7 research outputs found
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
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Active debris removal: overview and figures of merit of debris grabbing strategies
During the last two decades the problem of space debris and safe access to Low Earth Orbit has been one of the most controversial and discussed issue in the space community. Along with mitigation actions (e.g. the 25-year Post Mission Disposal rule currently adopted by most agencies), analyses of the current situation and future projections have shown the necessity of active debris removal (ADR) operations aimed to a direct intervention in relatively short time as a remediation action.
Apart from the problem of considering the potential political and legal consequences of dealing with spent space objects, many methods have been proposed for the despinning and grabbing phases of ADR missions, but in spite of the variety in the ideas and concepts on the ground, not all of them are ready to be sent to space.
Starting from an overview on the different approaches proposed for in-orbit grabbing of uncooperative targets, this work analyses the current status of the solutions designed so far, both in terms of technical readiness and methodological maturity, and identifies the characteristics that can be used as a metric for the quality and feasibility of those systems.
From these figures of merit, different scenarios will be simulated to obtain additional supporting data in order to validate the results of the preliminary analyses
Effectiveness of abiraterone acetate plus prednisone in chemotherapy-naïve patients with metastatic castration-resistant prostate cancer in a large prospective real-world cohort: the ABItude study
Real-world data on chemotherapy-naïve patients with metastatic castration-resistant prostate cancer (mCRPC) treated with abiraterone plus prednisone are limited, largely deriving from small retrospective studies
Effects of abiraterone acetate plus prednisone on bone turnover markers in chemotherapy-naïve mCRPC patients after ADT failure: a prospective analysis of the italian real-world study ABITUDE
Background: Bone remodeling is disrupted in metastatic disease, which affects > 70% of metastatic castration-resistant prostate cancer (mCRPC) patients. As a result, abnormal levels of specific bone turnover biomarkers (BTMs) are released. In this prospective ancillary analysis of the Italian real-world study ABITUDE, four markers were measured during abiraterone acetate plus prednisone (AAP) treatment in chemotherapy-naïve mCRPC men failing androgen-deprivation therapy. Methods: Patients were enrolled if a blood sample was obtained before the first administration of abiraterone (baseline); ad-hoc blood samples were withdrawn during routine tests after 3, 6, and 12 months. A centralized lab measured bone alkaline phosphatase (BALP, osteoblast activity marker), type-I collagen-C-telopeptide (CTX-1, bone resorption marker), parathyroid hormone (PTH) and vitamin D (vitD). At each time point, intra-patient variations vs baseline were compared by the signed-rank test (statistical significance: P-value < 0.05). Results: Of 481 patients enrolled in ABITUDE, 186 (median age: 76 [range: 53-93] years) met the substudy criteria: 74.7% had bone metastases, 11.8% were on bone-targeted therapies (BTT) and 14.0% on vitD supplementation. BALP decreased significantly at month 6 (P = 0.0010) and 12 (P < 0.0001) and CTX-1 at month 6 (P = 0.0028); PTH increased at month 3 (P < 0.0001); no significant difference in vitD levels was observed. Similar findings were observed in BTT-untreated patients. The reduction in BALP and CTX-1 levels was more pronounced in patients with than without bone metastases; in the latter group, no significant variation in BALP and CTX-1 levels was observed. Conclusions: AAP seems to exert an effect on the microenvironment of metastatic but not of normal bone, which likely contributes to its antitumoral activity
Impact of second-line cetuximab-containing therapy in patients with KRAS wild-type metastatic colorectal cancer: results from the ITACa randomized clinical trial
