Pharmacokinetic analysis of a combined chemoendocrine treatment with paclitaxel and toremifene for metastatic breast cancer

Toshiaki Saeki, Atsushi Okita, Kenjiro Aogi, Tomokazu Kakishita, Riki Okita, Naruto Taira, Yumi Ohama, Shigemitsu Takashima, Kiyohiro Nishikawa

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3 Citations (Scopus)

Abstract

Background: Multidrug resistance protein could be a target for improving the efficacy of paclitaxel (PXL). Toremifene (TOR) may moderate P-gp-related drug resistance in vitro. Some P-gp moderators may change the pharmacokinetic parameters of PXL in vivo. A pharmacokinetic (PK) study in metastatic breast cancer patients (MBC) was conducted to determine the safety and efficacy of PXL and TOR. Method and patients: Fifteen patients received 80 mg/m2 PXL (i.v.) weekly and 120 mg/body TOR (p.o.) daily. For the pharmacokinetic study, PXL was administered on days 1, 8, 15, 32, and 39; TOR was given from day 18 to the end of study. On days 1, 8, 15, 18, 32, and 39, blood samples were collected from the patients who received either PXL alone or PXL + TOR, and these were analyzed by high-performance liquid chromatography. Results: Among the 15 patients enrolled in the study, one showed a partial response, and eight had a stable disease. TOR caused no specific adverse events that were greater than grade 3, and its toxicity profile in combination with PXL was similar to that of PXL monotherapy. The PK profile of PXL was similar with or without TOR. The PK parameters of PXL indicated no inter- or intra-patient variability in previously treated patients with MBC. No increased PXL toxicity was observed. Conclusion: The PK profile of combined PXL and TOR was similar to that of PXL monotherapy. The addition of TOR to PXL in previously treated patients with MBC appears safe.

Original languageEnglish
Pages (from-to)113-120
Number of pages8
JournalBreast Cancer
Volume16
Issue number2
DOIs
Publication statusPublished - 2009

Keywords

  • Antiestrogens
  • Breast cancer
  • Chemoendocrine therapy
  • Drug resistance
  • Paclitaxel
  • Toremifene

ASJC Scopus subject areas

  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Pharmacology (medical)

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    Saeki, T., Okita, A., Aogi, K., Kakishita, T., Okita, R., Taira, N., Ohama, Y., Takashima, S., & Nishikawa, K. (2009). Pharmacokinetic analysis of a combined chemoendocrine treatment with paclitaxel and toremifene for metastatic breast cancer. Breast Cancer, 16(2), 113-120. https://doi.org/10.1007/s12282-008-0075-7