A phase III study to evaluate the long-term safety and efficacy of fasinumab in patients with pain due to osteoarthritis of the knee or hip.

Background: Pain associated with osteoarthritis (OA) is frequently disabling; treatments are often ineffective or intolerable. Fasinumab selectively inhibits nerve-growth factor and has shown efficacy for the management of OA pain.

Methods: In this randomized, double-blind, phase III safety study, patients with moderate-to-severe OA pain and history of inadequate pain relief received placebo or fasinumab (at 1, 3, 6, and 9 ​mg every 4 weeks [Q4W] and 1 and 6 ​mg every 8 weeks [Q8W] for 52 weeks).

Cutaneous nerve fiber and peripheral Nav1.7 assessment in a large cohort of patients with postherpetic neuralgia.

The mechanisms of pain in postherpetic neuralgia (PHN) are still unclear, with some studies showing loss of cutaneous sensory nerve fibers that seemed to correlate with pain level. We report results of skin biopsies and correlations with baseline pain scores, mechanical hyperalgesia, and the Neuropathic Pain Symptom Inventory (NPSI) in 294 patients who participated in a clinical trial of TV-45070, a topical semiselective sodium 1.7 channel (Nav1.

Central nervous system effects of the histamine-3 receptor antagonist CEP-26401, in comparison with modafinil and donepezil, after a single dose in a cross-over study in healthy volunteers.

Aims: In previous studies, the histamine-3 receptor antagonist CEP-26401 had a subtle effect on spatial working memory, with the best effect seen at the lowest dose tested (20 μg), and a dose-dependent disruption of sleep. In the current study, 3 low-dose levels of CEP-26401 were compared with modafinil and donepezil.

Methods: In this double-blind, placebo- and positive-controlled, randomized, partial 6-way cross-over study, 40 healthy subjects received single doses of placebo, CEP-26401 (5, 25 or 125 μg) or modafinil 200 mg or donepezil 10 mg.

Safety and Efficacy of a Topical Sodium Channel Inhibitor (TV-45070) in Patients With Postherpetic Neuralgia (PHN): A Randomized, Controlled, Proof-of-Concept, Crossover Study, With a Subgroup Analysis of the Nav1.7 R1150W Genotype.

Objective: The objective was to evaluate the safety and efficacy of TV-45070 ointment, as a treatment for postherpetic neuralgia, and to explore the response in patients with the Nav1.7 R1150W gain-of-function polymorphism.

Materials And Methods: This was a randomized, placebo-controlled, 2-period, 2-treatment crossover trial.

Talampanel suppresses the acute and chronic effects of seizures in a rodent neonatal seizure model.

Purpose: To test the efficacy of the novel candidate anticonvulsant talampanel (GYKI 53773) in a rodent model of hypoxic neonatal seizures. Talampanel is a noncompetitive antagonist of the alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid subtype of the glutamate receptor (AMPAR). We have previously shown that AMPARs play a critical role in the generation of acute seizures and later-life seizure susceptibility in this model of neonatal seizures.

Novel paclitaxel formulations for oral application: a phase I pharmacokinetic study in patients with solid tumours.

Purpose: To explore the pharmacokinetics (PKs) of paclitaxel and two major metabolites after three single oral administrations of a novel drinking solution and two capsule formulations in combination with cyclosporin A (CsA) in patients with advanced cancer. Moreover, the tolerability and safety of the formulations was studied. In addition, single nucleotide polymorphisms in the multidrug resistance (MDR1) gene were determined.

Metastases to the pineal gland.

We identified 10 patients with symptomatic metastases to the pineal gland. We present the clinical and radiographic findings in this syndrome. Leptomeningeal metastases occur frequently and are a poor prognostic factor.

Randomized study of paclitaxel and tamoxifen deposition into human brain tumors: implications for the treatment of metastatic brain tumors.

Purpose: Drug resistance in brain tumors is partially mediated by the blood-brain barrier of which a key component is P-glycoprotein, which is highly expressed in cerebral capillaries. Tamoxifen is a nontoxic inhibitor of P-glycoprotein. This trial assessed, in primary and metastatic brain tumors, the differential deposition of paclitaxel and whether tamoxifen could increase paclitaxel deposition.

A randomized, double-blind, placebo-controlled, phase 2 study of RMP-7 in combination with carboplatin administered intravenously for the treatment of recurrent malignant glioma.

RMP-7, a bradykinin analog, temporarily increases the permeability of the blood-brain tumor barrier to chemotherapy drugs like carboplatin. We conducted a randomized, controlled trial of carboplatin and RMP-7 versus carboplatin and placebo in patients with recurrent malignant glioma. The primary outcome measure was time to tumor progression (TTP).

A phase I study of high-dose BCNU, etoposide and escalating-dose thiotepa (BTE) with hematopoietic progenitor cell support in adults with recurrent and high-risk brain tumors.

This phase I dose-escalation study was performed to determine the tolerability of three-drug combination high-dose BCNU (B) (450 mg/m2), escalating-dose thiotepa (500-800 mg/m2) and etoposide (1200 mg/m2) in divided doses over four days in 22 adults with malignant primary brain tumors. Patients received G-CSF and hematopoeitic support with peripheral blood progenitor cells (PBPC) (n = 18) or both PBPC and marrow (n = 4). The maximum tolerated dose of thiotepa with acceptable toxicity was determined as 800 mg/m2.

Supratentorial ependymomas in adult patients.

Objective: Ependymomas arise from different areas in the neuraxis and have variable outcomes that depend on tumor location and patient age at the time of presentation. The predictive value of histology for these tumors is unresolved. We report a series of adult patients with supratentorial ependymomas to characterize the roles of surgery, histology, ploidy, and proliferation index in tumor control.

