The combination of serum insulin, osteopontin, and hepatocyte growth factor predicts time to castration-resistant progression in androgen dependent metastatic prostate cancer- an exploratory study.

Background: We hypothesized that pretreatment serum levels of insulin and other serum markers would predict Progression-free survival (PFS), defined as time to castration-resistant progression or death, in metastatic androgen-dependent prostate cancer (mADPC).

Methods: Serum samples from treatment-naïve men participating in a randomized phase 3 trial of ADT +/- chemotherapy were retrospectively analyzed using multiplex assays for insulin and multiple other soluble factors. Cox proportional hazards regression models were used to identify associations between individual factor levels and PFS.

A Phase l Study of a Tumor-targeted Systemic Nanodelivery System, SGT-94, in Genitourinary Cancers.

Gene therapy development has been limited by our inability to target multifocal cancer with systemic delivery. We developed a systemically administered, tumor-targeted liposomal nanodelivery complex (SGT-94) carrying a plasmid encoding RB94, a truncated form of the RB gene. In preclinical studies, RB94 showed marked cytotoxicity against tumor but not normal cells.

A Prognostic Gene Expression Signature in the Molecular Classification of Chemotherapy-naïve Urothelial Cancer is Predictive of Clinical Outcomes from Neoadjuvant Chemotherapy: A Phase 2 Trial of Dose-dense Methotrexate, Vinblastine, Doxorubicin, and Cisplatin with Bevacizumab in Urothelial Cancer.

Background: Gene expression profiling (GEP) suggests there are three subtypes of muscle-invasive urothelial cancer (UC): basal, which has the worst prognosis; p53-like; and luminal. We hypothesized that GEP of transurethral resection (TUR) and cystectomy specimens would predict subtypes that could benefit from chemotherapy.

Objective: To explore clinical outcomes for patients treated with dose-dense (DD) methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC) and bevacizumab (B) and the impact of UC subtype.

Targeting the interleukin-11 receptor α in metastatic prostate cancer: A first-in-man study.

Background: Receptors in tumor blood vessels are attractive targets for ligand-directed drug discovery and development. The authors have worked systematically to map human endothelial receptors ("vascular zip codes") within tumors through direct peptide library selection in cancer patients. Previously, they selected a ligand-binding motif to the interleukin-11 receptor alpha (IL-11Rα) in the human vasculature.

Phase I trial of sunitinib and temsirolimus in metastatic renal cell carcinoma.

Background: Preclinical data suggest that anti-vascular endothelial growth factor agents combined with mammalian target of rapamycin inhibitors yield synergistic antitumor effects. A phase I trial with a 3+3 dose escalation design of S with T was stopped after the first dose pair led to 2 of 3 patients experiencing dose-limiting toxicity (DLT).

Patients And Methods: To explore multiple potential dosing pairs of S and T, a 2-stage outcome-adaptive Bayesian dose-finding method was designed.

Mammalian target of rapamycin (mTOR) inhibitor-associated non-infectious pneumonitis in patients with renal cell cancer: predictors, management, and outcomes.

Objective: To characterise the incidence, onset, management, predictors, and clinical impact of mammalian target of rapamycin (mTOR) inhibitor-associated non-infectious pneumonitis (NIP) on patients with metastatic renal cell carcinoma (mRCC).

Patients And Methods: Retrospective review of 310 patients with mRCC who received temsirolimus and/or everolimus between June 2007 and October 2010. Clinical correlations were made with serial radiological imaging.

Refining patient selection for neoadjuvant chemotherapy before radical cystectomy.

Purpose: We evaluated the survival of patients with muscle invasive bladder cancer undergoing radical cystectomy without neoadjuvant chemotherapy to confirm the utility of existing clinical tools to identify low risk patients who could be treated with radical cystectomy alone and a high risk group most likely to benefit from neoadjuvant chemotherapy.

Materials And Methods: We identified patients with muscle invasive bladder cancer who underwent radical cystectomy without neoadjuvant chemotherapy at our institution between 2000 and 2010. Patients were considered high risk based on the clinical presence of hydroureteronephrosis, cT3b-T4a disease, and/or histological evidence of lymphovascular invasion, micropapillary or neuroendocrine features on transurethral resection.

