An Italian, multicenter, real-world, retrospective study of first-line pazopanib in unselected metastatic renal-cell carcinoma patients: the 'Pamerit' study.

OBJECTIVE: Despite the current immunotherapy era, VEGFR inhibitors maintain effectiveness in metastatic renal cell cancer. Real-world data concerning pazopanib are limited. The aim of this study is to add information about efficacy and safety of pazopanib as first-line treatment in metastatic renal cell cancer patients not enrolled into clinical trials. METHODS: Retrospective analysis (the PAMERIT study) of first-line pazopanib in real-world metastatic renal cell cancer patients among 39 Centers in Italy. Outcomes were progression-free survival, overall survival, objective response rate and treatment-related adverse events. Kaplan-Meier curves, log-rank test and multivariable Cox's models were used and adjusted for age, histology, previous renal surgery, International Metastatic RCC Database Consortium score and pazopanib initial dose. RESULTS: Among 474 patients, 87.3% had clear cell metastatic renal cell cancer histology. Most of them (84.6%) had upfront renal surgery. Median progression-free survival and overall survival were 15.8 and 34.4 months, respectively, significantly correlating with International Metastatic RCC Database Consortium's good prognosis (P < 0.001), ECOG PS 0 (P < 0.001), age (<75 years, P = 0.005), surgery (P < 0.001) and response to pazopanib (P < 0.001). After 3 months of pazopanib, overall disease control rate have been observed in 76.6% patients. Among International Metastatic RCC Database Consortium's favorable group patients, 57/121 (47%) showed complete/partial response. No unexpected AEs emerged. CONCLUSIONS: In this real-world study, metastatic renal cell cancer patients treated with first-line pazopanib reached greater progression-free survival and overall survival than in pivotal studies and had high response rates when belonging to International Metastatic RCC Database Consortium's favorable group, without new toxicities. Pazopanib has been confirmed a valid first-line option for International Metastatic RCC Database Consortium's good prognosis metastatic renal cell cancer patients who cannot be submitted to immunotherapy.

ZeOxaNMulti Trial: A Randomized, Double-Blinded, Placebo-Controlled Trial of Oral PMA-zeolite to prevent Chemotherapy-Induced Side Effects, in particular, Peripheral Neuropathy.

Chemotherapy-induced peripheral neuropathy (CIPN) is the most frequently reported adverse effect of oxaliplatin. In this study, we set out to evaluate the role of the panaceo-micro-activation (PMA) zeolite in the reduction of the incidence of CIPN and hematological and liver toxicity. The possible impact of the PMA-zeolite as an adjuvant therapeutic agent is based on its detoxification properties toward agents promoting the development of neuropathy (e.g., ammonium - recognized as a neurotoxic agent produced by tumors), as well as its positive impact on immunity and oxidative stress through its effects in the gastrointestinal tract. From April 2015 to October 2018, a total of 120 patients (pts) diagnosed with predominantly colorectal cancer requiring oxaliplatin-based chemotherapy were randomized to receive either the PMA-zeolite (Multizeo Med) or placebo while undergoing oxaliplatin-based chemotherapy. A nerve-conduction study (NCS) was planned at the baseline, after three and six months of chemotherapy, to evaluate CIPN. Furthermore, the evaluation of hematological and liver toxicity was performed during every cycle of chemotherapy. 70.6% and 64.3% of patients developed CIPN in the placebo and the PMA-zeolite group, respectively. Patients treated with the PMA-zeolite were able to undergo more cycles of chemotherapy (p = 0.03), which also indicates a significant improvement in tolerance to the therapy. The group treated with the PMA-zeolite showed a lower CIPN (although not statistically significant within the whole group of subjects) compared to patients receiving placebo. This advantage was, however, statistically significant in men (p = 0.047). In addition, supplementation with the PMA-zeolite resulted in a lower incidence of severe-grade hematological toxicity (trend toward statistical significance of p = 0.09 was observed). Cancer patients may benefit from the therapy with the appropriate certified zeolite-products (e.g., the PMA-zeolite) for human use in CIPN. The lower CIPN (statistically significant results in the male subgroup) was accompanied by a trend of lower incidence of severe-grade hematological toxicity. Furthermore, these benefits led to a better tolerance toward chemotherapy (increase in cycles) and allow an improved compliance with the oncological treatment protocol.

