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Unlabelled: Metastatic castration-resistant prostate cancer mainly affects older men, opening issues about the efficacy and safety of therapies in this population. We have demonstrated that abiraterone, a selective androgen biosynthesis inhibitor, is a safe and active therapeutic option in a subgroup of 47 very elderly adults (aged > 80 years) enrolled in the Italian named patient program, with a tolerability profile and clinical outcomes comparable to those of younger population., Background: Prostate cancer mainly affects elderly men, who are often frail and whose reduced physiological reserves and multiple comorbidities increase the risk of side effects. The availability of new drugs has improved the overall survival (OS) of patients with castration-resistant prostate cancer (CRPC) but has increased the number of very elderly CRPC patients receiving anticancer drugs, raising questions about their efficacy and safety in this population., Patients and Methods: We assessed the tolerability of abiraterone (AA) in a cohort of very elderly adults with metastatic CRPC (mCRPC) enrolled in the Italian AA named patient program and analyzed their clinical outcomes. We retrospectively reviewed the clinical records of 47 mCRPC patients aged > 80 years who had received AA after docetaxel. The Kaplan-Meier method was used to calculate OS and progression-free survival (PFS). Safety and clinical outcomes were also analyzed by age group (< 80 and > 80 years). Cox regression analysis was used to calculate the differences in PFS and OS between the groups according to the stratification variables., Results: In very elderly men, the prostate-specific antigen response rate was 48.9%, and the median PFS and OS were 8 and 18 months, respectively. The differences in toxicities between the older and younger age groups were not major. The limitation of the present study was mainly its retrospective nature., Conclusion: Our data show that AA is active and safe in very elderly patients and leads to outcomes similar to those observed in younger patients, thus confirming that AA is a manageable therapeutic option for this patient population., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Cabazitaxel provided a survival advantage compared with mitoxantrone in patients with castration-resistant prostate cancer refractory to docetaxel. Grade 3 to 4 (G3-4) neutropenia and febrile neutropenia were relatively frequent in the registrative XRP6258 Plus Prednisone Compared to Mitoxantrone Plus Prednisone in Hormone Refractory Metastatic Prostate Cancer (TROPIC) trial, but their incidence was lower in the Expanded Access Program (EAP). Although cumulative doses of docetaxel are associated with neuropathy, the effect of cumulative doses of cabazitaxel is unknown. In this retrospective review of prospectively collected data, the authors assessed "per cycle" incidence and predictors of toxicity in the Italian cohort of the EAP, with a focus on the effect of cumulative doses of cabazitaxel.The study population consisted of 218 Italian patients enrolled in the cabazitaxel EAP. The influence of selected variables on the most relevant adverse events identified was assessed using a Generalized Estimating Equations model at univariate and multivariate analysis."Per cycle" incidence of G 3 to 4 neutropenia was 8.7%, whereas febrile neutropenia was reported in 0.9% of cycles. All events of febrile neutropenia occurred during the first 3 cycles. Multivariate logistic regression analysis showed that higher prior dose of cabazitaxel was associated with decreased odds of having G3 to 4 neutropenia (OR = 0.90; 95% CI: 0.86-0.93; P < 0.01), febrile neutropenia (OR = 0.52; 95% CI: 0.34-0.81; P < 0.01) and G3 to 4 anemia (OR = 0.93; 95% CI: 0.86-1; P = 0.07). Patients with a body surface area >2 m2 presented increased odds of having G 3 to 4 neutropenia (OR = 0.93; 95% CI: 0.86-1; P = 0.07), but decreased odds of having G3 to 4 anemia.Among the toxicities assessed, the authors did not identify any that appeared to be associated with a higher number of cabazitaxel cycles delivered. Prior cumulative dose was associated with reduced G3 to 4 neutropenia and anemia. The apparent protective effect associated with higher doses of cabazitaxel is likely to be affected by early dose reduction and early toxicity-related treatment discontinuation. Because this analysis is limited by its retrospective design, prospective trials are required to assess the optimal duration of cabazitaxel treatment.

