Brain Cancer Research Today is a free monthly online journal that collates and summarizes the latest research about Brain Cancer, including details on symptoms, benign and malignant tumors, gliomas, treatment.

Phase II clinical trial of neoadjuvant alternating doublet chemotherapy with ifosfamide/doxorubicin and etoposide/cisplatin in small-cell urothelial cancer.

Siefker-Radtke AO, Kamat AM, Grossman HB, Williams DL, Qiao W, Thall PF, Dinney CP, Millikan RE

Department of Genitourinary Medical Oncology, Urology, and Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA. asiefker@mdanderson.org

PURPOSE: Currently, treatment recommendations for small-cell urothelial cancer (SCUC) are based on anecdotal case reports and small retrospective series. We now report results from the first phase II clinical trial developed exclusively for SCUC, to our knowledge. PATIENTS AND METHODS: From 2001 to 2006, 30 patients with SCUC provided consent and were treated with alternating doublet chemotherapy. Patients with surgically resectable disease (< or = cT4aN0M0) received a total of four cycles of neoadjuvant chemotherapy, whereas those with unresectable disease (> or = cT4b, N+, or M+) received two cycles beyond maximal response. RESULTS: Eighteen patients with surgically resectable SCUC received neoadjuvant treatment with a median overall survival (OS) of 58 months; 13 of these patients remain alive and cancer free. For patients with cT2N0M0 SCUC, the 5-year OS rate is 80%; only one of four patients with cT3b-4aN0M0 remains alive (median OS, 37.8 months). For 12 patients with unresectable or metastatic SCUC, the median OS was 13.3 months. Chemotherapy was well tolerated, with transfusion, neutropenic fever, and infection remaining the most frequent grade 3 and 4 toxicities. There was only one postsurgical death. Brain metastases were strongly associated with more advanced-stage disease, developing in eight of 16 patients with either bulky tumors (> or = cT3b) or metastatic disease (P = .004). CONCLUSION: These clinical trial results are consistent with previously reported retrospective data demonstrating long-term survival with four cycles of neoadjuvant chemotherapy for surgically resectable SCUC. Once metastases develop, the prognosis remains poor. The strong positive association between disease stage and brain metastases highlights a patient subset that may potentially benefit from prophylactic cranial irradiation.

Published 29 May 2009 in J Clin Oncol, 27(16): 2592-7.
Full-text of this article is available online (may require subscription).

Articles on Brain Cancer published 27 May 2009:

Demethoxycurcumin induces Bcl-2 mediated G2/M arrest and apoptosis in human glioma U87 cells.   Biochem Biophys Res Commun, 384(4): 420-5.

Docking analysis of curcumin (C1), demethoxycurcumin (C2) and bisdemethoxycurcumin (C3) with Bcl-2 illustrated that among the three curcuminoids, C2 binds more efficiently into its putative active site. C1, C2 and C3 were purified from turmeric rhizomes to demonstrate the molecular mechanism of their anticancer activity on human glioma U87 cells. Human glioma U87 cells treated with curcuminoids resulted in activation of Bcl-2 mediated G2 checkpoint, which was associated with the induction of ... [Abstract] [Full-text]

The role side effects play in the choice of antiepileptic therapy in brain tumor-related epilepsy: a comparative study on traditional antiepileptic drugs versus oxcarbazepine.   J Exp Clin Cancer Res, 28: 60.

BACKGROUND: Seizure control doesn't represent the only challenging goal in patients with brain tumor-related epilepsy. Side effects have often taken precedence for patients' quality of life. METHODS: We performed an observational retrospective study on patients with brain tumor-related epilepsy: 35 who had assumed oxcarbazepine monotherapy and 35 patients who had undergone treatment with traditional antiepileptic drugs. Primary variable of efficacy was the mean seizure frequency per month and ... [Abstract] [Full-text]

Articles on Brain Cancer published 21 May 2009:

Ursolic acid inhibits IL-1beta or TNF-alpha-induced C6 glioma invasion through suppressing the association ZIP/p62 with PKC-zeta and downregulating the MMP-9 expression.   Mol Carcinog, 48(6): 517-31.

