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Phase I study of docetaxel and cyclophosphamide in patients with advanced or recurrent breast cancer

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Abstract

Background

A phase I clinical study of combination chemotherapy with docetaxel and cyclophosphamide (CPA) was performed to determine the maximum tolerated dose (MTD), the incidence and severity of toxicities and the pharmacokinetics in patients with advanced or recurrent breast cancer.

Methods

Docetaxel was administered by intravenous drip infusion over 60 minutes, followed by intravenous bolus injection of CPA every 3-4 weeks. The dosage of docetaxel/CPA was 40/200, 40/400, 50/400, or 60/400 mg/m2/day.

Results

Fifteen patients were enrolled and received a total of 33 cycles of the combined therapy. The dose limiting toxicities (DLTs) were leukopenia, neutropenia and thrombocytopenia. The MTD was estimated to be docetaxel 60 mg/m2 in combination with CPA 400 mg/m2 per day. Plasma clearance of both drugs was similar regardless of dose. The recommended doses of docetaxel/CPA for a phase II trial are 50/400 mg/m2/day every 3-4 weeks.

Conclusion

The MTD of this combined therapy was docetaxel 60 mg/m2 and CPA 400 mg/m2. Neutropenia and leukopeina were common and severe. It is important to stress the need for modification of the dosing scheme.

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Abbreviations

CPA:

Cyclophosphamide

DLT:

Dose limiting toxicity

MTD:

Maximum-tolerated dose

CR:

Complete response

PR:

Partial response

NC:

No change

PD:

Progressive disease

Cmax:

Peak plasma concentration; t1/2, Terminal half-lives

AUC:

Area under the plasma concentration-time curve

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Authors and Affiliations

  1. Department of Surgery, Tokyo Women’s Medical University Daini Hospital, Japan

    Tadao Shimizu & Shunsuke Haga

  2. Department of Surgery, School of Medicine, Keio University, Japan

    Kohji Enomoto & Tadashi lkeda

  3. Department of Surgery I, St. Marianna University School of Medicine, Japan

    Mamoru Fukuda

  4. Department of Surgery E, Gunma University Faculty of Medicine, Japan

    Yuichi lino

  5. Japan Society for Cancer Chemotherapy, Japan Society for Cancer Chemotherapy, Japan

    Tetsuo Taguchi

Authors
  1. Tadao Shimizu
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  2. Kohji Enomoto
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  3. Shunsuke Haga
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  4. Mamoru Fukuda
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  5. Yuichi lino
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  6. Tadashi lkeda
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  7. Tetsuo Taguchi
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Corresponding author

Correspondence to Tadao Shimizu.

Additional information

Reprint requests to Tadashi Shimizu, Department of Surgery, Tokyo Women’s Medical University Daini Hospital, 2-1-10, Nishiogu, Arakawa-ku, Tokyo 116-8567, Japan.

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Shimizu, T., Enomoto, K., Haga, S. et al. Phase I study of docetaxel and cyclophosphamide in patients with advanced or recurrent breast cancer. Breast Cancer 10, 140–148 (2003). https://doi.org/10.1007/BF02967639

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  • DOI: https://doi.org/10.1007/BF02967639

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