OBJECTIVE: Temozolomide is a novel oral alkylating agent, which has been reported to be effective in treating patients with recurrent malignant gliomas. This study report an analysis of the activity and toxicity of temozolomide as second-line therapy for patients with recurrent and progressive malignant gliomas after surgery and standard radiation therapy with or without chemotherapy. METHODS: Twenty patients with malignant gliomas of which thirteen(65%) had glioblastoma multiforme(GBM), five(25%) with anaplastic astrocytoma(AA), and two(10%) with anaplastic oligodendroglioma(AO) were enrolled in this study. They had been treated in our institution since July, 2000 and had been previously irradiated with or without chemotherapy. For the patients with recurrent and progressive disease, temozolomide(150-200mg/m2/d x5 days) was administered every 28 days until the progression of the tumor or toxicity developed. RESULTS: The median number of treatment cycles was 3(total 86). Of the 20 patients, 2(10%) achieved a complete response(CR), 5(25%) achieved a partial response(PR), 5(25%) had stable disease(SD), and 8(40%) had progressive disease(PD). One patient achieved a CR, 3 patients achieved a PR, 2 patients had SD and 7 patients had PD in GBM, and 1 patient achieved a CR, 2 patients achieved a PR, 3 patients had SD, 1 patient had PD in the non-GBM patients. Median progression free survival(PFS) was 8 weeks in GBM and 22 weeks in the non-GBM patients. No hematological toxicity greater than grade 2 was observed, and hepatotoxicity of grade 2 was encountered in 1(5%) patient. CONCLUSION: Temozolomide demonstrate moderate activity in recurrent and progressive malignant brain tumors, and the response rate and PFS were better in the non-GBM tumors than in the GBM tumors. The treatment is well tolerated without any serious toxicity.
Brain Neoplasms ; Drug Therapy* ; Glioblastoma ; Glioma* ; Humans

No abstract available
Drug Therapy ; Glioma* ; Humans ; Nimustine* ; Radiotherapy*

Brain Neoplasms ; therapy ; Glioma ; therapy ; Humans ; Palliative Care

No abstract available.
Astrocytoma ; Brain* ; Drug Therapy ; Glioblastoma ; Glioma* ; Humans ; Nimustine* ; Radiotherapy*

The authors analyzed preliminary outcome of 10 patients with mixed glioma(3 patients with low-grade oligoastrocytoma and 7 patients with anaplastic oligoastrocytoma) who underwent surgical resection and were treated or are in treatment with or without adjuvant therapy at our institute since May 1993. In the low-grade oligoastrocytoma group, gross total tumor resection was done in all three cases and postoperative radiation therapy was performed in 2 cases. In the anaplastic oligoastrocytoma group, all seven cases were divided as to the amount of tumor removal(gross total resection; 4 cases, subtotal resection; 1 case, partial resection; 2 cases) and clinical course and prognosis were analyzed as to performing postoperative radiation therapy with or without chemotherapy. In the low-grade oligoastrocytoma group, one patient who didn't undergo postoperative radiation therapy suffered from tumor recurrence that showed histopathologically malignant transformation. In the anaplastic oligoastrocytoma group, 2 patients who underwent subtotal tumor resection and partial tumor resection with postoperative radiation therapy showed tumor progression and histopathologically more malignant transformation. The authors propose that gross total tumor resection with postoperative radiation therapy in low-grade oligoastrocytoma and adding chemotherapy(especially with procarbazine, lomustine, vincristine; PCV regimen) in anaplastic oligoastrocytoma appear to be associated with more prolongation of patient's survival.
Drug Therapy ; Glioma* ; Humans ; Lomustine ; Procarbazine ; Prognosis ; Recurrence ; Vincristine

In the treatment of the intracranial gliomas surgical intervention is recommended as the standard procedure which should be performed in all cases when the tumor is accessible. While surgery will not bring about a cure and clearly, radiation therapy and chemotherapy have made a significant impact of long-term survival in the treatment of the malignant gliomas, nevertheless surgery still remains the single most effective method for achieving a rapid reduction of tumor burden reducing increased intracranial pressure and provides a tissue diagnosis. Following surgery, the other antitumor programs have the best chance of achieving a significant increment of tumor cell kill, therefore, surgery has a distinct role to play in the multidisciplinable approach to the treatment of these highly aggressive malignant tumors. It is very unlikely that future advances will obviate the necessity for conventional surgery in the treatment of benign gliomas. The surgical management of gliomas with major emphasis on malignant ones is presented including the pathophysiology, radiological diagnosis, aim of surgery, surgical procedure and some different possibility of surgical treatment. Prospective future development of surgical treatment of brain tumor is also considered.
Brain Neoplasms ; Diagnosis ; Drug Therapy ; Glioma* ; Intracranial Pressure ; Tumor Burden

