Chemotherapy for malignant gliomas of the brain: a review of ten-years experience

Paoletti, P; Butti, G.; Knerich, R; Gaetani, Paolo; Assietti, Roberto

doi:10.1007/bf01420190

Cited by 21 publications

(6 citation statements)

References 68 publications

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“…But they reported a higher in vitro sensitivity in glioblastomas and astrocytomas grade 4 against BCNU than in astrocytomas grade 1 or 2, which corresponds well to our findings. At present, BCNU is still one of the favorite drugs in chemotherapy of human gliomas [6,7]. An in vitro sensititivity rate of 46% against mitoxantrone, as seen with the MTT assay and the CFA, opens up the questions, if this response is not due to a 'wrong' cut-off-concentration (350 ng/ml).…”

Section: Discussionmentioning

confidence: 99%

“…Even though this has been a subject of major interest for many years [1], recent reports have shown, that surgery and radiation have a significant but only modest effect in prolonging patients survival time or increasing their quality of life [2][3][4][5]. Since the introduction of chemotherapy for human brain tumors in the 1960s, this treatment has been rather disappointing in improving the long-term results in these tumors [6][7][8].…”

Section: Introductionmentioning

confidence: 99%

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The MTT assay for chemosensitivity testing of human tumors of the central nervous system

et al. 1992

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In this study we assessed the influence of patient- and drug-specific parameters in the short-term MTT-chemosensitivity assay in 150 primary cell cultures derived from human brain tumors. In 45 patients the MTT assay was directly compared with the CFA (Colony Forming Assay). Resistance was 10-20% higher in the MTT assay than in the CFA, but there was a good agreement in both assays, that more malignant gliomas had a higher in vitro chemosensitivity against ACNU and BCNU. Overall the results demonstrate, that there is no uniform correlation between the in vitro chemosensitivity and the histopathological classification of the tumors, which corresponds well to the clinical situation. On the basis of this study we suggest prospective clinical trials with the MTT assay in human brain tumors.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The MTT assay for chemosensitivity testing of human tumors of the central nervous system

et al. 1992

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“…The corresponding values for D-54Mg cells were 30 hr (monolayer) and 5 days (spheroids) (data not shown). The growth characteristics of the spheroids are thus more comparable with those observed in vivo, where the growth fraction is usually below 0.5 (Paoletti et al, 1990), and the cell-cycle time is 70 to 80 hr (Paoletti et al, 1990). This emphasizes the importance of using a relevant biological model when testing cytotoxic drugs, especially when the drug is a cell-cycle-phase-specific agent like the antifolates.…”

Section: Discussionmentioning

confidence: 99%

“…Although the tumor may appear macroscopically limited at operation, microscopical examination nearly always rcveals infiltrating tumor cells in surrounding brain. Surgery in combination with radiotherapy are vital elements in therapy of such tumors, while chemotherapy has been more controversial (Paoletti et al, 1990). The central nervous system was long considered as a pharmacological sanctuary for most systemically delivered chemotherapeutic agents, and the view still prevails that properties such as lipid solubility and low molecular weight favour the distribution of drugs across the intact blood-brain barrier (Grieg, 1987).…”

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confidence: 99%

Proliferation, migration and invasion of human glioma cells exposed to antifolate drugs

Terzis

Fiskerstrand

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et al. 1993

Intl Journal of Cancer

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The present study describes the effects of 2 folate antagonists, methotrexate (MTX) and the lipophilic antifolate trimetrexate (TMX) on 2 permanent human glioma cell lines (GaMg and D-54Mg) grown as monolayers and as multicellular tumor spheroids. In addition, the effects of drug exposure on tumor cell invasion was studied using a three-dimensional organ co-culture system. In monolayer cultures, TMX was a more potent inhibitor of cell growth than MTX, especially towards the GaMg cell line. The 2 drugs, however, showed similar cytotoxicity as assessed by the plating efficiency assay. Reduced ability of directional migration of cells on a plastic surface was seen by either antifolate usually at concentrations to 10-fold higher than those exerting a cytotoxic effect in the plating efficiency assay. TMX was somewhat more potent than MTX as an inhibitor of spheroid growth. When tumor spheroids were exposed to MTX or TMX at concentrations that caused 65 to 70% inhibition of cell migration, there was a latent period of 4 to 5 days before inhibition of spheroid growth ensued. Invasion was investigated in a co-culture system, where tumor spheroids were confronted with fetal rat brain cell aggregates. Neither drug reduced tumor cell invasion, although histological examination revealed toxic effects both in GaMg and in D-54Mg spheroids. We conclude that spheroids from human glioma cells were less sensitive to the antifolates than monolayers. For both drugs a latency period was observed before inhibition of spheroid growth. The spheroids retained their ability to invade normal brain tissue when exposed to levels of folate antagonists inhibiting spheroid growth.

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“…Because of differences in their availability, ACNU (nimustine) has been used as a core agent for glioblastoma treatment in Korea and Japan, while BCNU (carmustine) or CCNU (lomustine) have been widely used in Western countries [8] . Several studies have demonstrated that the usage of nitrosourea as an adjuvant therapy to surgery and/or radiation leads to increased survival in patients with glioma [6,7,9,10] .…”

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Preradiation Chemotherapy with ACNU-CDDP in Patients with Newly Diagnosed Glioblastoma: A Retrospective Analysis

et al. 2009

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Objective: We evaluated the benefit of preradiation chemotherapy with ACNU (nimustine) and CDDP (cisplatin) in patients with newly diagnosed glioblastoma by retrospective analysis. Methods: A total of 151 patients were newly confirmed to have glioblastoma between January 2000 and December 2004. All patients underwent surgical resection: 38 (25.2%) patients underwent complete resection, 73 (48.3%) underwent incomplete resection and 40 (26.5%) underwent biopsy. Preradiation chemotherapy using ACNU-CDDP was administered as an initial adjuvant therapy for 87 (57.6%) patients (ACNU-CDDP group), radiation therapy was performed in 31 (20.5%) patients (RT group) and the remaining 33 (21.9%) patients were treated with other regimens or refused to undergo further treatment. Results: The median survival time was 13 months (95% CI 11.29–14.71), and the overall survival rate was 54.0% at 1 year and 21.3% at 2 years. The differences in median survival time between the complete resection group and biopsy group and between the ACNU-CDDP group and RT group were significant (15.0 vs. 10 months, p = 0.028, and 16.0 vs. 12.0 months, p = 0.036, respectively) in the univariate analyses. Even in the multivariate analysis, preradiation chemotherapy using ACNU-CDDP had a significant effect on survival prolongation (HR = 0.628, p = 0.042). The usage of temozolomide for adjuvant or salvage therapy also had an independent and significantly positive effect on survival (HR = 0.511, p = 0.006). Grade 3 and 4 hematologic toxicities occurred in 28 (32.1%) patients in the ACNU-CDDP group, but there were no treatment-related deaths. Conclusion: Preradiation chemotherapy with ACNU-CDDP as an initial therapy for patients with newly diagnosed glioblastoma is feasible and should be assessed in a randomized phase III study.

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Chemotherapy for malignant gliomas of the brain: a review of ten-years experience

Cited by 21 publications

References 68 publications

The MTT assay for chemosensitivity testing of human tumors of the central nervous system

The MTT assay for chemosensitivity testing of human tumors of the central nervous system

Proliferation, migration and invasion of human glioma cells exposed to antifolate drugs

Preradiation Chemotherapy with ACNU-CDDP in Patients with Newly Diagnosed Glioblastoma: A Retrospective Analysis

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