1. Carboplatin, given through intracerebral, convection-enhanced delivery, may be a viable adjunct in recurrent high-grade glioma treatment.
Evidence Rating Level: 1 (Excellent)
Patients with glioblastomas (GBM), which will invariably recur despite maximal therapy, have a poor prognosis, with a median overall survival of 15 months. The current treatment for newly diagnosed GBM includes surgical resection, concurrent radiation, and temozolomide with subsequent adjuvant temozolomide. Carboplatin is highly effective in treating other malignancies. However, while gliomas have been shown to be sensitive to this anti-cancer drug, using carboplatin has been limited by its systemic toxicity and its inability to penetrate the blood-brain barrier at effective concentrations. In this open-label, nonrandomized dose-escalation trial, 10 patients with recurrent WHO grade III or IV gliomas, who had previously undergone surgery and chemoradiation, were divided into cohorts of 3 patients each. They were treated with escalating doses of carboplatin at 1ug, 2ug, and 4ug in 54mL, delivered intracerebrally via convection enhanced delivery (CED) over 72 hours. No treatment-related deaths occurred, and no dose-limiting toxicities were observed. Neither were reported adverse events (total of 9) considered treatment-related, aside from one patient which experienced an isolated grade 2 generalized tonic-clonic seizure; this incident was resolved after halting carboplatin infusion (1.3ug dose) and the patient recovered to baseline medical status after infusion was halted within 24 hours. Progression-free survival at 6 months post-infusion was 20% (median 2.1 months) and 12-month overall survival was 40% (median 9.6 months). It is of note however, that the study’s inclusion and exclusion criteria led to a predominantly younger cohort (mean age= 46.8years) with high baseline KPS (Karnofsky performance score), may have contributed to the low incidence of adverse events and the trend towards more favourable survival. While this study shows intracerebral CED of carboplatin of up to 4ug is a safe and feasible adjunct to re-resection of recurrent GBMs, further research is needed with a larger sample size to determine maximum tolerated dose and the generalizability of these results.
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