Pinocchio di Ancona, Italy
Pinocchio di Ancona, Italy

Time filter

Source Type

Sanna G.,Instituto Toscano Tumori | Fabi A.,Instituto Nazionale Tumori Regina Elena | Crivellari D.,Centro Of Riferimento Oncologico | Saracchini S.,Azienda Ospedaliera S Maria degli Angeli | And 11 more authors.
Tumori | Year: 2014

Methods: A subgroup analysis was carried out to report on the safety (primary endpoint) and efficacy (secondary endpoint) outcomes of patients recruited from Italian Centers.Results: A total of 278 patients were included. Median age was 57 years (range, 26-85), and ECOG performance status was 0 or 1 in 96% of the patients. Bevacizumab was predominantly combined with a taxane monotherapy: paclitaxel (41.4%), docetaxel (21.9%), or a taxane-based combination therapy (12.2%). The most frequent grade.3 adverse events previously associated with bevacizumab were hypertension (3.2%), proteinuria (2.9%), and cardiac disorders (0.7%). Median time to progression was 10.9 months. Median overall survival was 29.9 months, and 1-year survival probability was 85%. Objective responses were observed in 62.6% of the patients, and an additional 30% achieved stable disease.Conclusions: Results from the study support the safety and efficacy of bevacizumab in combination with chemotherapy for the treatment of locally recurrent/metastatic breast cancer in the context of routine oncology practice in Italy.Aims and background: The ATHENA international study investigated the safety and efficacy of bevacizumab plus first-line chemotherapy in locally recurrent/metastatic breast cancer in routine oncology practice. The present paper focuses on the outcomes of the Italian cohort of the study.


Lambertini M.,U.O. Oncologia Medica 2 | Ferreira A.R.,University of Lisbon | Poggio F.,U.O. Oncologia Medica 2 | Puglisi F.,University of Udine | And 15 more authors.
Oncologist | Year: 2015

Background. We evaluated the patterns of care and clinical outcomes of metastatic breast cancer patients treated with first-line trastuzumab-based therapy after previous (neo)adjuvant trastuzumab. Materials and Methods. A total of 416 consecutive, HER2-positive metastatic breast cancer patients who had received first-line trastuzumab-based therapy were identified at 14 Italian centers. A total of 113 patients had presented with de novo stage IV disease and were analyzed separately. Dichotomous clinical outcomes were analyzed using logistic regression and time-to-event outcomes using Cox proportional hazards models. Results. In the 202 trastuzumab-naive patients and 101 patients with previous trastuzumab exposure, we observed the following outcomes, respectively: overall response rate, 69.9% versus 61.3% (adjusted odds ratio [OR], 0.62; p =.131), clinical benefit rate, 79.1% versus 72.5% (adjusted OR, 0.73; p =.370), median progression-free survival (PFS), 16.1 months versus 12.0 months (adjusted hazards ratio [HR], 1.33; p =.045), and median overall survival (OS), 52.2 months versus 48.2 months (adjusted HR, 1.18; p =.404). Patients with a trastuzumab-free interval (TFI) <6 months, visceral involvement, and hormone receptor-negative disease showed a worse OS compared with patients with aTFI of $6 months (29.5 vs. 48.3 months; p =.331), nonvisceral involvement (48.0 vs. 60.3 months;p =.270), and hormone receptor-positive disease (39.8 vs. 58.6 months; p =.003), respectively. Conclusion. Despite the inferior median PFS, trastuzumab-based therapy was an effective first-line treatment for patients relapsing after (neo)adjuvant trastuzumab. Previous trastuzumab exposure and the respective TFI, type of first site of disease relapse, and hormone receptor status should be considered in the choice of the best first-line treatment option for HER2-positive metastatic breast cancer patients. © AlphaMed Press.


Spitaleri G.,Instituto Europeo Of Oncologia | Berardi R.,Clinica di Oncologia Medica | Pierantoni C.,Clinica di Oncologia Medica | De Pas T.,Instituto Europeo Of Oncologia | And 8 more authors.
Journal of Cancer Research and Clinical Oncology | Year: 2013

Purpose: L19-TNF is an armed antibody that selectively targets human TNF to extra domain B-fibronectin on tumour blood vessels. We performed a phase I/II first-in-man trial with L19-TNF monotherapy in metastatic solid cancer patients to study safety and signs of clinical activity. Methods: Six cohorts of patients were treated with increasing (1.3-13 μg/kg) doses of intravenous L19-TNF on day 1, 3, and 5 of repeated 3-weekly cycles, and 12 colorectal cancer patients were treated at 13 μg/kg. PK, antibody formation, changes in lymphocyte subsets, 5-HIAA plasma levels as well as safety and clinical activity were analysed. Results: Thirty-four patients received at least one L19-TNF dose. The serum half-life of L19-TNF at 13 μg/kg was 33.6 min, and maximum peak serum concentration was 73.14 μg/L. Mild chills, nausea and vomiting but no haemato- or unexpected toxicity were observed. Grade 3 lumbar pain in bone metastasis was the only dose-limiting toxicity found in one patient. Objective tumour responses were not detected. Transient stable disease occurred in 19 of 31 evaluable patients. Conclusions: Intravenous L19-TNF on day 1, 3, and 5 of a 3-weekly schedule was safe up to 13 μg/kg, but did not result in objective tumour responses. The maximally tolerated dose (MTD) was not reached, allowing for further dose escalation of L19-TNF possibly in combination with chemotherapy. © 2012 Springer-Verlag Berlin Heidelberg.


