Clinical Genitourinary Cancer

Administration of Cisplatin-Based Chemotherapy for Advanced Urothelial Carcinoma in the Community

2012-03-01

Micro-Abstract: Because the frequency of first-line cisplatin-based chemotherapy administration in patients with advanced urothelial carcinoma is unknown, a retrospective study was conducted. A first-line cisplatin-based regimen was administered to 35.9% of patients who presented with stage 4 urothelial carcinoma in a community-based cancer center network. Drug development focused on tolerable agents or combination regimens without a cisplatin backbone should be a priority. Abstract: Background: Renal dysfunction, poor performance status, and comorbidities may preclude frontline cisplatin-based chemotherapy in patients with advanced urothelial carcinoma (UC). The frequency of cisplatin-based chemotherapy administration in patients with advanced UC in community-based cancer centers is unknown. Patients and Methods: A retrospective study was conducted to evaluate chemotherapy regimens administered to patients with the AJCC (American Joint Committee on Cancer) stage-4 UC who, from 2001 to 2010, presented to Texas Oncology Cancer Centers. Frontline chemotherapy was classified as cisplatin based, carboplatin based, nonplatinum based, and as no chemotherapy administered. Results: A total of 298 patients were eligible for analysis, of whom 197 (66.1%) were men. The median age was 70 years (range, 28-97 years), and the primary sites of disease were bladder (243 [81.5%]), renal pelvis (41 [13.8%]), and ureter (14 [4.7%]). Overall, the regimens administered were cisplatin based in 107 patients (35.9%), carboplatin based in 81 (27.2%), and nonplatinum based in 25 (8.4%); no chemotherapy was administered in 71 (23.8%), and data were not available in 14 patients (4.7%). Cisplatin administration was more common in patients aged ≤70 years (62/150 [41.3%]) as opposed to >70 years (45/148 [30.4%]) (P = .05). Noncisplatin regimens or no chemotherapy were trending to be more commonly administered to patients >70 years (64.2 vs. 54.7%; P = .10). Limitations of a retrospective database study apply. Conclusion: A first-line cisplatin-based regimen was administered to 35.9% of patients who presented with AJCC stage 4 UC in a community-based cancer center network. Drug development focused on tolerable single-agent therapy or combination regimens without a cisplatin backbone should be a priority.

Association of Rash With Outcomes in a Randomized Phase II Trial Evaluating Cetuximab in Combination With Mitoxantrone Plus Prednisone After Docetaxel for Metastatic Castration-resistant Prostate Cancer

2012-03-01

Micro-Abstract: This randomized phase II clinical trial analyzed the efficacy of combining cetuximab with mitoxantrone plus prednisone in men with progressive metastatic castrate-resistant prostate cancer after receiving docetaxel. Although the time to progression and overall survival did not improve with the addition of cetuximab, a hypothesis-generating analysis strongly suggests that men receiving cetuximab and developing a rash may benefit clinically. Abstract: Purpose: Cetuximab (C), a chimeric monoclonal antibody that binds epidermal growth factor receptor (EGFR), is active against androgen-independent prostate cancer cell lines and might enhance the activity of chemotherapy. The efficacy of combining cetuximab with mitoxantrone (M) plus prednisone (MP) was evaluated in progressive metastatic castrate-resistant prostate cancer (CRPC) after receiving docetaxel. Materials and Methods: Patients with progression after receiving docetaxel were eligible and randomized 2:1 to CMP or MP. Therapy was mitoxantrone 12 mg/m2 intravenously (I.V.) on day 1, oral prednisone 10 mg daily in both arms, and cetuximab 250 mg/m2 I.V. (400 mg/m2 day 1, cycle 1) on days 1, 8, and 15 in the CMP arm. Cycles were repeated every 21 days. Radiologic assessments of disease and PSA (prostate-specific antigen) occurred every 4 cycles. The primary endpoint was time to progression (TTP). Results: A total of 115 patients were enrolled, 75 in the CMP and 40 in the MP arm: the median TTP was 4.9 and 6.6 months, respectively; the measurable disease response rate was 2% and 4%, the PSA response rate 7.7% and 17.6%, and median survival 11.9 and 15.7 months, respectively. Key grade 3-4 toxicities were neutropenia 44% and 25.6%, anemia 6.7% and 7.7%, thrombocytopenia 6.7% and 2.6%, and fatigue 8% in both arms. In an unplanned exploratory analysis, median TTP with (n = 24) and without rash (n = 51) in the CMP arm was 10.3 months vs. 2.8 months (P = .004). On multivariable analysis,rash was significantly associated with TTP (hazard ratio [HR] = 0.43; P = .01). Conclusions: The treatment with CMP is not recommended in unselected men with docetaxel-treated CRPC, although rash might help develop tailored therapy.

