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Open-label, randomized, single-dose, crossover study to evaluate the pharmacokinetics and safety differences between two docetaxel products, CKD-810 and Taxotere injection, in patients with advanced solid cancer

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Abstract

Purpose

The aim of this study was to compare CKD-810 (test docetaxel) with Taxotere® (reference docetaxel) in terms of pharmacokinetics and safety for patients with advanced or metastatic carcinoma.

Methods

A randomized, open-label, two-way crossover study was conducted in eligible patients. Patients received with reference or test drugs of 75 mg/m2 docetaxel by intravenous infusion for 60 min in the first period and the alternative drug in the second period with a washout of 3 weeks. Plasma concentrations of docetaxel were determined by validated high-performance liquid chromatography coupled to tandem mass spectrometry detection. Pharmacokinetic parameters, including the maximum plasma concentration (C max) and the area under the concentration–time curve (AUC), were determined by non-compartmental analysis.

Results

A total of 44 patients were included in the study, 21 patients received test drug and 23 received reference drug for the first cycle. The C max of docetaxel was 2,658.77 ng/mL for test drug and 2,827.60 ng/mL for reference drug, and two drugs showed no difference with a statistical significance. Time to reach C max (T max) of CKD-810 (0.94 h) versus reference docetaxel (0.97 h) was also not significantly different. Other pharmacokinetic parameters including the plasma AUC, elimination half-life, and total body clearance exhibited similar values without a significant difference. The most common grade 3 or 4 toxicity was neutropenia (CKD-810 19.5 or 29.3 %; reference docetaxel 14.6 or 41.5 %). Febrile neutropenia was experienced by only one patient in each group. Two patients died of progression of disease during the study.

Conclusion

Docetaxel anhydrous CKD-810 use with patients suffering advanced or metastatic solid malignancies was equivalent to reference docetaxel in terms of pharmacokinetic parameters and safety profile. Additionally, the test and reference drug met the regulatory criteria for pharmacokinetic equivalence.

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Acknowledgments

Chong Kun Dang Pharmaceutical Corporation provided financial support and study drugs to conduct this clinical study.

Conflict of interest

The authors have no vested interest of any kind in the materials or services referred to in this article.

Author information

Authors and Affiliations

  1. Division of Hematology and Oncology, Department of Internal Medicine, Gachon University Gil Medical Center, Incheon, South Korea

    Eun Kyung Cho

  2. Department of Clinicopharmacology, Korea University Anam Hospital, Seoul, South Korea

    Ji-Young Park

  3. Division of Hematology and Oncology, Department of Internal Medicine, Yeungnam University Medical Center, Daegu, South Korea

    Kyung Hee Lee

  4. Division of Hematology and Oncology, Department of Internal Medicine, Keimyung University Dongsan Medical Center, Daegu, South Korea

    Hong Suk Song

  5. Division of Hematology and Oncology, Department of Internal Medicine, Ulsan University Hospital, Ulsan, South Korea

    Young Joo Min

  6. Division of Hematology and Oncology, Department of Medicine, Korea University Anam Hospital, Seoul, South Korea

    Yeul Hong Kim

  7. Division of Oncology, Department of Internal Medicine, Catholic University Seoul St. Mary’s Hospital, 505 Banpo-dong, Seocho-gu, Seoul, 137-701, South Korea

    Jin-Hyoung Kang

Authors
  1. Eun Kyung Cho
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  2. Ji-Young Park
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Corresponding author

Correspondence to Jin-Hyoung Kang.

Additional information

Funded by Chong Kun Dang Pharmaceutical corp.; ClinicalTrials.gov number, NCT01019941.

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Cho, E.K., Park, JY., Lee, K.H. et al. Open-label, randomized, single-dose, crossover study to evaluate the pharmacokinetics and safety differences between two docetaxel products, CKD-810 and Taxotere injection, in patients with advanced solid cancer. Cancer Chemother Pharmacol 73, 9–16 (2014). https://doi.org/10.1007/s00280-013-2264-0

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  • DOI: https://doi.org/10.1007/s00280-013-2264-0

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