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.