A prospective phase II study of combined androgen blockade in patients with androgen receptor-positive metastatic or locally advanced unresectable salivary gland carcinoma.

Background: There is no standard first-line chemotherapy for recurrent/metastatic (RM) or unresectable locally advanced (LA) salivary gland carcinoma (SGC). Patients and methods: We conducted a single institution, open-label, single arm, phase II trial of combined androgen blockade (CAB) for androgen receptor (AR)-positive SGC. Leuprorelin acetate was administered subcutaneously at a dose of 3.75 mg every 4 weeks. Bicalutamide was administered orally at a daily dose of 80 mg. Patients were treated until progressive disease or unacceptable toxicities. Results: Thirty-six eligible patients were enrolled. Thirty-three patients had RM disease and three patients had LA disease. The pathological diagnoses were salivary duct carcinoma (34 patients, 94%) and adenocarcinoma, NOS (two patients, 6%). The best overall response rate was 41.7% [n = 15, 95% confidence interval (CI), 25.5%-59.2%], the clinical benefit rate was 75.0% (n = 27, 95% CI, 57.8%-87.9%). The median progression-free survival was 8.8 months (95% CI, 6.3-12.3 months) and the median overall survival was 30.5 months (95% CI, 16.8 months to not reached). Additional analyses between treatment outcomes and clinicopathological factors or biomarkers including AR positivity, human epidermal growth factor receptor 2 status, and its complex downstream signaling pathway gene mutations showed no statistically significant differences. Elevated grade 3 liver transaminases and increased serum creatinine were reported in two patients, respectively. Discontinuation of leuprorelin acetate or bicalutamide due to adverse event occurred in one patient. Conclusion: This study suggests that CAB has equivalent efficacy and less toxicity for patients with AR-positive RM or unresectable LA SGC compared with conventional chemotherapy, which warrants further study. Clinical Trial Registration: UMIN-CTR (http://www.umin.ac.jp/ctr/index-j.htm), identification number: UMIN000005703.

Intra-arterial chemoradiation therapy with weekly low-dose cisplatin for squamous cell carcinoma of the maxillary sinus.

A new intra-arterial chemoradiation regimen that involves infusing low-dose cisplatin in combination with definitive irradiation was used in 36 patients diagnosed with squamous cell carcinoma of the maxillary sinus. The safety and therapeutic efficacy of this regimen were reviewed retrospectively. An intra-arterial catheter was inserted in a retrograde manner into the target artery via the superficial temporal artery or occipital artery. Intra-arterial infusion was performed using cisplatin at a dose of 20-50mg/m(2) per week for 6-8 weeks. At the same time, sodium thiosulphate was infused as a neutralizing agent. Irradiation was performed at 60Gy in 30 fractions. All 36 patients completed treatment. Grade 3 adverse events occurred in only seven patients (19.4%) and no grade 4 events were noted. As a primary therapy, the complete response rate was 83.3%, the partial response rate was 16.7%, and the overall response rate was 100%. The 2-year local control rate was 63.0%, and the 2-year overall survival rate was 75.5%. The 2-year preservation rate of the hard palate was 97.1%, that of the eyeball was 97.2%, and that of visual function was 94.4%. This treatment regimen can contribute to improving the quality of life of patients without reducing the curability of the therapy.