Carboplatin and Etoposide in Heavily Pretreated Patients with Progressive High-Grade Glioma

Abstract

Background: Treatment of recurrent anaplastic glioma and glioblastoma remains a particular challenge in neurooncology. The lack of controlled trials results in poor evidence for all therapeutic options. Upon recurrence, many patients are treated with bevacizumab or one of the frequently used nitrosoureas such as lomustine. However, patients who still present in overall good condition after failure of multiple lines of therapy may ask for additional therapy. Methods: Here, we report our experience with the use of carboplatin in combination with etoposide as fourth- or fifth-line therapy in patients with progressive high-grade glioma. Results: The median Karnofsky performance status at the beginning of treatment was 80%. The median progression-free survival (PFS) was 2.5 months. PFS at 6 months was 0%. Administration of carboplatin and etoposide was associated with grade 3 or 4 hematotoxicity in 8 of 12 patients. Conclusion: Carboplatin in combination with etoposide has an unfavorable risk-benefit profile in heavily pretreated glioma patients.

Combined carboplatin and etoposide chemotherapy for patients with recurrent glioma

“…In this study, the efficacy of CE regimen in recurrent GBM was poor which was consistent with previous report (11). However, the efficacy of CE regime was better in patients with recurrent glioma of grade 2 or 3 compared with recurrent GBM.…”

“…Notably, CR was observed in 1 patient with grade 2 tumor after 2 cycles of CE chemotherapy, suggesting that salvage CE regimen may be effective for patients with grade 2 recurrent gliomas. Nonetheless, the preliminary results in this study suggested that CE regimen may confer a superior clinical benefit in patients with grade 2-3 tumors compared to patients with grade 4 tumors following disease progress or recurrence after initial surgery and adjuvant therapy Since CE regimen has been widely used in different malignant tumors for decades and the reported related adverse events is similar in different diseases (11,13,25), toxicity was not a primary endpoint in this study. However, hematological toxicity was the most common adverse event observed in this study cohort and most patients received granulocyte-colony stimulating factor (GSF) treatment during the course of chemotherapy.…”

“…Combination treatment consisting of carboplatin and etoposide (CE) is widely used in various malignant tumors including small cell lung cancer (SCLC) (10). However, there is a paucity of consistent data regarding the efficacy of CE therapy in relapsed gliomas (11)(12)(13). Therefore, clarification of the efficacy of CE treatment in relapse or progressive glioma patients is urgently warranted.…”

Congress of Neurological Surgeons systematic review and evidence-based guidelines update on the role of cytotoxic chemotherapy and other cytotoxic therapies in the management of progressive glioblastoma in adults

“…There were 8 studies eligible which examined the use of systemic chemotherapy other than TMZ or nitrosureas for the treatment of pGBM eligible and were included in this analysis. These studies summarized in Table 3 provided Class III evidence [27][28][29][30][31][32][33][34][35].…”

“…Tonder et al [33] conducted a retrospective review of 12 heavily pretreated recurrent high grade glioma patients including 8 glioblastoma patients treated with carboplatin (240mg/m2 on day 1) and etoposide (100mg/m2 on days 2 and 3) every 4 weeks. Signi cant toxicity was observed with grade 3-4 hematologic toxicity in 67% of patients.…”