[Preoperative chemotherapy for patients with upper tract urothelial carcinoma: Impact on renal function]. / Chimiothérapie préopératoire des tumeurs des voies excrétrices supérieures : impact sur la fonction rénale.

PURPOSE: Upper tract urothelial carcinoma (UTUC) are rare tumors with a poor prognosis. The standard treatment for localized disease is based on total nephroureterectomy (NUT) followed by platinum-based adjuvant chemotherapy for eligible patients at risk of recurrence. However, many patients have renal failure after surgery preventing chemotherapy. Thus, the place of preoperative chemotherapy (POC) is questioned with little information available about renal toxicity and efficacity. METHODS: A single center retrospective study was performed on patients with UTUC who received POC. RESULTS: In all, 24 patients with localized UTUC were treated with POC between 2013 and 2022. Twenty-one (91%) had secondarily NUT. In this cohort, POC did not result in degradation of median renal function (pre-POC median GFR: 70mL/min, post-POC median GFR: 77mL/min, P=0.79), unlike NUT (post-NUT median GFR: 51.5mL/min, P<0.001). In addition, the rate of complete pathological response to pathological examination was 29%. After a median follow-up of 27.4 months, the overall survival rate was 74% and the recurrence-free survival rate was 46%. CONCLUSION: POC for UTUC shows a very reassuring renal toxicity profile and encouraging histological results. These data encourage prospective studies assessing its place for UTUC management.

Perioperative results of radical cystectomy after neoadjuvant chemotherapy according to the implementation of ERAS pathway.

BACKGROUND: The effect of ERAS protocols in a population of radical cystectomy (RC) patients fit for neoadjuvant chemotherapy has not been specifically explored. OBJECTIVE: To compare perioperative outcomes of open RC according to the application of an ERAS protocol in a population of patients treated by cisplatin-based NAC. METHODS: All consecutive patients treated by NAC and RC between 2016 and 2019 were included. The ERAS pathway was implemented in June 2018 and followed the EAU recommendations. All data were prospectively collected. Patients' characteristics, operative outcomes, length of stay (LOS), complication rate according to Clavien-Dindo and pathological results were compared between pre- and post-ERAS. Statistical analysis was performed using R. RESULTS: In total, 79 patients were included, 29 in the ERAS group and 50 in the non-ERAS group. A median number of 19 out of 22 ERAS criteria were followed. Mean number of NAC cycles was 4.45 vs. 4.79 in the pre- and post-ERAS groups respectively (P=0.24). Median time between NAC and RC was 3.8months. Thirty-eight percent vs. 48% of patients received an ileal neobladder in the pre- and post-ERAS group respectively (P=0.51). No differences were observed regarding operative time, blood loss or operative transfusion rates. LOS was drastically reduced in the ERAS period (18.94 vs. 12.10days, P<0.001) as well as major (>Clavien 2) complications rate (65% vs. 28%, P=0.004). CONCLUSION: ERAS drastically reduced the LOS and the rate of high-grade complications and can be effectively applied to patients receiving NAC without delaying RC.

EAU-ESMO consensus statements on the management of advanced and variant bladder cancer-an international collaborative multi-stakeholder effort: under the auspices of the EAU and ESMO Guidelines Committees†.

BACKGROUND: Although guidelines exist for advanced and variant bladder cancer management, evidence is limited/conflicting in some areas and the optimal approach remains controversial. OBJECTIVE: To bring together a large multidisciplinary group of experts to develop consensus statements on controversial topics in bladder cancer management. DESIGN: A steering committee compiled proposed statements regarding advanced and variant bladder cancer management which were assessed by 113 experts in a Delphi survey. Statements not reaching consensus were reviewed; those prioritised were revised by a panel of 45 experts before voting during a consensus conference. SETTING: Online Delphi survey and consensus conference. PARTICIPANTS: The European Association of Urology (EAU), the European Society for Medical Oncology (ESMO), experts in bladder cancer management. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Statements were ranked by experts according to their level of agreement: 1-3 (disagree), 4-6 (equivocal), 7-9 (agree). A priori (level 1) consensus was defined as ≥70% agreement and ≤15% disagreement, or vice versa. In the Delphi survey, a second analysis was restricted to stakeholder group(s) considered to have adequate expertise relating to each statement (to achieve level 2 consensus). RESULTS AND LIMITATIONS: Overall, 116 statements were included in the Delphi survey. Of these, 33 (28%) statements achieved level 1 consensus and 49 (42%) statements achieved level 1 or 2 consensus. At the consensus conference, 22 of 27 (81%) statements achieved consensus. These consensus statements provide further guidance across a broad range of topics, including the management of variant histologies, the role/limitations of prognostic biomarkers in clinical decision making, bladder preservation strategies, modern radiotherapy techniques, the management of oligometastatic disease and the evolving role of checkpoint inhibitor therapy in metastatic disease. CONCLUSIONS: These consensus statements provide further guidance on controversial topics in advanced and variant bladder cancer management until a time where further evidence is available to guide our approach.

