RESIRT: A Phase 1 Study of Selective Internal Radiation Therapy Using Yttrium-90 Resin Microspheres in Patients With Primary Renal Cell Carcinoma.

Introduction: Selective internal radiation therapy (SIRT) is a potential treatment of primary renal cell carcinoma (RCC) deemed unsuitable for conventional therapy. RESIRT is the first-in-human study to evaluate safety and feasibility of SIRT for primary RCC.

Patients And Methods: Patients with RCC, unsuitable for, or who declined conventional therapy, were eligible.

The Effect of Drug Loading on Micelle Properties: Solid-State NMR as a Tool to Gain Structural Insight.

The present study highlights the importance of understanding the structural changes of micelles induced by drug loading on their physico-chemical properties. A block copolymer with attached fructose, which interacts with GLUT5 receptor, was used and conjugated with a low and a high amount of platinum drugs. Against expectations, the low-loading micelle, despite having a less defined morphology and larger nanoparticle size according to TEM, displays higher cellular uptake and higher toxicity.

Risk factors for erectile dysfunction in a cohort of 108 477 Australian men.

Objectives: To quantify relationships between erectile dysfunction (ED), ageing and health and lifestyle factors for men aged 45 years and older.

Design: Cross-sectional, population-based study seeking data on health, sociodemographic and lifestyle factors by questionnaire (the 45 and Up Study).

Participants And Setting: 108 477 men aged 45 years or older, living in New South Wales, and recruited into the 45 and Up Study between 10 January 2006 and 17 February 2010.

Folate conjugation to polymeric micelles via boronic acid ester to deliver platinum drugs to ovarian cancer cell lines.

In this study, a novel technique was used for the reversible attachment of folic acid on the surface of polymeric micelles for a tumor-specific drug delivery system. The reversible conjugation is based on the interaction between phenylboronic acid (PBA) and dopamine to form a borate ester. The conjugation is fast and efficient and in vitro experiments via confocal fluorescent microscopy show that the linker is stable in for several hours.

Cancer-related fatigue in women with breast cancer: outcomes of a 5-year prospective cohort study.

Purpose: Prolonged and disabling fatigue is prevalent after cancer treatment, but the early natural history of cancer-related fatigue (CRF) has not been systematically examined to document consistent presence of symptoms. Hence, relationships to cancer, surgery, and adjuvant therapy are unclear.

Patients And Methods: A prospective cohort study of women receiving adjuvant treatment for early-stage breast cancer was conducted.

Block copolymer micelles with pendant bifunctional chelator for platinum drugs: effect of spacer length on the viability of tumor cells.

Three monomers with 1,3-dicarboxylate functional groups but varying spacer lengths were synthesized via carbon Michael addition using malonate esters and ethylene- (MAETC), butylene- (MABTC), and hexylene (MAHTC) glycol dimethacrylate, respectively. Poly[oligo-(ethylene glycol) methylether methacrylate] (POEGMEMA) was prepared in the presence of a RAFT (reversible addition-fragmentation chain transfer) agent, followed by chain extension with the prepared monomers to generate three different block copolymers (BP-E80, BP-B82, and BP-H79) with similar numbers of repeating units, but various spacer lengths as distinguishing features. Conjugation with platinum drugs created macromolecular platinum drugs resembling carboplatin.

The pharmacological advantage of prolonged dose rate gemcitabine is restricted to patients with variant alleles of cytidine deaminase c.79A>C.

Aim: Controversy exists over the optimal dosing for the nucleoside analogue gemcitabine. A pharmacological advantage is achieved by prolonging infusion times but evidence for a clinical benefit has been conflicting. We hypothesized that polymorphisms in genes involved in gemcitabine accumulation, particularly the cytidine deaminase CDA c.

Pharmacokinetics of phenoxodiol, a novel isoflavone, following intravenous administration to patients with advanced cancer.

Background: Phenoxodiol is a novel isoflavone currently being studied in clinical trials for the treatment of cancer. This study reports the pharmacokinetics of phenoxodiol in patients with cancer.

Methods: The pharmacokinetics of phenoxodiol was studied following a single intravenous (iv) bolus dose and during a continuous intravenous infusion.

A phase II trial of weekly i.v. KW-2170 in advanced castrate-resistant prostate cancer.

Aim: KW-2170 is a novel pyrazoloacridone derivative that intercalates nucleic acids. It has promising in vitro properties against prostate and other cancers and is active in vivo against doxorubicin-resistant cell lines. We wished to investigate its activity and toxicity profile in this Phase II trial in androgen independent prostate cancer.

Clinical pharmacology of isoflavones and its relevance for potential prevention of prostate cancer.

Isoflavones are phytoestrogens that have pleiotropic effects in a wide variety of cancer cell lines. Many of these biological effects involve key components of signal transduction pathways within cancer cells, including prostate cancer cells. Epidemiological studies have raised the hypothesis that isoflavones may play an important role in the prevention and modulation of prostate cancer growth.

Efficacy and safety of pazopanib in patients with metastatic renal cell carcinoma.

Purpose: Inactivation of the von Hippel-Lindau gene in clear-cell renal cell carcinomas (RCC) leads to overexpression of hypoxia inducible factor, a transcription factor regulating vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF) gene expression. Pazopanib, an angiogenesis inhibitor targeting VEGF receptor, PDGF receptor, and c-KIT, was evaluated in patients with RCC.

Patients And Methods: This phase II study was designed as a randomized discontinuation study but was revised to an open-label study on the recommendation of the data monitoring committee (based on week 12 response rate [RR] of 38% in the first 60 patients).

Role of the Akt pathway in prostate cancer.

The Akt pathway, or more accurately, network, has assumed increasing importance with the understanding that it represents a key role in cancer cell survival and proliferation. Intense efforts to target proteins and enzymes within this pathway with highly selective compounds have led to the development of diverse agents now in Phase I-III clinical trials. Moreover, the notion that exploitation of multiple "druggable" targets simultaneously or in the appropriate sequence may provide better anti-tumour effects than single drugs hold promise that chemoresistance may be overcome, at least in part.

Randomized crossover study evaluating the effect of gemcitabine infusion dose rate: evidence of auto-induction of gemcitabine accumulation.

Purpose: Controversy exists over the optimal dose rate for administration of gemcitabine. There is a strong pharmacologic rationale for increased intracellular accumulation with prolonged infusions, but this failed to translate into a significant benefit in a large randomized study. The purpose of this study was to compare the intracellular pharmacokinetics of gemcitabine given for 30 minutes or for 100 minutes in a crossover design.

Phase I and pharmacokinetic study of weekly NV06 (Phenoxodiol), a novel isoflav-3-ene, in patients with advanced cancer.

Background: We wished to define the maximum tolerated dose (MTD), toxicity, and pharmacokinetics of the novel isoflav-3-ene, NV06 (Phenoxodioltrade mark), a compound with a diphenolic structure related chemically and biologically to genistein and flavopiridol.

Patients And Methods: Twenty-one patients with advanced cancers were treated with weekly intravenous administration of NV06 at escalating dose levels with 1-4 patients at each dose cohort. Plasma sampling was undertaken to characterize the pharmacokinetic (PK) profile of the compound.