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Intrapleural etoposide for malignant effusion.

P Y Holoye1, D G Jeffries, H M Dhingra

  • 1Department of Medical Oncology, University of Texas M. D. Anderson Cancer Center, Houston 77030.

Cancer Chemotherapy and Pharmacology
|January 1, 1990
PubMed
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Intrapleural etoposide (VP-16) showed mild toxicity at lower doses for malignant pleural effusion. Higher doses caused severe myelosuppression, but local drug concentrations suggest potential therapeutic benefit.

Area of Science:

  • Oncology
  • Pharmacology
  • Thoracic Medicine

Background:

  • Malignant pleural effusion is a common complication of various cancers.
  • Systemic chemotherapy has limited efficacy in managing malignant pleural effusion.
  • Intrapleural chemotherapy offers a localized treatment approach.

Purpose of the Study:

  • To evaluate the safety, tolerability, and preliminary efficacy of intrapleural etoposide (VP-16) in patients with malignant pleural effusion.
  • To determine the optimal dose and pharmacokinetic profile of intrapleural VP-16.
  • To assess the local therapeutic effect of VP-16 on pleural fluid markers.

Main Methods:

  • A Phase I clinical trial involving ten patients with malignant pleural effusion.
  • Intrapleural administration of etoposide (VP-16) at doses of 100, 150, or 225 mg/m2 over 2 hours.

Related Experiment Videos

  • Monitoring of drug levels in plasma and pleural fluid, assessment of toxicity, and analysis of pleural fluid characteristics (CEA, LDH, cytology).

    • Main Results:

    • Intrapleural VP-16 was generally well-tolerated, with no significant local adverse effects.
    • Myelosuppression was dose-dependent, being mild at 150 mg/m2 or less and severe at 225 mg/m2.
    • Low clearance from the pleural cavity resulted in high pleural fluid drug concentrations, significantly exceeding plasma levels.
    • No complete resolution of effusion was observed, but some local therapeutic benefit was suggested by changes in pleural fluid markers.

    Conclusions:

    • Intrapleural etoposide (VP-16) is a feasible treatment option for malignant pleural effusion with a manageable toxicity profile at doses up to 150 mg/m2.
    • The drug achieves high local concentrations in the pleural space, indicating potential for locoregional efficacy.
    • Further investigation is warranted to optimize dosing and confirm therapeutic benefit in larger trials.