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BACKGROUND Angiogenesis contributes to the progression of urothelial carcinoma (UC). In the current study, the authors investigated the role of maintenance sunitinib in patients with advanced UC. METHODS Patients with locally recurrent/metastatic UC and adequate organ function who achieved stable disease or a partial or complete response after 4 to 6 chemotherapy cycles were randomized to sunitinib at a dose of 50 mg/day (28 days on and 14 days off) or placebo. The primary endpoint was the 6-month progression rate. Secondary endpoints were safety, survival, change in serum vascular endothelial growth factor (VEGF)/soluble VEGF receptor-2 (sVEGFR2), and the activity of sunitinib in patients who developed disease progression while receiving placebo. A total of 38 eligible patients per treatment arm were required to select better therapy with 90% probability (α = .05). RESULTS A total of 54 eligible patients were randomized to either the sunitinib arm (26 patients) or the placebo arm (28 patients). The median number of cycles received was 2 cycles per treatment arm. The most common grade 3 to 4 adverse events (graded according to version 3.0 of the National Cancer Institute Common Terminology Criteria for Adverse Events) among patients receiving sunitinib were thrombocytopenia, diarrhea, mucositis, fatigue, and hypertension. There were no grade 3 or 4 adverse events noted among > 5% of patients receiving placebo. The 6-month progression rate was 72% versus 64%. The median progression-free survival (PFS) was 2.9 months (range, 0.5 months-32.5 months) versus 2.7 months (range, 0.8 months −65 months) for the sunitinib versus placebo arms, respectively. Patients receiving placebo were found to have no changes in their serum VEGF/sVEGFR2 levels over time. Patients treated with sunitinib had no significant change in their VEGF level, but the sVEGFR2 level significantly decreased after cycles 1 and 2 ( P < .0001) and at the time of disease progression ( P = .0002). A baseline VEGF level that was at or greater than the median was found to be correlated with a longer PFS. Sixteen patients who were receiving placebo received sunitinib at the time of disease progression, with the best responses being 1 partial response (6.3%), 6 cases of stable disease (37.5%), and 5 cases of progressive disease (31.3%); 4 patients were not evaluable for response. The median PFS was 3.7 months (range, 0.1 months-22 months). CONCLUSIONS The current multicenter study was limited by premature closure and a small sample size. Maintenance sunitinib did not appear to improve the 6-month progression rate. Open-label sunitinib was found to have only modest activity. The sVEGFR2 level decreased among patients receiving sunitinib. Cancer 2014;120:692-701. © 2013 American Cancer Society. [ABSTRACT FROM AUTHOR]

BACKGROUND There have been no improvements in the treatment of metastatic urothelial cancer in the past several decades. A census of contemporary clinical research in this disease was performed to identify potential barriers and opportunities. METHODS These authors performed a search for clinical trials exploring interventions in muscle-invasive and metastatic urothelial cancer, using the ClinicalTrials.gov registry. Data extracted from the registry included title, recruitment status, interventions, sponsor, phase, enrollment, study design, and study sites. RESULTS Among 120 eligible trials exploring interventions in muscle-invasive and metastatic urothelial cancer, 73% were phase 2 and 73% were nonrandomized. The majority (63%) involved treatment in the metastatic disease state. The median planned enrollment size per trial was 45 patients (interquartile range, 47 patients). The majority of trials (55%) involved ≤ 3 study sites. Trials most commonly explored interventions in the first-line metastatic (30%) or second-line metastatic (37%) settings. Targeted therapeutics were studied in 58% of the trials. Among 56 trials that completed enrollment, the median time to complete accrual was 50 months (range, 10-109 months), and these trials enrolled a median of 40 patients per trial (interquartile range, 44 patients). CONCLUSIONS The majority of contemporary clinical trials in muscle-invasive and metastatic urothelial cancer are small, nonrandomized, phase 2 trials involving 1 to 3 study sites. Enhanced communication and collaboration among the urothelial cancer community, and other stakeholders, is needed to facilitate the design and conduct of trials capable of expediting progress in this disease. Cancer 2013;119:1994-1998. © 2013 American Cancer Society. [ABSTRACT FROM AUTHOR]