Platinum-based chemotherapy for variant castrate-resistant prostate cancer.

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 prostate-specific antigen levels relative to tumor burden, or short response to androgen deprivation therapy.

Experimental Design: A 120-patient phase II trial of first-line 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.

Plasmacytoid urothelial carcinoma, a chemosensitive cancer with poor prognosis, and peritoneal carcinomatosis.

Purpose: Plasmacytoid urothelial carcinoma is a rare variant histology with poorly defined clinical behavior. We report clinical outcome information on patients with predominant plasmacytoid urothelial carcinoma.

Materials And Methods: We retrospectively analyzed treatments and outcomes in patients with predominant plasmacytoid urothelial carcinoma seen at our institution from 1990 through 2010.

Evaluation of Viable Dynamic Treatment Regimes in a Sequentially Randomized Trial of Advanced Prostate Cancer.

We present new statistical analyses of data arising from a clinical trial designed to compare two-stage dynamic treatment regimes (DTRs) for advanced prostate cancer. The trial protocol mandated that patients were to be initially randomized among four chemotherapies, and that those who responded poorly were to be rerandomized to one of the remaining candidate therapies. The primary aim was to compare the DTRs' overall success rates, with success defined by the occurrence of successful responses in each of two consecutive courses of the patient's therapy.

A phase 2 clinical trial of sequential neoadjuvant chemotherapy with ifosfamide, doxorubicin, and gemcitabine followed by cisplatin, gemcitabine, and ifosfamide in locally advanced urothelial cancer: final results.

Background: Neoadjuvant chemotherapy improves the survival of patients with high-risk urothelial cancer. However, the lack of curative alternatives to cisplatin-based chemotherapy is limiting for patients with neuropathy or hearing loss. Sequential chemotherapy also has not been well studied in the neoadjuvant setting.

Neoadjuvant chemotherapy in small cell urothelial cancer improves pathologic downstaging and long-term outcomes: results from a retrospective study at the MD Anderson Cancer Center.

Background: Small cell urothelial carcinoma (SCUC) is a rare, aggressive malignancy with a propensity for early microscopic metastases. Data suggest that neoadjuvant chemotherapy may lead to improved survival compared with initial surgery.

Objective: To determine the influence of neoadjuvant chemotherapy on survival of SCUC patients in a large single-institution cohort.

Survival outcomes for men with mediastinal germ-cell tumors: the University of Texas M. D. Anderson Cancer Center experience.

Objective: Primary mediastinal germ-cell tumors are rare, and the effect of newer drugs and treatment strategies in this disease on overall survival is not known. We retrospectively assessed treatment outcomes at a single institution.

Materials And Methods: We identified men seen at our institution from 1998 through 2005 for mediastinal germ-cell tumors.

The effectiveness of off-protocol adjuvant chemotherapy for patients with urothelial carcinoma of the urinary bladder.

Purpose: The role of adjuvant chemotherapy for patients with high-risk urothelial carcinoma of the bladder (UCB) is not well defined. Here we address the value of adjuvant chemotherapy in patients undergoing radical cystectomy for UCB in an off-protocol routine clinical setting.

Experimental Design: We collected and analyzed data from 11 centers contributing retrospective cohorts of patients with UCB treated with radical cystectomy without neoadjuvant chemotherapy.

Early results of chemotherapy with retroperitoneal lymph node dissection for isolated retroperitoneal recurrence of upper urinary tract urothelial carcinoma after nephroureterectomy.

Purpose: Retroperitoneal lymph nodes are a recognized site of relapse in patients undergoing nephroureterectomy (NU) for high grade upper tract urothelial carcinoma (UC). Retrospective studies suggest that retroperitoneal lymph node dissection (RPLND) may be curative at the time of NU for high grade upper tract UC. We hypothesized that chemotherapy followed by RPLND may successfully salvage select patients with isolated retroperitoneal relapse of upper tract UC following prior NU.

Phase II presurgical feasibility study of bevacizumab in untreated patients with metastatic renal cell carcinoma.

Purpose: To assess safety and efficacy of presurgical bevacizumab in patients with metastatic renal cell carcinoma (mRCC), and to explore the hypothesis that pretreatment of patients with antiangiogenic therapy will select patients who benefit most from cytoreductive nephrectomy.

