Browsing by Author "Petrylak, Daniel P"

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    ItemOpen Access
    Meta-Analysis Evaluating the Impact of Site of Metastasis on Overall Survival in Men With Castration-Resistant Prostate Cancer.
    (Journal of clinical oncology : official journal of the American Society of Clinical Oncology, 2016-05) Halabi, Susan; Kelly, William Kevin; Ma, Hua; Zhou, Haojin; Solomon, Nicole C; Fizazi, Karim; Tangen, Catherine M; Rosenthal, Mark; Petrylak, Daniel P; Hussain, Maha; Vogelzang, Nicholas J; Thompson, Ian M; Chi, Kim N; de Bono, Johann; Armstrong, Andrew J; Eisenberger, Mario A; Fandi, Abderrahim; Li, Shaoyi; Araujo, John C; Logothetis, Christopher J; Quinn, David I; Morris, Michael J; Higano, Celestia S; Tannock, Ian F; Small, Eric J

    Purpose

    Reports have suggested that metastatic site is an important predictor of overall survival (OS) in men with metastatic castration-resistant prostate cancer (mCRPC), but these were based on a limited number of patients. We investigate the impact of site of metastases on OS of a substantial sample of men with mCRPC who received docetaxel chemotherapy in nine phase III trials.

    Patients and methods

    Individual patient data from 8,820 men with mCRPC enrolled onto nine phase III trials were combined. Site of metastases was categorized as lymph node (LN) only, bone with or without LN (with no visceral metastases), any lung metastases (but no liver), and any liver metastases.

    Results

    Most patients had bone with or without LN metastases (72.8%), followed by visceral disease (20.8%) and LN-only disease (6.4%). Men with liver metastases had the worst median OS (13.5 months). Although men with lung metastases had better median OS (19.4 months) compared with men with liver metastases, they had significantly worse median survival duration than men with nonvisceral bone metastases (21.3 months). Men with LN-only disease had a median OS of 31.6 months. The pooled hazard ratios for death in men with lung metastases compared with men with bone with or without LN metastases and in men with any liver metastases compared with men with lung metastases were 1.14 (95% CI, 1.04 to 1.25; P = .007) and 1.52 (95% CI, 1.35 to 1.73; P < .0001), respectively.

    Conclusion

    Specific sites of metastases in men with mCRPC are associated with differential OS, with successive increased lethality for lung and liver metastases compared with bone and nonvisceral involvement. These data may help in treatment decisions, the design of future clinical trials, and understanding the variation in biology of different sites of metastases in men with mCRPC.
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    ItemOpen Access
    Videos of Sipuleucel-T Programmed T Cells Lysing Cells That Express Prostate Cancer Target Antigens.
    (Journal of the National Cancer Institute, 2021-02-25) Kibel, Adam S; Inman, Brant A; Pachynski, Russell K; Vu, Tuyen; Sheikh, Nadeem A; Petrylak, Daniel P
    Sipuleucel-T, an autologous cellular immunotherapy, was approved to treat metastatic castration-resistant prostate cancer in 2010 in the United States. Treatment with sipuleucel-T primes the immune system to target prostate acid phosphatase (PAP), which is expressed by prostate cancer cells, potentially leading to lysis of cancer cell. Expanding upon previously reported indirect evidence of cell killing with sipuleucel-T treatment, we sought to provide direct evidence of cell lysis through visualization. We used advanced video technology and available samples of peripheral blood mononuclear cells from subjects enrolled in the STAMP trial (NCT01487863). Isolated CD8+ T cells were used as effector cells and co-cultured with autologous monocytes pulsed with control or target antigens. Differentially stained effector and target cells were then video-recorded during co-culture. Here, we present video recordings and analyses of T cells from sipuleucel-T-treated subjects showing-for the first time-direct lysis of cells that express prostate cancer target antigens, PAP or prostate-specific antigen.