Background: The availability of new agents (NAs) active in patients with metastatic castration-resistant prostate cancer (mCRPC) progressing after docetaxel treatment (abiraterone acetate, cabazitaxel, and enzalutamide) has led to the possibility of using them sequentially to obtain a cumulative survival benefit., Objective: To provide clinical outcome data relating to a large cohort of mCRPC patients who received a third-line NA after the failure of docetaxel and another NA., Design, Setting, and Participants: We retrospectively reviewed the clinical records of patients who had received at least two successive NAs after the failure of docetaxel., Outcome Measurements and Statistical Analysis: The independent prognostic value of a series of pretreatment covariates on the primary outcome measure of overall survival was assessed using Cox regression analysis., Results and Limitations: We assessed 260 patients who received one third-line NA between January 2012 and December 2013, including 38 who received a further NA as fourth-line therapy. The median progression-free and overall survival from the start of third-line therapy was, respectively, 4 mo and 11 mo, with no significant differences between the NAs. Performance status, and haemoglobin and alkaline phosphatase levels were the only independent prognostic factors. The limitations of the study are mainly due its retrospective nature and the small number of patients treated with some of the sequences., Conclusions: We were unable to demonstrate a difference in the clinical outcomes of third-line NAs regardless of previous NA therapy., Patient Summary: It is debated which sequence of treatments to adopt after docetaxel. Our data do not support the superiority of any of the three new agents in third-line treatment, regardless of the previously administered new agent., (Copyright © 2014 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Objectives: Patients with metastatic renal cell carcinoma (mRCC) received sunitinib in a global expanded-access program (EAP). Here, we report the efficacy and safety results for the EAP subpopulation in Italy., Methods: Patients ≥18 years old with previously treated or treatment-naïve mRCC received oral sunitinib 50 mg/day on a 4-weeks-on/2-weeks-off schedule. Tumor measurements were scheduled per local practice (using Response Evaluation Criteria in Solid Tumors). Safety was regularly assessed., Results: A total of 521 patients participated, including 40% aged ≥65 years, 11% with an Eastern Cooperative Oncology Group performance status ≥2, 14% with non-clear cell RCC, and 11% with brain metastases. The median treatment duration and posttreatment follow-up were 7.4 and 12.3 months, respectively. The objective response rate was 12%, and the median progression-free and overall survival was 9.1 and 27.2 months, respectively. 514 patients (99%) discontinued treatment; reasons included death (17%), nonresponse (46%), or adverse events (AEs; 13%). The most common any-grade treatment-related AEs were asthenia (44%, plus 15% reporting fatigue), thrombocytopenia and stomatitis (both 37%), diarrhea (36%), mucosal inflammation (29%), hypertension (26%), and dysgeusia (25%). The most common grade 3/4 treatment-related AEs were thrombocytopenia (10%), asthenia (9%, plus 3% reporting fatigue), neutropenia, stomatitis (both 6%), and hypertension (5%)., Conclusion: In a large population of Italian mRCC patients, sunitinib had a manageable safety profile and encouraging efficacy., (2015 S. Karger AG, Basel)

Aim: The Italian Retrospective Analysis of Sorafenib as First or Second Target Therapy study assessed the efficacy and safety of sorafenib in metastatic renal cell carcinoma patients treated in the community., Patients & Methods: Patients receiving first- or second-line single-agent sorafenib between January 2008 and December 2010 were eligible. Retrospective data collection started in 2012 and covers at least 1-year follow-up. The primary end point was overall survival (OS)., Results: Median OS was 17.2 months (95% CI: 15.5-19.6): 19.9 months (95% CI: 15.9-25.3) in patients treated with first-line sorafenib and 16.3 months (95% CI: 13.1-18.2) with second-line sorafenib. Overall median (95% CI) progression-free survival was 5.9 months (95% CI: 4.9-6.7): 6.6 (95% CI: 4.9-9.3) and 5.3 months (95% CI: 4.3-6.0) in first- and second-line patients, respectively., Conclusion: The efficacy and safety of sorafenib in routine community practice was generally good, especially in relation to OS in patients treated in the second line, where results were similar to those seen in recent prospective clinical trials.

Aim: Cabazitaxel is a novel taxane that is approved for use in metastatic castration-resistant prostate cancer based on the Phase III TROPIC study, which showed improved overall survival with cabazitaxel/prednisone versus mitoxantrone/prednisone. A global early-access program was initiated in order to provide early access to cabazitaxel in docetaxel-pretreated patients and to obtain real-world data., Patients & Methods: We report interim safety results from an Italian prospective, single-arm, multicenter, open-label trial of 218 patients receiving cabazitaxel 25 mg/m2 every 3 weeks plus prednisolone 10 mg/day, until disease progression, unacceptable toxicity, investigator's decision or death., Results: Patients completing treatment received a median of six cabazitaxel cycles. The most common grade 3/4 adverse events were neutropenia (33.9%), leukopenia (15.6%), anemia (6%) and asthenia (6%). No peripheral neuropathy or nail disorders were observed., Conclusion: These results confirm that cabazitaxel has a manageable safety profile in daily clinical practice and support its use in patients with prostate cancer who progress during or after a docetaxel-based therapy.