Sisto Perdonà

Combination of Bevacizumab and Docetaxel in Docetaxel-Pretreated Hormone-Refractory Prostate Cancer: A Phase 2 Study

OBJECTIVE Although the taxanes represent the most active agents for the first-line treatment of metastatic hormone-refractory prostate cancer (HRPC), most patients eventually progress while receiving taxane-based treatments. No agents are approved for second-line therapy in HRPC, but common standard practice for the oncologists is to treat patients also after docetaxel failure. METHODS Twenty highly pretreated patients with HRPC received bevacizumab (10mg/kg) and docetaxel (60mg/m(2)) every 3 wk. All patients had bone metastases and eight had measurable lesions. RESULTS Eleven patients (55%) had major prostate-specific antigen (PSA) responses, and 3 (37.5%) had objective responses. Seven major PSA responses were recorded in the same patients who had reported a >50% PSA decrease after first-line docetaxel. However, four major PSA responses were observed in patients previously nonresponsive to docetaxel alone. The treatment was well tolerated. CONCLUSIONS Our results show that the combination of bevacizumab and docetaxel is active and well tolerated. Continued investigation of bevacizumab with cytotoxic chemotherapy is warranted in HRPC.

Phase II Study of Sorafenib in Patients With Sunitinib-Refractory Metastatic Renal Cell Cancer

PURPOSE No previous prospective trials have been reported with sorafenib in patients with sunitinib-refractory metastatic renal cell cancer (MRCC). We conducted a multicenter study to determine the activity and tolerability of sorafenib as second-line therapy after sunitinib progression in MRCC. PATIENTS AND METHODS Between January 2006 and September 2008, 52 patients were enrolled onto this single-arm phase II study. All patients received sorafenib 400 mg orally twice a day until disease progression or intolerable toxicity. The primary end point was objective response rate (complete or partial response) evaluated every 8 weeks by use of the Response Evaluation Criteria in Solid Tumors; secondary end points were toxicity, time to progression (TTP), and overall survival (OS). RESULTS All patients were included in response and safety analyses. Partial responses were observed in 9.6% of patients (five of 52 patients; 95% CI, 5% to 17%) after two cycles. Grade 1 to 2 fatigue, diarrhea, nausea/vomiting, rash, and neutropenia were the most common side effects, noted in 16 (30.8%), 19 (36.5%), 20 (38.5%), 19 (36.5%), and 20 patients (38.5%), respectively. The most common grade 3 toxicity was diarrhea, noted in six patients (11.5%). Median TTP was 16 weeks (range, 8 to 40 weeks), and median OS was 32 weeks (range, 16 to 64 weeks). CONCLUSION Although well tolerated, sorafenib shows limited efficacy in sunitinib-refractory MRCC. Further randomized trials comparing sorafenib with other drugs that target different biologic pathways are needed to define the best second-line treatment option in these patients.

Four-Year Outcome of a Prospective Randomised Trial Comparing Bipolar Plasmakinetic and Monopolar Transurethral Resection of the Prostate

BACKGROUND No data have been published on the midterm efficacy of bipolar transurethral resection of the prostate (TURP). OBJECTIVE To evaluate 4-yr results from a prospective randomised trial comparing bipolar TURP with standard monopolar TURP. DESIGN, SETTING, AND PARTICIPANTS Seventy patients with symptomatic benign prostatic hyperplasia were enrolled in this prospective randomised controlled trial in a tertiary-care institution. Inclusion criteria were age > 50 yr, good performance status, urinary retention, International Prostate Symptom Score (IPSS) > or = 18, and maximal flow rate (Q(max)) < or = 15 ml/s. Exclusion criteria were prostate volume < 30 cm(3), documented or suspected prostate cancer, neurogenic bladder, bladder stone or diverticula, urethral stricture, and maximal bladder capacity > 500 ml. INTERVENTION Patients underwent standard or bipolar plasmakinetic TURP performed by the same surgeon using the same surgical technique. MEASUREMENTS Treatment efficacy was evaluated at 1, 2, 3, and 4 yr by comparing urinary flow rates, IPSS, and estimated postvoid residual (PVR) urine volume. Midterm complications were also recorded. RESULTS AND LIMITATIONS The number of dropouts was not statistically significantly different in the two groups (p=0.2). The significant improvements in both groups were maintained at 4 yr for the IPSS, quality of life score, Q(max), and PVR versus baseline values. The main outcome variables at 4 yr for bipolar and monopolar TURP were mean IPSS 6.9 and 6.4 (p=0.58); mean Q(max) 19.8 ml/s and 21.2 ml/s (p=0.44), and mean PVR volume 42 ml and 45 ml (p=0.3). Overall, 2 of 32 (6.2%) and 3 of 31 (9.6%) patients required reoperation because of late complications (p=0.15). The major study limitation was the small sample size. CONCLUSIONS This study represents the secondary, midterm analysis of a previously published trial. Our 4-yr data confirm our initial positive findings for the efficacy and safety of bipolar plasmakinetic TURP. Larger well-designed studies are needed to corroborate these findings.

