49 research outputs found
Metronomic oral vinorelbine in advanced breast cancer and non-small-cell lung cancer: current status and future development
No full textMetronomic chemotherapy (mCT), a frequent administration of low-dose chemotherapy, allows prolonged treatment duration and minimizes the toxicity of standard-dose chemotherapy. mCT has multiple actions against cancer cells including inhibition of angiogenesis and modulation of the immune system. A number of studies lend support to the clinical efficacy of mCT in advanced breast cancer and non-small-cell lung cancer. However, further evidence is necessary to describe the optimal use of mCT and to identify suitable patients. Oral vinorelbine has emerged as a promising metronomic treatment in patients with metastatic breast cancer and non-small-cell lung cancer and is the only orally available microtubule-targeting agent. This paper reviews current evidence on metronomic oral vinorelbine, discusses its management and defines a suitable patient profile on the basis of a workshop of Italian experts
MDM2 and HIF1alpha expression levels in different histologic subtypes of malignant pleural mesothelioma: Correlation with pathological and clinical data
No full textMalignant pleural mesothelioma (MPM) is an aggressive tumor with poor prognosis and limited treatment options. Sarcomatoid/biphasic mesotheliomas are characterized by more aggressive behaviour and a poorer prognosis compared with the epithelioid subtype. To date prognostic and tailored therapeutic biomarkers are lacking. The present study analyzed the expression levels of MDM2 and HIF1alpha in different histologic subtypes from chemonaive MPM patients. Diagnostic biopsies of MPM patients from four Italian cancer centers were centrally collected and analyzed. MDM2 and HIF1alpha expression levels were investigated through immunohistochemistry and RT-qPCR. Pathological assessment of necrosis, inflammation and proliferation index was also performed. Molecular markers, pathological features and clinical characteristics were correlated to overall survival (OS) and progression free survival (PFS). Sixty MPM patients were included in the study (32 epithelioid and 28 non-epithelioid). Higher levels of MDM2 (p < 0.001), HIF1alpha (p = 0.013), necrosis (p = 0.013) and proliferation index (p < 0.001) were seen mainly in sarcomatoid/biphasic subtypes. Higher levels of inflammation were significantly associated with epithelioid subtype (p = 0.044). MDM2 expression levels were correlated with HIF1alpha levels (p = 0.0001), necrosis (p = 0.008) and proliferation index (p = 0.009). Univariate analysis showed a significant correlation of non-epithelioid histology (p = 0.04), high levels of necrosis (p = 0.037) and proliferation index (p = 0.0002) with shorter PFS. Sarcomatoid/biphasic and epithelioid mesotheliomas showed different MDM2 and HIF1alpha expression levels and were characterized by different levels of necrosis, proliferation and inflammation. Further studies are warranted to confirm a prognostic and predictive role of such markers and features
Pleural mesothelioma patients and ex-exposed asbestos workers are immunologically poor responders to oncogenic Merkel cell polyomavirus
No full textBackground: Pleural mesothelioma (PM) is an aggressive tumor of the serous cavities primarily caused by the inhalation of asbestos, a carcinogenic and immunomodulatory mineral. Other factors, such as oncogenic
viruses, might be involved in PM onset. Merkel cell polyomavirus (MCPyV) is a ubiquitous oncogenic DNA virus whose increased activity has been documented in conditions of immunosuppression. In this study, we
aimed to investigate the immunological response to MCPyV in PM patients and workers ex-exposed to asbestos (WEA).
Methods: MCPyV serology was investigated herein in sera from 108 PM patients, 102 WEA, and 110 healthy subjects (HS). Total serum immunoglobulin G (IgG) levels were evaluated. The presence of MCPyV DNA and viral protein (VP)1 and large T (LT) messenger RNAs (mRNAs) was evaluated by droplet-digital polymerase chain reaction (ddPCR)/quantitative polymerase chain reaction (qPCR) in 50 tumor specimens from PM patients unrelated to PM serum donors.
Results: Reduced serum anti-MCPyV IgG rates and optical densities (ODs) were detected in PM (26.9% and 0.08–0.09) and WEA (27.5% and 0.08–0.09) compared to HS (60.9% and 0.16–0.33) (P<0.001), while the mean total IgG concentrations were similar among groups (4.3–5.7 mg/mL) (P>0.05). Biphasic
PM histotype exhibited the lowest MCPyV IgG levels. WEAs with the highest asbestos exposure had the lowest rate and ODs of serum anti-MCPyV IgGs (5.6% and 0.074–0.083) in contrast to WEA (44.4% and 0.083–0.096) with lower exposure. Spearman analyses revealed an inverse correlation between ODs and both cumulative asbestos exposure and years of asbestos exposure (P<0.05), while a direct correlation was detected between years since last exposure and ODs (P=0.02). MCPyV DNA was detected in 32% of PM specimens with a mean viral DNA load of 0.39±0.2 copy/cell. VP1 mRNA was detected in all MCPyV DNA-positive PMs, while 69% of these specimens tested LT mRNA-positive.
