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Gemcitabine and metabolite pharmacokinetics in advanced NSCLC patients after bronchial artery infusion and intravenous infusion

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Abstract

Purpose

We investigated the safety, pharmacokinetics, and efficacy of gemcitabine administered via bronchial artery infusion (BAI) and IV infusion in advanced NSCLC patients.

Methods

Patients were eligible if they had received at least two prior cytotoxic chemotherapy regimens. Gemcitabine was administered via BAI as 600 mg/m2 on day one of cycle one, followed by IV as 1000 mg/m2 on day eight of cycle one, and IV on days one and eight of all subsequent cycles. Pharmacokinetics for gemcitabine and dFdU metabolite in plasma, and dFdCTP active metabolite in peripheral blood mononuclear cells (PBMC) were evaluated. Intensive pharmacokinetic sampling was performed after BAI and IV infusions during cycle one.

Results

Three male patients (age range 59–68 years) were evaluated. All patients responded with stable disease or better. One PR was observed after cycle three, and the remaining had SD. Cmax (mean ± SD) following BAI for gemcitabine, dFdCTP, and dFdU were 7.71 ± 0.13, 66.5 ± 40.6, and 38 ± 6.27 µM and following IV infusion, 17 ± 2.36, 50.8 ± 3.61, and 83.2 ± 12.3 µM, respectively. The AUCinf (mean ± SD) following BAI for gemcitabine, dFdCTP, and dFdU were 6.89 ± 1.2, 791.1 ± 551.2, and 829.9 ± 217.8 µM h and following IV infusion, 12.5 ± 3.13, 584 ± 86.6, and 1394.64 ± 682.2 µM h, respectively. The AUC and Cmax of dFdCTP after BAI were higher than IV. The median OS was 6.27 months. No grade 3 or 4 toxicity was observed. The most common side effects were all grade ≤ 2 involving nausea, vomiting, rigor, thrombocytopenia, and anemia.

Conclusions

Systemic exposure to dFdCTP was higher after BAI than IV in two out of three patients.

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Acknowledgements

We thank all the patients for their participation in this study. We would like to acknowledge the assistance of the Clinical Pharmacology Shared Resource of the Masonic Cancer Center, a comprehensive cancer center designated by the National Cancer Institute, supported in part by P30 CA77598.

Funding

This study was funded by Eli Lilly.

Author information

Authors and Affiliations

  1. Experimental and Clinical Pharmacology, College of Pharmacy, University of Minnesota, Minneapolis, MN, 55455, USA

    Abeer F. Alharbi, Kinjal Sanghavi & Mark N. Kirstein

  2. Hematology, Oncology and Transplantation, University of Minnesota, Minneapolis, MN, 55455, USA

    Robert A. Kratzke & Michael Anthony Maddaus

  3. Cardiothoracic Surgery, University of Pittsburgh, Pittsburgh, PA, 15213, USA

    Jonathan D’Cunha

  4. Masonic Cancer Center, University of Minnesota, Minneapolis, MN, 55455, USA

    Mark N. Kirstein

Authors
  1. Abeer F. Alharbi
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  2. Robert A. Kratzke
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  3. Jonathan D’Cunha
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  4. Michael Anthony Maddaus
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  5. Kinjal Sanghavi
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  6. Mark N. Kirstein
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Corresponding author

Correspondence to Mark N. Kirstein.

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Conflict of interest

The authors have no conflict of interest to report.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. This article does not contain any studies with animals performed by any of the authors.

Informed consent

Informed consent was obtained from all individual participants included in the study.

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Alharbi, A.F., Kratzke, R.A., D’Cunha, J. et al. Gemcitabine and metabolite pharmacokinetics in advanced NSCLC patients after bronchial artery infusion and intravenous infusion. Cancer Chemother Pharmacol 83, 387–391 (2019). https://doi.org/10.1007/s00280-018-3757-7

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  • DOI: https://doi.org/10.1007/s00280-018-3757-7

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