BACKGROUND: The current treatment of metastatic renal cell carcinoma (mRCC) with vascular endothelial growth factor (VEGF)-targeted agents is continuous therapy until progression of disease (PD) or unacceptable toxicity. Chronic mild to moderate toxicity and risk of long-term toxicity ensue for some patients. It is hypothesized that patients with an initial response to treatment can maintain disease control off all therapy for a period of time. METHODS: A retrospective study of patients with mRCC who initiated VEGF-targeted therapy between January 2004 and December 2009 at The Cleveland Clinic Foundation, Cleveland, Ohio, or Institut Gustave-Roussy, Villejuif, France, was conducted. Patients had achieved RECIST (Response Evaluation Criteria in Solid Tumors)-defined stable disease or better on therapy, and were then taken off all therapy for reasons not including disease progression. Patient, disease, and therapy characteristics were recorded. The primary objective was progression-free survival (PFS), measured as the time from discontinuation of therapy to RECIST-defined PD. RESULTS: Forty patients were identified. After a median follow-up of 29.7 months (range, 4.2 to 84.7 months), 25 patients (63%) had PD off therapy (median PFS, 10.0 months; range, 1.4-27.2 months). Among these patients, 8 (32%) had progression in sites that were not previously involved with disease. Heng risk group (hazard ratio, 2.49; 95% confidence interval, 1.19-5.22; P = .011) and achievement of a complete response prior to discontinuing therapy (hazard ratio, 0.20; 95% confidence interval, 0.04-0.86; P = .025) were independent predictors of PFS in a multivariable Cox proportional hazards model. CONCLUSIONS: A select subset of mRCC patients achieving stable disease or better on VEGF-targeted therapy can be observed off all therapy. Further prospective investigation is warranted. Cancer 2011. © 2011 American Cancer Society. [ABSTRACT FROM AUTHOR]

PURPOSE: Biomarkers that predict response or toxicity to antiangiogenic therapy are sought to favorably inform the risk/benefit ratio. This study evaluated the association of vascular endothelial growth factor (VEGF) and VEGF receptor 2 (VEGFR2) genetic polymorphisms with the development of hypertension (HTN) and clinical outcome in metastatic clear cell renal cell carcinoma (MCCRCC) patients treated with sunitinib. PATIENT AND METHODS: Sixty-three MCCRCC patients receiving sunitinib (50 mg 4/2) with available blood pressure (BP) data and germline DNA were retrospectively identified. A panel of candidate VEGF and VEGFR2 single nucleotide polymorphisms (SNPs) were evaluated for associations with the development of hypertension and clinical outcome. RESULTS: VEGF SNP −634 genotype was associated with the prevalence and duration of sunitinib-induced hypertension (as defined by systolic pressure ≥150 mmHg and/or diastolic pressure ≥90 mmHg) in both univariable analysis ( P = .03 and .01, respectively) and multivariable analysis, which adjusted for baseline BP and use of antihypertension medication ( P = .05 and .02, respectively). Patients with the GG genotype were estimated to have a greater likelihood of being hypertensive during treatment compared with patients with the CC genotype (odds ratio of 13.62, 95% confidence interval [CI] 3.71-50.04). No single VEGF or VEGFR SNPs were found to correlate with clinical outcome. However, the combination of VEGF SNP 936 and VEGFR2 SNP 889 were associated with overall survival after adjustment for prognostic risk group ( P = .03). CONCLUSIONS: In MCCRCC patients treated with sunitinib, VEGF SNP −634 is associated with hypertension and a combination of VEGF SNP 936 and VEGFR2 SNP 889 genotypes is associated with overall survival. Cancer 2012;. © 2011 American Cancer Society. [ABSTRACT FROM AUTHOR]

