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

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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.

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Acknowledgments

We thank Ms. Yumi Ohama and Ms. Mariko Ueki for their excellent technical assistance with the HPLC analysis and Dr. Kenichi Fujita for his valuable comments. This work was supported in part by a Grant in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science, and Technology of Japan, and by a grant from the Ministry of Health, Labor, and Welfare of Japan.

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Authors and Affiliations

  1. Department of Breast Oncology, Saitama International Medical Center, Saitama Medical University, 1397-1 Yamane, Hidaka, 350-1298, Japan

    Toshiaki Saeki

  2. Department of Surgery, Unnan Municipal General Hospital, 96-1 Iida, Daito-cho, Unnan, 699-1221, Japan

    Atsushi Okita

  3. Department of Clinical Research and Surgery, Shikoku Cancer Center, 160 Kou Minamiumemoto-machi, Matsuyama, 791-0288, Japan

    Kenjiro Aogi, Yumi Ohama & Shigemitsu Takashima

  4. Department of Cancer and Thoracic Surgery, Okayama University Graduate School of Medicine, 2-5-1 Shikada-cho, Okayama, 700-8558, Japan

    Tomokazu Kakishita & Naruto Taira

  5. Department of Surgical Oncology, Research Institute for Radiation Biology and Medicine, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8553, Japan

    Riki Okita

  6. Research and Development Division, Nippon Kayaku Co., Ltd, Tokyo, Japan

    Kiyohiro Nishikawa

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  1. Toshiaki Saeki
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Correspondence to Toshiaki Saeki.

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Saeki, T., Okita, A., Aogi, K. et al. Pharmacokinetic analysis of a combined chemoendocrine treatment with paclitaxel and toremifene for metastatic breast cancer. Breast Cancer 16, 113–120 (2009). https://doi.org/10.1007/s12282-008-0075-7

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  • DOI: https://doi.org/10.1007/s12282-008-0075-7

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