Department of Neurosurgery, Frenchay Hospital, Bristol, BS16 1LE, UK.
Contemp Clin Trials. 2012 Mar;33(2):320-31. doi: 10.1016/j.cct.2011.10.010. Epub 2011 Nov 12.
Glioblastoma multiforme (GBM) is the commonest primary malignant brain tumour in adults. Standard treatment comprises surgery, radiotherapy and chemotherapy; however this condition remains incurable as these tumours are highly invasive and involve critical areas of the brain making it impossible to remove them surgically or cure them with radiotherapy. In the majority of cases the tumour recurs within 2 to 3 cm of the original site of tumour resection. Furthermore, the blood-brain barrier profoundly limits the access of many systemically administered chemotherapeutics to the tumour. Convection-enhanced delivery (CED) is a promising technique of direct intracranial drug delivery involving the implantation of microcatheters into the brain. Carboplatin represents an ideal chemotherapy to administer using this technique as glioblastoma cells are highly sensitive to carboplatin in vitro at concentrations that are not toxic to normal brain in vivo. This protocol describes a single-centre phase I dose-escalation study of carboplatin administered by CED to patients with recurrent or progressive GBM despite full standard treatment. This trial will incorporate 6 cohorts of 3 patients each. Cohorts will be treated in a sequential manner with increasing doses of carboplatin, subject to dose-limiting toxicity not being observed. This protocol should facilitate the identification of the maximum-tolerated infused concentration of carboplatin by CED into the supratentorial brain. This should facilitate the safe application of this technique in a phase II trial, treating patients with GBM, as well as for the treatment of other forms of malignant brain tumours, including metastases.
多形性胶质母细胞瘤（GBM）是成人中最常见的原发性恶性脑肿瘤。标准治疗包括手术、放疗和化疗；然而，由于这些肿瘤具有高度侵袭性，涉及大脑的关键区域，因此无法通过手术切除或放疗治愈。在大多数情况下，肿瘤在肿瘤切除的原始部位 2 到 3 厘米范围内复发。此外，血脑屏障严重限制了许多全身性化疗药物进入肿瘤的机会。对流增强递送（CED）是一种有前途的直接颅内药物递送技术，涉及将微导管植入大脑。卡铂作为一种理想的化疗药物，通过该技术进行给药，因为在体外，胶质母细胞瘤细胞对卡铂高度敏感，而在体内对正常大脑无毒性的浓度。本方案描述了一项单中心 I 期剂量递增研究，在充分标准治疗后，对复发性或进行性 GBM 患者，通过 CED 给予卡铂。该试验将包括 6 组，每组 3 名患者。将根据剂量限制毒性的观察情况，以顺序方式对患者进行治疗，增加卡铂的剂量。该方案应有助于确定通过 CED 向大脑幕上区域输注卡铂的最大耐受浓度。这将有助于该技术在 II 期试验中治疗 GBM 患者以及治疗其他形式的恶性脑肿瘤，包括转移瘤的安全应用。