Ursolic acid (UA), a constant constituent of Rosmarinus officinalis extracts, is a triterpenoid compound which has been shown to have antioxidant and anticarcinogenic properties. In the present study, we found that UA was able to reduce interleukin-1 beta (IL-1beta) or tumor necrosis-alpha (TNF-alpha)-induced rat C6 glioma cell invasion, which was examined by a reconstituted basement membrane in a set of transwell chambers. However, the inhibitory effect of UA did not influence cell ... [Abstract] [Full-text]

Articles on Brain Cancer published 20 May 2009:

Intraindividual comparison between gadopentetate dimeglumine and gadobutrol for magnetic resonance perfusion in normal brain and intracranial tumors at 3 Tesla.   Acta Radiol, 50(5): 521-30.

BACKGROUND: In vitro studies have shown that the 3-Tesla (T) magnetic resonance (MR) characteristics of high- and standard-molar gadolinium-based contrast agents differ. Such differences may indicate that high-molar (1.0 M) agents offer advantages for perfusion-weighted imaging (PWI) at 3T, as has been previously reported at 1.5 T. PURPOSE: To investigate possible intraindividual differences of high- versus low-molar contrast agents on PWI at 3T in patients with intracranial space-occupying ... [Abstract] [Full-text]

Articles on Brain Cancer published 19 May 2009:

Edema control by cediranib, a vascular endothelial growth factor receptor-targeted kinase inhibitor, prolongs survival despite persistent brain tumor growth in mice.   J Clin Oncol, 27(15): 2542-52.

PURPOSE: Recent clinical trials of antivascular endothelial growth factor (VEGF) agents for glioblastoma showed promising progression-free and overall survival rates. However, available clinical imaging does not separate antitumor effects from antipermeability effects of these agents. Thus although anti-VEGF agents may decrease tumor contrast-enhancement, vascularity, and edema, the mechanisms leading to improved survival in patients remain incompletely understood. Our goal was to determine ... [Abstract] [Full-text]

Articles on Brain Cancer published 18 May 2009:

Oncogenic role of microRNAs in brain tumors.   Acta Neuropathol, 117(6): 599-611.

MicroRNAs (miRNAs) are short non-protein-coding RNAs that function as key regulators of diverse biological processes through negative control on gene expression at the post-transcriptional level. Emerging evidence indicates that miRNAs play an important role in the development of human cancers, with their deregulation resulting in altered activity of downstream tumor suppressors, oncogenes and other signaling molecules. Recent years have seen considerable progress in miRNA research in brain ... [Abstract] [Full-text]

Selective acquisition of IDH1 R132C mutations in astrocytomas associated with Li-Fraumeni syndrome.   Acta Neuropathol, 117(6): 653-6.

Mutations of the IDH1 gene are frequent in gliomas, with R132H (CGT-->CAT) being the most common (>85%). In astrocytomas, IDH1 mutations are typically co-present with, or precede, TP53 mutations. We assessed IDH1 mutations in brain tumors diagnosed in patients from three families with Li-Fraumeni syndrome. We identified IDH1 mutations in five astrocytomas that developed in carriers of a TP53 germline mutation. Without exception, all were R132C (CGT-->TGT), which in sporadic ... [Abstract] [Full-text]

Expression of EAAT-1 distinguishes choroid plexus tumors from normal and reactive choroid plexus epithelium.   Acta Neuropathol, 117(6): 667-75.

Microscopic distinction of normal choroid plexus (CP) from choroid plexus tumors (CPT) may be difficult, especially in small samples of well-differentiated CP papillomas. So far, there are no established markers that reliably distinguish normal and neoplastic CP epithelium. Recently, a correlation between expression/function of glial glutamate transporters EAAT-1 (GLAST) and EAAT-2 (Glt-1) and tumor proliferation has been reported. Furthermore, we previously found that CPTs frequently express ... [Abstract] [Full-text]

© 2004-2009 Brain Cancer Research Today. All Rights Reserved.