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Aim: To assess clinical outcomes in octogenarians treated with docetaxel (DOC) for metastatic castration-resistant prostate cancer. Patients & methods: The multicenter retrospective study was based on a review of the pre- and post-DOC clinical history, DOC treatment and outcomes. Results: We reviewed the records of 123 patients (median age: 82 years) who received DOC every 3 weeks or weekly, without significant grade 3–4 toxicities. Median progression-free survival was 7 months; median overall survival from the start of DOC was 20 months, but post-progression treatments significantly prolonged overall survival. Conclusion: The findings of this study suggest that toxicity is acceptable, survival is independent of patient's age and survival can be significantly prolonged by the use of new agents.

Study Type – Therapy (cohort) Level of Evidence 2b What’s known on the subject? and What does the study add? We show that (i) docetaxel re-treatment, after a treatment-free interval, preserves activity; (ii) the treatment is especially well tolerated in patients who were effectively pretreated with docetaxel; and (iii) it could be speculated that combining docetaxel with other agents in this setting might be safe and result in greater activity. OBJECTIVE To determine the activity and tolerability of docetaxel re-treatment after first-line therapy with docetaxel in castration-resistant prostate cancer (CRPC). PATIENTS AND METHODS Between November 2005 and January 2009, 45 patients initially responding to docetaxel and then experiencing disease progression after a period of biochemical remission of at least 5 months were enrolled in a prospective multicenter study and re-treated with docetaxel. The primary endpoint was the biochemical response (biochemical partial response defined as >50% prostate-specific antigen [PSA] decline); secondary endpoints were objective response, toxicity, progression-free survival (PFS) and overall survival (OS). RESULTS Partial PSA responses were observed in 11 patients (24.5%), 4 (25%) of whom also had an objective response. The treatment was well tolerated, with grade 1–2 neutropenia, thrombocytopenia, vomiting and peripheral neuropathy noted in 18 (40%), 11 (24.5%), 8 (17.8%), and 6 (13.3%) patients, respectively. The most common grade 3 toxicity was neutropenia, which was observed in 8 patients (17.8%). Median PFS was 5 months and median OS was 13 months. CONCLUSIONS Docetaxel re-treatment preserves anti-tumour activity and is well tolerated in a selected population of pretreated patients with CRPC. Further randomized trials are needed to confirm our preliminary results.

The treatment of metastatic renal cell carcinoma (MRCC) has evolved from being predominantly cytokine-based to being grounded in the use of drugs targeting vascular endothelial growth factor, platelet-derived growth factor and mammalian target of rapamycin (mTOR) pathways. New agents including the small-molecule targeted inhibitors sunitinib, sorafenib and temsirolimus and the monoclonal antibody bevacizumab have shown anti-tumor efficacy and have become the standard of care for most patients. Sunitinib and temsirolimus have shown significant improvements in overall survival (OS), in the first-line setting, when compared with interferon. Sorafenib has demonstrated prolonged progression-free survival (PFS) in a phase III study in comparison with placebo in the second-line setting. More recently, two phase III studies have compared bevacizumab and interferon with interferon alone. Both studies showed a statistically significant improvement in PFS for the combination arm but no difference in OS. Everolimus showed prolonged PFS in the second/third-line setting. Pazopanib prolongs PFS in naïve/cytokine refractory patients. Immunotherapy confers a small but significant OS advantage but only for the minority of patients with good prognostic features. The results of these trials and ongoing efforts to improve treatment of MRCC are the focus of this review.

SUMMARY Purpose Over the last few years, targeted agents have assumed a predominant role in treatment of metastatic renal cell carcinoma (mRCC). Our aim is to discuss recent developments on this rapidly evolving topic. Evidence synthesis Sunitinib represents front-line standard treatment for the good- and intermediate prognosis groups of patients with clear cell renal carcinoma. Bevacizumab/interferon and pazopanib have also been FDA-approved as first-line agents, while sorafenib has moved toward second-line and later therapy. Temsirolimus, an mTOR inhibitor, is recommended as front line therapy for patients in the poor-risk group and is the best front-line choice for patients with non-clear cell histology. Another mTOR inhibitor, everolimus, has shown clinical benefit post-tyrosine kinasis inhibitors failure in a phase III study and is considered the standard of care in this setting. Novel prognostic and efficacy markers might help to define most appropriate therapeutic strategy. Best sequence of use of these effective agents in mRCC patients remains up to the discretion of treating physician. Conclusions In light of the considerable advances in understanding the biology of mRCC, several new drugs have been recently developed, with an increasing number of treatment options. Several markers are under evaluation for diagnostic, prognostic and efficacy purposes. A treatment algorithm, based on the best scientific evidence produce so far, is presented and it will evolve as data from ongoing trials will be available.

