Tumour biology, metastatic sites and taxanes sensitivity as determinants of eribulin mesylate efficacy in breast cancer: results from the ERIBEX retrospective, international, multicenter study.

BACKGROUND: Our retrospective, international study aimed at evaluating the activity and safety of eribulin mesylate (EM) in pretreated metastatic breast cancer (MBC) in a routine clinical setting. METHODS: Patients treated with EM for a locally advanced or MBC between March 2011 and January 2014 were included in the study. Clinical and biological assessment of toxicity was performed at each visit. Tumour response was assessed every 3 cycles of treatment. A database was created to collect clinical, pathological and treatment data. RESULTS: Two hundred and fifty-eight patients were included in the study. Median age was 59 years old. Tumours were Hormone Receptor (HR)-positive (73.3 %) HER2-positive (10.2 %), and triple negative (TN, 22.5 %). 86.4 % of the patients presented with visceral metastases, mainly in the liver (67.4 %). Median previous metastatic chemotherapies number was 4 [1-9]. Previous treatments included anthracyclines and/or taxanes (100 %) and capecitabine (90.7 %). Median number of EM cycles was 5 [1-19]. The relative dose intensity was 0.917. At the time of analysis (median follow-up of 13.9 months), 42.3 % of the patients were still alive. The objective response rate was 25.2 % (95 %CI: 20-31) with a 36.1 % clinical benefit rate (CBR). Median time to progression (TTP) and overall survival were 3.97 (95 %CI: 3.25-4.3) and 11.2 (95 %CI: 9.3-12.1) months, respectively. One- and 2-year survival rates were 45.5 and 8.5 %, respectively. In multivariate analysis, HER2 positivity (HR = 0.29), the presence of lung metastases (HR = 2.49) and primary taxanes resistance (HR = 2.36) were the only three independent CBR predictive factors, while HR positivity (HR = 0.67), the presence of lung metastases (HR = 1.52) and primary taxanes resistance (HR = 1.50) were the only three TTP independent prognostic factors. Treatment was globally well tolerated. Most common grade 3-4 toxicities were neutropenia (20.9 %), peripheral neuropathy (3.9 %), anaemia (1.6 %), liver dysfunction (0.8 %) and thrombocytopenia (0.4 %). Thirteen patients (5 %) developed febrile neutropenia. CONCLUSION: EM is an effective new option in heavily pretreated MBC, with a favourable efficacy/safety ratio in a clinical practice setting. Our results comfort the use of this new molecule and pledge for the evaluation of EM-trastuzumab combination in this setting. Tumour biology, primary taxanes sensitivity and metastatic sites could represent useful predictive and prognostic factors.

Physicochemical stability of oxaliplatin in 5% dextrose injection stored in polyvinyl chloride, polyethylene, and polypropylene infusion bags.

PURPOSE: The physicochemical stability of extemporaneous dilutions of oxaliplatin in 5% dextrose injection stored in polyvinyl chloride (PVC), polypropylene, and polyethylene infusion bags was studied. METHODS: Oxaliplatin 100 mg/20 mL concentrated solution was diluted in 100 mL of 5% dextrose injection in PVC, polypropylene, and polyethylene infusion bags to produce nominal oxaliplatin concentrations of 0.2 and 1.3 mg/mL. The filled bags were stored for 14 days at 20 degrees C and protected from light, at 20 degrees C under normal fluorescent light, and at 4 degrees C. A 1-mL sample was removed from each bag at time 0 and at 24, 48, 72, 120, 168, and 336 hours. The samples were visually inspected for color and clarity, and the pH values of the solutions were measured. High-performance liquid chromatography was used to assay oxaliplatin concentration. Bacterial contamination was assessed on study day 14 after incubation in trypticase soy solution for three days at 37 degrees C. RESULTS: Solutions of oxaliplatin 0.2 and 1.3 mg/mL in 5% dextrose injection were stable in the three container types for at least 14 days at both 4 degrees C and 20 degrees C without regard to light exposure. No color change was detected during the storage period, and pH values remained stable. No microbial contamination was detected in any samples over the study period. CONCLUSION: Oxaliplatin solutions diluted in 5% dextrose injection to 0.2 and 1.3 mg/mL were stable in PVC and PVC-free infusion bags for at least 14 days at both 4 degrees C and 20 degrees C without regard to light exposure.