Study Type - Therapy (individual cohort) Level of Evidence 2b OBJECTIVE • To determine, in a phase I/II trial, the maximum tolerated dose (MTD), clinical activity and safety of concurrent subcutaneous (s.c.) interleukin-2 (IL-2), interferon-α2b (IFN-α) and granulocyte-macrophage colony-stimulating factor (GM-CSF). PATIENTS AND METHODS • Patients with metastatic renal cell carcinoma (RCC) received on a 3+3 trial design escalating doses of s.c. GM-CSF, IL-2 and IFN-α. • Dose-limiting toxicities (DLTs) during the first 6-week cycle were used to determine the MTD. • A phase II trial was then initiated to determine clinical activity. RESULTS • A total of sixty patients were enrolled in the study (phase I = 31; phase II = 29). • Two DLTs were observed (G3 nausea/vomiting and fatigue) and the MTD was determined to be GM-CSF 5.0 µg/kg/day, IL-2 9.0 mIU/m2/day and IFN-α 5.0 mU/m2/day. • Patients received a median (range) of four (one to 11) cycles of therapy. G3 adverse events were reported in 10 of 31 (32%) patients. • The overall response rate was 20% (one complete response and 11 partial responses), including patients who were rendered free of disease with surgery. • The median progression-free survival and overall survival were 6.0 and 23.4 months, respectively. CONCLUSIONS • Immunotherapy with concurrent s.c. GM-CSF, IL-2 and IFN-α is generally well tolerated. • The overall response rate observed with this combination continues to show the efficacy of immunotherapy in a selected group of metastatic RCC patients. [ABSTRACT FROM AUTHOR]

Key controversies concerning the management of genitourinary cancers across the treatment continua were discussed at the second annual Interactive Genitourinary Cancer Conference (IGUCC) held in February 2010 in Athens, Greece. Prostate cancer is the most common form of cancer among western men and prevention strategies are needed. Trials evaluating 5α-reductase inhibitors have reported beneficial and clinically meaningful results, but uptake remains low for primary prostate cancer prevention. Prostate cancer detection programmes are also important as curative treatments for advanced disease are unavailable. Two large landmark randomized controlled trials reported conflicting results concerning screening efficacy and uncovered high levels of over-diagnosis and potential over-treatment. Tailored management strategies after diagnosis are important and predictive markers that distinguish between aggressive and indolent tumours are needed. The majority of newly diagnosed cases of prostate cancer are clinically localized. Active surveillance of favourable risk patients may be beneficial in the intermediate term, while an integrated approach of multi-modality therapy in patients with adverse features is recommended. The benefits of new technologies such as high-intensity focused ultrasound (HIFU) and robotic prostatectomy have not been established in prospective randomized trials vs current standards of care. A multidisciplinary approach is essential to evolving the management of advanced prostate cancer into a chronic disease paradigm. Docetaxel plus prednisone is the standard first-line chemotherapy for patients with metastatic castration-resistant prostate cancer (mCRPC), but the optimal timing of chemotherapy initiation has not been addressed in randomized clinical trials. Retrospective analyses suggest that asymptomatic patients with adverse prognostic factors for survival may also benefit from receiving chemotherapy. Bladder cancer is a common malignancy and the most expensive cancer per patient. Non-muscle-invasive bladder cancer is a heterogenous disease that requires dynamic multidisciplinary management. Aggressive early intervention may be beneficial in some cases. Platinum-based therapies represent the first-line standard of care for advanced bladder cancer, but the maximum benefit may have been reached for conventional chemotherapies and new strategies are needed. Several ongoing clinical trials are assessing combination chemotherapy and targeted therapy. [ABSTRACT FROM AUTHOR]

