Temozolomide (TMZ) is currently recommended by the Oncology Specialty Group of the Neurosurgery Branch of the Chinese Medical Association for the chemotherapy of newly diagnosed malignant gliomas (multiple level I evidence, see the Chinese Consensus on the Diagnosis and Treatment of Malignant Gliomas of the Central Nervous System), and although it significantly improves the prognosis of malignant gliomas, the overall prognosis of the disease is still very unsatisfactory. TMZ-based combination chemotherapy may be one of the future therapeutic trends in the treatment of newly diagnosed/recurrent malignant gliomas. At present, TMZ combined with ACCUTANE regimen is often used for the treatment of malignant glioma in the United States, but there is no relevant report in China. The use of this regimen for three cases of recurrent glioma is reported as follows: 1. Case report Case 1: 58-year-old male, visited the hospital for headache, preoperative examination showed left temporal tumor, our hospital performed tumor resection, the tumor reached total excision, postoperative pathology confirmed as glioblastoma (GBM) He was treated with TMZ (Taito) synchronous radiotherapy from 29 days after surgery, followed by 6 courses of adjuvant Taito. The tumor was found to have recurred at 11 months postoperatively. The tumor was then treated with TEMODAR combined with ACCUTANE chemotherapy (TEMODAR 150mg/m2, d1-7; ACCUTANE 100mg/m2, d8-28), and partial remission was achieved after 2 courses, and complete remission was achieved after 5 courses. During this period, the blood routine and liver and kidney functions were normal, with elevated triglycerides, which returned to normal after diet and drug control. The skin was significantly dry during the treatment period. The tumor was found to have recurred at 11 months postoperatively (A), and PR was achieved after 2 courses of combined regimen (B) and CR after 5 courses. Case 2 A 34-year-old male presented to the hospital with unfavorable speech. Enhanced MRI showed a tumor of the left frontal and corpus callosum. He was treated with postoperative radiotherapy without chemotherapy (2 months postoperative, in radiotherapy) and showed CR at 14 months postoperative. 21 months postoperative, tumor recurrence was found, and then the above-mentioned combination chemotherapy was started, and the tumor reached PR after 6 courses. 2 more courses were followed by tumor progression. During this period there was dry skin, elevated triglycerides and mild myelosuppression, which improved with symptomatic management. Preoperative intensive MRI of a 34-year-old male showed a left frontal and corpus callosum tumor (A), which was largely resected, and the pathology was astrocytoma (grade II). Postoperative radiotherapy without chemotherapy was performed (2 months postoperatively, during radiotherapy,) and CR was shown 14 months postoperatively (C). Tumor recurrence was found 21 months after surgery (D), and the tumor reached PR after 6 courses of combined chemotherapy (E). Tumor PD after 2 more courses (F). Case 3 30-year-old male presented with headache, preoperative MRI showed a right frontal tumor, and enhanced MRI within 72 hours postoperatively showed a full tumor with pathology of GBM. postoperative Taito simultaneous radiotherapy, followed by adjuvant Taito at 3 courses of imaging is shown in Figure 3C, with a clear recurrence at 6 courses of treatment (Figure 3D). Subsequently, after one course of the above mentioned regimen, the tumor was still progressive in two courses of treatment as shown in Figure 3E. The side effects mentioned above were also present during this period and were tolerated. Right frontal tumor preoperatively (A), postoperative MRI at 72 hours (B), pathology of GBM, simultaneous radiotherapy and 3 courses of Taito are shown in C. After 6 courses, there was recurrence (D), and images after 1 and 2 courses of TMZ+ACCUTANE regimen are shown in E and F. (A-F are all enhanced images.) 2. Isotretinoin), was originally used for skin diseases. Its main component is 13-cis-retinoic acid (cRA), which belongs to the retinoic acid family. Retinoic acid is a derivative of vitamin A, which has anti-cancer and anti-cancer effects and is a classical inducer of cell differentiation. Chinese scholars have pioneered its application in the clinical treatment of acute leukemia and achieved remarkable success. In glioma, retinoic acid can induce increased expression of p55 tumor necrosis factor α, which can trigger the apoptotic process of tumor cells; it can increase the expression level of cell adhesion molecule 1 and promote anti-tumor immunity; more importantly, cRA can reduce the affinity of epidermal growth factor ligand and receptor and thus inhibit the growth of glioma cells; it can also reduce the invasiveness of glioma cells by inhibiting the expression of extracellular matrix protein. Glioma cell invasiveness by inhibiting the expression of extracellular matrix proteins. Even before the temozolomide era (1996), Yung et al. from MD Anderson, USA, conducted a phase II clinical trial in recurrent or progressive gliomas (after radiation and conventional chemotherapy) and showed encouraging results with high doses of ACCUTANE. Eight years later, they retrospectively evaluated ACCUTANE as a single agent in 85 recurrent glioblastomas, suggesting that 4% of patients achieved PR, 8% had a mild response (MR), and 34% achieved disease stabilization (SD). The mean progression-free survival time and overall survival time were 10 and 24.6 weeks, respectively [10]. These suggest the efficacy of ACCUTANE alone in relapsing gummies, but possibly better results in combination with other cytotoxic agents. Therefore, ACCUTANE is currently often used in combination with temozolomide in the United States. The main side effects of ACCUTANE are: dryness of the lips, nasal mucosa and eyes, itching and sweating of the skin; reversible hair loss; muscle and joint pain; rare colitis, ileitis and bleeding; excessive blood uric acid; benign intracranial hypertension; elevated triglycerides and cholesterol; teratogenicity; and rare psychiatric abnormalities. Contraindicated in pregnant and potentially pregnant female patients, nursing mothers, hepatic and renal insufficiency, hypersensitivity to this drug, and excessive vitamin A intake. Since ACCUTANE has no myelosuppressive effect, the combination with TMZ is more suitable for use in elderly patients and patients with deviations in bone marrow function. Case 1 of this group is a gumma patient, who was treated with standard TMZ with simultaneous radiotherapy and 6 courses of adjuvant chemotherapy after total resection. Local recurrence was detected before 2 months after the completion of adjuvant chemotherapy, and PR was achieved after two courses of TMZ combined with ACCUTANE and CR after 5 courses. Case 2 was an astrocytoma with a major surgical resection and postoperative radiotherapy only without chemotherapy. Case 3 was treated with regular postoperative radiotherapy and adjuvant TMZ chemotherapy, with signs of recurrence after three courses, and subsequent combination therapy was ineffective. This case also ended up not responding to AVASTIN (data not shown). Through the treatment of these three patients, we have learned that TMZ combined with ACCUTANE chemotherapy is safer and more reliable, easy to administer, and has acceptable side effects. It can also be tried in patients who have been previously treated with TMZ monotherapy and have relapsed, but it is not suitable for patients with fast-growing tumors and signs of relapse during adjuvant chemotherapy. Further data from prospective clinical trials are needed to support whether this combination regimen can be used in patients who have relapsed with other chemotherapeutic modalities, such as ACNU, and after surgery for primary malignant glioma. This work was supported by Professor Mark R. Gilbert of the Department of Neuro-Oncology, MD Anderson Cancer Center, USA, and Dr. Xiaosi Han of the Neuro-Oncology Group, Department of Neurology, University of Alabama at Birmingham Hospital, USA, whose help to the patients is greatly appreciated. We would like to express our sincere gratitude for their help to the patients. We also received a grant from the Shanghai Science and Technology Commission under Grant No. 08411953600.