Phase II and Pharmacological Study of Oral Docetaxel Plus Cyclosporin A in Anthracycline Pre-Treated Metastatic Breast Cancer

Title:Phase II and Pharmacological Study of Oral Docetaxel Plus Cyclosporin A in Anthracycline Pre-Treated Metastatic Breast Cancer

Volume: 9 Issue: 2

Author(s): Helgi H. Helgason, Stijn L.W. Koolen, Erik van Werkhoven, Mirte M. Malingre, C. Marielle F. Kruijtzer, Alwin D.R. Huitema, Margaret E. Schot, Wim M. Smit, Jos H. Beijnen and Jan H.M. Schellens

Affiliation:

Keywords: Anti-tumor activity, cyclosporin A, oral docetaxel, P-glycoprotein, phase II, safety.

Abstract: 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.

Cite this article as:

Helgason H. Helgi, Koolen L.W. Stijn, Werkhoven van Erik, Malingre M. Mirte, Kruijtzer F. C. Marielle, Huitema D.R. Alwin, Schot E. Margaret, Smit M. Wim, Beijnen H. Jos and Schellens H.M. Jan, Phase II and Pharmacological Study of Oral Docetaxel Plus Cyclosporin A in Anthracycline Pre-Treated Metastatic Breast Cancer, Current Clinical Pharmacology 2014; 9 (2) . https://dx.doi.org/10.2174/1574884708666131111193403

DOI https://dx.doi.org/10.2174/1574884708666131111193403	Print ISSN 1574-8847
Publisher Name Bentham Science Publisher	Online ISSN 2212-3938