1. ¹Department of Medical Oncology, The Netherlands Cancer Institute/Antoni van Leeuwenhoek Hospital, Plesmanlaan 121, 1066CX Amsterdam, The Netherlands
2. ²Rivierenland Hospital, Tiel, The Netherlands
3. ³Slotervaart Hospital, Louwesweg 6, 1066EC Amsterdam, The Netherlands
4. ⁴IVAX Research Inc., Miami, FL, USA
5. ⁵Faculty of Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands

Correspondence: Dr HH Helgason, E-mail: h.helgason@nki.nl

Received 20 February 2006; Revised 3 August 2006; Accepted 3 August 2006; Published online 12 September 2006.

Abstract

Paclitaxel is an important chemotherapeutic agent for breast cancer. Paclitaxel has high affinity for the P-glycoprotein (P-gp) (drug efflux pump) in the gastrointestinal tract causing low and variable oral bioavailability. Previously, we demonstrated that oral paclitaxel plus the P-gp inhibitor ciclosporin (CsA) is safe and results in adequate exposure to paclitaxel. This study evaluates the activity, toxicity and pharmacokinetics of paclitaxel combined with CsA in breast cancer patients. Patients with measurable metastatic breast cancer were given oral paclitaxel 90 mg m^-2 combined with CsA 10 mg kg^-1 (30 min prior to each paclitaxel administration) twice on one day, each week. Twenty-nine patients with a median age of 50 years were entered. All patients had received prior treatments, 25 had received prior anthracycline-containing chemotherapy and 19 had three or more metastatic sites. Total number of weekly administrations was 442 (median: 15/patient) and dose intensity of 97 mg m^-2 week^-1. Most patients needed treatment delay and 17 patients needed dose reductions. In intention to treat analysis, the overall response rate was 52%, the median time to progression was 6.5 months and overall survival was 16 months. The pharmacokinetics revealed moderate inter- and low intrapatient variability. Weekly oral paclitaxel, combined with CsA, is active in patients with advanced breast cancer.