Chronic oral etoposide in small-cell lung cancer: Clinical and pharmacokinetic results |
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Authors: | Sessa, C. Zucchetti, M. Torri, V. Pagani, O. D'Incalci, M. Gentili, D. Martinelli, G. DeJong, J. Alerci, M. Cavalli, F. |
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Affiliation: | 1Department of Oncology, Ospedale San Giovanni Bellinzona; Switzerland 2Mario Negri Institute for Pharmacological Research Milan, Italy 3Department of Radiology, Ospedale San Giovanni Bellinzona, Switzerland |
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Abstract: | AIMS:: To evaluate antitumour activity, toxicity, pharmacokinetics,and the pharmacodynamic relationship with neutropenia of chronicoral 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 receiving100 mg daily of oral E for 21 days every 4 weeks. CBC with differentialrepeated every week. E plasma levels determined by HPLC method(sensitivity limit: 0.1 µg/ml) with evaluation duringthe first cycle of weekly 24-hour drug concentrations. RESULTS:: Among 25 evaluable pts, 60% (95% CI: 39%79%) overallresponse, 144 and 217 days of median PFS and survival. Dose-limitingnon-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. Riskfactors for neutropenia(age, PS, serum creatinine and albumin)not identified. High inter-patient variability of 24-hour Eplasma levels. A weak correlation between mean 24-hour E plasmalevels and ANC nadir or relative decrease of ANC, but higherrelative decrease of ANC in pts with 24-hour E plasma levelsof >0.32 µg/ml. CONCLUSIONS:: Chronic oral E is effective in SCLC pts previously untreatedwith chemotherapy. Careful hematological monitoring is essentialto avoid severe myelosuppression. The degree of neutropeniamight be related to the maintenance of a critical drug concentrationlevel for a critical period of time. oral etoposide, small-cell lung cancer, pharmacodynamics |
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