Infigratinib in Patients with Recurrent Gliomas and FGFR Alterations: A Multicenter Phase II Study.

Purpose: FGFR genomic alterations (amplification, mutations, and/or fusions) occur in ∼8% of gliomas, particularly FGFR1 and FGFR3. We conducted a multicenter open-label, single-arm, phase II study of a selective FGFR1-3 inhibitor, infigratinib (BGJ398), in patients with FGFR-altered recurrent gliomas.

Patients And Methods: Adults with recurrent/progressive gliomas harboring FGFR alterations received oral infigratinib 125 mg on days 1 to 21 of 28-day cycles.

Impact of depatuxizumab mafodotin on health-related quality of life and neurological functioning in the phase II EORTC 1410/INTELLANCE 2 trial for EGFR-amplified recurrent glioblastoma.

Background: In the EORTC 1410/INTELLANCE 2 randomised, phase II study (NCT02343406), with the antibody-drug conjugate depatuxizumab mafodotin (Depatux-M, ABT-414) in patients with recurrent EGFR-amplified glioblastoma, the primary end-point (overall survival) was not met, and the drug had ocular dose-limiting toxicity. This study reports results from the prespecified health-related quality of life (HRQoL) and neurological deterioration-free survival (NDFS) exploratory analysis.

Patients And Methods: Patients (n = 260) were randomised 1:1:1 to receive either Depatux-M 1.

Clinically Relevant Response to Cisplatin-5-Fluorouracyl in Intestinal-Type Sinonasal Adenocarcinoma with Loss of Vision: A Case Report.

A 68-year-old man presented with rapid progressive visual loss caused by a progressive local invasive sinonasal intestinal-type adenocarcinoma (ITAC) with intracranial invasion. The local relapse of ITAC in the ethmoid sinus was previously treated with palliative radiotherapy and carboplatin-paclitaxel, without response, hence disease progression was seen. Ophthalmological examination revealed irreversible blindness of the left eye and a dramatic progressive visual loss of the right eye.

The use of high dosages of transdermal buprenorphine for pain management in palliative cancer patients: a case study.

Pain is a prevalent condition in patients with cancer, particularly in advanced stages of cancer. Although strong opioids are the mainstay of cancer pain management protocols, patients are often undertreated. Transdermal buprenorphine is currently available for the treatment of moderate to severe cancer pain and severe pain which does not respond to nonopioid analgesics; patch doses of 35, 52.

Zalutumumab plus best supportive care versus best supportive care alone in patients with recurrent or metastatic squamous-cell carcinoma of the head and neck after failure of platinum-based chemotherapy: an open-label, randomised phase 3 trial.

Background: No treatments are presently available to increase survival in patients with recurrent or metastatic squamous-cell carcinoma of the head and neck after failure of platinum-based chemotherapy. We aimed to assess efficacy and safety of zalutumumab, a human IgG1 monoclonal antibody targeting the epidermal growth factor receptor, for overall survival in such patients.

Methods: In our open-label, parallel-group, phase 3, randomised trial, we randomly allocated patients with squamous-cell carcinoma of the head and neck who were regarded as incurable with standard therapy, a WHO performance status of 0-2, and progressive disease within 6 months of platinum-based therapy in a 2:1 ratio to receive zalutumumab plus best supportive care (zalutumumab group) or best supportive care with optional methotrexate (control group) at medical centres in Europe, Brazil, and Canada.

Phase I/IIa study of cilengitide and temozolomide with concomitant radiotherapy followed by cilengitide and temozolomide maintenance therapy in patients with newly diagnosed glioblastoma.

Purpose: Invasion and migration are key processes of glioblastoma and are tightly linked to tumor recurrence. Integrin inhibition using cilengitide has shown synergy with chemotherapy and radiotherapy in vitro and promising activity in recurrent glioblastoma. This multicenter, phase I/IIa study investigated the efficacy and safety of cilengitide in combination with standard chemoradiotherapy in newly diagnosed glioblastoma.

Parotid carcinoma: Current diagnostic workup and treatment.

In this review we present recent progress in diagnostic workup, prognostic evaluation, treatment options and resulting outcomes. Whenever possible, complete resection remains the mainstay of treatment. Sacrifice of facial nerve branches is reserved for the clinically or electromyographically dysfunctioning facial nerve.

