorafenib) Summary of Product Characteristics 2013.
3Breaker K, Naam M, La Rosa FG. Skin cancer associated with the use of sorafenib and sunitinib for renal cell carcinoma. Dermatol Surg. 2013;39:981–987.
4Oberholzer A, et al. RAS mutations are associated with the development of cutaneous squamous cell tumors in patients treated with RAF inhibitors. J Clin Oncol. 2012;30: 316-321.
5McLellan B, Kerr H. Cutaneous toxicities of the multikinase inhibitors sorafenib and sunitinib. Dermatol Ther. 2011;24:396–400.
6Arnault JP, et al. Keratoacanthomas and squamous cell carcinomas in patients receiving sorafenib. J Clin Oncol. 2009;27:e59–e61.

Last update: 22 August 2014