Randomized phase III KEYNOTE-045 trial of pembrolizumab versus paclitaxel, docetaxel, or vinflunine in recurrent advanced urothelial cancer: results of >2 years of follow-up.

BACKGROUND: Novel second-line treatments are needed for patients with advanced urothelial cancer (UC). Interim analysis of the phase III KEYNOTE-045 study showed a superior overall survival (OS) benefit of pembrolizumab, a programmed death 1 inhibitor, versus chemotherapy in patients with advanced UC that progressed on platinum-based chemotherapy. Here we report the long-term safety and efficacy outcomes of KEYNOTE-045. PATIENTS AND METHODS: Adult patients with histologically/cytologically confirmed UC whose disease progressed after first-line, platinum-containing chemotherapy were enrolled. Patients were randomly assigned 1 : 1 to receive pembrolizumab [200 mg every 3 weeks (Q3W)] or investigator's choice of paclitaxel (175 mg/m2 Q3W), docetaxel (75 mg/m2 Q3W), or vinflunine (320 mg/m2 Q3W). Primary end points were OS and progression-free survival (PFS) per Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST v1.1) by blinded independent central radiology review (BICR). A key secondary end point was objective response rate per RECIST v1.1 by BICR. RESULTS: A total of 542 patients were enrolled (pembrolizumab, n = 270; chemotherapy, n = 272). Median follow-up as of 26 October 2017 was 27.7 months. Median 1- and 2-year OS rates were higher with pembrolizumab (44.2% and 26.9%, respectively) than chemotherapy (29.8% and 14.3%, respectively). PFS rates did not differ between treatment arms; however, 1- and 2-year PFS rates were higher with pembrolizumab. The objective response rate was also higher with pembrolizumab (21.1% versus 11.0%). Median duration of response to pembrolizumab was not reached (range 1.6+ to 30.0+ months) versus chemotherapy (4.4 months; range 1.4+ to 29.9+ months). Pembrolizumab had lower rates of any grade (62.0% versus 90.6%) and grade ≥3 (16.5% versus 50.2%) treatment-related adverse events than chemotherapy. CONCLUSIONS: Long-term results (>2 years' follow-up) were consistent with those of previously reported analyses, demonstrating continued clinical benefit of pembrolizumab over chemotherapy for efficacy and safety for treatment of locally advanced/metastatic, platinum-refractory UC. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02256436.

[Impact of neoadjuvant chemotherapy on the peri-operative morbidity of radical cystectomy for muscle invasive bladder cancer]. / Impact de la chimiothérapie néoadjuvante sur la morbidité péri-opératoire de la cystectomie pour tumeur de vessie infiltrant le muscle.

INTRODUCTION: Platinum-based neoadjvant chemotherapy (NAC) before radical cystectomy (RC) is the gold standard in the treatment of muscle invasive bladder cancer (MIBC). We aimed to compare the peri-operative morbidity in patients treated by NAC then RC and patients having RC alone. METHODS: Between 1st January 2008 and 31st December 2015, we retrospectively included consecutive patients undergoing RC for MIBC in 2centers. We collected clinical, pathological and peri-operative data (30day post operative complications according to the Clavien-Dindo score, delayed complications, pathological results). Patients treated by NAC (NAC-RC group) before RC were compared to patients performing RC alone. The NAC-RC group received 1 to 6cycle of high-dose MVAC, MVAC or gemcitabine-cisplatine chemotherapy. Logistic regression identified independant factors of peri-operative complications. RESULTS: We included 199 patients: 48in the NAC-RC group and 151in the RC group. Complications rate was 73.9% in the NAC-RC group versus 73.8% in the RC group (P=1.0). In multivariate analyses, only the Charlson score was associated with an increased risk of peri-operative complications (P=0.05). PT0 tumour rate was significantly higher in the NAC-CR group (50% vs 7%, P<0.001). CONCLUSION: NAC does not increase the peri-operative morbidity of the RC. Patients' pre operative comorbidities is the main risk factor for peri-operative complications.

