Prospective randomized double-blind multicentre phase II study comparing gemcitabine and cisplatin plus sorafenib chemotherapy with gemcitabine and cisplatin plus placebo in locally advanced and/or metastasized urothelial cancer: SUSE (AUO-AB 31/05).

OBJECTIVE: To evaluate the efficacy and safety of gemcitabine and cisplatin in combination with sorafenib, a tyrosine-kinase inhibitor, compared with chemotherapy alone as first-line treatment in advanced urothelial cancer. PATIENTS AND METHODS: The study was a randomized phase II trial. Its primary aim was to show an improvement in progression-free survival (PFS) of 4.5 months by adding sorafenib to conventional chemotherapy. Secondary objectives were objective response rate (ORR), overall survival (OS) and toxicity. The patients included in the trial had histologically confirmed locally advanced and/or metastatic urothelial cancer of the bladder or upper urinary tract. Chemotherapy with gemcitabine (1250 mg/qm on days 1 and 8) and cisplatin (70 mg/qm on day 1) repeated every 21 days, was administered to all patients in a double-blind randomization of additional sorafenib (400 mg twice daily) vs placebo (two tablets twice daily) on days 3-21. Treatment continued until progression or unacceptable toxicity, the maximum number of cycles was limited to eight. The response assessment was repeated after every two cycles. RESULTS: Between October 2006 and October 2010, 98 of 132 planned patients were recruited. Nine patients were ineligible. The final analysis included 40 patients in the sorafenib and 49 patients in the placebo arm. There were no significant differences between the two arms concerning ORR (sorafenib: complete response [CR] 12.5%, partial response [PR] 40%; placebo: CR 12%, PR 35%), median PFS (sorafenib: 6.3 months, placebo: 6.1 months) or OS (sorafenib: 11.3 months, placebo: 10.6 months). Toxicity was moderately higher in the sorafenib arm. Diarrrhoea occurred significantly more often in the sorafenib arm and hand-foot syndrome occurred only in the sorafenib arm. The study was closed prematurely because of slow recruitment. CONCLUSION: Although the addition of sorafenib to standard chemotherapy showed acceptable toxicity, the trial failed to show a 4.5 months improvement in PFS.

LHRH sparing therapy in patients with chemotherapy-naïve, mCRPC treated with abiraterone acetate plus prednisone: results of the randomized phase II SPARE trial.

BACKGROUND: Although the benefit of androgen deprivation therapy (ADT) continuation in metastatic castration-resistant prostate cancer (mCRPC) remains controversial, clinical evidence is lacking. Recent results indicated that treatment with abiraterone acetate (AA) plus prednisone (P) further suppresses serum testosterone levels over ADT alone, suggesting that continuation of ADT in the treatment of mCRPC may not be necessary. METHODS: In this exploratory phase 2 study, mCRPC patients were randomized with a 1:1 ratio to receive either continued ADT plus AA + P (Arm A) or AA + P alone (Arm B). The primary endpoint was the rate of radiographic progression-free survival (rPFS) at month 12. Secondary endpoints included PSA-response rate, objective response, time to PSA progression and safety. RESULTS: A total of 68 patients were equally randomized between the two study arms. Median testosterone-levels remained below castrate-levels throughout treatment in all patients. According to the intention-to-treat analysis the rPFS rate was 0.84 in Arm A and 0.89 in Arm B. Moderate and severe treatment-emergent adverse events were reported for 72% of the patients in Arm A and for 85% of the patients in Arm B. CONCLUSIONS: AA + P treatment without ADT may be effective in mCRPC patients and ADT may not be necessary in patients receiving AA + P.

[Practice Pattern of Systemic Therapy for Urothelial Cancer in Germany - A Survey of the German Cancer Society]. / Systemische Chemotherapie beim Urothelkarzinom in Deutschland ­ Eine Umfrage der Arbeitsgemeinschaften Urologische Onkologie und Internistische Onkologie der Deutschen Krebsgesellschaft e.V.

