Background-Growth of selected castration-resistant prostate cancer (CRPC) cell lines and animal models can be repressed by reexposure to androgens. Low doses of androgens, however, can stimulate tumor growth.Objective-We performed a phase 1 clinical trial to determine the safety of high-dose exogenous testosterone in patients with castration-resistant metastatic prostate cancer (CRMPC).Design, setting, and participants-Patients with progressive CRMPC who had been castrate for at least 1 yr received three times the standard replacement dose of transdermal testosterone.Intervention-Cohorts of 3-6 patients received testosterone for 1 wk, 1 mo, or until disease progression. Financial disclosures: I certify that all conflicts of interest, including specific financial interests and relationships and affiliations relevant to the subject matter or materials discussed in the manuscript (eg, employment/affiliation, grants or funding, consultancies, honoraria, stock ownership or options, expert testimony, royalties, or patents filed, received, or pending), are the following: none.Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Measurements-Toxicities, androgen levels, prostate-specific antigen (PSA) assays, computed tomography (CT) scans, bone scintigraphy, positron emission tomography (PET) scans, and metastatic tumor biopsy androgen receptor levels were assessed. NIH Public AccessResults and limitations-Twelve patients were treated-three in cohorts 1 and 2 and six in cohort 3. No pain flares were noted. One patient came off study because of epidural disease, which was treated with radiation. Average testosterone levels were within normal limits, although dihydrotestosterone (DHT) levels were supraphysiologic in cohort 3. One patient achieved a PSA decline of >50% from baseline. No objective responses were seen. For cohort 3, median time on treatment was 84 d (range: 23-247 d).Conclusions-We have demonstrated that patients with CRMPC can be safely treated in clinical trials using high-dose exogenous testosterone. Patients did not, on average, achieve sustained supraphysiologic serum testosterone levels. Future studies should employ strategies to maximize testosterone serum levels, use contemporary methods of identifying patients with androgen receptor overexpression, and utilize PSA Working Group II Consensus Criteria clinical trial end points.

Objective People with a serious mental health condition are no more likely to receive a diagnosis of cancer than the general population but fare more poorly in terms of outcomes. The current study investigated whether a background of mental health problems (measured by contact with mental health services and psychotropic medication) predicted treatment outcomes over and above demographic and medical confounds for cancer patients at Counties Manukau Health. Methods The sample consisted of 1652 patients diagnosed with cancer in the period 1 January 2016 to 31 December 2016. The sample was split into three groups: non‐mental health, moderate mental health, and serious mental health. Results Patients in the serious and moderate mental health groups were more likely to have physical comorbidities. Those in the serious mental health group were also marginally more likely to have advanced cancer at diagnosis. There were no differences between groups in terms of treatment delays, but patients in the serious mental health group were more likely to be hospitalised and die in the 12 months following diagnosis. Whilst differences in mortality may be explained by greater clinical complexity (being older, having other physical comorbidities) and later stage at presentation, mental health history was independently associated with hospitalisations. Conclusions Cancer patients with a history of more serious mental health issues fare more poorly than those with moderate mental health issues or no such history. The clinical complexity of working with these patients, indexed by mental and physical comorbidities, may be a factor contributing to this disparity.