Howard I Scher

..2 ng/mL was significantly associated with prostate cancer-specific mortality (PCSM)...

..On the basis of this schema, we discuss strategies that are focused on the AR either directly or indirectly, as single agents or in combination, that are in clinical development...

..To update eligibility and outcome measures in trials that evaluate systemic treatment for patients with progressive prostate cancer and castrate levels of testosterone...

..We also highlight the requirements of analytical validation, the sequence of trials needed for clinical validation and regulatory approval, and the future outlook for imaging and CTC biomarkers...

..We aimed to evaluate whether enzalutamide prolongs survival in men with castration-resistant prostate cancer after chemotherapy...

..The androgen receptor (AR) plays critical roles in both androgen-dependent and castrate-resistant prostate cancer (PCa). However, little is known about AR target genes that mediate the receptor's roles in disease progression...

..To determine the therapeutic effects of bicalutamide 200 mg in patients with prostate cancers of different hormone sensitivities...

..Proving the benefit of these approaches requires a series of unique trials with unique endpoints relevant to the clinical state of the patients and the specific therapy under evaluation...

..To define methodology to show clinical benefit for patients in the state of a rising prostate-specific antigen (PSA)...

..This trial evaluated the efficacy and safety of AA in combination with prednisone to reduce the symptoms of secondary hyperaldosteronism that can occur with AA monotherapy...

..To explore the association between progression-free survival and overall survival time in patients with castration-resistant prostate cancer treated with microtubule-targeted therapies...

..Because growth of castration-resistant prostate cancer is dependent on continued androgen-receptor signalling, we assessed the antitumour activity and safety of MDV3100 in men with this disease...

..To compare the efficacy and safety of docetaxel plus high-dose calcitriol (DN-101) to docetaxel plus prednisone in an open-label phase III trial...

..To relate clinical issues to the clinical manifestations of prostate cancers across disease states using the eligibility and outcome criteria defined by Response Evaluation Criteria in Solid Tumors (RECIST)...

..We also discuss circulating tumor cells measured with the CellSearch assay, recently cleared by the FDA for monitoring CRPC...

..The use of such an adaptive approach to clinical trial design has the potential to greatly improve the field of oncology and facilitate the development of personalized medicine...

..We propose that treatment regimes combining AAT with direct AR targeting strategies may provide a more complete blockade of androgen signaling, thereby preventing or significantly delaying the emergence of treatment-resistant disease...

..An analysis was performed to assess lesion detectability by (111)In-J591 gamma-camera imaging compared with standard imaging methods and the effect of increasing antibody mass on lesion detectability, biodistribution, and dosimetry...

..Substitution of i.v. EMP for the oral formulation was found to result in a lower incidence of severe nausea but increased hepatic toxicity...

..To build on this strategy and fully integrate a repetitively dosed bone-seeking radiopharmaceutical into a contemporary chemotherapy regimen, we conducted a phase I study of docetaxel and samarium-153 ((153)Sm) lexidronam...

..This novel immunoconjugate has shown cytotoxic anti-prostate cancer activity. This study investigated the safety profile, pharmacokinetics, immunogenicity, and preliminary antitumor activity of MLN2704...

..AA treatment results in dramatic declines in prostate-specific antigen (PSA) in some patients and no declines in others, suggesting the presence of molecular determinants of sensitivity in tumors...

..720 to 0.726, p=0.2). fPSA is routinely measured during prostate cancer detection. We suggest that the role of fPSA in aiding preoperative prediction should be investigated in further cohorts...

..Although the sample size was small, the proportion of patients achieving declining PSA at the end of six cycles was comparable with that reached with continuous androgen depletion therapy...

..Whether this represents a failure to abrogate androgen receptor mediated signaling with androgen depletion or early reactivation of signaling is under study...

..These long-term findings support the continued study of chemotherapy combined with RT as a potential alternative to prolonged androgen deprivation...

..No impact on PSA slope was detected. We address the relevance of the multivalent approach for prostate cancer treatment...

..We evaluated the association of baseline circulating tumor cell (CTC) number with clinical characteristics and survival in patients with castrate metastatic disease considered for different hormonal and cytotoxic therapies...

..Prior studies have shown the prognostic value of a baseline BSI. This study tested whether treatment-related changes in BSI are prognostic for survival and compared BSI to prostate-specific antigen (PSA) as an outcome measure...