BACKGROUND: In 2016, the first German guideline for bladder cancer was introduced. This survey evaluates current management of bladder cancer in Germany, focusing on systemic therapies and compares this to the guidelines. MATERIAL AND METHODS: More than 4000 urologists and oncologists in Germany received a questionnaire assessing surgical and systemic therapeutic management of bladder cancer. We received 278 evaluable responses. RESULTS: This is the largest nationwide survey evaluating current bladder cancer management in Germany. Management can be optimised of non-muscle invasive bladder cancer including intravesical instillation therapies, as well as of muscle invasive bladder cancer including (neo)adjuvant chemotherapies, particularly with respect to the numbers of chemotherapy courses. Management of metastasised bladder cancer is predominantly performed according to the guidelines. CONCLUSIONS: Adherence to bladder cancer guidelines in Germany can be optimised and could possibly decrease cancer-specific mortality, supported by the development of novel diagnostic and therapeutic options.

Abiraterone acetate plus LHRH therapy versus abiraterone acetate while sparing LHRH therapy in patients with progressive, metastatic and chemotherapy-naïve, castration-resistant prostate cancer (SPARE): study protocol for a randomized controlled trial.

BACKGROUND: The value of continuation of luteinizing hormone-releasing hormone (LHRH) therapy in castration-resistant prostate cancer (CRPC) remains controversial and clear evidence is lacking. Argumentation for cessation of LHRH therapy is the prolonged suppression of testosterone levels after the withdrawal of LHRH analogues and the fact that disease progression occurs despite castration levels of testosterone. Especially upon treatment with the life-prolonging cytochrome P450 17-alpha-hydroxylase (Cyp17)-inhibitor, abiraterone, which has the ability to further suppress testosterone serum levels over LHRH therapy alone, continuation of LHRH therapy seems to be negligible. However, the proven increase of luteinizing hormone levels after LHRH withdrawal, which is even further increased by abiraterone, may counteract the effects of abiraterone by the induction of enzymes of steroidogenesis. Therefore, cessation of LHRH therapy when starting treatment with abiraterone in CRPC may display an unpredictable hazard to the patients. This study will explore the role of continuation of LHRH therapy when starting treatment with abiraterone in patients with asymptomatic or mildly symptomatic, chemotherapy-naïve CPRC. METHODS/DESIGN: The trial will assess radiographic progression-free survival after 12 months of treatment with abiraterone/prednisone in patients who will be randomized to receive continuing LHRH therapy versus LHRH withdrawal at the time of starting abiraterone therapy. DISCUSSION: This multicenter, prospective, randomized, exploratory phase-II trial will bring about new data regarding the efficacy and safety of abiraterone/prednisone treatment with or without continuation of LHRH therapy. In addition, further insight into the complex hormonal changes under treatment will be gained and the results of this trial may give rise to a larger phase-III trial to examine the possibility of withdrawing LHRH therapy in patients with CRPC. TRIAL REGISTRATION: ClinicalTrials.gov, ID: NCT02077634 . Registered on 9 December 2013.

The Diagnosis, Treatment, and Follow-up of Renal Cell Carcinoma.

BACKGROUND: In 2014, 15 500 persons in Germany were given the diagnosis of renal cell carcinoma. This disease is the third most common cancer of the urogenital system. The mean age at diagnosis is 68 years in men and 71 in men. METHODS: Pertinent publications up to 2014 were retrieved by a systematic literature search and reviewed in a moderated, formalized consensus process. Key questions were generated and answered by the adaptation of existing international guidelines, on the basis of an independent literature review, and by expert consensus. Representatives of 30 medical specialty societies, patient self-help groups, and other organizations participated in the process. RESULTS: The search for guidelines yielded 80 hits, 23 of which were judged by DELBI to be potentially relevant; 7 were chosen for adaptation. Smoking, obesity, and hypertension increase the risk of renal cell carcinoma. Its 5-year survival rate is 75% for men and 77% for women. Renal cell carcinoma accounts for 2.6% of all deaths from cancer in men and 2.1% in women. Nephrectomy and partial nephrectomy are the standard treatments. Locally confined tumors in clinical stage T1 should be treated with kidney-preserving surgery. Minimally invasive surgery is often possible as long as the surgeon has the requisite experience. For patients with metastases, overall and progression-free survival can be prolonged with VEGF and mTOR inhibitors. The resection or irradiation of metastases can be a useful palliative treatment for patients with brain metastases or osseous metastases that are painful or increase the risk of fracture. CONCLUSION: Minimally invasive surgery and new systemic drugs have expanded the therapeutic options for patients with renal cell carcinoma. The search for new predictive and prognostic markers is now in progress.