Purpose
To assess the tumor response to the smoothened (SMO) inhibitor, sonidegib (LDE225), in patients with an advanced basal cell carcinoma (BCC) resistant to treatment with vismodegib (GDC0449).
Experimental Design
Nine patients with an advanced BCC that was previously resistant to treatment with vismodegib were given sonidegib in this investigational, open-label study. Tumor response was determined using the response evaluation criteria in solid tumors. SMO mutations were identified using biopsy samples from the target BCC location.
Results
The median duration of treatment with sonidegib was 6 weeks (range, 3–58 weeks). Five patients experienced progressive disease with sonidegib. Three patients experienced stable disease and discontinued sonidegib either due to adverse events (n = 1) or due to election for surgery (n = 2). The response of one patient was not evaluable. SMO mutations with in vitro data suggesting resistance to Hh pathway inhibition were identified in 5 patients, and none of these patients experienced responses while on sonidegib.
Conclusion
Patients with advanced BCCs that were previously resistant to treatment with vismodegib similarly demonstrated treatment resistance with sonidegib. Patients who have developed treatment resistance to an SMO inhibitor may continue to experience tumor progression in response to other SMO inhibitors.
A single-injection dose of betamethasone sodium phosphate and betamethasone acetate solution illustrated consistent and significant chondrotoxicity using a physiologically relevant in vitro model and should be used with caution. Given the observed chondrotoxicity of triamcinolone acetonide in a single trial, there may be some evidence that this medication is chondrotoxic. However, at 14 days, betamethasone sodium phosphate and betamethasone acetate was the only condition that caused significant cell death.
Background
Lymphatic malformations (LM) can be challenging to treat. Mainstay interventions including surgery and sclerotherapy are invasive and can result in local recurrence and complications.
Objective
To assess the effect of 20 weeks of oral sildenafil on reducing LM volume and symptoms in children.
Methods
Seven children (4 boys, 3 girls; ages 13–85 months) with LMs were given oral sildenafil for 20 weeks in this open-label study. The volume of the LM was calculated blindly using magnetic resonance imaging performed before and after 20 weeks of sildenafil. LMs were assessed clinically on weeks 4, 12, 20, and 32. Both the physician and parents evaluated the LM in comparison to baseline.
Results
Four subjects had a LM volume decrease (1.0–31.7%). In 2 subjects, despite a LM volume increase (1.1–3.7%), clinical improvement was noted while on sildenafil. One subject had a 29.6% increase in LM volume and no therapeutic response. LMs of all 6 subjects who experienced a therapeutic response on sildenafil softened and became easily compressible. Adverse events were minimal.
Limitations
A randomized-controlled trial will be necessary to verify the effects of sildenafil on LMs.
Conclusions
Sildenafil can reduce LM volume and symptoms in some children.
Summary
Background
Metastatic basal cell carcinoma (BCC) is a rare but life-threatening condition. Prior estimates of overall survival (OS) from time of diagnosis of distant metastasis to death are approximately 8–14 months. However, these estimates are based on analyses of case reports published prior to 1984.
Objectives
To assess an updated OS in patients with metastatic BCC at a single academic institution.
Methods
Using patients seen from 1997 to 2011, a retrospective chart review was performed on biopsy-confirmed cases of distant metastatic BCC at Stanford University School of Medicine. Kaplan–Meier analysis was used to determine OS and progression-free survival (PFS).
Results
Ten consecutive cases of distant metastatic BCC were identified. Median OS was 7·3 years [95% confidence interval (CI) 1·6–∞]; median PFS was 3·4 years (95% CI 1·1–5·2).
Conclusions
Our findings suggest that OS in patients with distant metastatic BCC may be more favourable than previously reported.
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