Phase II study of intravenous etoposide in patients with relapsed ependymoma (CNS 2001 04)

Apps, John R.; Maycock, Shanna; Ellison, David W.; Jaspan, Timothy; Ritzmann, Timothy A.; Macarthur, Donald; Mallucci, Conor; Wheatley, Keith; Veal, Gareth J.; Grundy, Richard G.; Picton, Susan

Abstract

Background
Relapsed ependymoma has a dismal prognosis, and the role of chemotherapy at relapse remains unclear. This study prospectively evaluated the efficacy of intensive intravenous (IV) etoposide in patients less than 21 years of age with relapsed intracranial ependymoma (NCT00278252).

Methods
This was a single-arm, open-label, phase II trial using Gehan’s two-stage design. Patients received IV etoposide 100 mg/m2 on days 1-3, 8-10, and 15-17 of each 28-day cycle, up to maximum of 6 cycles. Primary outcome was radiological response after 3 cycles. Pharmacokinetic analysis was performed in 10 patients.

Results
Twenty-five patients were enrolled and included in the intention-to-treat (ITT) analysis. Three patients were excluded in per-protocol (PP) analysis. After 3 cycles of etoposide, 5 patients (ITT 20%/PP 23%) had a complete response (CR), partial response (PR), or objective response (OR). Nine patients (ITT 36%/PP 41%,) had a best overall response of CR, PR, or OR. 1-year PFS was 24% in ITT and 23% in PP populations. 1-year OS was 56% and 59%, 5-year OS was 20% and 18%, respectively, in ITT and PP populations. Toxicity was predominantly hematological, with 20/25 patients experiencing a grade 3 or higher hematological adverse event.

Conclusions
This study confirms the activity of IV etoposide against relapsed ependymoma, however, this is modest, not sustained, and similar to that with oral etoposide, albeit with increased toxicity. These results confirm the dismal prognosis of this disease, provide a rationale to include etoposide within drug combinations, and highlight the need to develop novel treatments for recurrent ependymoma.

• Journal Article Type: Article
• Acceptance Date: Apr 12, 2022
• Online Publication Date: Apr 13, 2022
• Publication Date: Apr 13, 2022
• Deposit Date: May 21, 2022
• Publicly Available Date: May 24, 2022
• Journal: Neuro-Oncology Advances
• Electronic ISSN: 2632-2498
• Publisher: Oxford University Press (OUP)
• Peer Reviewed: Peer Reviewed
• Volume: 4
• Issue: 1
• Article Number: vdac053
• DOI: https://doi.org/10.1093/noajnl/vdac053
• Keywords: Ependymoma; brain tumour
• Public URL: https://nottingham-repository.worktribe.com/output/8191516
• Publisher URL: https://academic.oup.com/noa/article/4/1/vdac053/6568128