Basal cell carcinomas are the most common
skin cancers. They are usually localised and carry a good prognosis. There is no standard treatment for the rare patients with metastatic
basal cell carcinoma or very extensive
basal cell carcinoma for whom surgery or
radiotherapy is inappropriate.
Vismodegib, a cytotoxic
drug, is claimed to prevent tumour growth by inhibiting a pathway involved in tissue repair and embryogenesis. It has been authorised in the European Union for patients with metastatic or locally advanced and extensive
basal cell carcinoma. Clinical evaluation of
vismodegib is based on a non-comparative clinical trial involving 104 patients, providing only weak evidence. Twenty-one months after the start of the trial, 7 patients with
metastases (21%) and 6 patients with advanced
basal cell carcinoma (10%) had died. Given the lack of a placebo group, there is no way of knowing whether
vismodegib had any effect, positive or negative, on survival. There were no complete responses among patients with
metastases, but about one-third of them had partial responses. Among the 63 patients with locally advanced
basal cell carcinoma, there were 14 complete responses and 16 partial responses. The recurrence rate in patients with complete responses was not reported. Similar results were reported in two other uncontrolled trials available in mid-2014.
Vismodegib has frequent and sometimes serious adverse effects, including
muscle spasms,
fatigue and severe hyponatraemia. Cases of severe
weight loss,
alopecia, ocular disorders, other
cancers (including
squamous cell carcinoma) and anaemia have also been reported. More data are needed on possible hepatic and cardiovascular adverse effects. A potent teratogenic effect was seen in experimental animals. As
vismodegib enters semen,
contraception is mandatory for both men (
condoms) and women. In practice,
vismodegib has frequent and varied adverse effects, some of which are serious, while its benefits are poorly documented.
Vismodegib should only be proposed to patients in whom
basal cell cancer markedly undermines quality of life, and only in the context of clinical research.