leuprolide and Salivary-Gland-Neoplasms

There is no standard first-line chemotherapy for recurrent/metastatic (RM) or unresectable locally advanced (LA) salivary gland carcinoma (SGC).. 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.. 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.. 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.. UMIN-CTR (http://www.umin.ac.jp/ctr/index-j.htm), identification number: UMIN000005703.

Topics: Aged; Aged, 80 and over; Androgen Antagonists; Anilides; Disease-Free Survival; Female; Humans; Leuprolide; Male; Middle Aged; Neoplasm Metastasis; Nitriles; Prospective Studies; Receptors, Androgen; Salivary Gland Neoplasms; Tosyl Compounds; Treatment Outcome

BACKGROUND Salivary duct carcinoma (SDC) is a rare, aggressive head and neck cancer with frequent metastases. Current treatment options for recurrent or metastatic SDC include targeted anti-androgen therapy, HER2-targeted therapy, or systemic chemotherapy. We report the first use of a combination chemohormonal strategy. CASE REPORT A 68-year-old male who had never smoked with a past medical history of two-vessel coronary artery disease and systolic heart failure presented with a parotid mass and underwent surgical resection. Biopsy of the mass revealed high-grade, androgen receptor-positive and Erb-B2 receptor tyrosine kinase-2 (ERBB2)-amplified positive SDC. He subsequently received adjuvant radiation therapy. Four months after completion of adjuvant radiation therapy, recurrence with symptomatic pleural effusion and nodes, hepatic metastases, and boney metastases occurred. Due to significant symptomatic tumor, a rapid treatment response was desired. Combination chemohormonal therapy (CHT) was initiated with carboplatin area under the curve 4 and paclitaxel, 200 mg/m² in 21-day cycles along with combined androgen blockade using leuprolide, 45 mg subcutaneously every 6 months and bicalutamide, 50 mg daily. The treatment was well tolerated with fatigue as the main adverse event. Positron emission tomography-computed tomography at 3 and 6 months after treatment initiation showed good partial response. The patient experienced uveal progression after 8 months and alternate treatment was started. CONCLUSIONS Combination CHT with carboplatin, paclitaxel, and combined androgen deprivation may be a good treatment option in androgen receptor-positive recurrent or metastatic SDC if rapid treatment response is desired. Combination chemotherapy with androgen deprivation for validation through clinical trials.

Topics: Aged; Anilides; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Carboplatin; Carcinoma; Humans; Leuprolide; Male; Nitriles; Paclitaxel; Salivary Ducts; Salivary Gland Neoplasms; Tosyl Compounds

Topics: Androgen Antagonists; Anilides; Antineoplastic Combined Chemotherapy Protocols; Carcinoma; Clinical Trials, Phase II as Topic; Disease-Free Survival; Humans; Leuprolide; Nitriles; Receptors, Androgen; Salivary Gland Neoplasms; Signal Transduction; Tosyl Compounds; Treatment Outcome

Salivary duct carcinoma (SDC) is an aggressive malignancy with high recurrence rates. Standard management includes surgical resection followed by adjuvant radiation. Androgen receptor positivity has been described to be present in 40% to 90% of SDCs, and a recent case series showed a benefit to androgen deprivation therapy (ADT) in recurrent or metastatic disease.. We present the case of an 87-year-old woman with a locally advanced androgen receptor-positive parotid SDC treated definitively with ADT and external beam radiotherapy, a regimen modeled after the treatment of prostate cancer. She had a complete response on positron emission tomography (PET)/CT scan and had no evidence of disease 24 months after the completion of treatment.. To our knowledge, this case report is the first to describe the use of ADT plus radiation to definitively treat SDC. This regimen could be considered in patients with androgen receptor-positive SDCs who are considered unresectable or who refuse surgery.

Topics: Aged, 80 and over; Androgen Antagonists; Anilides; Biopsy, Needle; Combined Modality Therapy; Female; Follow-Up Studies; Humans; Immunohistochemistry; Leuprolide; Magnetic Resonance Imaging; Neoplasm Staging; Nitriles; Positron-Emission Tomography; Radiotherapy, Intensity-Modulated; Receptors, Androgen; Salivary Gland Neoplasms; Tosyl Compounds; Treatment Outcome