Conclusions: Our study provides the first evidence that PM and WEA may experience a specific impairment of their immune response to MCPyV. This might possibly depend on the immunomodulatory effect of asbestos, a well-known immunosuppressive mineral
Role of Baseline and Post-Therapy 18F-FDG PET in the Prognostic Stratification of Metastatic Castration-Resistant Prostate Cancer (mCRPC) Patients Treated with Radium-223
No full textRadium-223 dichloride (Ra223) represents the unique bone-directed treatment option that shows an improvement in overall survival (OS) in metastatic castrate resistant prostate cancer (mCRPC). However, there is an urgent need for the identification of reliable biomarkers to non-invasively determine its efficacy (possibly improving patients’ selection or identifying responders’ after therapy completion). 18F-Fluorodeoxyglucose (FDG)-avidity is low in naïve prostate cancer, but it is enhanced in advanced and chemotherapy-refractory mCRPC, providing prognostic insights. Moreover, this tool showed high potential for the evaluation of response in cancer patients with bone involvement. For these reasons, FDG Positron Emission Tomography (FDG-PET) might represent an effective tool that is able to provide prognostic stratification (improving patients selection) at baseline and assessing the treatment response to Ra223. We conducted a retrospective analysis of 28 mCRPC patients that were treated with Ra223 and submitted to bone scan and FDG-PET/CT for prognostic purposes at baseline and within two months after therapy completion. The following parameters were measured: number of bone lesions at bone scan, SUVmax of the hottest bone lesion, metabolic tumor volume (MTV), and total lesion glycolysis (TLG). In patients who underwent post-therapy 18F-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography (FDG-PET/CT), (20/28), PET Response Criteria in Solid Tumors (PERCIST), and European Organization for Research and Treatment of Cancer (EORTC) criteria were applied to evaluate the metabolic treatment response. The difference between end of therapy and baseline values was also calculated for Metabolic Tumor Volume (MTV), TLG, prostate-specific antigen (PSA), alkaline phosphatase (AP), and lactate dehydrogenase (LDH) (termed deltaMTV, deltaTLG, deltaPSA, deltaAP and deltaLDH, respectively). Predictive power of baseline and post-therapy PET- and biochemical-derived parameters on OS were assessed by Kaplan–Meier, univariate and multivariate analyses. At baseline, PSA, LDH, and MTV significantly predicted OS. However, MTV (but not PSA nor LDH) was able to identify a subgroup of patients with worse prognosis, even after adjusting for the number of lesions at bone scan (which, in turn, was not an independent predictor of OS). After therapy, PERCIST criteria were able to capture the response to Ra223 by demonstrating longer OS in patients with partial metabolic response. Moreover, the biochemical parameters were outperformed by PERCIST in the post-treatment setting, as their variation after therapy was not informative on long term OS. The present study supports the role of FDG-PET as a tool for patient’s selection and response assessment in mCRPC patients undergoing Ra223 administration
Solitary fibrous tumor
No full textSolitary fibrous tumor (SFT) is a rare mesenchymal neoplasm which may be found everywhere in the body. It is now distinguished into two forms, pleural and extrapleural, which morphologically resemble each other. Abdominal localizations are quite rare, with 10 cases only reported in bladder; rarely they can be source of paraneoplastic syndromes (i.e., hypoglycemia secondary to insulin-like growth factor). In April 2006 a 74-year-old white male presented with chills, diaphoresis and acute abdominal pain with hematuria. At admission in emergency he underwent an abdominal X-ray (no pathological findings) and an ultrasound examination of the kidneys and urinary tract, which revealed a pelvic hyperechogenic neoformation measuring approximately 10¥8¥7 cm, compressing the bladder. Blood chemistry at admission revealed only a mild neutrophilic leucocytosis (WBC 16600, N 80%, L 11%), elevated fibrinogen and ESR, and hypoglycemia (38 mg/dL). Macroscopic hematuria was evident, while urinocolture was negative. Contrast enhanced CT scan of the abdomen and pelvic region revealed a large round neoformation dislocating the bladder, with an evident contrast-enhanced periphery and a central necrotic area. Continuous infusion of glucose 5% solution was necessary in order to maintain blood glucose levels above 50 mg/dL. The patient underwent complete surgical resection of an ovoidal mass coated by adipose tissue, with well delimited margins; histological findings were consistent with solitary fibrous tumor (SFT). Hypoglycemia resolved completely with removal of the growth. In this case report we describe a SFT growing in the bladder, a quite rare localization, which presented a unique hypoglycemia. In contrast to the majority of cases reported in the literature, the behavior of this SFT was not aggressive, and, since the patient is still alive, surgical resection was considered conclusive
