Clinical Pharmacology of Carboplatin Administered in Alternating Sequence with Paclitaxel in Patients with Non-Small Cell Lung Cancer: A European Cancer Centre (ECC) Study

  • L. J. C. van Warmerdam
  • M. T. Huizing
  • G. Giaccone
  • P. J. M. Bakker
  • J. B. Vermorken
  • P. E. Postmus
  • N. van Zandwijk
  • M. G. J. Koolen
  • W. W. ten Bokkel Huinink
  • R. A. A. Maes
  • W. J. F. van der Vijgh
  • C. H. N. Veenhof
  • J. H. Beijnen


The clinical pharmacology of carboplatin, co-administered with paclitaxel, was investigated in a dose-finding and sequence-finding study in 56 previously untreated patients with non-small cell lung cancer (NSCLC). Carboplatin was administered over 30 minutes and paclitaxel over 3 hours every 4 weeks. Patients were randomized for the administration sequence, being first carboplatin (C) then followed by paclitaxel (P) or vice versa. Each patient received the alternate sequence during the second and subsequent courses. Total platinum concentrations in plasma and plasma ultrafiltrate (pUF) were measured applying flameless atomic absorption spectrometry. Ninety-five concentration-time curves were obtained in plasma and pUF.

Paclitaxel doses were initially escalated from P:100 mg/m2+ C:300 mg/m2 with 25 mg/m2 increments to P:225 mg/m2+ C:300 mg/m2. During the course of the study after six dose levels, it became clear that no sequence-depending effect on the toxicity was present, and it was decided to perform the last escalation steps with four patients per dose level. These dose levels were: level 7 (P:225 mg/m2+ C:350 mg/m2), 8 (P:250 mg/m2+ C:350 mg/m2), and 9 (P:225 mg/m2+ C:400 mg/m2). The mean pUF area under the concentration-time curve (AUC) per 300 mg/m2 carboplatin was for the sequence C→P 3.52 (range 1.94–5.83) mg/mL·min, and for the sequence P→C 3.62 (range 1.91–5.01) mg/mL·min, which is not significantly different (p=0.55). Also for other pharmacokinetic parameters no sequence depending effect was observed. Non-hematological toxicities consisted mainly of myalgia and bone pain. The most important hematologic toxicity was neutropenia, without, interestingly, any thrombocytopenic periods. The AUCs of carboplatin were probably too low to induce thrombocytopenia, although antagonistic properties of paclitaxel cannot be excluded.


Clin Oncol Mean Residence Time Alternate Sequence Administration Sequence Paclitaxel Dose 
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Copyright information

© Springer Science+Business Media New York 1996

Authors and Affiliations

  • L. J. C. van Warmerdam
  • M. T. Huizing
  • G. Giaccone
  • P. J. M. Bakker
  • J. B. Vermorken
  • P. E. Postmus
  • N. van Zandwijk
  • M. G. J. Koolen
  • W. W. ten Bokkel Huinink
  • R. A. A. Maes
  • W. J. F. van der Vijgh
  • C. H. N. Veenhof
  • J. H. Beijnen
    • 1
  1. 1.Dept of PharmacyNetherlands Cancer Institute/Antoni van Leeuwenhoek Hospital and Slotervaart HospitalAmsterdamThe Netherlands

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