Impact of the CKD-EPI Equation for Estimating Renal Function on Eligibility for Cisplatin-based Chemotherapy in Patients With Urothelial Cancer

2011-12-02

Micro-Abstract: Combination cisplatin-based chemotherapy is indicated for patients with advanced bladder cancer, but use is often limited due to renal insufficiency. In this study, we retrospectively evaluated the renal function in patients with urothelial cancer by using 2 formulas and determined that the Chronic Kidney Disease Epidemiology Collaboration formula is less likely to deem a patient ineligible for cisplatin-based therapy compared with the Cockroft-Gault formula by using standard renal function thresholds. This finding warrants further prospective evaluation. Abstract: Background: Although a creatinine clearance (CrCl) of <60 mL/min, as calculated by the Cockroft-Gault (CG) equation, is a commonly used threshold for “cisplatin-ineligibility,” the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation has recently emerged as a more accurate method of estimating renal function. We sought to determine the impact of using the CKD-EPI equation for estimating renal function on cisplatin eligibility. Methods: All patients pathologically diagnosed with muscle invasive and/or metastatic bladder urothelial carcinoma (T2-4, N or M positive) at Mount Sinai Medical Center between January 1, 2000, and January 27, 2011, were identified. For each patient, CrCl was estimated by using the CG equation and glomerular filtration rate (GFR) was estimated by using the CKD-EPI equation. The patients were considered cisplatin-ineligible if CrCl <60 mL/min or if GFR was <60 mL/min per 1.73 m2. Results: A total of 116 patients were included. The median CrCl estimated by CG was 58.93 mL/min, whereas the median GFR estimated by CKD-EPI was 64.67 mL/min per 1.73 m2. When using the CG formula, 53% of our cohort was cisplatin ineligible, whereas 46% of the cohort was ineligible when using the CKD-EPI formula. The probability of deeming a patient ineligible when using the CG formula was 17% higher than the probability of deeming a patient ineligible when using the CKD-EPI formula: PR 1.17 (95% CI, 1.03-1.34); P = .0203. Conclusion: In our retrospective study, the CKD-EPI formula was less likely to deem a patient ineligible for cisplatin-based therapy compared with the CG formula. This finding was hypothesis generating, and prospective evaluation is necessary to determine the clinical relevance of using this more accurate method of renal function assessment in chemotherapy decision making.

Hormonal Therapy or External-Beam Radiation With Brachytherapy and the Risk of Death From Prostate Cancer in Men With Intermediate Risk Prostate Cancer

2011-12-02

Micro-Abstract: Supplemental androgen suppression therapy may lower the risk of prostate-cancer-specific mortality in men with intermediate-risk prostate cancer who are undergoing brachytherapy. Prospective validation in a randomized controlled trial is needed. Abstract: Purpose: To determine whether external-beam radiotherapy (EBRT) improves disease control compared with supplemental androgen suppression therapy (AST) in men with intermediate-risk prostate cancer who are being treated with brachytherapy. Patients and Methods: A total of 807 men with intermediate-risk prostate cancer (T2bNXM0, Gleason ≤7, prostate-specific antigen [PSA] <20 ng/mL; or cT1c-T2bNXM0, Gleason 7) were consecutively treated with either AST and brachytherapy or EBRT and brachytherapy, between 1997 and 2007, and were followed up until September 21, 2007. A Fine and Gray competing risks multivariable regression model was used to assess whether AST or radiotherapy dose escalation reduced the risk of prostate-cancer–specific mortality (PCSM) when adjusting for age, PSA, Gleason score, and tumor category. Results: Treatment with brachytherapy and with EBRT was associated with a significant increase in the risk of PCSM compared with brachytherapy and AST (adjusted hazard ratio [HR] 4.027 [95% CI, 1.168-13.89]; P = .027) after adjusting for age and prostate cancer prognostic factors. A Gleason score of 4+3 and increasing PSA were associated with worse PCSM (adjusted HR 8.882 [95% CI, 1.095-72.04]; P = .041; and adjusted HR 8.029 [95% CI, 2.38-28.8]; P = .0014, respectively). Conclusion: Supplemental AST use compared with EBRT is associated with a lower risk of PCSM in men with intermediate-risk PC undergoing brachytherapy. Prospective validation in a randomized controlled trial is needed.