Choosing a career in oncology: results of a nationwide cross-sectional study.

BACKGROUND: Little information is currently available concerning young medical students desire to pursue a career in oncology, or their career expectations. METHODS: This project is a cross-sectional epidemiological study. A voluntary and anonymous questionnaire was distributed to all young oncologists studying in France between the 2nd of October 2013 and the 23rd of February 2014. RESULTS: The overall response rate was 75.6%. A total of 505 young oncologists completed the questionnaire. The main determining factors in the decision to practice oncology were the cross-sectional nature of the field (70.8%), the depth and variety of human relations (56.3%) and the multi-disciplinary field of work (50.2%). Most residents would like to complete a rotation outside of their assigned region (59.2%) or abroad (70.2%) in order to acquire additional expertise (67.7%). In addition, most interns would like to undertake a fellowship involving care, teaching and research in order to hone their skills (85.7%) and forge a career in public hospitals (46.4%). Career prospects mainly involve salaried positions in public hospitals. Many young oncologists are concerned about their professional future, due to the shortage of openings (40.8%), the workload (52.8%) and the lack of work-life balance (33.4%). CONCLUSIONS: This investigation provides a comprehensive profile of the reasons young oncologists chose to pursue a career in oncology, and their career prospects.

Patterns of relapse in poor-prognosis germ-cell tumours in the GETUG 13 trial: Implications for assessment of brain metastases.

BACKGROUND: The GETUG 13 phase III trial tested personalised chemotherapy based on tumour marker decline in patients with poor-prognosis germ-cell tumour (GCT) and demonstrated that a dose-dense regimen improves progression-free survival in patients with an unfavourable decline. We investigated the pattern of relapse for patients included in GETUG 13. METHODS: We conducted an analysis of relapse events in patients from GETUG 13. Baseline procedures before inclusion in the trial comprised a thoraco-abdomino-pelvic computed tomography scan and a magnetic resonance imaging of the brain. RESULTS: With a median follow-up of 4.1 years (0.3; 8.8 years), a progression event was observed in 109/254 patients (43%). First event consisted in a marker progression only in 47 patients (43%), a radiographic progression only in 35 patients (32%), a mix progression on both markers and imaging in 12 patients (11%) and death in 15 patients (14%). In patients with radiographic progression only, brain was the predominant site (n = 19/35, 54%). Among patients with unfavourable decline who experienced a radiographic progression (as first and subsequent progression event, n = 58), brain was a site of progression in 28 patients (48%): 12/30 (40%) in patients treated with cisplatin, bleomycin and etoposide and 16/28 (57%) in those treated with dose-dense chemotherapy. CONCLUSIONS: Brain metastases develop often, early and frequently as the only site of relapse in the course of poor-prognosis GCT. This raises the question of early detection and optimal treatment of brain metastases in these patients, e.g. by integrating a systematic brain MRI after 2-3 months of chemotherapy.

Q-TWiST analysis of patients with metastatic castrate naive prostate cancer treated by androgen deprivation therapy with or without docetaxel in the randomised phase III GETUG-AFU 15 trial.

BACKGROUND: Early chemotherapy has recently become a new standard of care for patients with metastatic castrate-naive prostate cancer (mCNPC). The survival benefit is evident in patients with high-volume disease, but less clear in those with low-volume disease. Here, we assessed the trade-offs between toxicity and survival using a Quality-adjusted Time Without Symptoms of disease and Toxicity of treatment (Q-TWiST) analysis. PATIENTS AND METHODS: This analysis was performed from the data of the Genito-Urinary Oncology Group (GETUG)-AFU 15 phase III trial evaluating the benefits of docetaxel (D) combined with androgen deprivation therapy (ADT) versus ADT alone in 385 mCNPC patients. Overall survival was partitioned into three periods, namely toxic phase of treatment (TOX), time before progression without toxicity (TWIST), and progression (PROG). These health states were weighted according to patients' utility to determine quality-adjusted survival times. In threshold analyses, utility for TOX and PROG were varied from 0 to 1. RESULTS: A better quality-adjusted survival was found in the ADT + D arm when the utility for PROG and TOX states were ≤0.2 and ≥ 0.8, respectively. When the utility for PROG was 0.4 or more, ADT + D and ADT alone yielded similar quality-adjusted survival. When patients were stratified into high-volume versus low-volume disease, we found a significant Q-TWiST benefit in favour of the ADT + D arm only for high-volume patients when the utility for PROG was less than 0.35, while we found no benefit in low-volume disease patients, whatever the coefficients tested. CONCLUSION: Early docetaxel may provide significant quality-adjusted survival benefits for patients with mCNPC, especially those with high-volume disease, depending on the values assigned to the times spent in the toxicity phase and after PROG. The Q-TWiST methodology is a useful tool for decision-making regarding trade-offs between survival, PROG and toxicity.