Adjuvant Sunitinib in High-Risk Renal-Cell Carcinoma after Nephrectomy.

BACKGROUND: Sunitinib, a vascular endothelial growth factor pathway inhibitor, is an effective treatment for metastatic renal-cell carcinoma. We sought to determine the efficacy and safety of sunitinib in patients with locoregional renal-cell carcinoma at high risk for tumor recurrence after nephrectomy. METHODS: In this randomized, double-blind, phase 3 trial, we assigned 615 patients with locoregional, high-risk clear-cell renal-cell carcinoma to receive either sunitinib (50 mg per day) or placebo on a 4-weeks-on, 2-weeks-off schedule for 1 year or until disease recurrence, unacceptable toxicity, or consent withdrawal. The primary end point was disease-free survival, according to blinded independent central review. Secondary end points included investigator-assessed disease-free survival, overall survival, and safety. RESULTS: The median duration of disease-free survival was 6.8 years (95% confidence interval [CI], 5.8 to not reached) in the sunitinib group and 5.6 years (95% CI, 3.8 to 6.6) in the placebo group (hazard ratio, 0.76; 95% CI, 0.59 to 0.98; P=0.03). Overall survival data were not mature at the time of data cutoff. Dose reductions because of adverse events were more frequent in the sunitinib group than in the placebo group (34.3% vs. 2%), as were dose interruptions (46.4% vs. 13.2%) and discontinuations (28.1% vs. 5.6%). Grade 3 or 4 adverse events were more frequent in the sunitinib group (48.4% for grade 3 events and 12.1% for grade 4 events) than in the placebo group (15.8% and 3.6%, respectively). There was a similar incidence of serious adverse events in the two groups (21.9% for sunitinib vs. 17.1% for placebo); no deaths were attributed to toxic effects. CONCLUSIONS: Among patients with locoregional clear-cell renal-cell carcinoma at high risk for tumor recurrence after nephrectomy, the median duration of disease-free survival was significantly longer in the sunitinib group than in the placebo group, at a cost of a higher rate of toxic events. (Funded by Pfizer; S-TRAC ClinicalTrials.gov number, NCT00375674 .).

Second line therapy with axitinib after only prior sunitinib in metastatic renal cell cancer: Italian multicenter real world SAX study final results.

BACKGROUND: This multi-institutional retrospective real life study was conducted in 22 Italian Oncology Centers and evaluated the role of Axitinib in second line treatment in not selected mRCC patients. METHODS: 148 mRCC patients were evaluated. According to Heng score 15.5%, 60.1% and 24.4% of patients were at poor risk, intermediate and favorable risk, respectively. RESULTS: PFS, OS, DCR and ORR were 7.14 months, 15.5 months, 70.6% and 16.6%, respectively. The duration of prior sunitinib treatment correlated with a longer significant mPFS, 8.8 vs 6.3 months, respectively. Axitinib therapy was safe, without grade 4 adverse events. The most frequent toxicities of all grades were: fatigue (50%), hypertension (26%), and hypothyroidism (18%). G3 blood pressure elevation significantly correlated with longer mPFS and mOS compared to G1-G2 or no toxicity. Dose titration (DT) to 7 mg and 10 mg bid was feasible in 24% with no statistically significant differences in mPFS and mOS. The sunitinib-axitinib sequence was safe and effective, the mOS was 41.15 months. At multivariate analysis, gender, DCR to axitinib and to previous sunitinib correlated significantly with PFS; whereas DCR to axitinib, nephrectomy and Heng score independently affected overall survival. CONCLUSIONS: Axitinib was effective and safe in a not selected real life mRCC population. Trial registration INT - Napoli - 11/16 oss. Registered 20 April 2016. http://www.istitutotumori.na.it.

