Principles of Chemotherapy in Brain Neoplasia

Gumerlock, Mary K.; Neuwelt, Edward A.

doi:10.1007/978-3-7091-8876-7_6

Cited by 10 publications

(29 citation statements)

References 128 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…where A 1 , A 2 , and A 3 are the amount in the absorption, plasma, and CSF compartments, respectively; K a is the absorption rate constant; CL indicates the oral clearance; V D is the volume of distribution of the central compartment; K 23 and K 32 are the two transfer rate constants from plasma to CSF (K 23 ) and from CSF to plasma (K 32 ). V p , the volume of distribution in the CSF, was fixed to 140 ml according to the literature (23,24) because this parameter could not be identified simultaneously with K 23 and K 32 .…”

Section: Methodsmentioning

confidence: 99%

“…V p , the volume of distribution in the CSF, was fixed to 140 ml according to the literature (23,24) because this parameter could not be identified simultaneously with K 23 and K 32 . C plasma and C CSF are the TMZ concentrations in plasma and CSF.…”

Section: Methodsmentioning

confidence: 99%

“…Considering that corticosteroids could partially restore the integrity of the blood-brain barrier, thereby limiting drug delivery to the tumor, and on the other hand also reduce intracranial pressure by decreasing peritumoral vasogenic edema resulting in a increased drug delivery (6,(31)(32)(33)(34), a relationship between corticotherapy and the two transfer rate constants, K 23 and K 32 , were examined. No significant influence could be observed (⌬OF ϭ Ϫ0.1).…”

Section: Demographicsmentioning

confidence: 99%

See 2 more Smart Citations

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

Ostermann

Csajka

Buclin

et al. 2004

Clinical Cancer Research

421

324

View full text Add to dashboard Cite

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.

show abstract

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Demographicsmentioning

confidence: 99%

See 1 more Smart Citation

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

Ostermann

Csajka

Buclin

et al. 2004

Clinical Cancer Research

421

324

View full text Add to dashboard Cite

show abstract

“…The rationale for intraarterial treatment is that it augments the local plasma peak drug concentration and local AUC compared with an equivalent intravenous dose. 29, 30 This method can potentially increase drug concentrations by two-to fourfold while reducing the risk of systemic toxicity. The benefits of intraarterial administration are maximized with drugs that have a high rate of biotransformation, metabolism, and excretion during the first pass (i.e., total body drug clearance).…”

Section: Intraarterialmentioning

confidence: 99%

“…Cyclophosphamide is initially hydroxylated to form 4-hydroxycyclophosphamide. 30 Further activation generates aldophosphamide, which then breaks down into phosphoramide mustard and acrolein. Ifosfamide undergoes similar metabolic activation by hepatic cytochrome P450 mixed-function oxidases.…”

Section: Nitrogen Mustardsmentioning

confidence: 99%

Clinical Presentation, Diagnosis, and Pharmacotherapy of Patients with Primary Brain Tumors

et al. 1999

View full text Add to dashboard Cite

show abstract

Implication of glucocorticoid receptors in the stimulation of human glioma cell proliferation by dexamethasone

Langeveld

Waas

Stoof

et al. 1992

J of Neuroscience Research

View full text Add to dashboard Cite

Dexamethasone is frequently used in the therapy of brain tumor patients. We investigated the effect of dexamethasone on the proliferation of three short-term and four established human glioma cell lines in vitro, using a microculture tetrazolium assay to determine growth rates. In one short-term culture and in one established cell line dexamethasone consistently stimulated the proliferation in a concentration-dependent way. The proliferation was maximally enhanced at a concentration of approximately 0.1 microM. In these two cell lines a relatively high level of glucocorticoid receptors was present, whereas low levels of glucocorticoid receptors were found in the other cell lines. In addition, we demonstrated that the stimulatory effects of dexamethasone on the proliferation of the glioma cell lines can be antagonized by the antiglucocorticoid RU38486. The results demonstrate unequivocally that the glucocorticoid receptor plays a role in the growth stimulating effect of dexamethasone.

show abstract

Principles of Chemotherapy in Brain Neoplasia

Cited by 10 publications

References 128 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

Clinical Presentation, Diagnosis, and Pharmacotherapy of Patients with Primary Brain Tumors

Implication of glucocorticoid receptors in the stimulation of human glioma cell proliferation by dexamethasone

Contact Info

Product

Resources

About