Metastatic Renal Cell Carcinoma in a Renal Allograft: A Sustained Complete Remission After Stimulated Rejection.

We report the case of a 40-year-old woman who recovered from a diffuse metastatic renal cell carcinoma that developed from a kidney allograft. She was successfully treated by the induction of tumor rejection. Immunosuppression was discontinued, and transplant nephrectomy was deliberately delayed based on the expectation that the tumor mass would trigger the alloimmune response, which was stimulated with pegylated interferon-α-2a. Three years later, the patient remained in complete remission. Despite this severe context, the present case shows that the poor prognosis of allograft metastatic renal cell carcinoma could be dramatically reversed by taking advantage of the donor tumor origin to actively induce a specific alloimmune rejection of the tumor.

Tumor heterogeneity of fibroblast growth factor receptor 3 (FGFR3) mutations in invasive bladder cancer: implications for perioperative anti-FGFR3 treatment.

BACKGROUND: Fibroblast growth factor receptor 3 (FGFR3) is an actionable target in bladder cancer. Preclinical studies show that anti-FGFR3 treatment slows down tumor growth, suggesting that this tyrosine kinase receptor is a candidate for personalized bladder cancer treatment, particularly in patients with mutated FGFR3. We addressed tumor heterogeneity in a large multicenter, multi-laboratory study, as this may have significant impact on therapeutic response. PATIENTS AND METHODS: We evaluated possible FGFR3 heterogeneity by the PCR-SNaPshot method in the superficial and deep compartments of tumors obtained by transurethral resection (TUR, n = 61) and in radical cystectomy (RC, n = 614) specimens and corresponding cancer-positive lymph nodes (LN+, n = 201). RESULTS: We found FGFR3 mutations in 13/34 (38%) T1 and 8/27 (30%) ≥T2-TUR samples, with 100% concordance between superficial and deeper parts in T1-TUR samples. Of eight FGFR3 mutant ≥T2-TUR samples, only 4 (50%) displayed the mutation in the deeper part. We found 67/614 (11%) FGFR3 mutations in RC specimens. FGFR3 mutation was associated with pN0 (P < 0.001) at RC. In 10/201 (5%) LN+, an FGFR3 mutation was found, all concordant with the corresponding RC specimen. In the remaining 191 cases, RC and LN+ were both wild type. CONCLUSIONS: FGFR3 mutation status seems promising to guide decision-making on adjuvant anti-FGFR3 therapy as it appeared homogeneous in RC and LN+. Based on the results of TUR, the deep part of the tumor needs to be assessed if neoadjuvant anti-FGFR3 treatment is considered. We conclude that studies on the heterogeneity of actionable molecular targets should precede clinical trials with these drugs in the perioperative setting.

[Castration modalities in prostate cancer: Are they all equal?]. / Modalités de castration dans la prise en charge du cancer de la prostate: sont-elles toutes équivalentes ?

AIM: The aim of this literature review was to focus on the new highlights regarding oncologic and safety outcomes depending on the type of castration used. MATERIAL: Literature search using various algorithms "prostate cancer", "castration", "agonist", "antagonist", "orchiectomy", "GnRH", "FSH", "androgen deprivation therapy" has been performed in April 2015, through the PubMed and Embase databases. RESULTS: GnRH agonists and antagonists are both currently used in clinical practice. Nevertheless, differences regarding their pharmacologic properties have been highlighted in recent studies, specifically regarding the rapidity, sustainability and depth of the castration, but also the decrease in FSH level. Such differences may have oncological impact on the patient, regarding the disease biological control and the time to progression, and a tolerability impact, especially on the cardiovascular risks. The role of the depth and the sustainability of the castration in one hand, the FSH impact in the other hand, as well as a direct inhibition on extra-pituitary GnRH receptors by antagonist might explain these differences. CONCLUSIONS: Recent studies suggest differences between GnRH agonists and antagonist that could impact the patient clinical outcomes. However, further high level of evidence comparative studies remains warranted.

