Phase II study of temozolomide and thalidomide with radiation therapy for newly diagnosed glioblastoma multiforme

Chang, Susan M.; Lamborn, Kathleen R.; Malec, Mary; Larson, David A.; Wara, William M.; Sneed, Penny K.; Rabbitt, Jane; Page, Margaretta; Nicholas, M. Kelly; Prados, Michael D.

doi:10.1016/j.ijrobp.2004.04.023

Cited by 126 publications

(65 citation statements)

References 20 publications

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“…In view of this, multimodality therapy for GBM has previously been demonstrated to improve a patient's survival, as has already been proposed by several authors and including the Canadian committee. 36,38 Several phase II trials have shown synergistic or additive effects of many drugs with different mechanisms of action when combined with radiation and Temozolomide in GBM [39][40][41] though, in practice, some of these tests have not been promising. Currently, new kinase inhibitors are being tested in combination with Temozolomide and radiation for cancer treatment; among them, it has been reported that Aurora kinase inhibitors could be suitable for use as chemoadjuvant treatment in GBM.…”

Section: Pezuk Et Almentioning

confidence: 99%

Inhibition of Polo-Like Kinase 1 Induces Cell Cycle Arrest and Sensitizes Glioblastoma Cells to Ionizing Radiation

Pezuk

Brassesco

Morales

et al. 2013

Cancer Biotherapy and Radiopharmaceuticals

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Despite efforts to improve surgical, radiologic, and chemotherapeutic strategies, the outcome of patients with glioblastoma (GBM) is still poor. Polo-like kinase 1 (PLK1) is a serine/threonine kinase that plays key roles in cell cycle control and has been associated with tumor growth and prognosis. Here, we aimed at testing the radiosensitizing effects of the PLK1 inhibitor BI 2536 on eight GBM cell lines. For cell cycle analysis, T98G, U251, U343 MG-a, LN319, SF188, U138 MG, and U87 MG cell lines were treated with 10, 50, or 100 nM of BI 2536 for 24 hours. In addition, cell cultures exposed to BI 2536 50 nM for 24 hours were irradiated with c-rays from 60 Cobalt source at final doses of 2, 4, and 6 Gy. Combinatorial effects were evaluated through proliferation and clonogenic capacity assays. Treatment with BI 2536 caused mitotic arrest after 24 hours, and increased apoptosis in GBM cells. Moreover, our results demonstrate that pretreatment with this drug sensitized six out of seven GBM cell lines to different doses of c-irradiation as shown by decreased growth and abrogation of colony-formation capacity. Our data suggest that PLK1 blockage has a radiosensitizing effect on GBM, which could improve treatment strategies for this devastating tumor.

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Section: Pezuk Et Almentioning

confidence: 99%

Inhibition of Polo-Like Kinase 1 Induces Cell Cycle Arrest and Sensitizes Glioblastoma Cells to Ionizing Radiation

Pezuk

Brassesco

Morales

et al. 2013

Cancer Biotherapy and Radiopharmaceuticals

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show abstract

“…[63][64][65][66][67][68] The more potent thalidomide analog lenalidomide has better tolerability; however, there was little suggestion of efficacy, either as a single agent 69 or in combination with radiation therapy. 70 These lenalidomide studies were phase I trials and were not designed to assess efficacy, but it is noteworthy that there were no radiographic responses with lenalidomide monotherapy in 24 recurrent GBM patients 69 and one response in 20 evaluable patients with lenalidomide in combination with radiation therapy in newly diagnosed GBM patients.…”

Section: Inhibitors Of Vegf-independent Angiogenic Signaling Pathwaysmentioning

confidence: 99%

Antiangiogenic Strategies for Treatment of Malignant Gliomas

2009

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“…5). radiation or other chemotherapeutic drugs (9,(31)(32)(33). IFN-ß has also been used for patients with solid tumors including malignant gliomas with only marginal benefit; a therapeutic guideline for optimal clinical efficacy has not been determined (23,34).…”

Section: Suppression Of U-87 Cell Migration By Tmz and Ifn-ß Combinatmentioning

confidence: 99%

Potentiation of antiglioma effect with combined temozolomide and interferon-β

Park

Joe²,

Kim³

et al. 2006

Oncol Rep

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Abstract. Temozolomide (TMZ) is a DNA methylating agent that has shown promising antitumor activity against high grade glioma. Interferon-ß (IFN-ß) is known to have antiproliferative and antiangiogenic activities. The aim of this study was to elucidate whether an antiglioma effect could be potentiated by the combination of TMZ and IFN-ß. In vitro, the combination of these drugs suppressed the proliferative and migratory activities, as well as enhance of the apoptosis and cell cycle (S phase) arrest of U-87 cells more efficiently than TMZ or IFN-ß alone. IFN-ß exerted a potent inhibitory effect on the proliferation of human umbilical vein endothelial cells (HUVEC); however, no additive or synergistic effect was observed with the addition of TMZ. To determine in vivo effect, nude mice bearing intracerebral U-87 xenograft inoculation were treated with intraperitoneal administration of PBS, TMZ (15 mg/kg for 3 days), IFN-ß (2x10 5 IU for 15 days), and a TMZ + IFN-ß combination. The combined treatment (median 62.0±8.6 days, P=0.0005) was observed to significantly increase the survival of the animals compared to treatment with PBS (median 30.0±2.5 days), TMZ (median 41.0±3.5 days) or IFN-ß (mean 36.0±2.5 days). These results suggest that antiglioma activity can be enhanced by the combination of TMZ and IFN-ß, providing the possibility for a new strategy development in the management of malignant glioma.

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Phase II study of temozolomide and thalidomide with radiation therapy for newly diagnosed glioblastoma multiforme

Cited by 126 publications

References 20 publications

Inhibition of Polo-Like Kinase 1 Induces Cell Cycle Arrest and Sensitizes Glioblastoma Cells to Ionizing Radiation

Inhibition of Polo-Like Kinase 1 Induces Cell Cycle Arrest and Sensitizes Glioblastoma Cells to Ionizing Radiation

Antiangiogenic Strategies for Treatment of Malignant Gliomas

Potentiation of antiglioma effect with combined temozolomide and interferon-β

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