BACKGROUND: An important goal of noncurative therapy for metastatic renal cell carcinoma (mRCC) is tumor burden (TB) control. However, to the authors' knowledge, the impact of TB characteristics on clinical outcome has not been studied in patients with mRCC who were treated with vascular endothelial growth factor-targeted therapy. METHODS: Patients with clear cell mRCC who were treated with sunitinib between June 2004 and October 2007 were retrospectively identified. Computed tomography scans were re-reviewed from baseline, at the time of maximal TB shrinkage (TS) while receiving sunitinib, and at the time of progressive disease (PD). Measurements were recorded as per Response Evaluation Criteria In Solid Tumors (RECIST). RESULTS: A total of 69 patients were identified. The majority (54%) were classified as being of favorable risk using Cleveland Clinic Foundation Tyrosine Kinase Inhibitor (CCF TKI) risk group criteria. All patients underwent prior nephrectomy and 77% received prior systemic therapy. There were a median of 8 metastatic deposits across all organs (range, 1-27 deposits). The median TB at the initiation of therapy was 14.0 cm (range, 3.0 cm-42.2 cm). On multivariable analysis, baseline characteristics of disease confined to above the diaphragm (P = .03) and a total TB <13 cm (P = .09) were found to be independent positive predictors of progression-free survival. A+ baseline, total number of metastases <10 (P < .001) and TB above the diaphragm <6.5 cm (P = .05) were found to be independent positive predictors of overall survival (OS). Increased TS while receiving sunitinib was found to be significantly associated with OS (P < .001). At the time of PD, tumor location and pattern of disease progression were not found to be associated with survival as measured from the date of PD. However, total TB (P = .003) and total number of metastatic deposits (≤12 vs >12; P < .001) were found to be significant predictors of survival after PD. CONCLUSIONS: The results of the current study indicate that TB characteristics are associated with clinical outcome in patients with mRCC who are treated with sunitinib. [ABSTRACT FROM AUTHOR]

BACKGROUND: Docetaxel is the standard of care for patients with metastatic, castrate-resistant prostate cancer (CRPC). Gemcitabine is a nucleoside analogue with broad antitumor activity. In a phase 2 study of combined docetaxel and gemcitabine, the authors assessed its safety and activity in patients with chemotherapy-naive, metastatic CRPC. METHODS: Eligible patients had untreated, metastatic CRPC with radiologic and/or biochemical evidence of progression after antiandrogen withdrawal with castrate testosterone levels, an Eastern Cooperative Oncology performance status (ECOG PS) of 0 to 2, and adequate organ function; no previous chemotherapy was permitted. Patients received gemcitabine (800 mg/m²) Days 1 and 8 and docetaxel (75 mg/m²) on Day 8 every 21 days for a maximum of 6 cycles. Response was evaluated using Response Evaluation Criteria in Solid Tumors (RECIST) for measurable disease. A prostate-specific antigen (PSA) response was defined as a decline ≥50% in baseline PSA level. RESULTS: Thirty-five patients with chemotherapy-naive, metastatic CRPC were enrolled. The median age was 67 years, and 60% of patients had an ECOG PS of 0. PSA responses were observed in 49% of patients. Among the patients who had measurable disease (n = 25), 3 patients (12%) had a confirmed, RECIST-defined partial response (PR); 4 patients (16%) had an unconfirmed PR; and 15 patients (60%) achieved stable disease. The most common adverse events included grade 1 and 2 fatigue (69%), alopecia (80%), and nausea/vomiting (54%). No treatment-related deaths were noted, but an unusually high incidence of grade 3 and 4 neutropenia was observed. CONCLUSIONS: The efficacy of combined gemcitabine and docetaxel in metastatic CRPC was similar to that observed with single-agent docetaxel. In contrast to single-agent docetaxel, the combination was moderately toxic and had an impact primarily on bone marrow reserve. Cancer 2011;117:752-7. [ABSTRACT FROM AUTHOR]