Vinflunine-gemcitabine versus vinflunine-carboplatin as first-line chemotherapy in cisplatin-unfit patients with advanced urothelial carcinoma: results of an international randomized phase II trial (JASINT1).

BACKGROUND: There is no standard first-line chemotherapy for advanced urothelial carcinoma (aUC) in cisplatin-ineligible (cisplatin-unfit) patients. The study assessed the efficacy and tolerability profile of two vinflunine-based cytotoxic regimens in this setting. PATIENTS AND METHODS: Patients with aUC a creatinine clearance (CrCl) of <60 but ≥30 ml/min, performance status 0 or 1 and no prior chemotherapy for advanced disease were randomized (1 : 1). They received vinflunine 250 or 280 mg/m(2) (based on baseline CrCl) on day 1, plus either gemcitabine [750 mg/m(2) escalated to 1000 mg/m(2) in cycle 2 if no toxicity grade (G) ≥2 on days 1 and 8 (VG) or plus carboplatin area under the curve 4.5 day 1 (VC) every 21 days]. To detect a 22% improvement in each arm compared with H0 (41%) in the primary end point, disease control rate (DCR = complete response + partial response + stable disease), 31 assessable patients per arm were required (α = 5%, ß = 20%). RESULTS: Sixty-nine patients were enrolled (34 VG, 35 VC). Less G3/4 haematological adverse events (AEs) were reported with VG: neutropaenia was seen in 38% (versus 68% with VC) and febrile neutropaenia in 3% (versus 14% with VC) of patients. No major differences were observed for non-haematological AEs. DCR was 77% in both groups; overall response rate (ORR) was 44.1% versus 28.6%, with a median progression-free survival of 5.9 versus 6.1 months and median OS of 14.0 versus 12.8 months with VG and VC, respectively. CONCLUSION: Both vinflunine-based doublets offer a similar DCR, ORR and OS. The better haematological tolerance favours the VG combination, which warrants further study. CLINICALTRIALS.GOV PROTOCOL IDENTIFIER: NCT 01599013.

[Neoadjuvant chemotherapy in muscular invasive bladder cancer: Complications and consequences with cystectomy]. / Chimiothérapie néoadjuvante dans le cancer de vessie infiltrant le muscle : complications et conséquences sur la réalisation de la cystectomie.

INTRODUCTION: The fear of the deterioration of the patient's condition related to the toxicity of neoadjuvant chemotherapy is a barrier to its development. This multicenter retrospective study aims to present the secondary effects of neoadjuvant chemotherapy and its impact on the achievement of cystectomy. MATERIALS AND METHODS: Patients with urothelial carcinoma classified cT2 to cT4a N0M0 were included. Chemotherapy with 6 cycles of MVAC (methotrexate, vinblastine, adriamycin, and cisplatin) followed by a cysto-prostatectomy or anterior pelvectomy was scheduled. RESULTS: A total 32 patients were included. Six cycles of neoadjuvant chemotherapy were performed in all 11 patients. Shutdown causes were toxicity in 85% of cases. Cystectomy was performed in 86.6% of patients. Surgery was not performed in 6 patients. The reasons were the alteration of the general condition in 2 cases, 2 patients had advanced cancers diagnosed intraoperatively, and 2 refused surgery. Complications of grades 3 and 4 according to the classification of Clavien and Dindo had occurred respectively in 15.3% and 11.5%. DISCUSSION: This study reports results close to what is found in the literature on the effects of neoadjuvant chemotherapy on achieving cystectomy, but it has some limitations: the retrospective analysis of data on surgery and the lack of control group. In addition, the short follow-up does not yet allow to know the long-term oncological results. CONCLUSION: This study supports the fact that the toxicity of neoadjuvant chemotherapy does not seem to cause a significant risk of non-completion of cystectomy. LEVEL OF EVIDENCE: 4.

First-line treatment with sunitinib for type 1 and type 2 locally advanced or metastatic papillary renal cell carcinoma: a phase II study (SUPAP) by the French Genitourinary Group (GETUG)†.

