8 research outputs found
Oxaliplatin and Raltitrexed in the Treatment of Inoperable Malignant Pleural Mesothelioma: Results of a Pilot Study
No full textAims and Background The treatment of inoperable malignant pleural mesothelioma is a challenge for the oncologist. Available chemotherapy regimens achieve poor results, therefore new agents or combinations are needed. In a phase I study, the combination of oxaliplatin and raltitrexed was shown to be active against malignant pleural mesothelioma. We herein report the results of a pilot study about the treatment of this disease. Methods From April 1999 to June 2000, we enrolled 11 chemotherapy-naïve patients with inoperable malignant pleural mesothelioma suitable to receive the following combination chemotherapy: raltitrexed, 3 mg/m2 iv, and oxaliplatin, 130 mg/m2, as a 2-hr infusion every 3 weeks. Results Four partial responses, 1 regression of disease (objective response rate, 45%; 95% Cl, 15.6-74.4%), 4 stable diseases and 2 progressions of disease were observed. An improvement in disease-related symptoms was recorded in all responders and in 2 patients with stable disease. Toxicity was mild, with no toxic-related death and only 1 episode of grade 4 neurotoxicity. Conclusions We consider the combination promising and worthy of further studies. </jats:sec
Volcanic events that have marked the anthropic history of the Aeolian Islands
No full textArchaeological and historical studies, conducted since 1950, allow us to trace a hypothetical demographic framework in which three crises attributed by scholars to unfavourable social-economic situations or to war aggression, can be observed. The comparison with volcanological studies highlights the occurrence during the crisis of volcanic events that can affect the local anthropic history. The first crisis occurred in 4th millennium BC involved all the Aeolian Islands and in particular Contrada Diana the main Neolithic site of Lipari. During the Diana Spatarella facies are documented the reduction of the coastal settlement of Contrada Diana, the choice to inhabit the Rocca del Castello, and the settlements development on areas protected from the volcanic activity. These facts support the hypothesis that Contrada Diana could be exposed to the effects of the tsunami waves caused by Sciara del Fuoco collapse of Stromboli, and indirectly to the eruptions of Gran Cratere of Vulcano that also caused problems to the sailors travelling from mainland to Lipari and back.The second crisis located between 9th and 6th century BC could be similarly caused by the effects of the strong eruptive phase occurred 2.9 ka at Vulcano and the tsunami produced by another sector collapse occurred at the end of the Neostromboli. As during the first crisis, even the navigation from mainland to Lipari will have been involved making difficult this destination.The third crisis is happened in the historical period between 6th and 11th century with a possible peak during the eruption of Monte Pilato occurred in 776 AD in the NE sector of the Lipari.
Dalla competizione all’integrazione nel Medio Oriente-Nord Africa. L’impatto degli Accordi di Abramo sugli equilibri regionali
No full textIn che modo sta mutando l’equilibrio regionale in Medio Oriente-Nord Africa? Quale impatto la firma degli Accordi di Abramo sta avendo sulla regione? Prendendo le mosse dalla firma degli accordi di normalizzazione tra Israele e quattro Paesi arabi – Bahrain, Emirati Arabi Uniti, Marocco, Sudan – avvenuta nel 2020, il volume riflette sul mutamento dell’equilibrio regionale innescato dal processo di integrazione tra Israele e alcuni Paesi del mondo arabo. A tale proposito, esamina da una prospettiva teorica la strategia negoziale dietro gli Accordi di Abramo per poi analizzare tre dimensioni chiave entro cui può essere suddivisa la nascente cooperazione tra gli attori coinvolti: piano regionale, geo-economico e socio-culturale. Energia, transizione ecologica, turismo e dialogo interreligioso sono solo alcuni dei settori di cooperazione che l’opera si prefigge di indagare, per comprendere se, almeno parzialmente, in Medio Oriente-Nord Africa la logica della competizione stia lasciando il passo a quella dell’integrazione. Infine, il volume prende in esame gli effetti indiretti degli Accordi di Abramo su alcuni attori regionali ed extra-regionali non firmatari degli stessi
Adjuvant anastrozole versus exemestane versus letrozole, upfront or after 2 years of tamoxifen, in endocrine-sensitive breast cancer (FATA-GIM3): a randomised, phase 3 trial
