A randomized comparison of intra-arterial versus intravenous with or without intravenous 5-fluorouracil, for newly diagnosed patients with malignant glioma

Wr, Shapiro; Sb, Green; Pc, Burger; Rg, Selker; Jc, VanGilder; Jt, Robertson; Mealey, John; Ransohff, J; Ms, Mahaley

doi:10.3171/jns.1992.76.5.0772

Cited by 217 publications

(87 citation statements)

References 43 publications

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“…5-Fluorouracil (5-FU) a pyrimidine analog, is one of the broad spectrum anticancer drugs [3][4][5] used in the treatment of malignancies like glioblastoma 6 and breast cancer. 7 Since 5-FU interferes with DNA synthesis, it principally acts as a thymidylate synthase inhibitor.…”

Section: Introductionmentioning

confidence: 99%

Biological evaluation of 5-fluorouracil nanoparticles for cancer chemotherapy and its dependence on the carrier, PLGA

K¹,

Jagadeeshan²,

Nair³

et al. 2011

IJN

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Nanoscaled devices have great potential for drug delivery applications due to their small size. In the present study, we report for the first time the preparation and evaluation of antitumor efficacy of 5-fluorouracil (5-FU)-entrapped poly (D, L-lactic-co-glycolic acid) (PLGA) nanoparticles with dependence on the lactide/glycolide combination of PLGA. 5-FU-loaded PLGA nanoparticles with two different monomer combinations, 50-50 and 90-10 were synthesized using a modified double emulsion method, and their biological evaluation was done in glioma (U87MG) and breast adenocarcinoma (MCF7) cell lines. 5-FU-entrapped PLGA 50-50 nanoparticles showed smaller size with a high encapsulation efficiency of 66%, which was equivalent to that of PLGA 90-10 nanoparticles. Physicochemical characterization of nanoparticles using differential scanning calorimetry and X-ray diffraction suggested the presence of 5-FU in molecular dispersion form. In vitro release studies showed the prolonged and sustained release of 5-FU from nanoparticles with both the PLGA combinations, where PLGA 50-50 nanoparticles showed faster release. Nanoparticles with PLGA 50-50 combination exhibited better cytotoxicity than free drug in a dose- and time-dependent manner against both the tumor cell lines. The enhanced efficiency of PLGA 50-50 nanoparticles to induce apoptosis was indicated by acridine orange/ethidium bromide staining. Cell cycle perturbations studied using flow cytometer showed better S-phase arrest by nanoparticles in comparison with free 5-FU. All the results indicate that PLGA 50-50 nanoparticles possess better antitumor efficacy than PLGA 90-10 nanoparticles and free 5-FU. Since, studies have shown that long-term exposure of ailing tissues to moderate drug concentrations is more favorable than regular administration of higher concentration of the drug; our results clearly indicate the potential of 5-FU-loaded PLGA nanoparticles with dependence on carrier combination as controlled release formulation to multiplex the therapeutic effect of cancer chemotherapy.

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Section: Introductionmentioning

confidence: 99%

Biological evaluation of 5-fluorouracil nanoparticles for cancer chemotherapy and its dependence on the carrier, PLGA

K¹,

Jagadeeshan²,

Nair³

et al. 2011

IJN

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“…Neuro-Oncology 5, 79-88, 2003(Posted to Neuro-Oncology [serial online], Doc. 02-023, February 10, 2003 P resently, malignant gliomas are treated by resection, external beam radiation, and, in some cases, systemic chemotherapy (Cairncross et al, 1992;Chang and Prados, 1995;Cristante et al, 1992;Fine et al, 1993;Hildebrand et al, 1997;Lesser and Grossman, 1994;Reulen et al, 1988;Shapiro et al, 1992;Walker et al, 1980). Randomized trials of radiotherapy have consistently shown an improvement in survival compared to surgery alone (Walker et al, 1980).…”

mentioning

confidence: 99%

A phase 3 trial of local chemotherapy with biodegradable carmustine (BCNU) wafers (Gliadel wafers) in patients with primary malignant glioma

Westphal

Hilt²,

Bortey³

et al. 2003

Neuro-Oncology

1,090

357

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A previous placebo-controlled trial has shown that biodegradable 1,3-bis (2-chloroethyl)-1-nitrosourea (BCNU) wafers (Gliadel wafers) prolong survival in patients with recurrent glioblastoma multiforme. A previously completed phase 3 trial, also placebo controlled, in 32 patients with newly diagnosed malignant glioma also demonstrated a survival benefit in those patients treated with BCNU wafers. Because of the small number of patients in that trial, a larger phase 3 trial was performed to confirm these results. Two hundred forty patients were randomized to receive either BCNU or placebo wafers at the time of primary surgical resection; both groups were treated with external beam radiation postoperatively. The two groups were similar for age, sex, Karnofsky performance status (KPS), and tumor histology. Median survival in the intentto-treat group was 13.9 months for the BCNU wafertreated group and 11.6 months for the placebo-treated group (log-rank P-value stratified by country = 0.03), with a 29% reduction in the risk of death in the treatment group. When adjusted for factors affecting survival, the treatment effect remained positive with a risk reduction of 28% (P = 0.03). Time to decline in KPS and in 10/11 neuroperformance measures was statistically significantly prolonged in the BCNU wafer-treated group (P ≤ 0.05). Adverse events were comparable for the 2 groups, except for CSF leak (5% in the BCNU wafer-treated group vs. 0.8% in the placebo-treated group) and intracranial hypertension (9.1% in the BCNU wafer-treated group vs. 1.7% in the placebo group). This study confirms that local chemotherapy with BCNU wafers is well tolerated and offers a survival benefit to patients with newly diagnosed malignant glioma. Neuro-Oncology 5, 79-88, 2003 (Posted to Neuro-Oncology [serial online], Doc. 02-023, February 10, 2003 P resently, malignant gliomas are treated by resection, external beam radiation, and, in some cases, systemic chemotherapy (Cairncross et al

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“…The route of chemotherapy administration was assessed in the BTSG trial 8301 (Shapiro et al, 1992). Patients with newly resected malignant glioma received either intra-carotid BCNU or intravenous BCNU with or without intravenous 5-fluorouracil (5-FU).…”

mentioning

confidence: 99%

Chemotherapy for high-grade gliomas

Galanis

Buckner²

2000

Br J Cancer

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A randomized comparison of intra-arterial versus intravenous with or without intravenous 5-fluorouracil, for newly diagnosed patients with malignant glioma

Cited by 217 publications

References 43 publications

Biological evaluation of 5-fluorouracil nanoparticles for cancer chemotherapy and its dependence on the carrier, PLGA

Biological evaluation of 5-fluorouracil nanoparticles for cancer chemotherapy and its dependence on the carrier, PLGA

A phase 3 trial of local chemotherapy with biodegradable carmustine (BCNU) wafers (Gliadel wafers) in patients with primary malignant glioma

Chemotherapy for high-grade gliomas

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