BACKGROUND: Papillary renal cell carcinoma (PRCC), type 1 and type 2, represents 10%-15% of renal cell carcinomas (RCC). There is no standard first-line treatment of metastatic PRCC (mPRCC). Anti-angiogenics have shown activity in retrospective studies but no prospective studies in pure papillary histology have been reported, but one with foretinib. PATIENTS AND METHODS: A prospective phase II study evaluated sunitinib in first-line treatment of mPRCC. The primary end point was overall response rate (ORR). Secondary end points were progression-free survival (PFS) and overall survival (OS). RESULTS: Fifteen and 46 patients, respectively, with type 1 and type 2 mPRCC were enrolled. Using the MSKCC scoring system: 12 (20%), 33 (55%) and 9 (15%) patients were, respectively, in the favourable, intermediate or poor risk group and 7 undetermined. Median follow-up is 51.4 months. In type 1, 2 patients 13% [95% confidence interval (CI) 0.1-30.5] had a partial response (PR), 10 had stable disease (SD) with 5 (33%) ≥12 weeks. In type 2, 5 patients 11% (95% CI 1.9-20.3) had a PR, 25 had SD with 10(22%) ≥12 weeks. Median PFS was 6.6 months (95% CI 2.8-14.8) in type 1 and 5.5 months (95% CI 3.8-7.1) in type 2. Median OS was 17.8 (95% CI 5.7-26.1) and 12.4 (95% CI 8.2-14.3) months, respectively, in type 1 and 2. Safety was as expected with sunitinib for metastatic RCC. CONCLUSION: Sunitinib showed activity in treatment of type 1 and 2 mPRCC but lower than in clear-cell mRCC. Both PFS and OS are longer in type I PRCC. Sunitinib represents an acceptable option in first-line treatment of mPRCC.

Combining gemcitabine, cisplatin, and ifosfamide (GIP) is active in patients with relapsed metastatic germ-cell tumors (GCT): a prospective multicenter GETUG phase II trial.

BACKGROUND: The standard treatment of patients with metastatic germ-cell tumor (GCT) relapsing after first-line chemotherapy is based on a cisplatin and ifosfamide-containing three-drug regimen, which usually yields a complete response (CR) rate <50%. As gemcitabine consistently displayed activity in patients with advanced GCT and as synergy with cisplatin was reported, we integrated this drug into the salvage triplet regimen and assessed its activity in this phase II study. PATIENTS AND METHODS: The GIP regimen consisted in gemcitabine 1000 mg/m(2) day 1 and 5, ifosfamide 1200 mg/m(2)/day day 1-5, cisplatin 20 mg/m(2)/day day 1-5, and granulocyte colony-stimulating factor 263 µg/day day 7-15, repeated every 3 weeks for four cycles. Eligibility criteria were that patients had favorable prognostic factors to conventional-dose salvage chemotherapy including a testis primary tumor and a previous CR to first-line chemotherapy for metastatic disease. The primary end point was the CR rate and a two-stage Simon design was used. RESULTS: Thirty-seven patients were accrued and 29 (78%) achieved a favorable response, including a CR in 20 (54%) and a partial response with normalization of tumor markers (PRm-) in 9 (24%). With a median follow-up of 53 months (13-81), the 2-year overall survival rate is 73% (57%-84%) and the continuous progression-free survival rate is 51% (35%-66%). Myelosuppression was the main toxicity including febrile neutropenia in 8 (22%) patients and 18 (50%) cases required platelet infusion. No grade 3 and 4 peripheral neurotoxicity or renal toxicity occurred. Two patients died of treatment-related toxicity, one of them with cancer progression. CONCLUSION: In a multicenter context, four cycles of the GIP regimen achieved a high CR rate in patients with relapsed testicular GCT. The GIP regimen avoided severe neurotoxicity and yielded a high survival rate. CLINICAL TRIAL NUMBER: NCT00127049.

Home parenteral nutrition improves quality of life and nutritional status in patients with cancer: a French observational multicentre study.