No full textBackground: Uncertainty exists about the optimal schedule of adjuvant treatment of breast cancer with aromatase inhibitors and, to our knowledge, no trial has directly compared the three aromatase inhibitors anastrozole, exemestane, and letrozole. We investigated the schedule and type of aromatase inhibitors to be used as adjuvant treatment for hormone receptor-positive early breast cancer. Methods: FATA-GIM3 is a multicentre, open-label, randomised, phase 3 trial of six different treatments in postmenopausal women with hormone receptor-positive early breast cancer. Eligible patients had histologically confirmed invasive hormone receptor-positive breast cancer that had been completely removed by surgery, any pathological tumour size, and axillary nodal status. Key exclusion criteria were hormone replacement therapy, recurrent or metastatic disease, previous treatment with tamoxifen, and another malignancy in the previous 10 years. Patients were randomly assigned in an equal ratio to one of six treatment groups: oral anastrozole (1 mg per day), exemestane (25 mg per day), or letrozole (2·5 mg per day) tablets upfront for 5 years (upfront strategy) or oral tamoxifen (20 mg per day) for 2 years followed by oral administration of one of the three aromatase inhibitors for 3 years (switch strategy). Randomisation was done by a computerised minimisation procedure stratified for oestrogen receptor, progesterone receptor, and HER2 status; previous chemotherapy; and pathological nodal status. Neither the patients nor the physicians were masked to treatment allocation. The primary endpoint was disease-free survival. The minimum cutoff to declare superiority of the upfront strategy over the switch strategy was assumed to be a 2% difference in disease-free survival at 5 years. Primary efficacy analyses were done by intention to treat; safety analyses included all patients for whom at least one safety case report form had been completed. Follow-up is ongoing. This trial is registered with the European Clinical Trials Database, number 2006-004018-42, and ClinicalTrials.gov, number NCT00541086. Findings: Between March 9, 2007, and July 31, 2012, 3697 patients were enrolled into the study. After a median follow-up of 60 months (IQR 46â72), 401 disease-free survival events were reported, including 211 (11%) of 1850 patients allocated to the switch strategy and 190 (10%) of 1847 patients allocated to upfront treatment. 5-year disease-free survival was 88·5% (95% CI 86·7â90·0) with the switch strategy and 89·8% (88·2â91·2) with upfront treatment (hazard ratio 0·89, 95% CI 0·73â1·08; p=0·23). 5-year disease-free survival was 90·0% (95% CI 87·9â91·7) with anastrozole (124 events), 88·0% (85·8â89·9) with exemestane (148 events), and 89·4% (87·3 to 91·1) with letrozole (129 events; p=0·24). No unexpected serious adverse reactions or treatment-related deaths occurred. Musculoskeletal side-effects were the most frequent grade 3â4 events, reported in 130 (7%) of 1761 patients who received the switch strategy and 128 (7%) of 1766 patients who received upfront treatment. Grade 1 musculoskeletal events were more frequent with the upfront schedule than with the switch schedule (924 [52%] of 1766 patients vs 745 [42%] of 1761 patients). All other grade 3â4 adverse events occurred in less than 2% of patients in either group. Interpretation: 5 years of treatment with aromatase inhibitors was not superior to 2 years of tamoxifen followed by 3 years of aromatase inhibitors. None of the three aromatase inhibitors was superior to the others in terms of efficacy. Therefore, patient preference, tolerability, and financial constraints should be considered when deciding the optimal treatment approach in this setting. Funding: Italian Drug Agency
Verso un nuovo concetto strategico NATO. Prospettive e interessi dell’Italia
No full textLa redistribuzione del potere in corso su scala globale pone l’Alleanza Atlantica di fronte a due dilemmi. Anzitutto, se preservare – o meno – la centralità della NATO rispetto alle dinamiche internazionali contemporanee, contribuendo in misura determinante alla difesa dello status quo emerso alla fine della Guerra fredda. In secondo luogo, identificare quali strumenti siano veramente efficaci per conseguire l’obiettivo minimo della sicurezza dei suoi Paesi membri. Questi interrogativi costituiranno con tutta probabilità il core business del prossimo Concetto Strategico, che dovrebbe venire alla luce in concomitanza con il Summit di Madrid (giugno 2022). Il volume riflette su questi e altri problemi che gravano sull’Alleanza assumendo la prospettiva italiana. Inutile nascondere, d’altronde, che anche all’interno di un’organizzazione tanto consolidata quanto la NATO si verifichi incessantemente un gioco di sovrapposizione, scontro e integrazione tra interessi generali e particolari. Al suo interno, ogni Paese membro cerca di massimizzare i vantaggi della partecipazione provando a ridurne – per quanto possibile – i costi. L’Italia non fa eccezione. I risultati qui presentati sono il frutto di una ricerca condotta dal Centro Studi Geopolitica.info, in collaborazione con il CEMAS Sapienza, nell’ambito delle attività dell’Osservatorio di Politica Internazionale (OPI), progetto di collaborazione tra Senato della Repubblica, Camera dei Deputati e Ministero degli Esteri e della Cooperazione Internazionale
