A phase II and pharmacodynamic study of sunitinib in relapsed/refractory oesophageal and gastro-oesophageal cancers.

BACKGROUND: Blockade of the vascular endothelial growth factor (VEGF) pathway shows evidence of activity in gastro-oesophageal (GE) and oesophageal cancer. We investigated the efficacy of sunitinib, a multikinase VEGF inhibitor, in patients with relapsed/refractory GE/oesophageal cancer. METHODS: This was a single-stage Fleming phase II study. The primary end point was progression-free survival (PFS) at 24 weeks. If five or more patients out of a total of 25 were free of progressive disease at 24 weeks, sunitinib would be recommended for further study. Patients received sunitinib 37.5 mg orally daily and imaged every 6 weeks. Exploratory correlative analysis included serum growth factors, tumour gene expression and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). RESULTS: Twenty-five evaluable patients participated in the study. Progression-free survival at 24 weeks was 8% (n=2 patients; confidence interval (CI): 95% 1.4-22.5%), and the duration of best response for the patients was 23 and 72 weeks. Ten patients (42%) had stable disease (SD) for >10 weeks. Overall response rate is 13%. Median PFS is 7 weeks (95% CI: 5.6-11.4 weeks) and the median overall survival is 17 weeks (95% CI: 8.9-25.3 weeks). Most common grade 3/4 toxicities included fatigue (24%), anaemia (20%) thrombocytopenia (16%), and leucopenia (16%). No patients discontinued therapy due to toxicity. Serum VEGF-A and -C levels, tumour complement factor B (CFB) gene expression, and DCE-MRI correlated with clinical benefit, defined as SD or better as best response. CONCLUSION: Sunitinib is well tolerated but only a select subgroup of patients benefited. Serum VEGF-A and -C may be early predictors of benefit. On this study, patients with clinical benefit from sunitinib had higher tumour CFB expression, and thus has identified CFB as a potential predictor for efficacy of anti-angiogenic therapy. These findings need validation from future prospective trials.

Evaluation of surgical experience and the use of an osteotomy guide on the apical angle of an Austin osteotomy.

BACKGROUND: Distal osteotomies of the first metatarsal are commonly used to correct hallux valgus deformities. Of the distal osteotomies, the Austin osteotomy is popular among foot surgeons on an international level. The precision of the osteotomy is important to achieve a congruous osteotomy. OBJECTIVES: The purpose of this study was to examine the effects of experience and technique on creating a precise Austin osteotomy. METHOD: Three individuals with varying levels of experience (student, resident and podiatric physician) created Austin osteotomies in metatarsal sawbones, using three different techniques (freehand, guide wire and osteotomy guide). The medial and lateral apical angles were measured, and the mean, standard deviation, and range of the angles were calculated. The differences between medial and lateral angles were also calculated. RESULTS: The results indicated that the mean and range of the angles varied considerably with the freehand and guide wire techniques at all experience levels. The angles were accurate and consistent for all experience levels; however, when an osteotomy guide was used. The use of an osteotomy guide also noticeably reduced the number of divergent and convergent osteotomies. CONCLUSIONS: The use of an osteotomy guide consistently resulted in a more precise Austin osteotomy for all experience levels.