OBJECTIVE Low-dose interleukin-2 (IL-2) is a historical treatment for metastatic renal cell carcinoma (mRCC). Increased vascular endothelial growth factor (VEGF) levels inhibit dendritic cell (DC) differentiation and augment production of immunosuppressive regulatory T (Treg) cells. Bevacizumab is an antibody that binds to VEGF, has activity in mRCC and may augment the anti-tumour immune effects of IL-2. To determine the clinical and immunomodulatory effects of this combination, a prospective, phase II trial of bevacizumab plus low-dose IL-2 was conducted. PATIENTS AND METHODS Patients with untreated mRCC received bevacizumab (10 mg/kg i.v. every 2 weeks) and IL-2 (125 000 units/kg/day subcutaneously from Monday to Friday for 6 consecutive weeks followed by a 2-week rest period). Endpoints included progression-free survival, Response Evaluation Criteria in Solid Tumors-defined objective response rate, immunomodulatory effects and safety. RESULTS Between January 2005 and September 2007, twenty-six patients with untreated mRCC were enrolled. The median progression-free survival was 9.6 months (95% CI, 4.1-16.9 months) The objective response rate was 15% and an additional 38% of patients had tumour burden reduction of < 30%. Grade 3 constitutional adverse events (fatigue, fever/ chills) and neutropenia were observed in 42% and 12% of patients, respectively. Peripheral blood CD1c + myeloid and CD303 + plasmacytoid DC increased during treatment as did IL-8 levels and CD4 + CD25 + FoxP3 + Treg cells. No changes in T helper type 1/2- associated cytokines were observed. CONCLUSION Bevacizumab plus low-dose IL-2 has modest clinical activity in mRCC. Toxicity was largely IL-2 related without enhancement of bevacizumab-related toxicity. Biological data indicate inhibition of VEGF levels and increase of immunosuppressive Treg cells without an effect on DC activation. [ABSTRACT FROM AUTHOR]

The article provides information on a study which investigated the safety and activity of sorafenib in bevacizumab- or sunitinib-refractory metastatic renal cell carcinoma (mRCC) patients. Background on vascular endothelial growth factor (VEGF)-targeted agents is offered. Outcome measures included tumor burden reduction rate, progression-free survival (PFS), duration of response, overall survival and safety. A discussion on the research findings is detailed. It observes that sorafenib is safe and possible in patients with mRCC refractory to either drugs.

Study Type - Therapy (case series) Level of Evidence 4 OBJECTIVE To determine if the fractional percentage of tumour volume (FPTV) removed with debulking nephrectomy was associated with progression-free survival (PFS) after subsequent targeted therapy, as a debulking nephrectomy is the standard of care in metastatic renal cell carcinoma (mRCC), but there are few data. PATIENTS AND METHODS The Cleveland Clinic Taussig Cancer Institute Urologic Oncology database was retrospectively reviewed from 2005 to 2008 to identify patients with mRCC who had undergone debulking nephrectomy followed by vascular endothelial growth factor (VEGF)-targeted therapy, defined as sunitinib-, sorafenib- or bevacizumab-based therapy. FPTV was calculated as the largest diameter of the primary tumour divided by the total tumour burden (as per the Response Evaluation Criteria in Solid Tumors, RECIST) through investigator re-review of imaging. PFS was defined from the start date of systemic therapy to disease progression per RECIST criteria. RESULTS Forty-six patients were identified (80% men, median age 61 years, all clear cell histology and 67% with an Eastern Cooperative Oncology Group performance status of 0). Patients received treatment with bevacizumab ± interleukin-2 (18), sunitinib (14), sorafenib (11) or sunitinib + bevacizumab (three). The median diameter of the primary tumour was 10.0 cm. The median (range) FPTV removed was 95 (80-99)%. In univariable analysis, the FPTV removed ( P= 0.002) and normal haemoglobin level ( P= 0.04) were associated with improved PFS. In multivariable analysis, the FPTV removed ( P < 0.001), male gender ( P= 0.001) and corrected calcium ( P= 0.05) were independent predictors of PFS. CONCLUSION A greater percentage of tumour burden removed at debulking nephrectomy is significantly associated with improved PFS on subsequent VEGF-targeted systemic therapy. [ABSTRACT FROM AUTHOR]

The article provides information on a study which examined the renal function of patients with upper tract urothelial carcinoma (UTUC) prior and following nephroureterectomy (NU) to identify the proportion of patients with optimal renal function to be considered for cisplatin-based combination chemotherapy (CBCC). A brief information on UTUC is offered. The Modification of Diet in Renal Disease formula was employed to estimate glomerular filtration rate (eGFR) in patients with UTUC. A discussion on the research findings is offered.

