Recently, the hedgehog inhibitor vismodegib (Erivedge; Genentech) has demonstrated efficacy in the treatment of locally advanced and metastatic basal cell carcinoma (BCC).1,2 Almost all BCC contains genetic alterations in the sonic hedgehog signaling pathway. Most mutations affect the function of patched homologue 1, which normally inhibits the signaling activity of the transmembrane protein smoothened homologue. In a phase 1 study of vismodegib,1 a 58% response rate among 33 patients with advanced BCC was observed. The approval of vismodegib treatment at 150 mg/d was based on results from the phase 2 study.2 That study found the response rate for metastatic BCC to 30% and for locally advanced BCC, 43%, with a complete response in 21% of the cases. Common adverse events reported by more than 30% of patients were muscle spasms, alopecia, dysgeusia, weight loss, and fatigue.
Vismodegib is metabolized in humans via oxidation, glucuronidation, and pyridine ring cleavage. The main metabolic pathways include CYP2C9, CYP3A4/5, and P glycoproteins. Vismodegib and its metabolites are mostly eliminated by the hepatic route, with 82% of the administered dose recovered in the feces and 4.4% in the urine.3
A 76-year-old man presented with locally advanced BCC of the right midface (Figure, A). The histologically confirmed ulcerated BCC had grown slowly over the past 20 years. Computed tomographic imaging revealed osseous and muscular infiltration of the masseter muscle, both orbits, the right nasal sinuses, and the nasal bridge. The tumor infiltration of both orbits caused loss of vision. At an earlier presentation, the patient had declined surgery and radiotherapy. He had undergone a previous surgical attempt to excise the BCC nearly 30 years earlier.
A, Osseous and muscular tumor infiltration of both orbits and the nasal bridge before vismodegib treatment initiation. B, Conversion of secreting tissue into dry tumor tissue after 11 months of treatment with vismodegib.
While the patient appeared in a good general condition, he had type 2 diabetes mellitus, hypertension, and chronic atrial fibrillation. He also had chronic stage 4 renal insufficiency (creatinine, 6.81 mg/dL [upper limit of normal, 1.2 mg/dL]) and had been undergoing dialysis treatment 3 times weekly for the last month. (To convert creatinine to micromoles per liter, multiply by 88.4.) Oral vismodegib treatment was initiated at the recommended full dose of 150 mg/d.
Four weeks after treatment initiation, a partial response of the BCC with clinically significant tumor shrinkage was detected. After 11 months of oral vismodegib treatment, the patient showed an ongoing partial response (Figure, B). However, tumor biopsies were declined by the patient. Furthermore, the creatinine level remained stable at 5.25 mg/dL. Vismodegib treatment was tolerated without any clinically relevant adverse effects. Interestingly, the common adverse effects such as muscle cramps of the lower leg, fatigue, weight loss, or dysgeusia were not reported. Only alopecia developed within the first 4 weeks of treatment.
The patient‘s quality of life was significantly improved by reepithelialization of ulcerated and bleeding areas of the tumor. In particular, the formation of an epiphysis of the right midface contributed to an improvement of the patient’s quality of life. At last follow-up, treatment with vismodegib was being continued at the same dose.
To our knowledge, this is the first case report that describes vismodegib use and its tolerability in a patient with chronic stage 4 kidney disease receiving dialysis treatment. This case indicates good efficacy and tolerability of vismodegib in a patient with advanced BCC. Based on this patient’s response and tolerability, we suggest that vismodegib may offer a safe treatment option to be considered in the setting of adequate medical monitoring for patients with renal insufficiency receiving dialysis therapy. However, further observations are needed to evaluate the safety profile of vismodegib in patients with renal impairment.
Corresponding Author: Lara Valeska Maul, MD, Department of Dermatology, University Hospital Schleswig-Holstein, Campus Kiel, Schittenhelmstr 7, 24105 Kiel, Germany (email@example.com).
Published Online: December 30, 2015. doi:10.1001/jamadermatol.2015.4592
Conflict of Interest Disclosures: Dr Maul reports grants and personal fees from Bristol-Myers Squibb, Merck & Co Inc, and Roche outside the scope of the present work. Dr Kähler reports grants and personal fees from Bristol-Myers Squibb, Merck & Co Inc, and Roche outside the scope of the present work. Prof Dr Hauschild reports grants and personal fees from Amgen, Bristol-Myers Squibb, Celgene, Eisai, GlaxoSmithKline, MedImmune, MelaSciences, Merck Serono, Merck & Co Inc, Novartis, Oncosec, and Roche outside the scope of the present work. No other disclosures are reported.
Additional Contributions: We thank the patient for granting permission to publish this information.
Maul LV, Kähler KC, Hauschild A. Effective and Tolerable Treatment of Advanced Basal Cell Carcinoma With Vismodegib Despite Renal Insufficiency. JAMA Dermatol. 2016;152(12):1387-1388. doi:10.1001/jamadermatol.2015.4592