Abstract The ITACa trial was designed to define the role of cetuximab (Cet) and bevacizumab (Bev) in combination with standard chemotherapy (CT, FOLFIRI or FOLFOX4) as first- and second-line treatment in metastatic colorectal cancer. All patients with WT KRAS tumors who had been enrolled in the first-line trial were randomized onto two independent second-line trials: CT or CT + Cet (study 2A) and CT + Bev or CT + Bev + Cet (study 2B). Patients with mutated KRAS were not eligible for randomization and were treated with CT alone (study 2A) or CT + Bev (study 2B). The primary endpoint was progression-free survival (PFS). 48 and 56 KRAS WT patients were randomized while 31 and 40 KRAS mutated patients were treated without randomization. Study 2A: median PFS was 3.4 (95%CI 2.3–4.6) and 6.2 (95%CI 4.3–7.8) months for the CT and CT + Cet arms, respectively, with a hazard ratio (HR) = 0.64 (95%CI 0.35–1.16, p = 0.144). Study 2B: median PFS was 7.7 (95%CI 4.1–10.1) and 4.9 (95%CI 3.2–7.0) months for CT + Bev and CT + Cet + Bev arms, respectively, with a HR = 1.31 (95%CI 0.76–2.26, p = 0.330). Notwithstanding limitations due to the small sample size, among patients with WT KRAS the addition of Cet to second-line CT increased PFS, whereas the addition of Cet to CT + Bev was associated with worse PFS
Cabozantinib in the elderly with metastatic renal cell carcinoma undergoing geriatric G8 screening test: A prospective multicenter observational study (ZEBRA/MEET-URO 9)
Background: Cabozantinib (CABO) is an oral tyrosine kinase inhibitor registered for the treatment of metastatic renal cell carcinoma (mRCC) for the first or subsequent lines. Tolerability in real world elderly patients is poorly documented. G8 is a short test for vulnerability gaining increased interest as a screening tool for trials in geriatric oncology. Methods: ZEBRA/MEET-URO 9 was a prospective multicenter study of safety and activity of CABO administered to pts ≥70 years with mRCC, either in the first or subsequent lines of treatment, until progression or unacceptable toxicity. All pts underwent G8 score at baseline, with a cut-off for vulnerability of 14 or below. Data on tolerability and activity were collected prospectively after signature of informed consent. Results: A total of 104 pts started CABO at 13 Italian Centers, 38,5% as first line. Median age was 75.8 yrs (range 70.2-87.4 yrs, 26 pts ≥80 yrs), 73.1% males. IMDC score was good 19.2%, intermediate 53.9%, poor 26.9%. Primary tumor had been removed in 82.7% of pts, histology was clear cell 78.8%, papillary 8.7%, chromophobe 5.8%, unclassified 6.7%. G8 score was ≤14 in 65.4% of pts. Up-front dose reduction of CABO was more frequent in pts with low G8 score (79.4 vs 41.7%, p=0.003), but eventually the majority of pts (91.4%) underwent dose reductions of CABO. After a median treatment of 6.4 months (0.5-26.1 months), 38.4% of pts developed G3-4 toxicities, 22.1% interrupted treatment due to adverse events, 2.8% (3 pts) died due to cardiovascular or thromboembolic events. Median PFS was 7.6 months (95% CI=5.8-12.6 months) in first line, 10.0 months (5.8-15.6) in second or further lines, median OS was 20.1 months (11.1-not reached) and 15.6 months (12.5-not reached), respectively. G8 score ≤14 did not correlate with rate of temporary interruptions >7 days, hospitalization, incidence of G3-5 toxicities, as well as with PFS. Pts with G8 score ≤14 had a trend for reduced OS, but difference was not statistically significant both in the first and further lines of treatment. Conclusions: Screening G8 test was positive in more than a half of pts, underlying the need for detailed geriatric assessment and increased clinical monitoring of such patients. A G8 score ≤14 correlated with up-front dose reduction of CABO but not with G3-5 toxicities probably due to the high rates of dose reductions in the whole cohort. Correlation between low G8 score and OS could not be demonstrated in this population
Association among metabolic syndrome, inflammation, and survival in prostate cancer
Metabolic syndrome (MS) and inflammation (INF) alterations are among the factors involved in cancer progression. The study aimed to assess the relationship between MS and INF and its effect on progression-free/overall survival (PFS/OS) in metastatic castration-resistant prostate cancer (mCRPC) treaed with abiraterone or enzalutamide