Purpose Clinical features characteristic of small-cell prostate carcinoma (SCPC), (““anaplastic””) often emerge during the progression of prostate cancer. We sought to determine the efficacy of platinum-based chemotherapy in patients meeting at least one of seven prospectively defined “anaplastic” clinical criteria, including exclusive visceral or predominantly lytic bone metastases, bulky tumor masses, low PSA levels relative to tumor burden or short response to androgen deprivation therapy. Experimental Design A 120-patient phase II trial of frontline carboplatin and docetaxel (CD) and second-line etoposide and cisplatin (EP) was designed to provide reliable clinical response estimates under a Bayesian probability model with early stopping rules in place for futility and toxicity. Results Seventy-four of 113 (65.4%) and 24 of 71 (33.8%) were progression free after 4 cycles of CD and EP, respectively. Median overall survival (OS) was 16 months (95% CI, 13.6-19.0 months). Of the 7 “anaplastic” criteria, bulky tumor mass was significantly associated with poor outcome. Lactic acid dehydrogenase (LDH) strongly predicted for OS and rapid progression. Serum carcinoembryonic antigen (CEA) concentration strongly predicted OS but not rapid progression. Neuroendocrine markers did not predict outcome or response to therapy. Conclusion Our findings support the hypothesis that patients with “anaplastic” prostate cancer are a recognizable subset characterized by a high response rate of short duration to platinum-containing chemotherapies, similar to SCPC. Our results suggest that CEA is useful for selecting therapy in men with CRPC and consolidative therapies to bulky high-grade tumor masses should be considered in this patient population.

Thiazolidinediones and metformin appear to be associated with improved overall survival of diabetic prostate cancer patients. The choice of antidiabetic pharmacotherapy may influence overall survival of these patients.

Playing it cool: The mass‐analyzed threshold ionization (MATI) spectrum of jet‐cooled cobaltocene shows a surprisingly rich vibronic structure which provides high‐resolution adiabatic (Iad.) and vertical (Ivert.) ionization energies of the neutral molecule, as well as vibrational frequencies of the gas‐phase cation. The spectrum is indicative of both Jahn–Teller (JT) and pseudo‐Jahn–Teller (PJT) activity in the 19‐electron [Cp2Co] sandwich complex.

Purpose Different vaccination strategies against the NY-ESO-1 antigen have been employed in an attempt to induce anti-tumor immune responses. Antigen-specific effector T cell responses have been reported in a subset of vaccinated patients; however, these responses have not consistently correlated with disease regression. Here we report for the first time clinical and immune responses generated by the NY-ESO-1 DNA vaccine administered by particle-mediated epidermal delivery to cancer patients. Experimental Design Eligible patients received treatment with the NY-ESO-1 DNA vaccine. Clinical outcomes and immune responses were assessed. Results The NY-ESO-1 DNA vaccine was safely administered and induced both antigen-specific effector CD4 and/or CD8 T cell responses in 93% (14/15) of patients who did not have detectable pre-vaccine immune responses. Despite the induction of antigen-specific T cell responses, clinical outcomes consisted predominantly of progressive disease. Detectable effector T cell responses were inconsistent and did not persist in all patients after completion of the scheduled vaccinations. However, high-avidity CD4 T cell responses that were either undetectable pre-vaccine or found to be diminished at a later time during the clinical trial were detected in certain patients’ samples after in vitro depletion of regulatory T cells. Conclusions Regulatory T cells play a role in diminishing vaccine-induced antigen-specific effector T cell responses in cancer patients. The NY-ESO-1 DNA vaccine represents a feasible immunotherapeutic strategy to induce antigen-specific T cell responses. Counteracting regulatory T cell activity prior to vaccination may lead to prolonged effector T cell responses and possibly anti-tumor responses in cancer patients.

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