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Sant'Ambrogio di Torino, Italy

Ferrario A.,University of Milan | Pulsoni A.,University of Rome La Sapienza | Olivero B.,University of Milan | Rossi G.,Spedali Civili | And 11 more authors.
Cancer | Year: 2012

BACKGROUND: Indolent nonfollicular non-Hodgkin B-cell lymphomas (INFLs) are clonal mature B-cell proliferations for which treatment has not been defined to date. METHODS: In this phase 2 study of patients with advanced INFL, the authors evaluated the efficacy and safety of first-line rituximab, fludarabine, and cyclophosphamide (FCR) as induction immunochemotherapy (rituximab 375 mg/m 2 intravenously on day 1 of each cycle and on days 1 and 14 of cycles 4 and 5; fludarabine 25 mg/m 2 intravenously on days 2-4, cyclophosphamide 250 mg/m 2 intravenously on Days 2-4) every 28 days for 6 cycles followed by a maintenance phase with 4 infusions of rituximab (375 mg/m 2 intravenously on day 1) every 2 months for responders. RESULTS: Forty-seven patients were enrolled. Among 46 evaluable patients (28 men; median age, 59 years), 19 were diagnosed with lymphoplasmacytic lymphoma, 21 were diagnosed with small lymphocytic lymphoma, and 6 were diagnosed with nodal marginal zone lymphoma. The overall response rate after maintenance was 89.1% with a 67.4% complete remission (CR) rate (CR/unconfirmed CR) and a 21.7% partial response rate. After a median follow-up of 40.9 months, the failure-free survival and progression-free survival rates both were 90.1%, and the overall survival rate was 97.4%. The main toxicity was hematologic, and related grade 3 and 4 neutropenia was observed in 55.3% of patients. CONCLUSIONS: FCR induction therapy followed by a short maintenance phase is a highly effective regimen with acceptable toxicity. Cancer 2012. © 2011 American Cancer Society. Indolent nonfollicular non-Hodgkin B-cell lymphomas are clonal mature B-cell proliferations for which treatment has not been defined to date. The combination of rituximab, fludarabine, and cyclophosphamide as induction immunochemotherapy followed by a short maintenance phase with rituximab is a highly effective regimen with acceptable toxicity in this subset of lymphomas. Copyright © 2011 American Cancer Society. Source

Galassi A.R.,University of Catania | Tomasello S.D.,University of Catania | Werner G.S.,Medizinische Klinik i Klinikum | Sianos G.,University Hospital | And 16 more authors.
EuroIntervention | Year: 2011

Aims: In comparison with non-occlusive lesions, percutaneous coronary intervention (PCI) of chronic total occlusions (CTO) represents a greater challenge for the interventionalist, due to lower procedural success rates, relatively higher incidence of procedural complications and the increased rate of restenosis. The European Registry of Chronic Total Occlusion (ERCTO) was created with the goal of evaluating the real impact of CTO PCI in the European context, trying to analyse the rates of procedural success, technical information from the CTO procedures and patient outcome. Methods and results: Data collection was carried out in 16 centres across Europe, starting from the beginning of January 2008. In two years of activity, a total of 1,914 patients with 1,983 CTO lesions were consecutively enrolled in the registry. Overall procedural success was achieved in 1,607 lesions (82.9%); anterograde procedures obtained higher procedural success of retrograde ones (83.2% versus 64.5%, p<0.001). Coronary perforation occurred more frequently in patients who underwent retrograde approach (4.7% versus 2.1%, p=0.04). Although no differences were observed in terms of 30-day major adverse cardiac events between anterograde and retrograde treated patients, a trend toward higher periprocedural non-Q-wave myocardial infarction was found in patients in which the retro- grade approach was attempted (2.1% versus 1% p=0.08). Moreover, retrograde approach was related with longer procedural and fluoroscopy times (156.9±62.5 min vs. 98.2±52.8 min and 73.3±59.9 min vs. 38.2±43.9 min respectively, p<0.001) and higher contrast load administration (402±161 cc vs. 302±184 cc, p<0.001). Conclusions: The first report of the ERCTO registry by the EuroCTO club shows a high procedural success rate obtained by expert European operators in a "real-world" consecutive series of patients, comparable with those reported by Japanese registries. The rate of observed procedural adverse events was low and similar to the non-CTO PCI series. In this registry, retrograde procedures were associated with extended fluoroscopy exposure and procedural time, increased contrast load administration as well as a higher incidence of coronary perforations. Such outcomes should become the standard of care that all centres undertaking CTO PCI should aspire to. © Europa Edition 2011. All rights reserved. Source

Braido F.,University of Genoa | Bagnasco D.,University of Genoa | Scichilone N.,Cervello | Santus P.,University of Milan | And 4 more authors.
Panminerva Medica | Year: 2012

