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PURPOSE: This randomised trial was designed to investigate the activity and toxicity of continuous infusion etoposide phosphate (EP), targeting a plasma etoposide concentration of either 3 micrograms/ml for five days (5d) or 1 microgram/ml for 15 days (15d), in previously untreated SCLC patients with extensive disease. PATIENTS AND METHODS: EP was used as a single agent. Plasma etoposide concentration was monitored on days 2 and 4 in patients receiving 5d EP and on days 2, 5, 8 and 11 in patients receiving 15d EP, with infusion modification to ensure target concentrations were achieved. Treatment was repeated every 21 days for up to six cycles, with a 25% reduction in target concentration in patients with toxicity. RESULTS: The study has closed early after entry of 29 patients (14 with 5d EP, 15 with 15d EP). Objective responses were seen in seven of 12 (58%, confidence interval (CI): 27%-85%) evaluable patients after 5d EP, and two of 14 (14%, CI: 4%-42%) evaluable patients after 15d EP (P = 0.038). Grade 3 or 4 neutropenia or leucopenia during the first cycle of treatment was observed in six of 12 patients after 5d EP and 0/14 patients after 15d EP (P = 0.004), with median nadir WBC count of 2.6 x 10(9)/1 after 5d and 5.0 x 10(9)/1 after 15d EP (P = 0.017). Only one of 49 cycles of 15d EP was associated with grade 3 or worse haematological toxicity, compared to 14 of 61 cycles of 5d EP. CONCLUSIONS: Although the number of patients entered into this trial was small, the low activity seen at 1 microgram/ml in the 15d arm suggests that this concentration is below the therapeutic window in this setting. Further concentration-controlled studies with prolonged EP infusions are required.


Journal article


Ann Oncol

Publication Date





1205 - 1211


Adult, Aged, Antineoplastic Agents, Carcinoma, Small Cell, Drug Administration Schedule, Etoposide, Female, Humans, Lung Neoplasms, Male, Middle Aged, Organophosphorus Compounds