Safety and efficacy of nivolumab for metastatic renal cell carcinoma: real-world results from an expanded access programme.

OBJECTIVE: To report the safety and efficacy results of patients enrolled in the Italian Nivolumab Renal Cell Cancer Expanded Access Programme. PATIENTS AND METHODS: Patients with metastatic renal cell cancer (mRCC) previously treated with agents targeting the vascular endothelial growth factor pathway were eligible to receive nivolumab 3 mg/kg once every 2 weeks. Patients included in the analysis had received ≥1 dose of nivolumab and were monitored for adverse events (AEs) using Common Terminology Criteria for Adverse Events (CTCAE) v.4.0. RESULTS: A total of 389 patients were enrolled between July 2015 and April 2016, of whom 18% were aged ≥75 years, 6.7% had non-clear cell RCC, 49.6% had bone and 8.2% brain metastases, and 79% had received ≥2 previous lines of therapy. The most common any-grade treatment-related AEs were fatigue (13%) and rash (9%). Twenty-two patients (5.7%) discontinued treatment because of AEs. There were no treatment-related deaths. The objective response rate was 23.1%. At a median follow-up of 12 months, the median progression-free survival was 4.5 months (95% confidence interval 3.7-6.2) and the 12-month overall survival rate was 63%. Similar survival rates were reported among patients with non-clear-cell histology, elderly patients, those with bone and/or brain metastases, and those who had received prior first-line sunitinib or pazopanib, or prior everolimus. CONCLUSION: The safety and efficacy observed were consistent with those reported in the pivotal Checkmate 025 trial. Results in patients with non-clear-cell mRCC who were elderly, pretreated with everolimus, and had bone and/or brain metastases encourage the use of nivolumab in these categories of patients.

Clinical management of metastatic kidney cancer: the role of new molecular drugs.

Over the last few years, the most recent advances of the molecular mechanisms involved in renal cell carcinoma have led to the use of new drugs targeting VEGF, such as bevacizumab plus interferon, sorafenib, sunitinib, pazopanib, and axitinib, or the mTOR, such as temsirolimus and everolimus. The purpose of this review is to analyze the results of Phase III trial with these targeted agents, and on the management of the treatment and, in particular, when to start and to stop therapy and the use of alternative schedule of sunitinib. Recent developments in immunotherapy are also discussed.

Prognostic factors in patients receiving third line targeted therapy for metastatic renal cell carcinoma.

PURPOSE: Several prognostic models have been proposed for metastatic renal cell carcinoma but none has been validated in patients who receive third line targeted agents. We evaluated prognostic factors in patients with metastatic renal cell carcinoma who received a third line targeted agent. MATERIALS AND METHODS: We retrospectively reviewed data on 2,065 patients with clear cell metastatic renal cell carcinoma who were treated with targeted therapy at a total of 23 centers in Italy. Included in final analysis were 281 patients treated with 3 targeted agents. Overall survival was the main outcome. Cox proportional hazards regression followed by bootstrap validation was used to identify independent prognostic factors. RESULTS: Three clinical characteristics (ECOG performance status greater than 1, metastasis at diagnosis and liver metastasis) and 2 biochemical factors (hemoglobin less than the lower limit of normal and neutrophil count greater than the upper limit of normal, respectively) were prognostic. Patients were classified into 3 risk categories, including low-zero or 1, intermediate-2 and high risk-more than 2 risk factors. Median overall survival was 19.7, 10.1 and 5.5 months, and 1-year overall survival was 71%, 43% and 15%, respectively. The major limitation was the retrospective nature of this study and absent external validation. CONCLUSIONS: This nomogram included clinical and biochemical prognostic factors. In clinical trials it may be useful to select patients and define the prognosis.

