A Phase I/II Study of a 72‐h Continuous Infusion of Etoposide in Advanced Soft Tissue Sarcoma

Abstract

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 mg m(-2) day(-1) x 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 mug ml-(1) in all patients and in patients treated at >/= 600 mg m -(2) the mean steady-state level was 14.4 mug 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 mm(-2) day(-1) x 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.

Chemotherapeutic drugs for soft tissue sarcomas: a review

“…As a widely used anticancer drug, etoposide has been tested repeatedly in STSs ( Belani et al, 1994 ). However, whether administered orally or intravenously, the activity of etoposide alone in the STS is weak ( Table 7 ) ( Licht et al, 1994 ; Crawley et al, 1997 ; Keizer et al, 1997 ; Kebudi et al, 2004 ). Although ifosfamide plus etoposide shows some activity in STSs ( Table 7 ) ( Saeter et al, 1997 ; Yalçin et al, 1998 ; Pápai et al, 2000 ), this combined regimen is rarely used in the real world ( Leahy et al, 2012 ; Nagar et al, 2018 ; Kim et al, 2019 ).…”

Management of Advanced Adult Soft Tissue Sarcoma

“…Etoposide is said to be synergistic with IFOS and this is a well-established combination regimen in paediatric sarcomas. 30 Etoposide is inactive in adult STS 31,32 and it is also unclear from published pilot studies 33,34 whether the combination is more active than IFOS alone.…”