Chronic oral etoposide in small-cell lung cancer: Clinical and pharmacokinetic results

C. Sessa, M. Zucchetti, V. Torri, O. Pagani, M. D'Incalci, D. Gentili, G. Martinelli, J. DeJong, M. Alerci, F. Cavalli

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Abstract

Aims: To evaluate antitumour activity, toxicity, pharmacokinetics, and the pharmacodynamic relationship with neutropenia of chronic oral etoposide (E) in patients (pts) with small-cell lung cancer (SCLC) previously untreated with chemotherapy. Patients and methods: Twenty-seven (14 extensive-, 13 limited-stage) pts receiving 100 mg daily of oral E for 21 days every 4 weeks. CBC with differential repeated every week. E plasma levels determined by HPLC method (sensitivity limit: 0.1 μg/ml) with evaluation during the first cycle of weekly 24-hour drug concentrations. Results: Among 25 evaluable pts, 60% (95% CI: 39%-79%) overall response, 144 and 217 days of median PFS and survival. Dose-limiting non-cumulative neutropenia of high interpatient variability. Linear reduction (30% per week) of absolute neutrophil counts (ANC) up to the 3rd week, recovering the following week. Risk factors for neutropenia (age, PS, serum creatinine and albumin) not identified. High inter-patient variability of 24-hour E plasma levels. A weak correlation between mean 24-hour E plasma levels and ANC nadir or relative decrease of ANC, but higher relative decrease of ANC in pts with 24-hour E plasma levels of >0.32 μg/ml. Conclusions: Chronic oral E is effective in SCLC pts previously untreated with chemotherapy. Careful hematological monitoring is essential to avoid severe myelosuppression. The degree of neutropenia might be related to the maintenance of a critical drug concentration level for a critical period of time.

Original languageEnglish
Pages (from-to)553-558
Number of pages6
JournalAnnals of Oncology
Volume4
Issue number7
Publication statusPublished - 1993

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ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Statistics, Probability and Uncertainty
  • Applied Mathematics
  • Public Health, Environmental and Occupational Health
  • Neuropsychology and Physiological Psychology
  • Hematology

Cite this

Sessa, C., Zucchetti, M., Torri, V., Pagani, O., D'Incalci, M., Gentili, D., Martinelli, G., DeJong, J., Alerci, M., & Cavalli, F. (1993). Chronic oral etoposide in small-cell lung cancer: Clinical and pharmacokinetic results. Annals of Oncology, 4(7), 553-558.