Sorafenib in Recurrent and/or Metastatic Salivary Gland Carcinomas: Phase II Study

This phase II trial was conducted on adult patients with RMSGC. Inclusion criteria were as follows: histologically proven diagnosis of RMSGC; availability of primary tissue (block or formalin fixed paraffin embedded [FFPE] tissue slides); age _18 years; Eastern Cooperative Oncology Group Performance Status (ECOG-PS) 0e1; adequate bone marrow, liver and renal function (haemoglobin >9.0 g/dl; neutrophil count >1500/mm3; platelet count _100,000/ml; total bilirubin <1.5 _ upper limit of normal [ULN]; ALT and AST <2.5 _ ULN and <5 _ ULN for patients with liver metastases; serum creatinine <1.5 _ ULN; alkaline phosphatase <4 _ ULN; PT-INR/PTT <1.5 _ ULN); _1 measurable unidimensional lesion by magnetic resonance imaging (MRI) or computed tomography (CT) scan according to the RECIST 1.1 criteria. Patients with cardiac disease (i.e. congestive heart failure New York Heart Association (NYHA) > 2, cardiac arrhythmia; uncontrolled hypertension) in the six months before study entry were excluded. Previous chemotherapy for metastatic disease was allowed and progression of disease was not required for the enrolment. All patients provided written informed consent. The study was conducted in accordance with Good Clinical Practice guidelines and the Declaration of Helsinki and was approved by the local Ethical Committee (Registry number, NCT01703455). 2.2. Treatment and assessments: Patients received 400 mg of sorafenib orally every 12 h on a continuous basis in 4-week cycles until disease progression and/or unacceptable toxicity. Biochemical and clinical evaluation, and drug safety monitoring according to the Common Terminology Criteria for Adverse Events (CTCAE) v3.0 were performed every 4 weeks. The attribution of adverse events (AEs) to the study drug was judged by the investigators. CT scans were performed every 8 weeks until disease progression. An independent evaluation of radiological response (RECIST and Choi criteria) was performed by two radiologists on anonymised CT scans. Stomatology evaluation was performed at baseline to exclude any sign of osteoradionecrosis. Dose reduction was adopted in cases of clinically significant haematologic or other AEs that were considered related to sorafenib. In such cases, doses were reduced to 400 mg once daily and then to 400 mg every other day. If further reductions were required, patients were withdrawn from the trial. Dose reescalation was not allowed.