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..These compounds thus appear to be promising candidates for treatment of advanced prostate cancer...

..In cancer treatment trials, clinicians traditionally report patient toxicity symptoms. Alternatively, patients could provide this information directly...

..We tested the hypothesis that serial fluorodeoxyglucose positron emission tomography (FDG-PET) scans can serve as an outcome measure for patients with castrate metastatic prostate cancer treated with antimicrotubule chemotherapy...

..We defined the antitumor effects of bortezomib alone and in combination with prednisone in patients with progressive, castration resistant metastatic prostate cancer...

..These data suggest that inhibitors of Hsp90 may represent a novel strategy for the treatment of patients with prostate cancer and clinical trials to test this hypothesis are currently ongoing...

..In this article, we review the rationale behind this approach, the targets being explored, the radiation sources available, and the antibodies currently under clinical development...

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..Post-treatment changes in the SUV tend to correlate with changes in PSA...

..These data support the dose selection of ongoing phase 2 studies of G3139 at 7 mg/kg/d and docetaxel 75 mg/m2...

..Furthermore, we hypothesized that intermittent dosing would allow for dose escalation and greater inhibition of EGFR-dependent antiapoptotic pathways...

..The design provides investigators increased confidence in making this decision...

..We calculated sensitivity and specificity of PET and correlated PET findings with PSA values, other clinical parameters, and conventional imaging, when available...

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..Our findings offer preclinical proof of principle for ARN-509 as a promising therapeutic in both castration-sensitive and castration-resistant forms of prostate cancer...

..To define the maximum tolerated dose (MTD), toxicities, and pharmacokinetics of 17-allylamino-17-demethoxygeldanamycin (17-AAG) when administered using continuous and intermittent dosing schedules...

..The relationship among dose, safety, pharmacokinetics, and antibody-dependent cellular cytotoxicity (ADCC) activation for unlabeled J591 has not been explored...

..The effect of ZD1839 was also examined in combination with either bicalutamide ("Casodex") or cytotoxic agents against a hormone-dependent or -independent variant of CWR22, respectively...

..Compared with a subsequent trial with the same bivalent vaccine plus QS-21 at the maximal tolerated dose of 100 microg, the 5000 microg dose of GPI-0100 produced comparable antibody titers...

..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...

..Pulse-dosed calcitriol and dexamethasone may maximize tolerability and efficacy. The authors examined the toxicity of pulse-dosed calcitriol with zoledronate and with the addition of dexamethasone at the time of disease progression...

..We evaluated rapid androgen cycling in combination with docetaxel for men with progressive noncastrate prostate cancers...

..To compare the diagnostic and prognostic value of [(18)F] fluorodeoxyglucose positron emission tomography (FDG-PET) and bone scans (BS) in the assessment of osseous lesions in patients with progressing prostate cancer...

..Although achieving an undetectable PSA level does not mean that a patient has been cured, it does establish an endpoint that can be used to identify approaches worthy of study in the Phase III setting...

..To evaluate the antitumor activity and safety of the epothilone B analog, ixabepilone, with or without estramustine phosphate (EMP), in chemotherapy-naive patients with progressive castrate metastatic prostate cancer...

..The results justify the inclusion of TF(c) at a dose of 1 microg as a relevant antigenic target in a multivalent phase II vaccine trial in patients in the high-risk minimal disease state...

..The secondary endpoint was to assess the efficacy of cetuximab in combination with doxorubicin as well as to determine the optimal biologic dose and the maximum tolerated dose...

..Prostate cancer is a heterogeneous disease with a variable natural history that is not accurately predicted by currently used prognostic tools...

..LN metastasis is overwhelmingly associated with high-grade, high-stage, and large volume disease. LN positivity is rarely associated with anterior dominant tumors...

..These results suggest that Hsp90 inhibitors can effectively suppress Akt activity in animal models of human cancer at nontoxic doses, thus sensitizing tumor cells to proapoptotic stimuli...

..These results establish the basis for clinical trials to test PSMA DNA vaccines in patients with solid tumors that either express PSMA directly or that depend on normal endothelial cells expressing PSMA for their continued growth...

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..We are currently conducting a phase I trial of human and mouse PSMA DNA vaccines in patients with recurrent prostate cancer, based on preclinical experiments described below...