Gemcitabine versus bacille Calmette-Guérin after initial bacille Calmette-Guérin failure in non-muscle-invasive bladder cancer: a multicenter prospective randomized trial.

The efficacy of intravesical gemcitabine was evaluated compared with repeated administration of bacille Calmette‐Guérin (BCG) after BCG failure in high‐risk, non‐muscle‐invasive bladder cancer (BC).

Efficacy of tamoxifen and radiotherapy for prevention and treatment of gynaecomastia and breast pain caused by bicalutamide in prostate cancer: a randomised controlled trial

BACKGROUND Gynaecomastia and breast pain are frequent adverse events with bicalutamide monotherapy, and might cause some patients to withdraw from treatment. We aimed to compare tamoxifen with radiotherapy for prevention and treatment of gynaecomastia, breast pain, or both during bicalutamide monotherapy for prostate cancer. METHODS 51 patients were randomly assigned to 150 mg bicalutamide per day, 50 patients to 150 mg bicalutamide per day and to 10 mg tamoxifen per day for 24 weeks, and 50 patients to 150 mg bicalutamide per day and radiotherapy (one 12-Gy fraction on the day of starting bicalutamide). 35 of the 51 patients allocated bicalutamide alone developed gynaecomastia or breast pain and were subsequently randomly allocated to tamoxifen (n=17) or radiotherapy (n=18) soon after symptoms started (median 180 days, range 160-195). Gynaecomastia and breast pain were assessed once a month. Severity of gynaecomastia was scored on the basis of the largest diameter. Breast pain was scored as none, mild, moderate, or severe. The primary outcome was frequency of gynaecomastia or breast pain; secondary outcomes were safety and tolerability, relapse-free survival, as assessed by concentration of prostate specific antigen, and quality of life. Analyses were by intention to treat. RESULTS 35 of 51 patients assigned bicalutamide alone developed gynaecomastia, compared with four of 50 assigned bicalutamide and tamoxifen (odds ratio [OR] 0.1 [95% CI 0.08-0.12], p=0.0009), and with 17 of 50 assigned bicalutamide and radiotherapy (0.51 [0.47-0.54], p=0.008). Breast pain was seen in 29 of 51 patients allocated bicalutamide alone, compared with three allocated bicalutamide and tamoxifen (0.1 [0.07-0.11], p=0.009), and with 15 allocated bicalutamide and radiotherapy (0.43 [0.40-0.45], p=0.02) In 35 patients assigned bicalutamide alone who subsequently developed gynaecomastia, breast pain, or both, tamoxifen significantly reduced the frequency of gynaecomastia (0.2 [0.18-0.22], p=0.02). INTERPRETATION Antioestrogen treatment with tamoxifen could help patients with prostate cancer to tolerate the hypergonadotropic effects of bicalutamide monotherapy.

Robotic versus laparoscopic adrenalectomy: a systematic review and meta-analysis.

CONTEXT Over the last decade, robot-assisted adrenalectomy has been included in the surgical armamentarium for the management of adrenal masses. OBJECTIVE To critically analyze the available evidence of studies comparing laparoscopic and robotic adrenalectomy. EVIDENCE ACQUISITION A systematic literature review was performed in August 2013 using PubMed, Scopus, and Web of Science electronic search engines. Article selection proceeded according to the search strategy based on Preferred Reporting Items for Systematic Reviews and Meta-analysis criteria. EVIDENCE SYNTHESIS Nine studies were selected for the analysis including 600 patients who underwent minimally invasive adrenalectomy (277 robot assisted and 323 laparoscopic). Only one of the studies was a randomized clinical trial (RCT) but of low quality according to the Jadad scale. However, the methodological quality of included nonrandomized studies was relatively high. Body mass index was higher for the laparoscopic group (weighted mean difference [WMD]: -2.37; 95% confidence interval [CI], - 3.01 to -1.74; p<0.00001). A transperitoneal approach was mostly used for both techniques (72.5% of robotic cases and 75.5% of laparoscopic cases; p=0.27). There was no significant difference between the two groups in terms of conversion rate (odds ratio [OR]: 0.82; 95% CI, 0.39-1.75; p=0.61) and operative time (WMD: 5.88; 95% CI, -6.02 to 17.79; p=0.33). There was a significantly longer hospital stay in the conventional laparoscopic group (WMD: -0.43; 95% CI, -0.56 to -0.30; p<0.00001), as well as a higher estimated blood loss (WMD: -18.21; 95% CI, -29.11 to -7.32; p=0.001). There was also no statistically significant difference in terms of postoperative complication rate (OR: 0.04; 95% CI, -0.07 to -0.00; p=0.05) between groups. Most of the postoperative complications were minor (80% for the robotic group and 68% for the conventional laparoscopic group). Limitations of the present analysis are the limited sample size and including only one low-quality RCT. CONCLUSIONS Robot-assisted adrenalectomy can be performed safely and effectively with operative time and conversion rates similar to laparoscopic adrenalectomy. In addition, it can provide potential advantages of a shorter hospital stay, less blood loss, and lower occurrence of postoperative complications. These findings seem to support the use of robotics for the minimally invasive surgical management of adrenal masses.