The article presents a study which determines the activity as well as the toxicity of sorafenib in a multi-institutional setting in patients who were given the treatment with one prior chemotherapy regimen. Study shows no therapy-related deaths nor was an effective second-line systemic chemotherapy for patients. It is concluded that investigation of tyrosine kinase inhibitors is warranted through the use of different trial designs.

The article discusses the result of neoadjuvant chemotherapy and open radical cystectomy associated with methotrexate, vinblastine, doxorubicin and cisplatin (MVAC). In the study, 2 patients where detected to have a pathologic complete response with nonorgan-confined residual cancer as well as median progression free survival. Patients experienced a pathologic response to neadjuvant chemotherapy with rapid disease progression.

Background: Sunitinib and sorafenib are small molecules that inhibit the vascular endothelial growth factor and related receptors with substantial clinical activity reported in metastatic renal cell carcinoma (RCC). Cytopenia and macrocytosis have been described in patients treated with these agents.Methods: A retrospective review of all patients with metastatic RCC who were treated with sunitinib or sorafenib for at least 3 months at the Cleveland Clinic Taussig Cancer Institute was undertaken. Complete blood count (CBC) data including red blood cell indices were recorded at baseline, after 3 months of therapy, and at the end of treatment.Results: A total of 61 patients were treated with sunitinib and 37 patients were treated with sorafenib with available CBC data. In patients treated with sunitinib, the median corpuscular volume (MCV) increased significantly at 3 months compared with baseline (median increase of 5.1 femtoliters [fL]; P < .001) and continued to increase throughout treatment. Patients who developed hypothyroidism had a larger MCV increase at 3 months than patients who remained euthyroid (P = .06), although macrocytosis was observed in patients without hypothyroidism. Ten patients discontinued sunitinib therapy, and the MCV decreased in all patients within 2 to 4 months, without further intervention. Bone marrow analysis of 4 patients revealed a hypocellular bone marrow with trilineage hematopoiesis and no evidence of metastasis. There was no evidence of folate or vitamin B12 deficiency. In contrast to sunitinib, there was no change in the MCV for patients treated with sorafenib.Conclusions: Macrocytosis was a common occurrence after treatment with sunitinib but not sorafenib in patients with metastatic RCC. Sunitinib-induced macrocytosis is reversible with drug discontinuation. [ABSTRACT FROM AUTHOR]

Background: There is a need to identify active new regimens in patients with advanced urothelial cancer. Pemetrexed and gemcitabine are active agents in advanced urothelial cancer. A phase 2 trial of the combination of these 2 agents was performed in patients with advanced urothelial cancer who were previously untreated for metastatic disease.Methods: Forty-six patients with advanced urothelial carcinoma received pemetrexed disodium 500 mg/m2 and gemcitabine 1000 mg/m2 intravenously on Day 1, with gemcitabine repeated on Day 8. Cycles were repeated every 3 weeks for a maximum of 6 cycles.Results: Two patients attained a complete response, and 12 patients attained a partial response for an overall response rate of 31.8% (90% confidence interval, 20.4%-45.2%). The median time to disease progression was 5.8 months, and the median overall survival was 13.4 months. Thirty-three patients (75%) experienced grade>or=3 neutropenia, and 5 patients (11%) had febrile neutropenia. There were 2 therapy-related deaths.Conclusions: The combination of pemetrexed and gemcitabine had moderate antitumor activity in previously untreated patients with advanced urothelial cancer at the expense of significant myelosuppression. [ABSTRACT FROM AUTHOR]

