BACKGROUND Glioblastoma multiforme is a CNS cancer characterized by diffuse infiltrative growth, aggressive clinical behavior and very poor prognosis. The state-of-art clinical approach to this disease consists of surgical resection followed by radiotherapy plus concurrent and adjuvant chemotherapy with temozolomide. Tumor recurrence occurs in virtually all cases, therefore, despite any treatment, the median survival is very low (14.6 months), which makes the approach to these patients a challenging clinical issue. MAIN BODY The escalating costs and times required for new medications to reach the bedside make repurposing or repositioning of old drugs, when scientific bases allow their use in other pathologies, an appealing strategy. Here, we analyze a number of literature data concerning the antipsychotic chlorpromazine, the founder of the phenothiazines class of drugs, a medication widely used in the clinics for approximately 60 years. The drug exerts its effects on psychiatric patients by interfering with the dopamine receptor D2, although more recent pharmacodynamics studies ascribe chlorpromazine a series of biological effects on cancer cells, all converging in hindering also glioblastoma survival capabilities. SHORT CONCLUSIONS On these bases, and assisted by the information on the well-established chlorpromazine toxicity and dosage in humans, we designed a Phase II clinical trial involving the combination of chlorpromazine with the standard treatment, temozolomide, in the adjuvant phase of the therapeutic protocol. Patients displaying hypo-methylation of the MGMT gene, and thus intrinsically resistant to temozolomide, will be enrolled. The endpoints of this study are the analysis of toxicity and clinical activity, as evaluated in terms of Progression-Free Survival, of the association of chlorpromazine with the first-line treatment for this very serious form of cancer.

中文翻译：

---

重新利用氯丙嗪治疗多形性胶质母细胞瘤：文献分析和即将采取的步骤。

背景技术多形性胶质母细胞瘤是一种以弥漫性浸润性生长、侵袭性临床行为和极差预后为特征的CNS癌症。治疗这种疾病的最先进的临床方法包括手术切除，然后是放疗加上替莫唑胺的同步和辅助化疗。几乎所有病例都会发生肿瘤复发，因此，尽管进行了任何治疗，但中位生存期非常低（14.6 个月），这使得这些患者的治疗成为一个具有挑战性的临床问题。主体 新药到达床边所需的成本和时间不断增加，这使得重新利用或重新定位旧药，当科学基础允许它们用于其他病理学时，这是一种有吸引力的策略。在这里，我们分析了一些关于抗精神病药氯丙嗪的文献数据，吩噻嗪类药物的创始人，这种药物在临床上广泛使用了大约 60 年。该药物通过干扰多巴胺受体 D2 对精神病患者产生影响，尽管最近的药效学研究将氯丙嗪归因于对癌细胞的一系列生物学效应，所有这些都集中在阻碍胶质母细胞瘤的存活能力上。简短结论 在这些基础上，并借助关于已证实的氯丙嗪对人体的毒性和剂量的信息，我们设计了一项 II 期临床试验，该试验涉及在治疗方案的辅助阶段将氯丙嗪与标准治疗药物替莫唑胺联合使用. 将招募显示 MGMT 基因低甲基化并因此对替莫唑胺具有内在抗性的患者。