Twelve patients with recurrent malignant glioma were treated with combination chemotherapy, consisting of procarbazine(60mg/m2, 8th-21th day), CCNU(110mg/m2, 1st day), and vincristine(1.4mg/m2, 8th and 29th day) every 6 weeks. Most patients had undergone initial resection of primary tumor, postoperative radiotherapy, and another form of chemotherapy. Response or progression was defined as improvement or deterioration in MRI scan. Assessment of response followed evaluation of MRI obtained after the completion of each two cycles of chemotherapy, if possible. Partial(more than 50% reduction of tumor mass) response at 15+ to 47+ weeks after chemotherapy was noted in three(60%) of the five patients with recurrent oligodendrogliomas. But in patients with recurrent anaplastic astrocytoma or gllioblastoma, partial response at 8+ weeks after chemotherapy was noted in one(14%) of the seven patients. It is suggested that PCV chemotherapy is more effective for patients with recurrent oligodendrogliomas than other recurre nt gliomas.
Astrocytoma ; Drug Therapy* ; Drug Therapy, Combination ; Glioma* ; Humans ; Magnetic Resonance Imaging ; Oligodendroglioma ; Radiotherapy

Isocitrate dehydrogenase (IDH) is an essential metabolic enzyme in the tricarboxylic acid cycle (TAC). The high mutation frequency of the IDH gene plays a complicated role in gliomas. In addition to affecting gliomas directly, mutations in IDH can also alter their immune microenvironment and can change immune-cell function in direct and indirect ways. IDH mutations mediate immune-cell infiltration and function by modulating immune-checkpoint gene expression and chemokine secretion. In addition, IDH mutation-derived D2-hydroxyglutarate can be absorbed by surrounding immune cells, also affecting their functioning. In this review, we summarize current knowledge about the effects of IDH mutations as well as other gene mutations on the immune microenvironment of gliomas. We also describe recent preclinical and clinical data related to IDH-mutant inhibitors for the treatment of gliomas. Finally, we discuss different types of immunotherapy and the immunotherapeutic potential of IDH mutations in gliomas.
Brain Neoplasms/therapy* ; Glioma/therapy* ; Humans ; Immunotherapy ; Isocitrate Dehydrogenase/genetics* ; Mutation/genetics* ; Tumor Microenvironment

In this issue of the Chinese Journal of Cancer, European experts review current standards, trends, and future prospects in the difficult domain of high-grade glioma. In all fields covered by the different authors, the progress has been impressive. For example, discoveries at the molecular level have already impacted imaging, surgery, radiotherapy, and systemic therapies, and they are expected to play an increasing role in the management of these cancers. The European Organization for Research and Treatment of Cancer (EORTC) has pioneered new treatment strategies and contributed to new standards. The articles in this issue will cover basic molecular biological principles applicable today, novel surgical approaches, innovations in radiotherapy planning and delivery, evidence-based standards for radiotherapy alone or combined with chemotherapy, current standards and novel approaches for systemic treatments, and the important but often neglected field of health-related quality of life. Despite the advances described in these articles, the overall prognosis of high-grade glioma, especially glioblastoma, remains poor, and more research is needed to address this problem.
Brain Neoplasms ; pathology ; therapy ; Combined Modality Therapy ; Glioblastoma ; pathology ; therapy ; Glioma ; pathology ; therapy ; Humans ; Neoplasm Grading ; Quality of Life

OBJECTIVE: Anti-malaria drugs may modulate tumor resistance to chemotherapeutic agents, but it has not been proven effective in the treatment of malignant gliomas. The aim of this study was to determine whether adequate pre-clinical data on co-administration of chemotherapeutic agents with anti-malaria drugs on malignant cell lines could be obtained that would warrant its further potential consideration for use in a clinical trial for malignant gliomas. METHODS: Two malignant glioma cell lines (U87MG, T98G) were treated with chemotherapeutic agents alone or with anti-malaria drugs. Cells were incubated with drugs for 4 days. Following the 4-day incubation, drug sensitivity assays were performed using 3-(4, 5-dimethyl-2-thiazol-2-yl) 2, 5-diphenyltetrazolium bromide (MTT) assay following optimization of experimental conditions for each cell lines and cell viability was calculated. RESULTS: In all of four chemotherapeutic agents(doxorubicin, vincrisitne, nimustine, and cisplatin), the cell viability was found to be markedly decreased when hydroxychloroquine was co-administered on both U87MG and T98G cell lines. The two way analysis of variance(ANOVA) yielded a statistically significant two-sided p-value of 0.0033(doxorubicin), 0.0005(vincrisitne), 0.0007(nimustine), and 0.0003(cisplatin) on U87MG cell lines and 0.0006(doxorubicin), 0.0421(vincrisitne), 0.0317(nimustine), and 0.0001(cisplatin) on T98G cell lines, respectively. However, treatment with chloroquine and primaquine did not induce a decrease in cell viability on both U87MG and T98G cell lines. CONCLUSION: Our data support further consideration of the use of hydroxychloroquine prior to systemic chemotherapy to maximize its tumoricidal effect for patients with malignant gliomas.
Cell Line* ; Cell Survival ; Chloroquine ; Drug Resistance, Multiple ; Drug Therapy ; Glioma* ; Humans ; Hydroxychloroquine* ; Nimustine ; Primaquine