Search results for "Temozolomide"

Pyrrolo[2,1-d][1,2,3,5]tetrazine-4(3H)-ones, a new class of azolotetrazines with potent antitumor activity.

2003

Pyrrolo[2,1-d][1,2,3,5]tetrazinones 10a-o, compounds that hold the deaza skeleton of the antitumor drug temozolomide, were prepared by reaction of 2-diazopyrroles 9 and isocyanates. Such a synthetic route represents, among those leading to azolotetrazinones reported so far, the only possible one since attempts to cyclize to the title ring system 2-amino-1-carbamoylpyrroles 11 or the mono substituted 2-triazenopyrrole 12 failed. Compounds 10 were screened at the National Cancer Institute (NCI) for their activity against a panel of about 60 human tumor cell lines. Most of them possess remarkable antineoplastic activity having GI(50) values in the low micromolar or sub-micromolar range and rea…

Cancer stem cell analysis and clinical outcome in patients with glioblastoma multiforme

2008

Abstract Purpose: Cancer stem cells (CSC) are thought to represent the population of tumorigenic cells responsible for tumor development. The stem cell antigen CD133 identifies such a tumorigenic population in a subset of glioblastoma patients. We conducted a prospective study to explore the prognostic potential of CSC analysis in glioblastoma patients. Experimental Design: We investigated the relationship between the in vitro growth potential of glioblastoma CSCs and patient death or disease progression in tumors of 44 consecutive glioblastoma patients treated with complete or partial tumorectomy followed by radiotherapy combined with temozolomide treatment. Moreover, we evaluated by immun…

Temozolomide (TMZ) in radio-chemotherapy combined schedule for treatment of newly-diagnosed high-grade gliomas (HGG)

2005

1578 Background: Temozolomide (TMZ) is an oral alkylating agent known to cross the blood-brain barrier with efficacy against HGG and a favourable safety profile compared to conventional chemotherap...

ACTR-58. PHASE III TRIAL OF CCNU/TEMOZOLOMIDE (TMZ) COMBINATION THERAPY VS. STANDARD TMZ THERAPY FOR NEWLY DIAGNOSED MGMT-METHYLATED GLIOBLASTOMA PAT…

2017

There is an urgent need for more effective therapies in glioblastoma (GBM). Data from the single arm UKT-03 trial (Glas et al., J Clin Oncol 27, 1257, 2009) suggested that combined lomustine/temozolomide (CCNU/TMZ) therapy might have superior activity in MGMT-methylated GBM. The phase III CeTeG/NOA-09 trial was set up to test this hypothesis in a randomized setting. Patients with MGMT-methylated GBM were randomized (1:1) for standard therapy with daily TMZ (75 mg/m2) during local radiotherapy (RT, 30 x 2 Gy) followed by 6 courses of TMZ (150–200 mg/m2/day for 5 days q4w) or experimental therapy with CCNU/TMZ in addition to local RT. Six 6-week courses of CCNU/TMZ (CCNU 100 mg/m2 d1, TMZ 100…

Phase II study of irinotecan in combination with temozolomide (TEMIRI) in children with recurrent or refractory medulloblastoma: a joint ITCC and SIO…

2013

BackgroundThis multicenter phase II study investigated temozolomide + irinotecan (TEMIRI) treatment in children with relapsed or refractory medulloblastoma.MethodsPatients received temozolomide 100–125 mg/m2/day (days 1–5) and irinotecan 10 mg/m2/day (days 1–5 and 8–12) every 3 weeks. The primary endpoint was tumor response within the first 4 cycles confirmed ≥4 weeks and assessed by an external response review committee (ERRC). In a 2-stage Optimum Simon design, ≥6 responses in the first 15 evaluable patients were required within the first 4 cycles for continued enrollment; a total of 19 responses from the first 46 evaluable patients was considered successful.ResultsSixty-six patients were…

Oral Chemotherapy for the Older Patient with Cancer

2002

Oral chemotherapy presents a number of theoretical advantages in older cancer patients, including convenience of administration and dosage flexibility. Of the oral fluorinated pyrimidines, capecitabine is the most promising, because it minimizes the exposure of normal tissue to the active drug and substantially reduces the risk of mucositis, that is particularly common and severe in the aged. Despite promising initial results, oral etoposide does not offer any special advantage over the intravenous formulation for older patients, while oral temozolomide may have a role in the palliation of malignant melanoma and primary and secondary brain tumors. Of the experimental agents, oral platinum (…

Updated results of the PARP1/2 inhibitor pamiparib in combination with low-dose (ld) temozolomide (TMZ) in patients (pts) with locally advanced or me…

2019

530MO Clinical benefit in biomarker-positive patients (pts) with locally advanced or metastatic solid tumours treated with the PARP1/2 inhibitor pami…

2020

Lomustine-temozolomide combination therapy versus standard temozolomide therapy in patients with newly diagnosed glioblastoma with methylated MGMT pr…

2019

Summary Background There is an urgent need for more effective therapies for glioblastoma. Data from a previous unrandomised phase 2 trial suggested that lomustine-temozolomide plus radiotherapy might be superior to temozolomide chemoradiotherapy in newly diagnosed glioblastoma with methylation of the MGMT promoter. In the CeTeG/NOA-09 trial, we aimed to further investigate the effect of lomustine-temozolomide therapy in the setting of a randomised phase 3 trial. Methods In this open-label, randomised, phase 3 trial, we enrolled patients from 17 German university hospitals who were aged 18–70 years, with newly diagnosed glioblastoma with methylated MGMT promoter, and a Karnofsky Performance …

460. MGMTP140K Vector Constructs for Efficient In Vivo Enrichment of Genetically Corrected Cells Following Hematopoietic Cell Gene Transfer

2006

MGMTP140K, a mutant of the DNA repair protein O6-methylguanine-DNA methyltransferase (MGMT) resistant to the inhibitor O6-benzylguanine (BG), protects hematopoietic stem cells (HSC) from the toxicity of alkylating agents such as temozolomide (TMZ) and, therefore, allows efficient in vivo enrichment of transduced cells by BG/TMZ therapy. MGMTP140K has been proposed as a selection marker in gene therapy of monogeneic diseases. If used for this purpose, however, MGMTP140K expression in vectors containing internal ribosomal entry sites (IRES) would be from the compromised 3' position, as the 5' position will be required for the therapeutic gene. Thus, we have investigated SFFV/MESV-based vector…