Safety and efficacy of sunitinib in patients from Italy with metastatic renal cell carcinoma: final results from an expanded-access trial.

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.

Horner's syndrome: An unusual presentation of metastatic disease in breast cancer.

Horner's syndrome (HS) is caused by an interruption of the cervical sympathetic pathway to the eye and the face. Acquired HS is mainly caused by benign or malignant neoplasms, and in patients with a history of cancer, it is almost always the result of tumor infiltration into the periphery or the central region of the cervical sympathetic chain.We present the case of a 52-year-old patient with long-term disease-free survival (6 years) after a radical mastectomy for breast cancer who presented with cervicobrachialgia and typical HS due to a left lateral-cervical and supraclavicular lymph nodal mass. Treatment of the metastatic disease with taxanes and concurrent trastuzumab resulted in a complete pain resolution, as well as long-term clinical and radiologic remission; however, the neurological cohort of HS remained as the expression of permanent damage to the sympathetic pathway.This report presents a highly rare case of HS as the first and solitary appearance of metastatic disease in a breast cancer patient. This neurologic involvement should always raise suspicion of metastatic infiltration, and the early recognition of the syndrome may prevent permanent nerve injury.

Everolimus as second-line therapy for metastatic renal cell carcinoma: a 'real-life' study.

AIMS: This study, conducted in a 'field-practice' scenario, investigates the effectiveness and safety of everolimus in the second-line treatment of metastatic renal cell carcinoma (mRCC) patients. PATIENTS & METHODS: mRCC patients, who started everolimus 10 mg/day after failure of first-line VEGF receptor-targeted tyrosine kinase inhibitor, were included in this study. Study end points were treatment response, progression-free survival and tolerability. RESULTS: In total, 100 patients were assessed; the median duration of everolimus treatment was 7.1 months (95% CI: 5.7-8.5). A total of 19% of patients experienced a partial response and 62% of patients reached a stable disease. Median progression-free survival was 8 months (95% CI: 6.7-9.3). A total of 75% of patients experienced adverse events; no grade 4 adverse events were reported. CONCLUSION: These findings, obtained in a 'field-practice' scenario, support the use of everolimus for mRCC patients who failed one VEGF receptor-targeted tyrosine kinase inhibitor.

Real-world study of everolimus in advanced progressive neuroendocrine tumors.

Everolimus is a valid therapeutic option for neuroendocrine tumors (NETs); however, data in a real-world setting outside regulatory trials are sparse. The aim of this study was to determine everolimus tolerability and efficacy, in relation to previous treatments, in a compassionate use program. A total of 169 patients with advanced progressive NETs treated with everolimus were enrolled, including 85 with pancreatic NETs (pNETs) and 84 with nonpancreatic NETs (non-pNETs). Previous treatments included somatostatin analogs (92.9%), peptide receptor radionuclide therapy (PRRT; 50.3%), chemotherapy (49.7%), and PRRT and chemotherapy (22.8%). Overall, 85.2% of patients experienced adverse events (AEs), which were severe (grade 3-4) in 46.1%. The most frequent severe AEs were pneumonitis (8.3%), thrombocytopenia (7.7%), anemia (5.3%), and renal failure (3.5%). In patients previously treated with PRRT and chemotherapy, a 12-fold increased risk for severe toxicity was observed, with grade 3-4 AEs reported in 86.8% (vs. 34.3% in other patients). In addition, 63.3% of patients required temporarily everolimus discontinuation due to toxicity. Overall, 27.8% of patients died during a median follow-up of 12 months. Median progression-free survival (PFS) and overall survival (OS) were 12 months and 32 months, respectively. Similar disease control rates, PFS, and OS were reported in pNETs and non-pNETs. In the real-world setting, everolimus is safe and effective for the treatment of NETs of different origins. Higher severe toxicity occurred in patients previously treated with systemic chemotherapy and PRRT. This finding prompts caution when using this drug in pretreated patients and raises the issue of planning for everolimus before PRRT and chemotherapy in the therapeutic algorithm for advanced NETs.

