Predictors of long-term response to abiraterone in patients with metastastic castration-resistant prostate cancer: a retrospective cohort study

We aimed to identify clinical predictors of long-term response to abiraterone (defined as >12 months drug exposure) in a retrospective cohort of metastatic castration-resistant prostate cancer patients treated in post-docetaxel setting at 24 Italian centers. The Cox proportional hazards model was used to analyze the association between clinical features and the duration of drug exposure. Results were expressed as hazard ratios (HR) with associated 95% confidence intervals (CI). A total of 143 patients met the inclusion criteria. Their median age was 73 years, median Gleason score 8 and median abiraterone exposure 20 months. At the univariate analysis, a significant correlation with the duration of abiraterone exposure was found for Gleason score (HR 0.82, 95% CI 0.71-0.96; p=0.012), PSA (HR 1.10, 95% CI 1.03-1.18; p=0.08) and lactic dehydrogenase levels (HR 1.22, 95% CI 1.02-1.46; p=0.027), while the association between lower alkaline phosphatase levels and treatment duration was marginally significant (HR 1.07, 95% CI 0.99-1.16; p=0.074). Only PSA and Gleason score were predictive of long-term treatment duration in the multivariate analysis. No other clinical factors resulted to be predictive of sustained response to abiraterone, including metastatic disease at diagnosis and visceral disease, suggesting that all subgroups of patients may derive a substantial clinical benefit from abiraterone treatment. These findings need to be validated in prospective, larger studies

Hepatocarcinoma: from pathogenic mechanisms to target therapy

Hepatocellular carcinoma (HCC) is among the most prevalent and lethal cancers worldwide. It is currently estimated that there are 14,000–18,000 new cases of hepatocellular carcinoma in the United States each year. It is often difficult to identify individuals at risk for HCC. The main associated diseases are chronic hepatitis B and chronic hepatitis C viral infections. While a significant number of potential mutations have been generated including p53 and Insulin-like Growth Factor, our understanding of the molecular mechanisms driving the genesis and progression of HCC remain limited. HCC screening is recommended in high-risk patients. High-risk patients include virtually all patients with cirrhosis and some HBV-infected patients irrespective of cirrhosis (>40 years in men and >50 years in women). A diagnostic approach to HCC has been developed incorporating serology, cytohistology, and radiological characteristics. A precise staging of the disease may help decide on prognosis as well as choice of therapy with the greatest survival potential. Liver transplantation, in theory, is the optimal therapeutic option for HCC; it simultaneously removes the tumor and underlying cirrhosis thus minimizing the risk of HCC recurrence. When it is impossible for this to be performed, percutaneous ablation, chemoembolization, chemotherapy and the newer molecular therapies can be used. Sorafenib is the only drug registered today for the treatment of advanced HCC

Paclitaxel and epirubicin followed by cyclophosphamide, methotrexate and 5-fluorouracil for patients with stage IIIC breast cancer with ten or more involved axillary lymph nodes

Objective: The aim of this study was to evaluate the feasibility of a combination of epirubicin and paclitaxel followed by intravenous (iv) cyclophosphamide, methotrexate, and 5-fluorouracile (CMF) as adjuvant treatment of breast cancer patients with 10 or more metastatic axillary lymph nodes. Methods: Forty-four patients entered this multicenter study and received 4 cycles of epirubicin (E 120 mg/m2 day 1, q3 weeks) and paclitaxel (T 135 mg/m2 day 1, q3 weeks), followed by 4 cycles of iv CMF (days 1 and 8, q4 weeks). Patients with positive hormonal receptors received sequentially tamoxifen associated with LH-RH analogue if premenopausal. The endpoints were the evaluation of the feasibility of this schedule and disease free survival (DFS). Results: Median age of patients was 55; median number of positive axillary nodes was 14 (range, 10–47). Hormonal receptor status was positive in 57% of patients. The combination of epirubicin and paclitaxel was well tolerated; NCI grade 3/4 events were: leucopenia in 27% of patients, neutropenic fever in 5 patients, anemia in 7%, thrombocytopenia in 7%, nausea in 18%, vomiting in 14%, and neurotoxicity in 4%. CMF regimen caused a few cases of grade 3/4 hematologic toxicity. No cardiac toxicity was recorded. With a median follow-up of 59 months, 18 (41%) patients relapsed. Sites of relapse were mainly bone, skin/soft tissues, liver, and lung. Median DFS was 78 months, with a 5-year rate of 60%. Conclusions: The combination of paclitaxel at low dose and epirubicin followed by CMF is a feasible regimen, which seems to be effective in high-risk node positive breast cancer patients and requires further investigations

BOOST: a phase 3 trial of sorafenib vs. best supportive care in first line treatment of hepatocellular carcinoma in patients with deteriorated liver function

Aim: Only patients with good liver function {[Child-Pugh (CP)] A class} were eligible for trials testing sorafenib as first-line treatment of hepatocellular carcinoma (HCC); nevertheless, the drug was authorized without restrictions based on liver function. Therefore, we planned to test sorafenib efficacy and safety in patients with HCC and deteriorated liver function (CP-B).Methods: This was an open-label, multicenter, randomized phase 3 trial. Patients with HCC, no previous systemic therapy, and CP-B score 7-9 were assigned 1:1 to best supportive care alone (control arm) or with standard dose sorafenib (experimental arm). Overall survival (OS) was the primary endpoint. To detect a 0.70 HR of death, with 80% power, and two-tailed α error 0.05, 234 events were required. The study closed prematurely because of slow accrual. Descriptive analyses are reported.Results: From 2012 to 2017, 13 Italian centers randomized 35 patients. In total, 28 deaths were recorded, 12 without and 16 with sorafenib; median OS was 4.9 (95%CI: 1.2-5.6) and 3.5 months (95%CI: 1.3-5.3), respectively. At least one severe adverse event was reported in 2/15 (13.3%) without and 9/17 (52.9%) patients with sorafenib.Conclusions: This trial failed its planned enrolment goal, showing the difficulty in performing clinical trials with drugs already registered with a label broader than what available evidence supports