Purpose. The study was performed to assess the antitumour activity and toxicity of a 72-h continuous infusion of
single-agent etoposide as second-line treatment for patients with locally advanced or metastatic soft tissue sarcoma (STS),
following reports of substantial activity using this schedule of etoposide administration as first-line treatment in
combination with ifosfamide.Patients/method. This was an open phase I/II trial performed at a single institution in patients with metastatic or locally
advanced STS who had failed first-line treatment with doxorubicin + ifosfamide combination chemotherapy or, less
commonly, single-agent treatment with doxorubicin or ifosfamide. Etoposide was given as a continuous intravenous
infusion over 72 h. The starting dose level was
200 mgm−2
day−1 × 3 escalating in 10% steps in cohorts of three patients
until dose-limiting toxicity was encountered.Results. Seventeen patients were treated, median age 47 years (range 26–71 years). No responses were seen in 16
assessable patients despite etoposide levels in the cotoxic range. The steady-state plasma concentration exceeded
8 μg ml−1 in all patients and in patients treated at ≥ 600 mg m−2 the mean steady-state level was 14.4 μg ml−1. The
median event-free survival was 6 weeks (95% confidence interval (CI) 3.31–8.69) and the overall survival 16 weeks (95%
CI 9.28–22.72). The maximum tolerated dose in this pretreated patient group was 200 mg m−2
day−1 × 3. The dose-limiting toxicity was myelosuppression.Discussion. Etoposide given by 72-h infusion is inactive as second-line chemotherapy in STS.
It is associated with significant toxicity when given in these doses, in this patient group.
