Treatment Decision Making in Patients with Bladder Cancer.

Background: Each stage of bladder cancer involves varying treatment issues and concerns that are discussed between patients and providers during the pre-treatment consultation. There is no documentation of how patients engage in decision making. Objective: To describe aspects of treatment decision making perceived by patients with bladder cancer using qualitative analysis of data from individual interviews. Methods: Patients with any stage bladder cancer were recruited from urology and medical oncology services at a comprehensive cancer center. A qualitative approach to data collection and analysis was applied. Individual, semi-structured interviews were conducted, recorded and transcribed. Coding of the transcripts was conducted by research team members, discussed for consensus and major themes derived. Results: 45 men and 15 women, the majority college educated, were recruited. Where to receive care, including from whom, was the initial and major decision. Challenges of decisions regarding urinary reconstruction were dominant. Personal characteristics, including age and being active, were considered. Participants with early stage tumors (n = 28) typically perceived only one treatment option and followed the physician's recommendation. The 18 participants with stage II-III were aware of multiple options. In 14 stage IV participants, balancing quality of life and outcomes between treatments was common to the decision process. Conclusions: For this educated sample with bladder cancer, recruited at a comprehensive cancer center, the major decision was to seek treatment at a location with the highest level of physician expertise. Personal preferences informed decisions surrounding bladder reconstruction. Further research will be conducted in a diverse sample of patients making decisions in a non-urban, community setting.

Vinflunine: drug safety evaluation of this novel synthetic vinca alkaloid.

INTRODUCTION: Vinca alkaloid agents have been widely used in several different types of malignancies. However, cancer cells, ultimately, develop resistance to these agents. Therefore, the development of new agents with improved efficacy is warranted. Recently, a new synthetic vinca alkaloid, vinflunine, was developed through the addition of two fluor molecules by superacidic chemistry. AREAS COVERED: The authors describe the development of the new vinca alkaloid vinflunine from preclinical studies to the late-stage clinical trials, highlighting the most important clinical and safety data of vinflunine. In vitro and in vivo studies have shown a superior efficacy of vinflunine over other vinca alkaloids and with an improved safety profile. Early clinical trials have demonstrated a significant activity of vinflunine against different malignancies. Phase III trials showed that vinflunine increases survival in patients with advanced transitional cell carcinoma of the urothelium (TCCU) tract treated in the second-line and is as effective as docetaxel in second-line NSCLC. EXPERT OPINION: Vinflunine is currently approved in Europe for the treatment of second-line TCCU and is currently being developed in other malignancies. It has been shown to have predictable and manageable adverse effects, such as neutropenia, anemia, constipation and fatigue.

A phase 1 study of everolimus and sorafenib for metastatic clear cell renal cell carcinoma.

BACKGROUND: The current study was conducted to assess the maximum tolerated dose (MTD), safety, pharmacokinetics, and preliminary antitumor effect of everolimus, a mammalian target of rapamycin inhibitor, in combination with sorafenib, a tyrosine kinase inhibitor, in patients with metastatic clear cell renal cell carcinoma. METHODS: Sequential cohorts of patients received escalating doses of everolimus and sorafenib in 28-day cycles in the absence of a dose-limiting toxicity (DLT) or disease progression were examined. RESULTS: Twenty patients with a median age of 65 years received therapy in 3 cohorts. Dose level 1 was comprised of everolimus at a dose of 2.5 mg daily and sorafenib at a dose of 400 mg twice daily (6 patients), dose level 2 was comprised of everolimus at a dose of 5 mg daily and sorafenib at a dose of 400 mg twice daily (8 patients), and dose level 3 was comprised of everolimus at a dose of 10 mg daily and sorafenib at a dose of 200 mg twice daily (6 patients). DLTs included grade 4 (according to National Cancer Institute Common Terminology Criteria for Adverse Events [version 3.0]) hyperuricemia with grade 2 gout and grade 3 lipase associated with grade 2 pancreatitis at dose level 2, and grade 3 rash in 2 patients at dose level 3. Dose level 2 (everolimus at a dose of 5 mg daily and sorafenib at a dose of 400 mg twice daily) was established as the maximum tolerated dose. Treatment-related adverse events occurring in >20% of patients included diarrhea, hand-foot syndrome, hypertension, hypophosphatemia, hypothyroidism, and rash. Five of 20 patients achieved Response Evaluation Criteria In Solid Tumors (RECIST)-defined partial responses, all of which occurred in patients without a history of prior systemic therapy. Seven of 8 patients treated at dose level 2 experienced a partial response or stable disease. Pharmacokinetic analysis revealed no interaction between everolimus and sorafenib. CONCLUSIONS: The combination of everolimus and sorafenib was associated with acceptable toxicity and evidence of antitumor activity in previously untreated patients with metastatic renal cell carcinoma.

Carbonic anhydrase IX and pathological features as predictors of outcome in patients with metastatic clear-cell renal cell carcinoma receiving vascular endothelial growth factor-targeted therapy.

OBJECTIVE: To investigate the utility of tumour carbonic anhydrase IX (CAIX) expression and histological features for predicting the outcome in patients with metastatic clear-cell renal cell carcinoma (mRCC) treated with vascular endothelial growth factor (VEGF)-targeted therapy. PATIENTS AND METHODS: We identified 118 patients with mRCC initiating first-line VEGF-targeted therapy, including 94 with clinical and histological data, and available tissue. The primary endpoint was to detect an interaction between sorafenib vs sunitinib treatment and CAIX status on tumour shrinkage. Other treatment outcomes were also assessed. RESULTS: There was heterogeneity in tumour responsiveness to sunitinib or sorafenib according to CAIX status; the mean shrinkage was -17% vs -25% for sunitinib-treated patients with high vs low tumour CAIX expression, compared to -13% vs +9% for sorafenib-treated patients (P interaction, 0.05). A higher tumour clear-cell component was independently associated with greater tumour shrinkage (P= 0.02), response (P= 0.02) and treatment duration (P= 0.02). CONCLUSIONS: Although CAIX expression had no prognostic value in patients with clear-cell mRCC treated with VEGF-targeted therapy, it might be a predictive biomarker for response to sorafenib treatment. Patients with a higher clear-cell component in their tumours are likely to have a superior clinical benefit from VEGF-targeted therapy.

Targeting angiogenesis in bladder cancer.

In most cases, death from bladder cancer results from metastatic disease. Understanding the closely linked mechanisms of invasion, metastasis, and angiogenesis in bladder cancer has allowed development of new therapeutic strategies that may lead to improvements in patient survival. Vascular endothelial growth factor levels appear to be prognostic for outcomes in advanced bladder cancer, and preclinical evaluation of angiogenesis inhibition demonstrates anticancer activity. Antiangiogenic agents such as sunitinib, sorafenib, and bevacizumab are being tested in advanced bladder cancer. This review highlights the key developments in antiangiogenic therapy as it relates to bladder cancer treatment.