PURPOSE: Malnutrition is a predictor of poor outcomes in patients with cancer. Little is known about the benefit of nutritional support in these patients. The purpose of this study was to assess the impact of home parenteral nutrition (HPN) on quality of life (Qol) in cancer patients. METHODS: We performed an observational prospective study to determine the impact of HPN on Qol in a population of patients with heterogeneous cancer. Physicians, patients and family members had to complete a questionnaire before HPN administration and 28 days after the course of HPN. Qol was evaluated using the self-administered questionnaire FACT-G. RESULTS: We included 767 patients with cancer of whom 437 ended the study. Mean patient age was 63±11.4 years and 60.5% were men. Primary gastrointestinal cancer was reported in 50% of patients and 65.3% were presenting metastases. Malnutrition was reported in 98.3%. After 28 days of HPN intake, significant improvement was observed in the Qol (49.95±5.82 vs. 48.35±5.01 at baseline, p<0.0001). The mean weight, serum albumin and the nutrition risk index had also improved significantly. Most patients (78%) had perceived a positive impact of the HPN. A significant improvement in patient's well-being was perceived also by family members and physicians. CONCLUSIONS: Our data suggest that preventing and correcting malnutrition using HPN in patients with cancer might have a significant benefit on their well-being. Randomized controlled studies are required to confirm this finding.

Long-term survival results of a randomized phase III trial of vinflunine plus best supportive care versus best supportive care alone in advanced urothelial carcinoma patients after failure of platinum-based chemotherapy.

BACKGROUND: To compare long-term, updated overall survival (OS) of patients with advanced transitional cell carcinoma of the urothelium (TCCU) treated with vinflunine plus best supportive care (BSC) or BSC alone, after failure of platinum-based chemotherapy. PATIENTS AND METHODS: Three hundred and seventy patients were randomly assigned in a phase III trial and allocated (2:1) to vinflunine (320 or 280 mg/m(2)) plus BSC or BSC alone. The first report (Bellmunt J, Theodore C, Demkov T et al. Phase III trial of vinflunine plus best supportive care compared with best supportive care alone after a platinumcontaining regimen in patients with advanced transitional cell carcinoma of the urothelial tract. J Clin Oncol 2009; 27(27): 4454-4461) had a median follow-up of 22.1 m and the current report has a follow-up of 45.4 m. RESULTS: Three hundred and fifty-two patients had died (censoring rate 5%). In the intention-to-treat (ITT) population, the median OS was 6.9 m and 4.6 m for vinflunine plus BSC versus BSC alone, respectively (n.s.). In multivariate Cox analysis, the addition of vinflunine was independently correlated with improved survival (HR: 0.719; 95% CI:0.570-0.906, P = 0.0052). In the eligible population, the median OS in both the arms was 6.9 and 4.3 m, respectively (HR: 0.78; 95% CI:0.61-0.96; P = 0.0227), indicating an estimated 22% reduction in the risk of death. CONCLUSIONS: The updated OS data confirm the positive treatment effect of vinflunine on survival that was previously reported. These results are consistent over time and confirm that vinflunine is a valuable option for second-line treatment in patients with advanced TCCU after failure of platinum-based regimens.

[Novel agents for the therapy of castration-resistant prostate cancer: overview of pivotal studies and new strategies to come]. / Nouvelles thérapeutiques dans le cancer de la prostate résistant à la castration : panorama des études pivotales et nouveaux schémas thérapeutiques à venir.

OBJECTIVE: Recently, new agents have been developed in the treatment of prostate cancer. Our aim was to review phase III studies that involved novel agents in the treatment of castration resistant prostate cancer. METHODS: PubMed databases were searched for original articles published with the search terms: prostate cancer, castration resistant, metastatic, targeted therapy, biologic agents, immunotherapy and clinical trials. Proceedings from 2008 of conferences of the American Society of Clinical Oncology, American Urological Association, and the European Association of Urology were also searched. We included phase III studies that involved: abiraterone, MDV 3100, cabazitaxel, sipuleucel-T, radium-223, and denosumab. RESULTS: Abiraterone and MDV 3100 are two new hormotherapies that showed an increased overall survival of 15 and 18 months respectively before after docetaxel based chemotherapy in randomized trials. Cabazitaxel became the standard second line chemotherapy after docetaxel. Sipuleucel-T has emerged as the first approved vaccine in prostate cancer. It showed a 22 % reduction of mortality and a prolonged survival time of 4.1 months compared to placebo. A radium-223 based metabolic radiotherapy has showed a better overall survival, delayed and reduced skeletal-related events in placebo controlled randomized trials. Denosumab also delayed the first skeletal-related event in a zoledronic acid controlled trial (20.7 versus 17.1 months, P=0.0002). Moreover, Denosumab delays bone metastases by 4.1 months compared to placebo. CONCLUSION: The novel agents that emerged in the treatment of prostate cancer showed an efficacy in placebo controlled trials. They added new tools in the armamentarium of therapies of castration resistant prostate cancer.