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Gemcitabine pharmacokinetics and interaction with paclitaxel in patients with advanced non-small-cell lung cancer

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Abstract

Purpose

Gemcitabine administered at a fixed dose rate of 10 mg/m2 per min has been reported to achieve plasma steady-state concentrations ranging from 10 to 20 μM in patients with acute leukemia. These concentrations have been shown to saturate the intracellular accumulation of the active triphosphate metabolite. We designed this pharmacokinetic study to assess the ability of a fixed dose rate of gemcitabine to achieve the desired steady-state concentration in the absence and presence of paclitaxel in patients with solid tumors.

Patients and methods

A group of 14 patients with advanced non-small-cell lung cancer received paclitaxel 110 mg/m2 over 3 h on days 1 and 8 and gemcitabine 800 mg/m2 over 80 min on days 1 and 8 every 21 days. Patients received gemcitabine alone on cycle (C) 1, day (D) 1. Pharmacokinetic samples were collected at 0, 15, 30, 45, 60 and 80 min during infusion and 0.25, 0.5, 1, 2, 4, 6, and 8 h after infusion on C1D1, C1D8, C2D1, C4D1 and C6D1.

Results

Of 13 patients included in the pharmacokinetic analysis, 61% achieved the desired steady-state concentration (Css) with gemcitabine alone (C1D1), whereas only 0 to 45% of patients achieved the desired Css with paclitaxel and gemcitabine, depending on the treatment cycle. Paclitaxel significantly decreased systemic clearance (ClT; P=0.012) and volume of distribution (Vd; P=0.050) and significantly increased Css (P=0.009). Gemcitabine plasma pharmacokinetic parameters demonstrated great interpatient variability in the absence of paclitaxel (Css 30%, ClT 30%, Vd 55%). Interpatient and intrapatient variability in gemcitabine pharmacokinetics were not observed when gemcitabine was administered in combination with paclitaxel (P>0.05).

Conclusions

Gemcitabine plasma pharmacokinetic parameters are significantly altered in the presence of paclitaxel.

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Authors and Affiliations

  1. School of Pharmacy, CB #7360, Beard Hall, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, 27599, USA

    Stacy S. Shord, Stephanie R. Faucette, Scott L. Pescatore, Roy L. Hawke & Celeste Lindley

  2. School of Medicine, CB#7305, Old Clinic Building, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, 27599, USA

    Heidi H. Gillenwater & Mark A. Socinski

Authors
  1. Stacy S. Shord
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  2. Stephanie R. Faucette
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  3. Heidi H. Gillenwater
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  7. Celeste Lindley
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Correspondence to Celeste Lindley.

Additional information

Supported by a Clinical/Translational Research Award granted by the Lineberger Comprehensive Cancer Center and a grant (RR00046) from the General Clinical Research Centers Program of the Division of Research Resources, National Institutes of Health.

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Shord, S.S., Faucette, S.R., Gillenwater, H.H. et al. Gemcitabine pharmacokinetics and interaction with paclitaxel in patients with advanced non-small-cell lung cancer. Cancer Chemother Pharmacol 51, 328–336 (2003). https://doi.org/10.1007/s00280-002-0560-1

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  • DOI: https://doi.org/10.1007/s00280-002-0560-1

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