Chemotherapy for high-grade gliomas

Galanis, Evanthia; Buckner, Jan C.

doi:10.1054/bjoc.1999.1075

Cited by 72 publications

(40 citation statements)

References 84 publications

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“…Despite surgery followed by standard fractionated radiotherapy with or without adjuvant chemotherapy (3,4), these tumors almost invariably recur and lead rapidly to death. Many of the commonly used chemotherapy agents (e.g., nitrosoureas or the combination regimen procarbazine, lomustine, vincristine) have limited activity against glioma (5). Although the blood-brain barrier is partially disrupted in malignant gliomas, penetration into the brain of many chemotherapy agents appears to be insufficient.…”

Section: Introductionmentioning

confidence: 99%

Plasma and Cerebrospinal Fluid Population Pharmacokinetics of Temozolomide in Malignant Glioma Patients

Ostermann

Csajka

Buclin

et al. 2004

Clinical Cancer Research

430

324

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Purpose: Scarce information is available on the brain penetration of temozolomide (TMZ), although this novel methylating agent is mainly used for the treatment of malignant brain tumors. The purpose was to assess TMZ pharmacokinetics in plasma and cerebrospinal fluid (CSF) along with its inter-individual variability, to characterize covariates and to explore relationships between systemic or cerebral drug exposure and clinical outcomes.Experimental Design: TMZ levels were measured by high-performance liquid chromatography in plasma and CSF samples from 35 patients with newly diagnosed or recurrent malignant gliomas. The population pharmacokinetic analysis was performed with nonlinear mixed-effect modeling software. Drug exposure, defined by the area under the concentration-time curve (AUC) in plasma and CSF, was estimated for each patient and correlated with toxicity, survival, and progression-free survival.Results: A three-compartment model with first-order absorption and transfer rates between plasma and CSF described the data appropriately. Oral clearance was 10 liter/h; volume of distribution (V D ), 30.3 liters; absorption constant rate, 5.8 h ؊1 ; elimination half-time, 2.1 h; transfer rate from plasma to CSF (K plasma3 CSF ), 7.2 ؋ 10 ؊4 h ؊1 and the backwards rate, 0.76 h ؊1 . Body surface area significantly influenced both clearance and V D , and clearance was sex dependent. The AUC CSF corresponded to 20% of the AUC plasma . A trend toward an increased K plasma3 CSF of 15% was observed in case of concomitant radiochemotherapy. No significant correlations between AUC in plasma or CSF and toxicity, survival, or progression-free survival were apparent after deduction of dose-effect.Conclusions: This is the first human pharmacokinetic study on TMZ to quantify CSF penetration. The AUC CSF / AUC plasma ratio was 20%. Systemic or cerebral exposures are not better predictors than the cumulative dose alone for both efficacy and safety.

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Section: Introductionmentioning

confidence: 99%

Plasma and Cerebrospinal Fluid Population Pharmacokinetics of Temozolomide in Malignant Glioma Patients

Ostermann

Csajka

Buclin

et al. 2004

Clinical Cancer Research

430

324

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“…In addition to surgical resection, the standard clinical management of this tumour entity involves radiotherapy with or without adjuvant chemotherapy (Kristiansen et al, 1981;Fisher et al, 2001;Stupp et al, 2002). In spite of this multidisciplinary approach, the prognosis for patients with GBM remains poor (Levin et al, 1997;Galanis and Buckner, 2000).…”

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confidence: 99%

Irradiation differentially affects substratum-dependent survival, adhesion, and invasion of glioblastoma cell lines

Cordes¹,

Hansmeier²,

Beinke³

et al. 2003

Br J Cancer

102

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Effects of ionising radiation on extracellular matrix (ECM)-modulated cell survival and on adhesion and invasion are not well understood. In particular, the aggressiveness of glioblastoma multiforme has been associated with tumour cell invasion into adjacent normal brain tissue. To examine these effects in more depth, four human glioblastoma cell lines (A-172, U-138, were irradiated on fibronectin (FN), Matrigel, BSA or polystyrene. Major findings of this study include a significantly increased survival of irradiated A-172 but not of irradiated U-138, LN-229, and LN-18 cells on FN or Matrigel compared to cells irradiated on polystyrene or BSA. Irradiation induced a dose-dependent increase in functional b1-and b3-integrins in all four glioma cell lines. This integrin induction caused improved cell adhesion to FN or Matrigel. In contrast to U-138, LN-229 and LN-18 cells, irradiation strongly impaired A-172 cell invasion. Invasion of all cell lines was inhibited by anti-integrin antibodies, the disintegrin echistatin and the MMP-2/-9 inhibitor III. Additionally, b1-and b3-integrins modulated basal and radiation-altered gelatinolytic activity of MMP-2. Tested glioblastoma cell lines showed a differential cellular susceptibility to FN or Matrigel which affected the cellular radiosensitivity. Three out of four glioma cell lines demonstrated a combination of a substratum-independent survival after irradiation and an invasive potential which was not affected by irradiation. b1-and b3-integrins were identified to play a substantial, regulatory role in survival, adhesion, invasion and MMP-2 activity. Detailed insights into radioresistance and invasion processes might offer new therapeutic strategies to enhance cell killing of lethal high-grade astrocytoma.

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“…Tumour response is of uncertain usefulness as an outcome measure in gliomas (Galanis and Buckner, 2000) and is not reported here. More important is the assessment of survival (progression free or overall).…”

Section: Outcome Measuresmentioning

confidence: 92%

A rapid and systematic review of the effectiveness of temozolomide for the treatment of recurrent malignant glioma

et al. 2002

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A rapid and systematic review of the effectiveness and cost-effectiveness of temozolomide in the treatment of recurrent malignant glioma was commissioned by the NHS HTA Programme on behalf of NICE. The full report has been published elsewhere. This paper summarizes the results for the effectiveness of temozolomide in people with recurrent glioblastoma multiforme and anaplastic astrocytoma. The review was conducted using standard systematic review methodology involving a systematic literature search, quality assessment of included studies with systematic data extraction and data synthesis. One randomized controlled trial and four uncontrolled studies were identified for inclusion. The key results were that temozolomide may increase progression-free survival but has no significant impact on overall length of survival. The main effect from temozolomide may have been in those patients who had not received any prior chemotherapy regimens, however further randomized controlled trials are required to confirm this suggestion. Temozolomide appears to produce few serious adverse effects and may also have a positive impact on health-related quality of life. Overall the evidence-base is weak and few strong conclusions can be drawn regarding the effectiveness of temozolomide. Large, well-designed randomized controlled trails conducted in a wider patient population are needed.

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Chemotherapy for high-grade gliomas

Cited by 72 publications

References 84 publications

Plasma and Cerebrospinal Fluid Population Pharmacokinetics of Temozolomide in Malignant Glioma Patients

Plasma and Cerebrospinal Fluid Population Pharmacokinetics of Temozolomide in Malignant Glioma Patients

Irradiation differentially affects substratum-dependent survival, adhesion, and invasion of glioblastoma cell lines

A rapid and systematic review of the effectiveness of temozolomide for the treatment of recurrent malignant glioma

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