Chronic oral etoposide in small-cell lung cancer: clinical and pharmacokinetic results.
OBJECTIVE
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.


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 microgram/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 microgram/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.
Sessa
C
C
Department of Oncology, Ospedale San Giovanni, Bellinzona, Switzerland.
Zucchetti
M
M
Torri
V
V
Pagani
O
O
D'Incalci
M
M
Gentili
D
D
Martinelli
G
G
deJong
J
J
Alerci
M
M
Cavalli
F
F
D000284:Administration, Oral; D000368:Aged; D018288:Carcinoma, Small Cell / Q000188:drug therapy*; D004334:Drug Administration Schedule; D005047:Etoposide / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D009503:Neutropenia / Q000139:chemically induced
D005047:Etoposide