Chemotherapy for Muscle-invasive Bladder Cancer: Impact of Cisplatin Delivery on Renal Function and Local Control Rate in the Randomized Phase III VESPER (GETUG-AFU V05) Trial.

BACKGROUND: Cisplatin-based combination chemotherapy before surgery is the standard of care for muscle-invasive bladder cancer. However, the optimal chemotherapy modalities have not been precisely defined to date. PATIENTS AND METHODS: In the VESPER trial, patients received after randomization either gemcitabine and cisplatin (GC, 4 cycles) or methotrexate, vinblastine, doxorubicin and cisplatin (dose dense [dd]-MVAC, 6 cycles). Creatinine clearance (CrCl) was calculated before each cycle according to the Cockroft and Gault formula. Definition criteria for local control after neoadjuvant chemotherapy included pathological complete response (ypT0N0), pathological downstaging (

Evaluation of Nurses' and Patients' Overall Satisfaction with New and Previous Formulations of Octreotide Long-acting Release (Sandostatin LAR®): A French Observational Study.

INTRODUCTION: The first long-acting release (LAR) formulation of octreotide was marketed in France in the late 1990s. An injectable formulation of Sandostatin LAR® (Novartis SAS) with a new diluent has been developed to facilitate its preparation and administration and to improve its use in practice. METHODS: We conducted an observational, cross-sectional and multicenter study in France whose main outcome was to compare nurses' satisfaction with the preparation and administration of both previous and new formulations of octreotide LAR. Secondary outcomes included assessment of patient satisfaction (quality of life and pain felt during the injection) and product tolerance. Data were collected at two time points (one for the first formulation group and one for the second formulation group) through paper questionnaires administered to physicians, patients and nurses including a visual analog scale (VAS) from 0 (unsatisfied) to 10 (very satisfied). RESULTS: Results showed that overall nurse satisfaction improved from 5.3 (95% CI 4.9-5.8) with the previous formulation to 7.5 (95% CI 7-7.9) with the new formulation (p < 0.0001). Regarding secondary outcomes, the simplicity of the injection increased (84% for the previous formulation and 94% for the new formulation) and the purge problem disappeared (36% for the previous formulation and 4% for the new formulation). CONCLUSION: The improvement due to the new formulation of Sandostatin LAR® was reported in terms of handling, ease of use and overall nurse satisfaction. The new formulation greatly reduced treatment administration problems associated with the previous formulation, while maintaining low injection site pain and an equivalent safety profile in both indications.

Targeted and immune therapies among patients with metastatic renal carcinoma undergoing hemodialysis: A systemic review.

BACKGROUND: Patients with severe renal impairment or undergoing hemodialysis are usually excluded from clinical trials. Available data regarding safety and activity of systemic therapies (ST) in hemodialyzed patients are scarce. METHODS: Clinical data were searched through PubMed database until April 2020 according to PRISMA criteria. Efficacy, safety and pharmacokinetic (PK) assessment of ST were reported. RESULTS: Among 270 references, 56 reports were evaluated in full text: 41 were included for efficacy and 42 for safety analysis (sunitinib n = 68, bevacizumab n = 6, everolimus n = 28, temsirolimus n = 17, sorafenib n = 55, axitinib n = 13, pazopanib n = 13, nivolumab n = 18, cabozantinib n = 0, lenvatinib n = 0, and ipilimumab n = 0). Twelve of the reports included PK assessment among dialyzed patients. Hemodialysis did not seem to modify the expected efficacy and safety of each compound among patients undergoing hemodialysis. PK assessments were not modified in comparison with a population not undergoing dialysis. CONCLUSION: Targeted and Immune therapies seem to be effective and can be used among patients undergoing hemodialysis. Due to frailty and comorbidities associated to chronic hemodialysis enhanced vigilance for these therapies within this specific population is recommended. Dedicated prospective clinical trials would definitely help to obtain data with a higher level of evidence.