The role of immunotherapy in solid tumors: report from the Campania Society of Oncology Immunotherapy (SCITO) meeting, Naples 2014.

The therapeutic approach to advanced or metastatic solid tumors, either with chemotherapy or targeted therapies, is mainly palliative. Resistance to chemotherapy occurs very frequently and is one of the most important reasons for disease progression. Immunotherapy has the potential to mount an ongoing, dynamic immune response that can kill tumor cells for an extended time after the conventional therapy has been administered. Such a long-lasting response is potentially able to completely eradicate tumor cells, rather than producing only a temporary killing of cells. The most promising immune-based treatments are monoclonal antibodies that act as checkpoint inhibitors (e.g. ipilimumab and nivolumab), adoptive cell therapy (e.g. T-cells expressing chimeric antigen receptors) and vaccines (e.g. sipuleucel-T). Ipilimumab is currently approved for the treatment of metastatic melanoma and sipuleucel-T is approved for advanced prostate cancer. There is great interest in immunotherapy in other solid tumors, potentially used alone or in a multimodal fashion with chemotherapy and/or biological drugs. In this paper, we review recent advances in immuno-oncology in solid malignancies (except melanoma) as were discussed at the inaugural meeting of the Campania Society of Oncology Immunotherapy (SCITO).

Real-world cabazitaxel safety: the Italian early-access program in metastatic castration-resistant prostate cancer.

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.

Pancreatic solitary and synchronous metastasis from breast cancer: a case report and systematic review of controversies in diagnosis and treatment.

BACKGROUND: Metastases from breast cancer cause the frequent involvement of lung, bone, liver, and brain, while the occurrence of metastases to the gastrointestinal tract is rare, and more frequently discovered after a primary diagnosis of breast cancer. Solitary pancreatic metastases from breast cancer, without widespread disease, are actually unusual, and only 19 cases have been previously described; truly exceptional is a solitary pancreatic metastasis becoming evident together with the primary breast cancer. CASE PRESENTATION: A 68-year-old woman reported general fatigue, lethargy, and jaundice. Abdominal ultrasound (US) and magnetic resonance imaging (MRI) showed an ampulloma of Vater's papilla; moreover, a neoplastic nodule in the left breast was diagnosed. She underwent surgery for both breast cancer and ampulloma of Vater's papilla. Pathological examination of pancreatic specimen, however, did not confirm primary carcinoma of the duodenal papilla, but showed a metastatic involvement of pancreas from lobular breast cancer. Immunohistochemistry has been essential to confirm the origin of the malignancy: hormone receptors and mammaglobin were expressed in both the primary breast tumor and the pancreatic metastasis. CONCLUSIONS: This is one of the few reported cases in literature of an isolated and synchronous pancreatic metastasis from breast cancer, where the definitive diagnosis was obtained only after surgery. We discuss the controversies in this diagnosis and the choice of correct treatment. The surgical resection of solitary metastases can be performed in the absence of disseminated disease.

The treating scenario in genitourinary oncology: what is new? Part 2.

The objectives of this innovative meeting were to discuss developments in the management of genitourinary cancer worldwide and how Italian clinicians could harness these innovations in their everyday practice. The 2-day meeting was divided into two sessions covering kidney and prostate cancer, and a large part was given over to the presentation and discussion of new recently presented data at major international congresses in 2012. There were no restrictions on content and all subjects from pathology, surgery and genetics to therapy and patient outcomes were covered.

The treating scenario in genitourinary oncology: what is new? Part 1.

The objectives of this innovative meeting were to discuss developments in the management of genitourinary cancer worldwide and how Italian clinicians could harness these innovations in their everyday practice. The 2-day meeting was divided into two sessions covering kidney and prostate cancer, and a large part was given over to the presentation and discussion of new recently presented data at major international congresses in 2012. There were no restrictions on content and all subjects from pathology, surgery and genetics to therapy and patient outcomes were covered.