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..The information is useful to assess prognosis, guide treatment selection, and design clinical trials...

..PFS, however, is vulnerable to inter-study design variability. The authors sought to identify and quantify this variability and the resultant error in PFS across prostate cancer clinical trials...

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..e., prostate-specific antigen (PSA)] and KLK2 mRNAs. We also assessed the association of CTCs with disease characteristics and survival...

..Based on these pre-clinical studies, we suggest that anti-CTLA-4 should be tested with xenogeneic DNA vaccines against cancer and that special attention should be given to sequence and schedule of administration...

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..A first-in-man phase I study was conducted to define the safety and tolerability of oral BMS-641988 in patients with castration-resistant prostate cancer (CRPC)...

..These results suggest that significant gains in treatment effectiveness may be obtained by combining these treatment modalities, warranting additional preclinical investigation...

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..Directed approaches must account for this changing dynamic so that clinical outcomes may be improved...

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..Our aim was to detect the proportion of bone and soft-tissue lesions that represent metabolically active tumor sites in patients with progressive metastatic prostate cancer...

..The results support the use of cytotoxic drugs in the relapsed setting and definitive trials are ongoing to prove any benefit to survival...

..Another modality offering information about anatomy and metabolism of the local disease is PET/CT. The value of PET/CT at present is controversial, but new studies exploring the role of PET/CT in aggressive prostate cancer are promising...

..The genomic and clinical outcome data from these patients are now made available as a public resource...

..These results suggest that this drug may represent a new strategy for the treatment of prostate cancer...

..This robust platform has broad applications in patient diagnosis, treatment management, and prognostication...

..Current randomized trials are using the highest daily dose established in this study given by shorter infusion periods (i.e., 7 mg/kg/day for 5-7 days) to enhance the antitumor activity of standard cytotoxic drugs...

..These approaches combine those listed above with tumor-directed targeting of osseous disease and manipulation of the biology that underlies the cancer's relationship to bone...

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..Using a population-based approach, we explore the relationship between PSA and survival and generate a measure to demonstrate the amount of the variation in survival explained by PSA...

..To identify predictors of distant metastases (DM) among patients who develop an isolated prostate-specific antigen (PSA) relapse after definitive external-beam radiotherapy for clinically localized prostate cancer...

..We sought to determine the proportion of phase II trials that require historical data to establish the null and to determine how these historical estimates were derived...

..We aimed to use immunomagnetic-capture technology to isolate and analyze circulating tumor cells (CTC) from small volumes of peripheral blood of patients with advanced prostate cancer...

..In addition, levels of both NF-kappaB and AR were strongly correlated in human prostate cancer. Our data suggest that NF-kappaB can regulate AR expression in prostate cancer and that NF-kappaB inhibitors may have therapeutic potential...

..When finalized, it may provide a blueprint for evaluations of PRO measures that can be considered by sponsors and investigators involved in PRO research and drug registration trials...

..Many of these strategies are currently being tested in clinical trials in CRPC...

..High-throughput preclinical assays of gene expression are being developed to enhance selection of drug sequences and combinations for clinical testing...

..By adjusting for patient risk, this method can provide a more precise assessment of phase 2 treatment efficacy, thereby improving the decision whether to proceed to a phase 3 clinical trial...

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..The focus of this document is on the use, combinations, and timing of various forms of androgen deprivation therapy (ADT) for the palliation of men with androgen-sensitive disease...

..Pretreatment plasma samples were also obtained from 12 healthy volunteers. Plasma IGFBP-2 and Her-2 ECD concentrations were quantitated by ELISA...

..These findings suggest that chemoprevention strategies with retinoids may be most effective if applied during the early stages of transformation...

..Part 2 of this two-part article, which began in the August issue, discusses the role of PSA in hormonal and drug therapies and in primary and secondary chemoprevention...

..These data support the further evaluation and clinical testing of huPr1-vcMMAE as a novel therapeutic for the treatment of metastatic and hormone-resistant prostate cancer...

..To update the 2004 American Society of Clinical Oncology (ASCO) guideline on initial hormonal management of androgen-sensitive, metastatic, recurrent, or progressive prostate cancer (PCa)...

..Part 1 of this two-part article, which concludes in the September issue, focuses on the physiology of PSA, its measurement and use in clinical practice, and its predictive value following radical prostatectomy and radiation therapy...