Factors Influencing Overall Survival for Patients With Metastatic Clear-Cell Renal-Cell Carcinoma in Daily Practice.

PURPOSE: To describe factors associated with overall survival (OS) among patients with metastatic clear-cell renal-cell carcinoma (mccRCC) in regard to evolution of systemic therapies. PATIENTS AND METHODS: Two hundred twenty-four consecutive patients with histologically confirmed mccRCC who received targeted therapy on first-line treatment between January 2007 and March 2015 were included. The primary end point was OS for metastatic first-line or second-line treatment. An analysis of prognostic factors of long survival was performed using a 2-step approach: univariate, then multivariate analysis. RESULTS: Median OS [95% confidence interval] was 19.4 months [16.1-24.9]. Three prognostic factors were identified in first-line treatment: Memorial Sloan Kettering Cancer Center (MSKCC) favorable and intermediate risks (hazard ratio [95% confidence interval] = 0.362 [0.207-0.630] and 0.561 [0.393-0.801], respectively, P = 4.10-4), metastasectomy (0.667 [0.468-0.951], P = .03), and lack of lymph node metastasis (0.715 [0.513-0.994], P = .049). In second-line treatment, median OS [95% confidence interval] was 11.0 months [8.9-14.4] for 167 patients. Three different prognostic factors predicted long survival: toxicity for first-line treatment discontinuation (HR [95% confidence interval] = 0.298 [0.180-0.493], P < 10-4), duration of disease control in first-line therapy (0.961 [0.942-0.979], P = 2.10-4), and MSKCC favorable and intermediate risks (0.461 [0.252-0.843] and 0.936 [0.607-1.443], respectively, P = .02). CONCLUSION: These real-life data confirm the positive impact of targeted therapy in the mccRCC setting. Moreover, it emphasizes the importance of considering many factors in order to better estimate prognosis in patient pretreated with systemic therapy.

Open-label, randomized multicentre phase II study to assess the efficacy and tolerability of sunitinib by dose administration regimen (dose modification or dose interruptions) in patients with advanced or metastatic renal cell carcinoma: study protocol of the SURF trial.

BACKGROUND: Sunitinib is a tyrosine kinase inhibitor approved in the first-line metastatic renal cell carcinoma (MRCC) setting at the dose of 50 mg daily for 4 weeks followed by a pause of 2 weeks. Due to toxicity, this standard schedule (50 mg daily 4/2) can induce up to 50% of sunitinib dose modification (reduction and/or interruption). The current recommendation in such case is to reduce the dose to 37.5 mg per day (standard schedule 4/2). Recent data highlight an alternative schedule: 2 weeks of treatment followed by 1 week of pause (experimental schedule 2/1). The SURF trial is set up to evaluate prospectively experimental schedule 2/1 when toxicity occurs. This article displays the key elements of the study protocol. METHODS/DESIGN: SURF [NCT02689167] is a prospective, randomized, open-label phase IIb study. Patients are included at sunitinib initiation while receiving standard schedule 4/2 (50 mg daily) according to the marketing authorization indication. When a dose adjustment of sunitinib is required, patients are randomized between standard schedule 4/2 (37.5 mg daily) and experimental schedule 2/1 (50 mg daily). Key eligibility criteria are the following: patients with locally advanced inoperable or MRCC who are starting first-line treatment with sunitinib, with histologically or cytologically confirmed renal cancer clear cell variant or with a clear cell component, and with Karnofsky performance status ≥70%. The primary objective is to assess the median duration of sunitinib treatment (DOT) in each group. The key secondary objectives are progression-free survival, overall survival, time to randomization, objective response rate, safety, sunitinib dose intensity, health-related quality of life, and the description of main drivers triggering randomization. We hypothesized that experimental schedule 2/1 would result in an improvement in median DOT from 6 to 8.5 months. It was estimated that 112 patients would be needed in each arm during 24 months. In order to take into account the possibility of treatment discontinuation before randomization, 248 patients are necessary. DISCUSSION: The SURF trial is asking a pragmatic question adapted to the current practice on what is the best way to adapt sunitinib when treatment-related adverse events occur. The results of the SURF trial will bring high-value data to support the use of an alternative schedule in sunitinib treatment. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02689167 . Registered on 26 February 2016.