Insulin-like growth factor receptor 1 (IGF-1R) with its ligands and intracellular pathway is involved in cell growth and survival control. Many studies have shown how IGF-1R is over-expressed in various tumor cell lines and histological samples. In recent years many trials have been conducted investigating IGF-1R as a possible cancer therapy, with major efforts focusing on the use of monoclonal antibodies and small molecules directed against the IGF-1R-driven pathway. Several drugs are currently under intense investigation and in different experimental phases. Available data suggest that this class of drugs is well tolerated with mild to moderate side effects, when used alone or in combination with other therapeutic agents. The efficacy profile seems to be promising. However, further studies are needed to define the exact role of IGF-1R inhibitors in clinical practice.


PubMed | Clinica di Oncologia Medica
Type: Journal Article | Journal: Discovery medicine | Year: 2011

Insulin-like growth factor receptor 1 (IGF-1R) with its ligands and intracellular pathway is involved in cell growth and survival control. Many studies have shown how IGF-1R is over-expressed in various tumor cell lines and histological samples. In recent years many trials have been conducted investigating IGF-1R as a possible cancer therapy, with major efforts focusing on the use of monoclonal antibodies and small molecules directed against the IGF-1R-driven pathway. Several drugs are currently under intense investigation and in different experimental phases. Available data suggest that this class of drugs is well tolerated with mild to moderate side effects, when used alone or in combination with other therapeutic agents. The efficacy profile seems to be promising. However, further studies are needed to define the exact role of IGF-1R inhibitors in clinical practice.


PubMed | Clinica di Oncologia Medica, Marche Polytechnic University and University of Camerino
Type: Journal Article | Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology | Year: 2017

270 Background: Tyrosine kinase inhibitors (TKI), such as sunitinib, sorafenib and pazopanib, have replaced immunotherapy as the standard of care for metastatic renal cell carcinoma (mRCC). However, their use in sequential or combined strategies is limited by the lack of evidences on the ability of TKIs to induce cell death in cancer cells. Aim of our study was to evaluate the different mechanisms responsible of the cytotoxic effects induced in vitro by M doses of sunitinib, sorafenib and pazopanib in 5637 and J82 bladder cancer (BC) cell lines.The viability of BC cell lines were tested by MTT assay. Autophagy was evaluated by western blot analysis with the anti-LC3 and anti-p62 antibodies, acridine orange staining and cytofluorimetric analysis. Necrosis and apoptosis, (We found that treatment of 5637 and J82 BC cells with the three TKI agents markedly reduced cell viability. Treatment for 24 h with sunitinib and sorafenib at 20 M dose, triggers an incomplete autophagy of BC cells. In addition, inhibition of autophagy induced by sunitinib and sorafenib triggers cell death of BC cells. Thus, sunitinib by imparing the cathepsin B activity induces lysosomal-dependent necrosis. Similarly, sorafenib by defective lysosomial degradation triggers ROS- and mitochondrial-dependent apoptosis. As regard to pazopanib, we first demonstrate that treatment of BC cells for 72 hrs (20 M) induces autophagic Type II cell death, which was markedly reversed in a dose-dependent manner by 3MA and chloroquine autophagic inhibitors. Finally, pazopanib upregulates the mRNA expression of -glucosidase (GAA) and TP73 belonging to the p53 tumor suppressor genes.Overall, our results showing different TKI-induced cell death mechanisms provide the rationale for the sequential use of these agents and the biological basis for novel molecularly targeted approaches.


PubMed | Polithecnic University of the Marche Region Ospedali Riuniti, Medical Oncology, Marche Polytechnic University, Clinica di Oncologia Medica and Institute of Pathological Anatomy
Type: Journal Article | Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology | Year: 2017

388 Background: For the last few years, sunitinib has been considered the standard treatment for first-line metastatic renal cell carcinoma, but in 2010 a new drug pazopanib had been approved for treatment in this setting. Recent data from the COMPARZ and PISCES study seem to suggest a non-inferiority of pazopanib confronted with sunitinib in PFS and OS and a patients preference for pazopanib if we consider quality of life parameters. The aim of our study is to investigate whether polymorphisms of VEGF and VEGFR can influence PFS and OS when patients are treated either with sunitinib or pazopanib as first-line treatment.97 histologic samples of mRCC patients were tested for VEGF-A, VEGF-C, and VEGFR-1, 2, 3 single nucleotide polymorphisms (SNPs). Patients progression free survival (PFS) and overall survival (OS) were analyzed for first-line treatment.In patients treated with sunitinib VEGF-A rs833061 resulted significant in PFS (CC+CT vs TT, p < 0.0001) and OS (p < 0.0001). VEGF-A rs699947 was significant for PFS (AA+AC vs. CC) p = 0.0001) and OS (p < 0.0001). VEGF-A rs2010963 was significant in PFS (CC vs. CG vs. GG, p = 0.0001) and in OS (p = 0.0045). VEGR3 rs6877011 was significant in PFS (CC vs. CG, p = 0.0075) and OS (p = 0.0001). At multivariate analysis rs833061, rs2010963, and rs68877011 were significant in PFS. rs833061 and rs68877011 were independent factors in OS. In the pazopanib treated groups of patients VEGF-A rs833061 resulted significant in PFS (TT+CT vs. CC p = 0.027) Conclusions: In our analysis patients with CC or CT polymorphism of rc833061 had a favourable PFS and OS if treated with sunitinib instead patients treated with pazopanib seems to have benefit if CT+TT polymorphism, A polymorphism rs699947 and G polymorphism of rs2010963 seem to have a better PFS and OS in first line with sunitinib. Patients with C polymorphism of rs6877011 and G polymorphism of rs307822 seem equally to have a favourable impact in first-line therapy with sunitinib. Our data seem to suggest that biology could have a role in the choice of first-line treatment for mRCC patients. Further data will be presented at the Symposium.

Loading Clinica di Oncologia Medica collaborators
Loading Clinica di Oncologia Medica collaborators