The past of chemotherapy for malignant gliomas Alkylating agent-based antitumor agents have always played an important role in the treatment of gliomas. The use of nitrogen mustard for central nervous system malignancies began as early as 1960, but the response rate for glioblastoma was also unsatisfactory at only 4.3% for nitrogen mustard-based chemotherapy regimens in the late 1990s. Another large class of alkylating agents, the nitrosoureas, was used in the experimental treatment of malignant glioma chemotherapy from the late 1970s, and this class of drugs dominated malignant glioma chemotherapy regimens from the 1980s to the early 1990s. These drugs cross the blood-brain barrier well by virtue of their high lipid solubility and nonionicity. Their mechanism of action includes DNA alkylation, DNA cross-linking and DNA carbamylation. Among them, carmustine (BCNU) has been widely used as the “benchmark” drug for malignant glioma chemotherapy, and its counterparts, CCNU, PCNU, and ACNU, have been frequently shown in clinical trials, but there is no evidence that the latter three are more effective than the former. Disadvantages of these drugs include myelosuppression, nausea and vomiting, as well as hepatic and renal toxicity, and BCNU has since been found to carry serious long-term side effects such as pulmonary fibrosis. It is important to note that the use of nitrosoureas in a single dose is of little significance for the vast majority of malignant tumors, and almost all studies suggest that nitrosoureas should be combined with radiation therapy and other agents to achieve better therapeutic outcomes. Other alkylating agents used in malignant gliomas include procarbazide, which has no evidence of superiority over BCNU but is used in combination with nitrosourea alkylating agents and other cytotoxic drugs because it is not cross-resistant to nitrosourea alkylating agents. As early as the 1960s, plant alkaloids began to be utilized in clinical trials, primarily including vincristine (VCR) and teniposide (VM-26).VCR and VM-26 functioned primarily in combination with nitrosoureas. Such clinical trials were conducted throughout the 1970s and 1980s, with drug response rates ranging from 25%-72%.Side effects of VCR include peripheral neuropathy and intestinal obstruction, but it does not cause bone marrow suppression, which is why it is often co-administered with nitrosoureas. A 1983 study showed that the three-year survival rate for glioblastoma treated with a combination of VCR and ACNU was 12.3%.Large-scale clinical trials by the European Organization for Research in Cancer Therapy (EORTC) in the early 1990s demonstrated that neither the nitrosourea alkylating agent CCNU alone, nor the combination of VM-26 and CCNU, significantly prolonged patients’ survival time and time to recurrence. Time. Early antimetabolites used in chemotherapy for malignant gliomas included tegafur, 5-fluorouracil (5-FU), cytarabine (Ara-C), and methotrexate (MTX). Controlled studies have shown that 34.2% of patients in the ACNU group had a reduction in tumor volume of more than 50%, compared to 41.2% in the ACNU+tigafur group, with no significant difference between the two, suggesting that tigafur does not significantly increase the chemotherapeutic effect of ACNU. Early 5-FU was used only in combination with nitrosourea alkylating agents. Studies have shown that the combination of BCNU and 5-FU did not improve the survival rate of malignant gliomas compared to BCNU alone.Ara-C is mostly used in combination with cisplatin in the clinical treatment of malignant gliomas, and some studies have suggested that the response rate of first-treated glioblastomas is higher.The biggest problem with MTX in the treatment of gliomas is that it has a low blood-brain-barrier passage rate, and a recent study has utilized MTX-loaded Polyether dendrimer copolyester for intraoperative treatment of gliomas has been reported, which plays a role in crossing the blood-brain barrier and preventing MTX resistance, and is a potential adjuvant method for the treatment of malignant gliomas. Antibiotic analogs used for glioma chemotherapy include bleomycin, streptomycin, and adriamycin. Studies on the efficacy of the first two for malignant gliomas have been mainly at the animal level, with more limited clinical trial data. Clinical studies of the latter began in the 1970s, but there have been insufficient clinical trials to demonstrate definitive efficacy.