Background Defining the optimal treatment for patients with inoperable non small cell lung cancer (NSCLC), presenting with metastatic mediastinal lymph nodes, is challenging. Nevertheless, preoperative chemotherapy or radiotherapy might offer a chance for these patients for radical surgical resection and, possibly, complete recovery. Case Presentation A 62-year old man with IIIA-N2 inoperable NSCLC was treated with first-line single agent docetaxel. A platinum-based treatment, though considered more active, was ruled out because of renal impairment. The patient tolerated the treatment very well and, although his initial response was not impressive, after 14 cycles he obtained a complete clinical response, which was confirmed pathologically after he underwent surgical lobectomy. Conclusion In non-operable NSCLC patients not eligible for a platinum-based treatment, single-agent docetaxel can provide complete pathologic responses. Failure to obtain a response after the first few cycles should not automatically discourage to continue treatment.

e16017 Background: After DOC became the reference first line treatment for mCRPC pts, cabazitaxel (CABA), abiraterone acetate (AA), and enzalutamide (ENZ) significantly prolonged overall survival (OS) after DOC. Since a quote of pts develops mCRPC at very old age, often after 80 years, it could be questionable if the administration of these expensive NAs is justifiable in this population. We retrospectively evaluated the impact of post-DOC treatments on OS of octogenarians mCRPC pts treated with first-line DOC in 30 Italian hospitals. Methods: In this multicentric retrospective study, after Ethical Committee approval, we have reviewed the clinical records of all octogenarians mCRPC pts from participating institutions, treated with DOC in clinical practice, recording the pre and post-DOC clinical history, the DOC treatment details and outcomes. Results: We collected a consecutive series of 121 octogenarians pts treated between May 2003 and November 2013. The median age was 82 yrs (range 80-90). All pts had...

5050 Background: Since prostate cancer is mainly diagnosed in pts over 65 yrs of age, castration resistance is usually observed in older pts. In the case of very old pts (≥ 80 years), fear of high toxicity degree limit chemotherapy use due to both pts frailty and several comorbidities occurrence. Moreover, if treated these pts usually receive an adapted chemotherapy, often with a weekly schedule, which in TAX327 trial failed to show survival advantage compared to mitoxantrone. The present retrospective study is aimed to assess CO in this very elderly CRPC population. Methods: In this multicentric retrospective study, after Ethical Committee approval, we have reviewed the clinical records of all ≥ 80 yrs CRPC pts from participating institutions, treated with DOC in clinical practice, recording the pre and post-DOC clinical history, the DOC treatment details and outcomes. Results: To date we collected a consecutive series of 81 pts from 17 Italian hospitals. The median age was 82 yrs (range 80-90). The median baseline PSA was 107 ng/ml (range 3-1597); 81% of the pts had bone metastases, while nodal, lung and liver metastases were observed in 37%, 6%, and 6% of the pts, respectively. Median Cumulative Illness Rating Scale score was 3 (range 0-11), median Activity Daily Living index score was 0 (range 0-5), median Instrumental Activities of Daily Living score was 0 (range 0-5). The DOC was administered on 3-week or weekly schedule basis (41%/59%). A PSA reduction > 50% and an objective response were observed in 74% and 11% of the pts, respectively. Grade 3-4 toxicities were: neutropenia (11%) , fatigue (8%), diarrhea (1%), renal (2%), and febrile neutropenia (1%). The median PFS and OS were 7 mos and 22 mos, while the 1-year PFS and OS rates were 17.3% and 43.9%, respectively. Conclusions: This data suggests that DOC treatment, both on 3-week or weekly schedule, is able to produce good survival outcomes, comparable to pivotal trials (18 mos), also in highly selected very older (≥ 80 yrs) CRPC pts.