OBJECTIVES To evaluate the presentation, location and overall survival of pelvic recurrence after radical cystectomy (RC) for transitional cell carcinoma (TCC) of the bladder. PATIENTS AND METHODS We reviewed a consecutive series of 130 patients who had a limited bilateral pelvic lymph node dissection (PLND) and RC between 1987 and 2000, and who later developed pelvic recurrence. All patients were staged N0M0 before RC and no patient received neoadjuvant radio/chemotherapy. The boundaries of the limited PLND were the pelvic side-wall between the genitofemoral and obturator nerves, and the bifurcation of iliac vessels to the circumflex iliac vein. Pelvic recurrence was defined as a radiographic soft-tissue density of ≥2 cm below the bifurcation of the aorta. Kaplan-Meier and Cox proportional hazards analyses were used to determine if imaging or symptomatic presentation, age, pT stage, and pN status were predictive of overall survival. RESULTS The median (range) time from RC to pelvic recurrence was 7.3 (1.2–55.4) months. No patients had concomitant distant metastasis. Of the patients, 61.5% were diagnosed with pelvic recurrence because of symptoms, and 38.5% by surveillance computed tomography (CT). Of the 130 patients, 128 died, with a median survival from the time of pelvic recurrence of 4.9 (0.1–129.3) months. The median overall survival time for pelvic recurrence diagnosed with CT was 21.6 months, vs 10.6 months for symptomatic presentations ( P < 0.001). In the uni- and multivariate models, type of presentation (CT vs symptomatic) and pT stage were predictors of overall survival, while age and pN status were not. CONCLUSION The prognosis of patients with pelvic recurrence after RC for TCC is poor even with subsequent therapy, emphasizing the need for optimum local control at the time of initial treatment. [ABSTRACT FROM AUTHOR]

This article discusses findings of a study, which determined the histologic and molecular changes that occurred in patients with high-risk, localized prostate cancer (PCA) after neoadjuvant docetaxel chemotherapy. Considered the third leading cause of cancer death in men, patients who have locally advanced prostate cancer have worse outcomes after radical prostatectomy as compared with patients who have more favorable parameters. Based on clinical trials, docetaxel-based chemotherapy improves survival in patients with hormone-refractory PCA.

Background: Paclitaxel and docetaxel are active agents in advanced urothelial cancer. BMS-247550 (ixabepilone) has activity in preclinical models in paclitaxel resistant models. A phase 2 trial of this epothilone was performed to determine the activity and toxicity of this agent in a multi-institutional setting in patients previously treated with 1 prior chemotherapy regimen.Methods: Forty-five patients with advanced urothelial carcinoma were treated with BMS-247550 40 mg/m(2) over 3 hours intravenously on Day 1 of a 21-day cycle and continued therapy until progression or unacceptable toxicity.Results: Five patients obtained an objective partial response (PR) among the 42 eligible patients for an overall response rate of 11.9% (90% confidence interval [5.3%, 26.5%]). Median overall survival of the group was 8 months. Toxicity was moderate with granulocytopenia, fatigue, and sensory neuropathy being the most common side effects noted.Conclusions: BMS-247550 (ixabepilone) has very modest activity as a second-line therapy for advanced urothelial cancer. Responses in visceral, nodal, and soft tissues sites were observed. Granulocytopenia without fever, fatigue, and sensory neuropathy was common. [ABSTRACT FROM AUTHOR]

The article discusses the systemic management options and the second-line therapy for patients with metastatic bladder cancer. Advanced bladder cancer is the most depressing genitourinary neoplasm in the management of advanced renal cell carcinoma. Furthermore, variety of molecular pathways that are amenable to treatment with current agents including overexpression of epidermal growth factor receptor and vascular endothelial growth factor greatly influences bladder cancer.