Chronic obstructive pulmonary disease (COPD) is characterized by chronic inflammation of the airways, with the involvement of many inflammatory cells and mediators. Traditionally, this inflammation is thought to spread to a systemic level, thus inducing damage of different organs. However, other pathogenetic mechanisms could take part to the above-described process, and some open questions need to be solved. Due to the burden and increasing prevalence of COPD, the opportunity to find biomarkers that can potentially be useful in identifying individuals with the disease, or better, prior to symptoms onset, to diagnose and properly manage the respiratory symptoms, as well as to evaluate the response to treatment and to select specific subtypes of patients for tailored treatments is strongly advocated. Several mediators, enzymes, hormones and cells have been claimed to adhere to this objective. Moreover, the presence of comorbid or concomitant diseases can variably influence the concentration of specific biomarkers in samples of individuals with COPD, and age-related functional and structural changes (inflammaging) can further confuse the biological pattern. Several observations have been performed in the last decades; nevertheless, no biomarker is currently considered as satisfying all the abovementioned issues. The "Evaluation of COPD longitudinally to identify predictive surrogates and points (ECLIPSE)" study has specifically explored the possibility to identify novel biomarkers that correlate with clinically relevant COPD subtypes and with markers of disease progression. Among the thirty-four biomarkers considered, 15 resulted to be increased in COPD patients rather than in smoker and non-smoker controls. Specific lung proteins such as CC-16 and SPD are promising in detecting lung damage, exacerbation susceptibility or responsiveness to treatment. The ECLIPSE findings confirm that, to date, the use of a single biomarker is not sufficient, but the combination of novel biomarkers with the already existing tools could improve our skills in optimizing treatment of COPD patients. Source

Rolfo C.,University of Antwerp | Raez L.E.,Memorial Cancer Institute | Bronte G.,University of Palermo | Santos E.S.,Lynn Cancer Institute | And 4 more authors.
Expert Opinion on Investigational Drugs | Year: 2013

Introduction: Several new targeted agents with anti-angiogenic properties have been developed recently, including vandetanib, sunitinib, sorafenib, bevacizumab and others. Tumor development, progression, metastasis are strongly linked to angiogenesis. Targeted agents like bevacizumab, a monoclonal antibody which targets VEGF, have been fully developed in several solid tumors. These new agents strongly advocate that targeting angiogenesis is one of the best approaches for cancer therapy. Areas covered: Those agents that target additional pro-angiogenic intracellular signaling pathways beyond VEGF signaling have also the potential to contribute to anticancer therapies. The authors present here nintedanib (BIBF 1120), a triple angiokinase inhibitor. It targets not only VEGFRs, but also FGFR and PDGFR. All the available clinical information regarding Phase I-II trials and the toxicity and efficacy of BIBF 1120 both as single agent and in combination with cytotoxic agents in non-small cell lung cancer (NSCLC) is reviewed and discussed here. Expert opinion: Up till now, Phase I and II trials with nintedanib showed an improvement for survival of advanced NSCLC patients. Tolerability profile seems to be acceptable in these clinical trials. However, Phase III trials are mandatory to translate these findings into clinical practice. The research for predictive biomarkers could improve the success of these anti-angiogenic agents. © 2013 Informa UK, Ltd. Source

Rolfo C.,University of Antwerp | Giovannetti E.,VU University Amsterdam | Hong D.S.,University of Houston | Bivona T.,University of California at San Francisco | And 15 more authors.
Cancer Treatment Reviews | Year: 2014

Introduction: Treatment with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) yields tumour responses in non-small cell lung cancer (NSCLC) patients harbouring activating EGFR mutations. However, even in long-lasting responses, resistance to EGFR TKIs invariably occurs. Areas covered: This review examines resistance mechanisms to EGFR TKI treatment, which mainly arise from secondary EGFR mutations. Other resistance-inducing processes include mesenchymal-epithelial transition factor (MET) amplification, epithelial-mesenchymal transformation, phenotypic change from NSCLC to small-cell lung carcinoma, and modifications in parallel signalling pathways. Current therapeutic strategies to overcome these EGFR TKI resistance mechanisms focus on the inhibition or blocking of multiple members of the ErbB family. Several molecules which target multiple ErbB receptors are being investigated in NSCLC and other indications including afatinib, an ErbB Family Blocker, as well as dacomitinib and lapatinib. Novel, non-quinazoline, EGFR inhibitors, that also target EGFR activating and resistance (T790M) mutations, are currently under clinical development. Other therapeutic strategies include inhibition of parallel and downstream pathways, using agents which target heat shock protein (HSP)90 or poly (ADP-ribose) polymerase in addition to mammalian target of rapamycin (mTOR), monoclonal antibodies against the insulin-like growth factor-1 receptor, and fulvestrant-mediated oestrogen receptor regulation. Conclusion: Improved understanding of mechanisms underlying resistance to EGFR TKIs emphasises the importance of a genotype-guided approach to therapy. Elucidation of resistance mechanisms is indeed crucial to target innovative therapeutic approaches and to improve the efficacy of anticancer regimes in NSCLC. © 2014 Elsevier Ltd. Source

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