Central nervous system metastases from castration-resistant prostate cancer in the docetaxel era.

Central nervous system (brain or leptomeningeal) metastases (BLm) are considered rare in castration-resistant prostate cancer (CRPC) patients. Now that docetaxel has become the reference drug for first-line treatment of CRPC, patients whose disease is not controlled by hormonal manipulations may live much longer than before and have higher risk of developing BLm. We retrospectively reviewed the records of all patients with CRPC attending our centres from 2002 to 2010, and identified all of those who were diagnosed as having BLm and received (or were considered to have been eligible to receive) docetaxel-based treatment. We identified 31 cases of BLm (22 brain metastases and 9 leptomeningeal metastases) with an incidence of 3.3%. BLm-free survival was 43.5 months, and survival after BLm discovery was 4 months. With six patients surviving for more than 1 year after developing BLm, the projected 1-year BL-S rate was 25.8%. The findings of our study may be relevant in clinical practice as they indicate that incidence of BLm in CRPC patients in the docetaxel era seems to be higher than in historical reports, meaning that special attention should be paid to the appearance of neurological symptoms in long-term CRPC survivors because they may be related to BLm.

The Emerging Role of c-Met in Carcinogenesis and Clinical Implications as a Possible Therapeutic Target.

BACKGROUND: c-MET is a receptor tyrosine kinase receptor (RTK) for the hepatocyte growth factor (HGF). The binding of HGF to c-MET regulates several cellular functions: differentiation, proliferation, epithelial cell motility, angiogenesis, and epithelial-mesenchymal transition (EMT). Moreover, it is known to be involved in carcinogenesis. Comprehension of HGF-c-MET signaling pathway might have important clinical consequences allowing to predict prognosis, response to treatment, and survival rates based on its expression and dysregulation. Discussion. c-MET represents a useful molecular target for novel engineered drugs. Several clinical trials are underway for various solid tumors and the development of new specific monoclonal antibodies depends on the recent knowledge about the definite c-MET role in each different malignance. Recent clinical trials based on c-MET molecular targets result in good safety profile and represent a promising therapeutic strategy for solid cancers, in monotherapy or in combination with other target drugs. CONCLUSION: The list of cell surface receptors crosslinking with the c-MET signaling is constantly growing, highlighting the importance of this pathway for personalized target therapy. Research on the combination of c-MET inhibitors with other drugs will hopefully lead to discovery of new effective treatment options.

Compassionate Use Program of Ipilimumab and Nivolumab in Intermediate or Poor Risk Metastatic Renal Cell Carcinoma: A Large Multicenter Italian Study.

This is a retrospective analysis on the safety and activity of compassionate Ipilimumab and Nivolumab (IPI-NIVO) administered to patients with metastatic Renal Cell Carcinoma (mRCC) with intermediate or poor International Metastatic RCC Database Consortium (IMDC) score as a first-line regimen. IPI was infused at 1 mg/kg in combination with Nivolumab 3 mg/kg every three weeks for four doses, followed by maintenance Nivolumab (240 or 480 mg flat dose every two or four weeks, respectively) until disease progression or unacceptable toxicity. A total of 324 patients started IPI-NIVO at 86 Italian centers. Median age was 62 years, 68.2% IMDC intermediate risk. Primary tumor had been removed in 65.1% of patients. Two hundred and twenty patients (67.9%) completed the four IPI-NIVO doses. Investigator-assessed overall response rate was 37.6% (2.8% complete). Twelve-month survival rate was 66.8%, median progression-free survival was 8.3 months. Grade 3 or 4 treatment-related adverse events occurred in 67 patients (26.9%). IMDC intermediate risk, nephrectomy, BMI ≥ 25 kg/m2, and steroid use for toxicities correlated with improved survival, while age < 70 years did not. IPI-NIVO combination is a feasible and effective regimen for the first-line treatment of intermediate-poor IMDC risk mRCC patients in routine clinical practice.

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

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.