Investigating the relationship between serum thrombopoietin kinetics and the platelet-sparing effect: A clinical pharmacological evaluation of combined paclitaxel and carboplatin in patients with non-small cell lung cancer

  • Authors:
    • Haruko Daga
    • Takeshi Isobe
    • Mitsuru Miyazaki
    • Kazunori Fujitaka
    • Keiichi Kondo
    • Nobuoki Kohno
  • View Affiliations

  • Published online on: June 1, 2004     https://doi.org/10.3892/or.11.6.1225
  • Pages: 1225-1231
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Abstract

We conducted a clinical pharmacological evaluation of paclitaxel/carboplatin combination in Japanese patients with non-small cell lung cancer. The purpose of this study was to identify the optimal dose of this combination and to investigate the relationships between the pharmacokinetic profiles of these 2 drugs, serum thrombopoietin (TPO) kinetics and the platelet-sparing effect. Patients received paclitaxel at 180-225 mg/m2 by intravenous infusion over 3 h, followed by carboplatin at a target area under the concentration-time curve (AUC) of 6 mg/ml x min as a 1-h infusion. Serum paclitaxel, free platinum and TPO concentrations were measured using high-performance liquid chromatography, atomic absorption spectrometry and a double-sandwich enzyme-linked immunosorbent assay, respectively. Thirteen patients were enrolled. Neutropenia was the most frequent hematological toxicity and was significantly related to the time for which paclitaxel concentrations remained above 0.05 µmol/ml. The prominent non-hematological toxicities were myalgia and sensory-dominant neuropathy. In this study, platelet and serum TPO kinetics were clearly different from those in our previous study of single-agent carboplatin (21). The platelet counts at the nadir were significantly higher (p<0.0001) in patients treated with paclitaxel/carboplatin combination (161,000±38,000/µl) compared with single-agent carboplatin (92,000±28,000/µl). The early increase in TPO (the percentage increase in TPO at day 4) was significantly greater (p=0.0345) in patients treated with paclitaxel/carboplatin combination (57.8±44.5%) compared with single-agent carboplatin (21.3±34.1%). The recommended doses are paclitaxel 210 mg/m2 and carboplatin at an AUC of 6 mg/ml x min every 3 weeks. The observed platelet-sparing effect of the paclitaxel/carboplatin might be related to the early increase in circulating TPO levels, although the precise mechanism remains to be elucidated.

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June 2004
Volume 11 Issue 6

Print ISSN: 1021-335X
Online ISSN:1791-2431

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Spandidos Publications style
Daga H, Isobe T, Miyazaki M, Fujitaka K, Kondo K and Kohno N: Investigating the relationship between serum thrombopoietin kinetics and the platelet-sparing effect: A clinical pharmacological evaluation of combined paclitaxel and carboplatin in patients with non-small cell lung cancer. Oncol Rep 11: 1225-1231, 2004
APA
Daga, H., Isobe, T., Miyazaki, M., Fujitaka, K., Kondo, K., & Kohno, N. (2004). Investigating the relationship between serum thrombopoietin kinetics and the platelet-sparing effect: A clinical pharmacological evaluation of combined paclitaxel and carboplatin in patients with non-small cell lung cancer. Oncology Reports, 11, 1225-1231. https://doi.org/10.3892/or.11.6.1225
MLA
Daga, H., Isobe, T., Miyazaki, M., Fujitaka, K., Kondo, K., Kohno, N."Investigating the relationship between serum thrombopoietin kinetics and the platelet-sparing effect: A clinical pharmacological evaluation of combined paclitaxel and carboplatin in patients with non-small cell lung cancer". Oncology Reports 11.6 (2004): 1225-1231.
Chicago
Daga, H., Isobe, T., Miyazaki, M., Fujitaka, K., Kondo, K., Kohno, N."Investigating the relationship between serum thrombopoietin kinetics and the platelet-sparing effect: A clinical pharmacological evaluation of combined paclitaxel and carboplatin in patients with non-small cell lung cancer". Oncology Reports 11, no. 6 (2004): 1225-1231. https://doi.org/10.3892/or.11.6.1225