Studies on Hemotoxicity of Cyclophosphamide, Doxorubicin and Cis-Diamminodichloroplatinum Combined with Sodium-2-Mercaptoethane Sulfonate
No full text The possible protective action of sodium-2-mercaptoethanesulfonate (mesna) on hemotoxicity induced by anticancer drugs was tested in normal mice. Mesna (100 mg/kg b.w.) was injected i.v. 1 h before the i.v. administration of cyclophosphamide (10, 120, and 200 mg/kg b.w.), doxorubicin (4.32, 7.2, and 12 mg/kg b.w.) and cis-diamminedichloroplatinum (5.4, 9, and 15 mg/kg b.w.). Results show that in this experimental model mesna does not seem to protect against toxicity of the tested anticancer drug on hemopoietic progenitor cells. </jats:p
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
No full textbackground: 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
Cisplatin-Based First-Line Treatment of Elderly Patients With Advanced Non-Small-Cell Lung Cancer: Joint Analysis of MILES-3 and MILES-4 Phase III Trials
No full textPurpose To test the efficacy of adding cisplatin to first-line treatment for elderly patients with advanced non-small-cell lung cancer (NSCLC) within a combined analysis of two parallel phase III trials, MILES-3 and MILES-4. Patients and methods Patients with advanced NSCLC who were older than age 70 years with Eastern Cooperative Oncology Group performance status 0 to 1 were randomly assigned to gemcitabine or pemetrexed, without or with cisplatin. In each trial, 382 events were required to detect a hazard ratio (HR) of death of 0.75, with 80% power and two-tailed α of .05. Trials were closed prematurely because of slow accrual, but the joint database allowed us to analyze the efficacy of cisplatin on the basis of intention-to-treat and adjusted by trial, histotype, non-platinum companion drug, stage, performance status, sex, age, and size of the study center. Results From March 2011 to August 2016, 531 patients (MILES-3, 299; MILES-4, 232) were assigned to gemcitabine or pemetrexed without (n = 268) or with cisplatin (n = 263). Median age was 75 years, 79% were male, and 70% had nonsquamous histology. At a median 2-year follow-up, 384 deaths and 448 progression-free survival events were recorded. Overall survival was not significantly prolonged with cisplatin (HR, 0.86; 95% CI, 0.70 to 1.05; P = .14) and global health status score of quality of life was not improved, whereas progression-free survival (HR, 0.76; 95% CI, 0.63 to 0.92; P = .005) and objective response rate (15.5% v 8.5%; P = .02) were significantly better. Significantly more severe hematologic toxicity, fatigue, and anorexia were found with cisplatin. Conclusion The addition of cisplatin to single-agent chemotherapy does not significantly prolong overall survival, and it does not improve global health status score of quality of life in elderly patients with advanced NSCLC
Atezolizumab Plus Carboplatin and Etoposide in Patients with Untreated Extensive-Stage Small-Cell Lung Cancer: Interim Results of the MAURIS Phase IIIb Trial
No full textBackground: MAURIS is an Italian multicenter, open-label, phase IIIb ongoing trial, aiming at evaluating the safety and effectiveness of atezolizumab+carboplatin/etoposide in patients with newly diagnosed, extensive-stage small-cell lung cancer (ES-SCLC). The primary objective is the safety evaluation. Materials and Methods: Patients received atezolizumab+carboplatin/etoposide Q3W for 4-6 cycles in the induction phase, followed by atezolizumab maintenance Q3W. We presented the interim analysis on safety (referring to the induction phase) and clinical effectiveness, in all patients (N=154) and in subgroups that received ≤3 (N=23), 4 (N=43), and 5-6 cycles (N=89) of induction. Results: At a median follow-up of 10.5 months, 139 patients (90.3%) discontinued treatment. Serious adverse events occurred in 29.9% of patients overall, and the rate was lower in patients with 5-6 cycles (19.1%) than in those with 4 (34.9%) or ≤3 (63.6%) cycles. Immune-mediated adverse events were reported in 14.9%, 15.7%, 11.6%, and 18.2% of patients, overall and by subgroup, respectively. The median overall survival and progression-free survival were 10.7 and 5.5 months, respectively. Overall, 111 patients (71.6%) had a tumor response. Conclusions: Interim results provide further evidences about safety and efficacy profile of atezolizumab+carboplatin/etoposide treatment in a ES-SCLC patient population closer to that observed in clinical practice. Clinical Trial Registration: Eudract No. 2019-001146-17, NCT04028050