High-dose thiotepa and etoposide-based regimens with autologous hematopoietic support for high-risk or recurrent CNS tumors in children and adults.

The prognosis in patients with primary brain tumors treated with surgery, radiotherapy and conventional chemotherapy remains poor. To improve outcome, combination high-dose chemotherapy (HDC) has been explored in children, but rarely in adults. This study was performed to determine the tolerability of three-drug combination high-dose thiotepa (T) and etoposide (E)-based regimens in pediatric and adult patients with high-risk or recurrent primary brain tumors.

Disparity in expression of protein kinase C alpha in human glioma versus glioma-derived primary cell lines: therapeutic implications.

Intracellular signal transduction by the protein kinase C (PKC) family of enzymes plays a critical role in carcinogenesis and cellular growth regulation. Recent studies have suggested that the PKC isoform alpha may be a critical target for antiglioma therapy in humans (G. H.

Phase I trial of retroviral-mediated transfer of the human MDR1 gene as marrow chemoprotection in patients undergoing high-dose chemotherapy and autologous stem-cell transplantation.

Purpose: Normal bone marrow cells have little or no expression of the MDR p-glycoprotein product and, therefore, are particularly susceptible to killing by MDR-sensitive drugs, such as vinca alkaloids, anthracyclines, podophyllins, and paclitaxel and its congeners. Here we report the results of a phase I clinical trial that tested the safety and efficacy of transfer of the human multiple drug resistance (MDR1, MDR) gene into hematopoietic stem cells and progenitors in bone marrow as a means of providing resistance of these cells to the toxic effects of cancer chemotherapy.

Patients And Methods: Up to one third of the harvested cells of patients who were undergoing autologous bone marrow transplantation as part of a high-dose chemotherapy treatment for advanced cancer were transduced with an MDR cDNA-containing retrovirus; these transduced cells were reinfused together with unmanipulated cells after chemotherapy.

Preirradiation paclitaxel in glioblastoma multiforme: efficacy, pharmacology, and drug interactions. New Approaches to Brain Tumor Therapy Central Nervous System Consortium.

Purpose: The purpose of this study was to determine the response rate of paclitaxel administered at maximal tolerated doses (MTD) in patients with newly diagnosed glioblastoma multiform.

Patients And Methods: All patients in this multicenter study were 45 years or older and had measurable residual tumor on postoperative MRI scans. Up to 3 cycles of paclitaxel were administered as a continuous 96-hour intravenous infusion prior to radiation, provided that the tumor did not enlarge on serial MRIs.

Thiotepa and etoposide treatment of recurrent malignant gliomas: phase I study.

Purpose: To determine: (1) the maximum tolerable dose (MTD) of thiotepa (TT) that can be administered with etoposide without stem cell support; (2) whether this regimen is active against recurrent malignant gliomas.

Background: Although several chemotherapeutic agents show minor activity against recurrent brain tumors, there is no consensus about the most effective regimen. The alkylating agent TT has excellent central nervous system (CNS) penetration and is synergistic with the topoisomerase II inhibitor etoposide.

Sentinel lesions of primary CNS lymphoma.

Some patients ultimately diagnosed with primary CNS lymphoma (PCNSL) have transient symptomatic contrast enhancing lesions. These "sentinel lesions" of PCNSL recede spontaneously or with corticosteroid treatment and present an important diagnostic dilemma because they show variable, but non-diagnostic histopathological features. Four previously healthy, immunocompetent patients aged 49 to 58 years had contrast enhancing intraparenchymal brain lesions.

Reversible dementia due to macroprolactinoma. Case report.

Subfrontal tumors are an infrequent cause of dementia. Most of those that do cause dementia are meningiomas, and the symptoms may recede when the tumor is resected. A patient with a huge prolactinoma who came to medical attention because of dementia is described.

Nevus of Ota and leptomeningeal melanocytic lesions.

Two patients with congenital nevus of Ota developed intracranial malignant melanocytic tumors. One had a localized tumor that resembled a melanocytoma, but the other had a more highly malignant tumor that diffusely seeded the leptomeninges. There are 10 prior cases in the world literature.

Neurolymphomatosis: a clinicopathologic syndrome re-emerges.

We describe a patient with sensorimotor peripheral neuropathy and cranial neuropathy due to autopsy-proven neurolymphomatosis defined by infiltration of peripheral nerves by tumor cells and review the findings in 39 previously reported patients. The cause of the neuropathy is not known. The association with immune-deficient states suggests virally mediated pathogenesis, possibly a retrovirus.

Induction of growth suppression and modification of gene expression in multi-drug-resistant human glioblastoma multiforme cells by recombinant human fibroblast and immune interferon.

The combination of recombinant human fibroblast (IFN-beta) and immune (IFN-gamma) interferon induces enhanced growth suppression and modifies the antigenic phenotype in parental and multi-drug-resistant (MDR) human glioblastoma multiforme (GBM) cells. The present study was conducted to explore the mechanism underlying this cooperative interaction between interferons in inducing growth suppression in MDR-GBM cells. For this analysis we have utilized 2 MDR-GBM cell lines which display a differential sensitivity to growth suppression when exposed to IFN-beta or IFN-gamma.

Intravenous recombinant interferon beta in patients with recurrent malignant gliomas: a phase I/II study.

A multicenter phase I/II trial of a human recombinant interferon beta (Betaseron; Triton Biosciences, Alameda, CA) was conducted in patients with recurrent glioblastoma and anaplastic astrocytoma in six centers between 1986 and 1988. Betaseron was given intravenously three times per week, starting at 90 x 10(6) IU per dose and escalating by 90 x 10(6) IU every 2 weeks up to a maximum dose of 540 x 10(6) per treatment. All patients had failed prior radiotherapy, and most had failed one or more courses of chemotherapy.