Phase II and pharmacological study of oral docetaxel plus cyclosporin A in anthracycline pre-treated metastatic breast cancer.

INTRODUCTION: Previously, we demonstrated that oral docetaxel plus the P-glycoprotein (Pgp; ABCB1) inhibitor cyclosporin A (CsA) is safe and results in adequate exposure to docetaxel. This phase II study evaluates the anti-tumor activity, safety and pharmacokinetics of oral docetaxel in combination with CsA in women with advanced breast cancer. MATERIALS AND METHODS: Patients with measurable advanced breast cancer were given one flat dose of 100 mg oral docetaxel, preceded by one single dose of 15 mg/kg CsA, weekly for 6 weeks in a cycle of 8 weeks. Pharmacokinetic monitoring of docetaxel and CsA was performed in week 1 and 9. RESULTS: Thirty-three patients with a median age of 50 years were recruited. Thirty patients were evaluable for toxicity and twenty-six for response. All had received prior anthracycline treatment. The treatment was generally well tolerated with manageable toxicity although many patients needed a dose reduction, most commonly because of fatigue and uncomplicated neutropenia. The median treatment duration was 16 weeks (range 6 - 32). The overall response rate in evaluable patients was 42% (95% CI: 23 - 63) and the median overall survival was 12.2 months (8.4 - 23.1). The interpatient variability in the area under the curve of 100 mg orally administered docetaxel was moderate, respectively 49 and 30% in week 1 and 9. CONCLUSION: Weekly oral docetaxel, combined with the booster drug CsA, is an active and safe treatment in anthracycline pre-treated patients with advanced breast cancer.

Feasibility of FDG PET/CT to monitor the response of axillary lymph node metastases to neoadjuvant chemotherapy in breast cancer patients.

PURPOSE: The aim of this study was to assess the accuracy of (18)F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT to visualize lymph node metastases before the start of neoadjuvant chemotherapy and to determine how often the visualization is sufficiently prominent to allow monitoring of the axillary response. METHODS: Thirty-eight patients with invasive breast cancer of >3 cm and/or lymph node metastasis underwent FDG PET/CT before neoadjuvant chemotherapy. The results of the FDG PET/CT were compared with those from ultrasonography with fine-needle aspiration (FNA) cytology or sentinel node biopsy. Patients suitable for response monitoring of the axilla were defined as having either a maximum standardized uptake value (SUV(max)) >or= 2.5 or a tumour to background ratio >or=5 in the most intense lymph node. RESULTS: The sensitivity and specificity of FDG PET/CT in detecting axillary involvement were 97 and 100%, respectively. No difference existed between the SUV(max) of the primary tumour and that from the related most intense lymph node metastasis. Moreover, the mean tumour to background ratio was 90% higher in the lymph nodes compared to the primary tumour (p = 0.006). Ninety-three per cent of the patients had sufficient uptake in the lymph nodes to qualify for subsequent response monitoring of the axilla. A considerable distinction in metabolic activity was observed between the different subtypes of breast cancer. The mean SUV(max) in lymph node metastases of oestrogen receptor (ER)-positive, triple-negative and human epidermal growth factor receptor 2 (HER2)-positive tumours was 6.6, 11.6 and 6.6, respectively. CONCLUSION: The high accuracy in visualizing lymph node metastases and the sufficiently high SUV(max) and tumour to background ratio at baseline suggest that it is feasible to monitor the axillary response with FDG PET/CT, especially in triple-negative tumours.