Adjuvant anastrozole versus exemestane versus letrozole, upfront or after 2 years of tamoxifen, in endocrine-sensitive breast cancer (FATA-GIM3): a randomised, phase 3 trial
No full textBackground: Uncertainty exists about the optimal schedule of adjuvant treatment of breast cancer with aromatase inhibitors and, to our knowledge, no trial has directly compared the three aromatase inhibitors anastrozole, exemestane, and letrozole. We investigated the schedule and type of aromatase inhibitors to be used as adjuvant treatment for hormone receptor-positive early breast cancer. Methods: FATA-GIM3 is a multicentre, open-label, randomised, phase 3 trial of six different treatments in postmenopausal women with hormone receptor-positive early breast cancer. Eligible patients had histologically confirmed invasive hormone receptor-positive breast cancer that had been completely removed by surgery, any pathological tumour size, and axillary nodal status. Key exclusion criteria were hormone replacement therapy, recurrent or metastatic disease, previous treatment with tamoxifen, and another malignancy in the previous 10 years. Patients were randomly assigned in an equal ratio to one of six treatment groups: oral anastrozole (1 mg per day), exemestane (25 mg per day), or letrozole (2·5 mg per day) tablets upfront for 5 years (upfront strategy) or oral tamoxifen (20 mg per day) for 2 years followed by oral administration of one of the three aromatase inhibitors for 3 years (switch strategy). Randomisation was done by a computerised minimisation procedure stratified for oestrogen receptor, progesterone receptor, and HER2 status; previous chemotherapy; and pathological nodal status. Neither the patients nor the physicians were masked to treatment allocation. The primary endpoint was disease-free survival. The minimum cutoff to declare superiority of the upfront strategy over the switch strategy was assumed to be a 2% difference in disease-free survival at 5 years. Primary efficacy analyses were done by intention to treat; safety analyses included all patients for whom at least one safety case report form had been completed. Follow-up is ongoing. This trial is registered with the European Clinical Trials Database, number 2006-004018-42, and ClinicalTrials.gov, number NCT00541086. Findings: Between March 9, 2007, and July 31, 2012, 3697 patients were enrolled into the study. After a median follow-up of 60 months (IQR 46–72), 401 disease-free survival events were reported, including 211 (11%) of 1850 patients allocated to the switch strategy and 190 (10%) of 1847 patients allocated to upfront treatment. 5-year disease-free survival was 88·5% (95% CI 86·7–90·0) with the switch strategy and 89·8% (88·2–91·2) with upfront treatment (hazard ratio 0·89, 95% CI 0·73–1·08; p=0·23). 5-year disease-free survival was 90·0% (95% CI 87·9–91·7) with anastrozole (124 events), 88·0% (85·8–89·9) with exemestane (148 events), and 89·4% (87·3 to 91·1) with letrozole (129 events; p=0·24). No unexpected serious adverse reactions or treatment-related deaths occurred. Musculoskeletal side-effects were the most frequent grade 3–4 events, reported in 130 (7%) of 1761 patients who received the switch strategy and 128 (7%) of 1766 patients who received upfront treatment. Grade 1 musculoskeletal events were more frequent with the upfront schedule than with the switch schedule (924 [52%] of 1766 patients vs 745 [42%] of 1761 patients). All other grade 3–4 adverse events occurred in less than 2% of patients in either group. Interpretation: 5 years of treatment with aromatase inhibitors was not superior to 2 years of tamoxifen followed by 3 years of aromatase inhibitors. None of the three aromatase inhibitors was superior to the others in terms of efficacy. Therefore, patient preference, tolerability, and financial constraints should be considered when deciding the optimal treatment approach in this setting. Funding: Italian Drug Agency