Efficacy and Safety of Sequential Use of Everolimus in Patients With Metastatic Renal Cell Carcinoma Previously Treated With Bevacizumab With or Without Interferon Therapy: Results From the European AVATOR Study.

BACKGROUND: Everolimus is a mammalian target of rapamycin (mTOR) inhibitor. It gained approval based on the results of the RECORD-1 (Regulation of Coagulation in Orthopedic Surgery to Prevent Deep Venous Thrombosis and Pulmonary Embolism 1) trial, which included patients with metastatic renal cell carcinoma (mRCC) whose disease progressed after receiving vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitors (TKIs). Bevacizumab is a monoclonal antibody targeting angiogenesis that is approved in patients with mRCC. The sequence of everolimus second-line therapy after failure of bevacizumab ± interferon (IFN) first-line therapy has not yet been studied. METHODS: AVAstin(®) followed by afiniTOR(®) (AVATOR) was a noninterventional retrospective multicenter European observational study of 42 unselected patients with mRCC who were previously or currently treated with everolimus after failure of bevacizumab ± IFN. The primary end point was everolimus progression-free survival (PFS). Secondary end points were related to the overall survival (OS) of patients receiving the drug sequence and everolimus treatment and safety. RESULTS: Exploring the duration of second-line everolimus treatment, 63.8% of patients received at least 3 months of everolimus and 28.8% received at least 8 months of treatment. At the time of data analysis, 15 patients (36%) were still receiving everolimus, 40% had stopped because of progressive disease, and 24% had discontinued treatment for other reasons. Patients receiving everolimus after bevacizumab experienced a median PFS of 17 months (95% confidence interval [CI], 5 [not reached]). Median OS was not reached with everolimus second-line therapy. At 32 months after the start of first-line therapy, 53.3% of patients were still alive. All grades of common adverse events (AEs) were consistent with the known safety profile of everolimus. CONCLUSION: The AVATOR-studied sequence displayed a longer than expected median PFS. Further prospective exploratory studies need to be performed to confirm these encouraging results in a larger cohort of patients.

Clinical impact of targeted therapies in patients with metastatic clear-cell renal cell carcinoma.

INTRODUCTION: The aim of this retrospective clinical study was to assess, in the context of the recent evolution of systemic therapies, the potential effect of targeted therapies on overall survival (OS) of patients with metastatic clear-cell renal cell carcinoma (mccRCC) in daily practice. PATIENTS AND METHODS: All consecutive patients with histologically confirmed mccRCC who received systemic therapy between January 2000 and December 2010 in two oncology treatment centers in our Franche-Comté region in eastern France were included in the analysis. The primary end point was OS. The analysis of prognostic factors was performed using a two-step approach: univariate then multivariate analysis with a stepwise Cox proportional hazards regression model. RESULTS: For the entire cohort of 111 patients, the median OS was 17 months (95% confidence interval [CI]; 13-22 months) and the two-year OS was 39%. Three prognostic factors were independent predictors of long survival: prior nephrectomy (hazard ratio =0.38 [0.22-0.64], P<0.0001); systemic therapy by targeted therapy (hazard ratio =0.50 [0.31-0.80], P=0.005); and lack of liver metastasis (hazard ratio =0.43 [0.22-0.82], P=0.002). Median OS was 21 months [14-29 months] for patients who received at least one targeted therapy compared with 12 months [7-15 months] for patients who were treated only by immunotherapy agents (P=0.003). CONCLUSION: Our results suggest that targeted therapies are associated with improved OS in comparison with cytokines, which is in line with other publications.