Mutations in ESR1 have been associated with resistance to aromatase inhibitor (AI) therapy in patients with ER+ metastatic breast cancer. Little is known of the impact of these mutations in patients receiving selective oestrogen receptor degrader (SERD) therapy. In this study, hotspot mutations in ESR1 and PIK3CA from ctDNA were assayed in clinical trial samples from ER+ metastatic breast cancer patients randomized either to the SERD fulvestrant or fulvestrant plus a pan-PI3K inhibitor. ESR1 mutations are present in 37% of baseline samples and are enriched in patients with luminal A and PIK3CA-mutated tumours. ESR1 mutations are often polyclonal and longitudinal analysis shows distinct clones exhibiting divergent behaviour over time. ESR1 mutation allele frequency does not show a consistent pattern of increases during fulvestrant treatment, and progression-free survival is not different in patients with ESR1 mutations compared with wild-type patients. ESR1 mutations are not associated with clinical resistance to fulvestrant in this study.

CG7870 is a replication-selective oncolytic adenovirus genetically engineered to replicate preferentially in prostate tissue. In a previous phase I/II clinical trial of intraprostatic delivery of CG7870 for locally recurrent prostate cancer this virus was well tolerated. In this phase I study CG7870 was administered as a single intravenous infusion in a group-sequential dose escalation design (1 x 10(10) to 6 x 10(12) viral particles (vp)) to 23 patients with hormone-refractory metastatic prostate cancer. Flulike symptoms (fever, fatigue, rigors, nausea, and/or vomiting) were the most common adverse events. Three therapy-related grade 3 adverse events were reported, one of which (fatigue) was serious. At doses greater than 10(12) vp all five patients experienced asymptomatic grade 1 to 2 transaminitis and/or isolated d-dimer elevations starting on day 2 through 8; dose escalation was therefore halted at 6 x 10(12) vp. All tested patients had CG7870 genomes present in the peripheral blood for at least 90 minutes after infusion; patients in the highest dose group had persistence of genomes through 29 days. A "secondary" or "delayed" peak in plasma CG7870 genome copies (defined as a >10-fold increase in CG7870 genomes from nadir concentration) suggestive of active viral replication and shedding into the bloodstream was detected in 16/23 (70%) patients. CG7870 was detected in the saliva of 3 patients, whereas all urine samples tested negative. All patients developed antibodies to CG7870. Dose-related increases in interleukins 6 and 10 (IL-6, IL-10) blood levels were detected. The peak IL-6 concentration after CG7870 treatment was associated with a transient, asymptomatic decrease in blood pressure. No partial or complete prostate-specific antigen (PSA) responses were observed; however, 5 patients had a decrease in serum PSA of 25% to 49% following a single treatment, including 3 of 8 patients at the highest dose levels.

Nonvolatile room-temperature luminescent molecular liquids are a new generation of organic soft materials. They possess high stability, versatile optical properties, solvent-free fluid behaviour and can effectively accommodate dopant dye molecules. Here we introduce an approach to optimize anthracene-based liquid materials, focussing on enhanced stability, fluorescence quantum yield, colour tunability and processability, with a view to flexible electronic applications. Enveloping the anthracene core in low-viscosity branched aliphatic chains results in stable, nonvolatile, emissive liquid materials. Up to 96% efficient energy-transfer-assisted tunable emission is achieved by doping a minute amount of acceptor dye in the solvent-free state. Furthermore, we use a thermoresponsive dopant to impart thermally controllable luminescence colours. The introduced strategy leading to diverse luminescence colours at a single blue-light excitation can be an innovative replacement for currently used luminescent materials, providing useful continuous emissive layers in developing foldable devices.

Intravesical CG0070 was associated with a tolerable safety profile and antibladder cancer activity. Granulocyte-monocyte colony-stimulating factor transgene expression and CG0070 replication were also suggested.

BACKGROUNDThis open‐label, multicenter, dose‐escalation study evaluated multiple dose levels of immunotherapy in patients with metastatic hormone‐refractory prostate cancer (HRPC). The immunotherapy, based on the GVAX platform, consisted of 2 allogeneic prostate‐carcinoma cell lines modified to secrete granulocyte‐macrophage‐colony‐stimulating factor (GM‐CSF).METHODSDose levels ranged from 100 × 106 cells q28d × 6 to 500 × 106 cells prime/300 × 106 cells boost q14d × 11. Endpoints included safety, immunogenicity, overall survival, radiologic response, prostate‐specific antigen (PSA) kinetics, and serum GM‐CSF pharmacokinetics.RESULTSEighty men, median age 69 years (range, 49‐90 years), were treated. The most common adverse effect was injection‐site erythema. Overall, the immunotherapy was well tolerated. A maximal tolerated dose was not established. The median survival time was 35.0 months in the high‐dose group, 20.0 months in the mid‐dose, group, and 23.1 months in the low‐dose group. PSA stabilization occurred in 15 (19%) patients, and a >50% decline in PSA was seen in 1 patient. The proportion of patients who generated an antibody response to 1 or both cell lines increased with dose and included 10 of 23 (43%) in the low‐dose group, 13 of 18 (72%) in the mid‐dose group, and 16 of 18 (89%) in the high‐dose group (P = .002; Cochran‐Armitage trend test).CONCLUSIONSThis immunotherapy was well tolerated. Immunogenicity and overall survival varied by dose. Two phase 3 trials in patients with metastatic HRPC are underway. Cancer 2008. © 2008 American Cancer Society.