Phase I Trial of Everolimus Plus Sorafenib for Patients with Advanced Renal Cell Cancer

Robert J. Amato, Amber L. Flaherty, Mika Stepankiw — 2011-12-14

Micro-Abstract: This study evaluated the maximum tolerated dose (MTD) of combining everolimus and sorafenib for potential additive effects to treat metastatic renal cell cancer (mRCC). Patients received daily everolimus and twice-daily sorafenib at escalating dose levels of 2.5 mg/400 mg, 5 mg/400 mg, and 10 mg/400 mg. The MTD was 10 mg/400 mg, with patients experiencing less severe adverse events with the higher dosage. Abstract: Background: Everolimus, a mammalian target of rapamycin (mTOR) inhibitor, and sorafenib, a RAF kinase inhibitor, has shown efficacy in renal cell cancer (RCC) as single agents. We conducted a phase I study to evaluate the maximum tolerated dose (MTD) of combining these agents for potential additive or synergistic effects when treating progressive metastatic RCC (mRCC). Patients and Methods: The 15 patients enrolled in the study had predominantly clear cell RCC (cRCC) and progressive measurable disease with previous treatment that included immunotherapy, tyrosine kinase inhibitors, and/or everolimus. Patients received daily everolimus and twice-daily sorafenib at escalating dose levels of 2.5 mg/400 mg (cohort 1), 5 mg/400 mg (cohort 2), and 10 mg/400 mg (cohort 3), and they were evaluated weekly for toxicity and every 8 weeks for response, using computed tomography/positron emission tomography (CT/PET) and CT at baseline and at first staging. Results: In cohort 1, 2 of 6 patients experienced dose-limited toxicity (DLT) of thrombocytopenia/leukopenia and pneumonitis. In cohort 2, 1 of 6 patients experienced a DLT of pulmonary embolism, and the 3 patients in cohort 3 experienced no DLTs. The MTD was 10 mg/400 mg. Common adverse events included grade 1/2 hand-foot syndrome. Using Response Evaluation Criteria in Solid Tumors (RECIST), 1 patient achieved a pathologic complete response (CR), 1 patient achieved a radiographic CR, and 1 patient achieved a surgical CR. Seven patients achieved stable disease; 10 patients had decreased fluorine-18 fluorodeoxyglucose uptake. Median progressive-free survival was 5.6 months; overall survival was 7.9 months. Conclusion: The MTD of daily everolimus 10 mg and twice-daily sorafenib 400 mg is safe and effective for progressive mRCC.

Pathological Outcomes of Men Eligible for Active Surveillance After Undergoing Radical Prostatectomy: Are Results Predictable?

Turang Ed Behbahani, Jörg Ellinger, Daniel Garcia Caratozzolo, Stefan C. Müller — 2011-11-21

Micro-Abstract: The increasing incidence of low-risk prostate cancer, associated with a downward migration in clinical staging and grading leads to a critical reflection of 612 patients with prostate cancer and their potential eligibility to participate in an active surveillance program. Abstract: Introduction: To analyze pathological results in patients with prostate cancer eligible for active surveillance (AS) after radical prostatectomy and available prediction systems. Methods: A retrospective analysis was performed of 612 patients who underwent radical prostatectomy during a 14-year period. Subsequently, we selected those patients who would have been eligible for AS according to 2 different published criteria. Group AS-A matched the following criteria: ≤T2a; Gleason Score ≤6; and prostate-specific antigen <10 ng/mL, while group AS-B applied to different criteria: ≤T2a; Gleason Score <7; and prostate-specific antigen ≤15 ng/mL. Pathological outcomes were compared with results of the 2001 Partin tables. Results: Altogether, 125 (20.4%) patients were included in group AS-A and 159 (25.9%) in group AS-B. We detected 32 cases of >pT2c (25.6%) for group AS-A and 47 cases (29.6%) for AS-B, respectively. Gleason score upgrading was recorded in 34.4% (AS-A) and 38.3% (AS-B). Results of the Partin tables showed good discrimination among patients at risk for positive lymph nodes but limited discrimination for organ-confined disease, seminal vesicle. Conclusions: Overall >25% of patients eligible for AS showed either upstaging or Gleason score upgrading, which could not be measured with the examined predictive tools. Patients should be informed about the risks of inaccurate preoperative diagnostic.