Phase II study of docetaxel re-treatment in docetaxel-pretreated castration-resistant prostate cancer

Study Type – Therapy (cohort)
Level of Evidence 2b

Bladder-sparing, combined-modality approach for muscle-invasive bladder cancer: a multi-institutional, long-term experience.

The authors evaluated their long‐term experience with combined‐modality, conservative treatment in patients with muscle‐invasive bladder cancer.

Concomitant CXCR4 and CXCR7 Expression Predicts Poor Prognosis in Renal Cancer

CXCR4 is a chemokine receptor implicated in the metastatic process. The CXCR4 ligand, CXCL12, was shown to bind also the CXCR7 receptor, a recently deorphanized chemokine receptor whose signalling pathway and function are still controversial. This study was conducted to determine patients clinic-pathological factors and outcome according to the expressions of CXCR4 and CXCR7 in renal cell carcinoma (RCC). CXCR4 and CXCR7 expression was evaluated in 223 RCC patients through immunohistochemistry; moreover CXCR4 and CXCR7 was detected in 49 others consecutive RCC patients trough RT- PCR. CXCR4 expression was low in 42/223 RCC (18.8%), intermediate in 71/223 (31.9%) and high in 110/223 (49.3%). CXCR7 expression was low in 44/223 RCC patients (19.8%), intermediate in 65/223 (29.1%) and high in 114/223 (51.1%). High CXCR4 and high CXCR7 expression predicted shorter disease free survival. In multivariate analysis, high CXCR4 expression (p= 0.0061), high CXCR7 (p= 0.0194) expression and the concomitant high expression of CXCR4 and CXCR7 (p= 0.0235) are independent prognosis factors. Through RT-PCR, CXCR4 was overexpressed in 36/49 and CXCR7 in 33/49 samples correlating with symptoms at diagnosis and lymph nodes status. So we can hypothesize that CXCR4 and CXCR7, singularly evaluated and in combination, are valuable prognostic factors in RCC patients.

Health related quality of life after radical cystectomy: Comparison of ileal conduit to continent orthotopic neobladder

AIMS To compare health related quality of life (HRQOL) between patients with two different types of urinary diversion, ileal conduit and orthotopic neobladder, and between them and an age-matched population of healthy subjects. MATERIALS AND METHODS Eighty eight patients treated with radical cystectomy for bladder cancer at our institutions between 2002 and 2007 were contacted for this survey. All of them had a follow-up of more than 12 months after surgery and were recurrence free. The SF-36 questionnaire was provided to each patient during a follow-up visit at outpatient clinics. Overall, 79 patients (90%) returned the questionnaire and were included in this analysis. They were divided into two groups: group 1 comprised 44 patients with an ileal conduit diversion, and group 2 included 35 patients with a neobladder. As a control, normative values of an age-matched healthy Italian population were considered. RESULTS No significant difference was found in scale scores between the neobladder and ileal conduit groups. Scale scores for role-physical functioning, social functioning and role-emotional functioning in both the neobladder and ileal conduit groups were significantly below the Italian population norm. Patients with a neobladder 65 years old or older (n=18) had significantly lower scores for role-physical functioning and role-emotional functioning than those younger than 65 years (n=17; p<0.05). CONCLUSION Few differences between ileal conduit and orthotopic bladder substitution have been detected. Thus, the assumption that continent reconstruction provides better HRQOL than ileal conduit diversion cannot be supported. Patient education and active participation in treatment decisions seem to be the key to postoperative satisfaction.