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Background SB939 is a potent oral inhibitor of class 1, 2, and 4 histone deacetylases (HDACs). These three HDAC classes are highly expressed in castration resistant prostate cancer (CRPC) and associated with poor clinical outcomes. We designed a phase II study of SB939 in men with metastatic CRPC. Methods Patients received SB939 60 mg on alternate days three times per week for 3 weeks on a 4-week cycle. Primary endpoints were PSA response rate (RR) and progression-free survival (PFS). Secondary endpoints included objective response rate and duration; overall survival; circulating tumor cell (CTC) enumeration and safety. Exploratory correlative studies of the TMPRSS2-ERG fusion and PTEN biomarkers were also performed. Results Thirty-two patients were enrolled of whom 88 % had received no prior chemotherapy. The median number of SB939 cycles administered was three (range 1-8). Adverse events were generally grade 1-2, with five pts experiencing one or more grade three event. One patient died due to myocardial infarction. A confirmed PSA response was noted in two pts (6 %), lasting 3.0 and 21.6 months. In patients with measurable disease there were no objective responses. Six patients had stable disease lasting 1.7 to 8.0 months. CTC response (from ≥5 at baseline to <5 at 6 or 12 weeks) occurred in 9/14 evaluable patients (64 %). Conclusion Although SB939 was tolerable at the dose/schedule given, and showed declines in CTC in the majority of evaluable patients, it did not show sufficient activity based on PSA RR to warrant further study as a single agent in unselected patients with CRPC. [ABSTRACT FROM AUTHOR]

Purpose AT9283 is a potent inhibitor of the mitotic regulators, Aurora-kinases A and B, and has shown anti-tumor activity in patients with solid and haematological malignancies. This phase I study assessed safety, tolerability, pharmacokinetic and pharmacodynamic properties of AT9283. Patients and methods Patients with advanced, incurable solid tumors or non-Hodgkin's lymphoma received AT9283 as a continuous 24-hour infusion on days 1, 8 of a 21-day cycle. A 3 + 3 dose escalation design was used with a starting dose of 1.5 mg/m/day. Pharmacokinetic samples were collected from all patients on cycle one, and pharmacodynamic samples were collected from 4 patients at the recommended phase II dose (RP2D). Results 35 patients were evaluable for toxicity and 32 were evaluable for response. AT9283 was well tolerated, with main toxicities being reversible dose-related fatigue, gastrointestinal disturbance, anemia, lymphocytopenia and neutropenia. The dose limiting toxicities were febrile neutropenia (two patients) and neutropenia with grade 3 infection (1 patient) at 47 mg/m/day (established as the maximum tolerated dose). The RP2D was 40 mg/m/day. Pharmacokinetic analyses showed AT9283 appeared to follow linear kinetics, with a mean elimination half-life of 8.2 h. Pharmacodynamic analyses showed no consistent or significant changes, but trends suggested evidence of AT9283 inhibition and anti-proliferative activity. One patient had partial response and four patients experienced RECIST stable disease (median 2.6 months). Conclusion In this study, AT9283 was well tolerated. The RP2D is 40 mg/m/day on days 1, 8 of a 21-day cycle. Ongoing AT9283 trials will assess efficacy and safety in solid and haematological cancers. [ABSTRACT FROM AUTHOR]

Objectives: We sought to evaluate the association between patient sociodemographic status and breast screening volumes (BSVs) during the COVID-19 pandemic in a large, population-based breast screening program that serves a provincial population of over 5 million. Methods: All patients who completed breast screening between April 1 st , 2017 and March 31 st , 2021 were eligible to participate. An average of 3 annual periods between April 1 st , 2017 and March 31 st , 2020 were defined as the pre-COVID period while the period between April 1 st , 2020 and March 31 st , 2021 was defined as the COVID-impacted period. The Postal Code OM Conversion File Plus was applied to map patient residential postal codes to 2016 census standard geographical areas, which provided information on community size, income quintile and dissemination areas. Dissemination areas were subsequently linked to the Canadian Index of Multiple Deprivation (CIMD)., Results: Overall BSV was reduced by 23.0% during the COVID-impacted period as compared to the pre-COVID period. Percent reductions in BSVs were greatest among younger patients aged 40 to 49 years (31.3%) and patients residing in communities with a population of less than 10,000 (27.0%). Percent reduction in BSV was greatest among patients in the lowest income quintile (28.1%). Percent reductions in BSVs were greatest for patients in the most deprived quintiles across all 4 dimensions of the CIMD., Conclusion: Disproportionate reductions in BSVs were observed during the COVID-19 pandemic among younger patients, patients residing in rural communities, patients in lower income quintiles, and patients in the most deprived quintiles across all 4 dimensions of the CIMD., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Purpose: A multi-institution phase II study was undertaken by National Cancer Institute of Canada-Clinical Trials Group to evaluate the efficacy and toxicity of intravenous troxacitabine (Troxatyl; Shire Pharmaceuticals Plc, Laval, Quebec, Canada), in patients with renal cell carcinoma., Patients and Methods: Between June 1999 and March 2000, 35 patients (24 male) with a mean age of 60 years who had advanced and/or metastatic disease were treated with troxacitabine given as an intravenous infusion over 30 minutes at a dose of 10 mg/m2 intravenously, once every 3 weeks., Results: Of the 33 of 35 patients evaluable for response, there were two confirmed partial responses, 21 patients had stable disease (median duration, 4.4 months), and 10 patients had progressive disease. Eight patients remained stable for more than 6 months, of whom six remain free of progression. The most common drug-related nonhematologic toxicities observed were skin rash (77.1%), hand-foot syndrome (68.6%), alopecia (51.4%), fatigue (51.4%), and nausea (57.1%). Out of a total of 145 cycles of treatment, 98 were given without steroid premedication, whereas 47 cycles were given with steroid premedication. Without premedication, skin rash occurred in 37% of cycles compared with 26% when steroids were given prophylactically., Conclusion: Troxacitabine given at a dose of 10 mg/m2 once every 3 weeks was well tolerated in patients with metastatic renal cell cancer, with common toxicities being a moderate to severe granulocytopenia and skin rash. Steroid premedication may reduce the frequency and severity of the skin rash. Our current study suggests that the nucleoside analog troxacitabine may have modest activity against renal cell carcinoma; however, larger studies are required to confirm this.