Patients And Methods: Patients with newly diagnosed, clear cell mRCC whose primary tumors were considered resectable were enrolled. In this single-arm, phase II trial, patients received bevacizumab plus erlotinib (first patients, n = 23) or bevacizumab alone (n = 27 patients) for 8 weeks followed by restaging.

Phase II clinical trial of neoadjuvant alternating doublet chemotherapy with ifosfamide/doxorubicin and etoposide/cisplatin in small-cell urothelial cancer.

Purpose: Currently, treatment recommendations for small-cell urothelial cancer (SCUC) are based on anecdotal case reports and small retrospective series. We now report results from the first phase II clinical trial developed exclusively for SCUC, to our knowledge.

Patients And Methods: From 2001 to 2006, 30 patients with SCUC provided consent and were treated with alternating doublet chemotherapy.

Phase III trial of androgen ablation with or without three cycles of systemic chemotherapy for advanced prostate cancer.

Purpose: We conducted a phase III trial in patients with previously untreated metastatic prostate cancer to test the hypothesis that three 8-week cycles of ketoconazole and doxorubicin alternating with vinblastine and estramustine, given in addition to standard androgen deprivation, would delay the appearance of castrate-resistant disease.

Patients And Methods: Eligible patients had metastatic prostate cancer threatening enough to justify sustained androgen ablation and were fit enough for chemotherapy. The primary end point was time to castrate-resistant progression as shown by increasing prostate-specific antigen, new radiographic lesions, worsening cancer-related symptoms, or receipt of any other systemic therapy.

Adaptive therapy for androgen-independent prostate cancer: a randomized selection trial of four regimens.

Background: Physicians typically switch therapies unless clinically relevant thresholds of response are observed, and treatments that produce high-quality responses and that are active in the salvage setting are generally felt to be promising. With the goal of efficiently selecting promising regimens for more advanced trials, we conducted a randomized selection trial of four regimens to identify promising treatments for androgen-independent prostate cancer.

Methods: Patients without prior exposure to cytotoxic therapy were randomly assigned to one of four regimens (i.

Bayesian and frequentist two-stage treatment strategies based on sequential failure times subject to interval censoring.

For many diseases, therapy involves multiple stages, with the treatment in each stage chosen adaptively based on the patient's current disease status and history of previous treatments and clinical outcomes. Physicians routinely use such multi-stage treatment strategies, also called dynamic treatment regimes or treatment policies. We present a Bayesian framework for a clinical trial comparing two-stage strategies based on the time to overall failure, defined as either second disease worsening or discontinuation of therapy.

Chemotherapy for bladder cancer: treatment guidelines for neoadjuvant chemotherapy, bladder preservation, adjuvant chemotherapy, and metastatic cancer.

To determine the optimal use of chemotherapy in the neoadjuvant, adjuvant, and metastatic setting in patients with advanced urothelial cell carcinoma, a consensus conference was convened by the World Health Organization (WHO) and the Société Internationale d'Urologie (SIU) to critically review the published literature on chemotherapy for patients with locally advanced bladder cancer. This article reports the development of international guidelines for the treatment of patients with locally advanced bladder cancer with neoadjuvant and adjuvant chemotherapy. Bladder preservation is also discussed, as is chemotherapy for patients with metastatic urothelial cancer.

Prostate cancer progression in the presence of undetectable or low serum prostate-specific antigen level.

Background: The serum prostate-specific antigen (PSA) level after definitive treatment for prostate cancer (PC) is a powerful predictor of outcome. Occasionally, PC progression can occur despite low or undetectable PSA levels. The authors report on the clinical and pathologic characteristics of patients who experienced PC progression with undetectable or low PSA levels.

The case for early cystectomy in the treatment of nonmuscle invasive micropapillary bladder carcinoma.

Purpose: Micropapillary bladder carcinoma is a rare variant of UC. Due to paucity of data regarding treatment outcomes, patients with nonmuscle invasive micropapillary UC often receive intravesical therapy in an attempt at bladder preservation.

Materials And Methods: We reviewed the records of all patients evaluated at our institution who had micropapillary UC of the bladder.