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Pharmacology of the paclitaxel–cisplatin, gemcitabine–cisplatin, and paclitaxel–gemcitabine combinations in patients with advanced non-small cell lung cancer

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Abstract

Purpose: To compare the pharmacology of the paclitaxel–cisplatin, gemcitabine–cisplatin and paclitaxel–gemcitabine combinations in patients with advanced non-small cell lung cancer (NSCLC). Patients and methods: Twenty-four chemo-naive patients with advanced NSCLC were randomized to receive one of the three regimens. Plasma pharmacokinetics and pharmacologic parameters in mononuclear cells were compared and related to toxicity and efficacy. Results: Pharmacological parameters of gemcitabine and cisplatin were not influenced by the combination with one of the other agents, while the paclitaxel clearance was significantly lower for the combination with cisplatin as compared to gemcitabine (P=0.024). The percentage decrease in platelets was significantly higher for the gemcitabine combinations (P=0.004) and related to the dFdCTP-Cmax (P=0.030). Pharmacologic parameters were not related to response or survival. Conclusions: Gemcitabine and cisplatin pharmacology were not influenced by the combination with one of the other agents, while paclitaxel has a lower clearance in combination with cisplatin as compared to gemcitabine.

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Acknowledgements

This study was financially supported by Eli Lilly & Co International, The Netherlands.

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Authors and Affiliations

  1. Department of Medical Oncology, VU University Medical Center, PO Box 7057, 1007 MB, Amsterdam, The Netherlands

    J. R. Kroep, G. Giaccone, K. Van der Born, C. J. Van Groeningen, W. J. F. Van der Vijgh, H. M. Pinedo & G. J. Peters

  2. Department of Pulmonary Diseases, VU University Medical Center, Amsterdam, The Netherlands

    E. F. Smit & P. E. Postmus

  3. Department of Pharmacy and Pharmacology, Slotervaart Hospital, Amsterdam, The Netherlands

    J. H. Beijnen

Authors
  1. J. R. Kroep
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  2. E. F. Smit
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  3. G. Giaccone
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  4. K. Van der Born
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  5. J. H. Beijnen
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  6. C. J. Van Groeningen
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  7. W. J. F. Van der Vijgh
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  8. P. E. Postmus
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  9. H. M. Pinedo
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  10. G. J. Peters
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Correspondence to G. J. Peters.

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Kroep, J.R., Smit, E.F., Giaccone, G. et al. Pharmacology of the paclitaxel–cisplatin, gemcitabine–cisplatin, and paclitaxel–gemcitabine combinations in patients with advanced non-small cell lung cancer. Cancer Chemother Pharmacol 58, 509–516 (2006). https://doi.org/10.1007/s00280-006-0191-z

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  • DOI: https://doi.org/10.1007/s00280-006-0191-z

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