Atropine, hyoscine butylbromide, or scopolamine are equally effective for the treatment of death rattle in terminal care.

Death rattle is a frequent symptom (25%-50%) in the terminal stage of life, but there is neither standardized treatment nor prospective investigation performed on the effectiveness of anticholinergic drugs. The aim of the present study was to investigate the effectiveness of three different anticholinergic drugs in the treatment of death rattle in the terminal stage of life. Terminal patients who developed death rattle were randomly assigned 0.

Phase II study of imatinib in patients with recurrent gliomas of various histologies: a European Organisation for Research and Treatment of Cancer Brain Tumor Group Study.

Purpose: To evaluate the safety and the efficacy of imatinib in recurrent malignant gliomas.

Patients And Methods: This was a single-arm, phase II study. Eligible patients had recurrent glioma after prior radiotherapy with an enhancing lesion on magnetic resonance imaging.

Impact of adding concomitant chemotherapy to hyperfractionated accelerated radiotherapy for advanced head-and-neck squamous cell carcinoma.

Purpose: To evaluate the feasibility and efficacy of a hyperfractionated accelerated radiotherapy (RT) schedule combined with concomitant chemotherapy (Cx) in patients with locally advanced head-and-neck squamous cell carcinoma.

Methods And Materials: Between 2004 and 2007, a total of 90 patients with locoregionally advanced head-and-neck squamous cell carcinoma underwent irradiation according to a hybrid fractionation schedule consisting of 20 fractions of 2 Gy (once daily) followed by 20 fractions of 1.6 Gy (twice daily) to a total dose of 72 Gy.

Ecteinascidin-743: evidence of activity in advanced, pretreated soft tissue and bone sarcoma patients.

Purpose. To evaluate the activity and safety of ecteinascidin (ET-743) in pretreated patients with advanced or metastatic soft tissue and bone sarcoma. Patients or subjects.

Differential expression of eIF5A-1 and eIF5A-2 in human cancer cells.

Eukaryotic translation initiation factor 5A (eIF5A) is the only cellular protein that contains the unusual amino acid hypusine [N(epsilon)-(4-amino-2-hydroxybutyl)lysine]. Vertebrates carry two genes that encode two eIF5A isoforms, eIF5A-1 and eIF5A-2, which, in humans, are 84% identical. eIF5A-1 mRNA (1.

Eukaryotic initiation factor 5A-1 (eIF5A-1) as a diagnostic marker for aberrant proliferation in intraepithelial neoplasia of the vulva.

Objective: The mature eukaryotic translation initiation factor 5A contains the unusual amino acid hypusine, formed post-translationally from a specific lysine residue and essential for proliferation of eukaryotic cells. We hypothesized that the major eIF5A isoform, eIF5A-1, is an in situ biomarker for proliferation. NIH-353, a polyclonal immunoreagent specific for hypusine-containing eIF5A-1, was used to test this proposal in biopsies of vulvar high-grade intraepithelial neoplasia (VIN), characterized by the presence of proliferating cells throughout the thickness of the epithelium.

Identification and characterization of eukaryotic initiation factor 5A-2.

The phylogenetically conserved eukaryotic translation initiation factor 5A (eIF5A) is the only known cellular protein to contain the post-translationally derived amino acid hypusine [Nepsilon-(4-amino-2-hydroxybutyl)lysine]. Both eIF5A and its hypusine modification are essential for sustained cell proliferation. Normally only one eIF5A protein is expressed in human cells.

The antifungal drug ciclopirox inhibits deoxyhypusine and proline hydroxylation, endothelial cell growth and angiogenesis in vitro.

The hypusine biosynthetic steps represent novel targets for intervention in cell proliferation. Hypusine is a rare amino acid, formed posttranslationally in one cellular protein, eIF5A, and is essential for cell proliferation. Deoxyhypusine hydroxylase, the metalloenzyme catalyzing the final step in hypusine biosynthesis, and prolyl 4-hydroxylase, a non-heme iron enzyme critical for collagen processing, can be inhibited by small chelating molecules that target their essential metal atom.