Outcome Assessment of Patients With Metastatic Renal Cell Carcinoma Under Systemic Therapy Using Artificial Neural Networks

2011-11-07

Micro-Abstract: The aim of this study was to evaluate the accuracy of artificial neural networks for outcome prediction in metastatic renal cell carcinoma by using clinical and histopathologic data from 175 patients with metastatic renal cell carcinoma who started systemic therapy. Artificial neural networks achieved 95% accuracy for survival prediction and significantly outperformed regression models. Artificial neural networks are a promising approach for risk stratification and therapy optimization. Abstract: Background: The outcome of patients with advanced renal cell carcinoma (RCC) under systemic therapy shows remarkable variability, and there is a need to identify prognostic parameters that allow individual prognostic stratification and selection of optimal therapy. Artificial neural networks (ANN) are software systems that can be trained to recognize complex data patterns. In this study, we used ANNs to identify poor prognosis of patients with RCC based on common clinical parameters available at the beginning of systemic therapy. Patients and Methods: Data from patients with RCC who started systemic therapy were collected prospectively in a single center database; 175 data sets with follow-up data (median, 36 months) were available for analysis. Age, sex, body mass index, performance status, histopathologic parameters, time interval between primary tumor and detection of metastases, type of systemic therapy, number of metastases, and metastatic sites were used as input data for the ANN. The target variable was overall survival after 36 months. Logistic regression models were constructed by using the same variables. Results: Death after 36 months occurred in 26% of the patients in the tyrosine kinase inhibitors group and in 37% of the patients in the immunotherapy group (P = .22). ANN achieved 95% overall accuracy and significantly outperformed logistic regression models (78% accuracy). Pathologic T classification, invasion of vessels, and tumor grade had the highest impact on the network's decision. Conclusion: ANN is a promising approach for individual risk stratification of patients with advanced RCC under systemic therapy, based on clinical parameters, and can help to optimize the therapeutic strategy.

Initial PSA Oscillations Precede Prolonged Stable Disease in a Patient Treated With a Therapeutic Cancer Vaccine

Joseph W. Kim, Ravi A. Madan, James L. Gulley — 2011-10-24

Metastatic Clear Cell Adenocarcinoma of the Urethra in a Male Patient: Report of a Case

2011-11-07

Prolonged Hypocalcemia After Zoledronic Acid in a Patient With Metastatic Prostate Carcinoma: Did Zoledronic Acid Trigger Osteoblastic Activity and Avid Calcium Uptake?

Joon Wee Ho, Santhanam Sundar — 2012-01-16

Paraganglioma Arising from the Prostate: A Case Report and Review of the Literature

Yue Chen, Ranlu Liu, Zhihong Zhang, Yong Xu — 2011-10-24

Nuclear p53 Expression Is Associated With Allelic Imbalance (TP53) in Glandular Dysplasia and Typical Cystitis Glandularis: A LCM-Based Molecular Analysis

2011-11-28

Primary Lymphoma of the Kidney: Case Report and Review of Literature

2012-03-01

Malignant Small Round Blue Cell Tumor of the Kidney Without EWSR1 Rearrangement: Report of a Case and Review of the Literature

William E. Osai, Elizabeth G. Demicco, Lance C. Pagliaro — 2011-12-08

Editorial Board

2012-03-01

Clinical Genitourinary Cancer

Administration of Cisplatin-Based Chemotherapy for Advanced Urothelial Carcinoma in the Community

Association of Rash With Outcomes in a Randomized Phase II Trial Evaluating Cetuximab in Combination With Mitoxantrone Plus Prednisone After Docetaxel for Metastatic Castration-resistant Prostate Cancer

Impact of the CKD-EPI Equation for Estimating Renal Function on Eligibility for Cisplatin-based Chemotherapy in Patients With Urothelial Cancer

Hormonal Therapy or External-Beam Radiation With Brachytherapy and the Risk of Death From Prostate Cancer in Men With Intermediate Risk Prostate Cancer

Phase I Trial of Everolimus Plus Sorafenib for Patients with Advanced Renal Cell Cancer

Pathological Outcomes of Men Eligible for Active Surveillance After Undergoing Radical Prostatectomy: Are Results Predictable?

Outcome Assessment of Patients With Metastatic Renal Cell Carcinoma Under Systemic Therapy Using Artificial Neural Networks

Initial PSA Oscillations Precede Prolonged Stable Disease in a Patient Treated With a Therapeutic Cancer Vaccine

Metastatic Clear Cell Adenocarcinoma of the Urethra in a Male Patient: Report of a Case

Prolonged Hypocalcemia After Zoledronic Acid in a Patient With Metastatic Prostate Carcinoma: Did Zoledronic Acid Trigger Osteoblastic Activity and Avid Calcium Uptake?

Paraganglioma Arising from the Prostate: A Case Report and Review of the Literature

Nuclear p53 Expression Is Associated With Allelic Imbalance (TP53) in Glandular Dysplasia and Typical Cystitis Glandularis: A LCM-Based Molecular Analysis

Primary Lymphoma of the Kidney: Case Report and Review of Literature

Malignant Small Round Blue Cell Tumor of the Kidney Without EWSR1 Rearrangement: Report of a Case and Review of the Literature

Editorial Board

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