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Bracarda S.,UOC Medical Oncology | Montironi R.,Anathomo Pathology Unit | Porta C.,Policlinico San Matteo | Szczylic C.,Military Institute of Health | And 3 more authors.
Future Oncology | Year: 2013

The objectives of this innovative meeting were to discuss developments in the management of genitourinary cancer worldwide and how Italian clinicians could harness these innovations in their everyday practice. The 2-day meeting was divided into two sessions covering kidney and prostate cancer, and a large part was given over to the presentation and discussion of new recently presented data at major international congresses in 2012. There were no restrictions on content and all subjects from pathology, surgery and genetics to therapy and patient outcomes were covered. © 2013 Future Medicine Ltd.


Bracarda S.,UOC Medical Oncology | Montironi R.,Anathomo Pathology Unit | Porta C.,Policlinico San Matteo | Szczylic C.,Military Institute of Health | And 3 more authors.
Future Oncology | Year: 2013

The objectives of this innovative meeting were to discuss developments in the management of genitourinary cancer worldwide and how Italian clinicians could harness these innovations in their everyday practice. The 2-day meeting was divided into two sessions covering kidney and prostate cancer, and a large part was given over to the presentation and discussion of new recently presented data at major international congresses in 2012. There were no restrictions on content and all subjects from pathology, surgery and genetics to therapy and patient outcomes were covered. © 2013 Future Medicine Ltd.


Porta C.,University of Pavia | Procopio G.,Italian National Cancer Institute | Carteni G.,Cardarelli Hospital | Sabbatini R.,University of Modena and Reggio Emilia | And 15 more authors.
BJU International | Year: 2011

Study Type - Therapy (retrospective cohort) Level of Evidence 2b What's known on the subject? and What does the study add? Various targeted agents with differing mechanisms of action and toxicity profiles have now been approved for the treatment of advanced RCC. However, the optimal use of these agents remains a challenge. Since the approval of sorafenib and sunitinib, many patients have been treated with these two tyrosine kinase inhibitors (TKIs) in sequence, with current evidence suggesting that this approach is associated with continued clinical benefit, with limited or no cross-resistance between the two agents. The mammalian target of rapamycin (mTOR) inhibitor, everolimus, has been shown to be as effective after two TKIs as it is after one TKI, emphasizing the importance of understanding the optimal TKI sequence before switching to an mTOR inhibitor, to provide patients with the longest progression-free survival (PFS) benefit. This retrospective analysis of 189 patients treated sequentially with sorafenib (800 mg/day) and sunitinib (50 mg/day; 4 weeks on 2 weeks off) showed that initial therapy with either agent was associated with similar PFS benefits (median PFS 8.4 months [sorafenib] vs 7.8 months [sunitinib]; HR 1.05, 95% CI 0.78-1.40; P = 0.758). However, patients treated with sorafenib followed by sunitinib (SoSu) appeared to derive a greater PFS benefit than those treated with SuSo (median PFS with second TKI: 7.9 months [SoSu] vs 4.2 months [SuSo]; HR 0.54, 95% CI 0.39-0.74; P < 0.001). Consistent with previous studies, these findings suggest that sequential TKI therapy is associated with continued clinical benefit and that SoSu may result in a longer PFS than SuSo. OBJECTIVE To conduct a retrospective, multicentre, cohort analysis to assess the sequential use of the tyrosine kinase inhibitors (TKIs) sorafenib and sunitinib. PATIENTS AND METHODS Records of 189 patients with renal-cell carcinoma (RCC) who were treated with sorafenib and sunitinib sequentially between March 2004 and April 2009 at 12 Italian study centres were analysed. Patients were treated under European Expanded Access Programmes or, following market approval, in general clinical practice. Interventions were sorafenib (800 mg/day) and sunitinib (50 mg every day; 4 weeks on and 2 weeks off). Progression-free survival (PFS) during treatment with the first and second TKI was evaluated. RESULTS In all, 99 patients were treated with sunitinib followed by sorafenib (SuSo) and 90 were treated with sorafenib followed by sunitinib (SoSu); 104 (55%) patients had received prior systemic therapy, mostly with cytokines. The median (range) PFS on the first TKI was similar between treatment groups [sorafenib 8.4 (1.1-28.9) months; sunitinib 7.8 (0.5-30.4) months; hazard ratio (HR) 1.05, 95% confidence interval (CI) 0.78-1.40, P = 0.758]. Multivariate analysis showed that good Memorial Sloan-Kettering Cancer Center status was associated with increased PFS. After the second TKI, patients in the SoSu group had a longer median PFS than those in the SuSo group (7.9 months vs 4.2 months, respectively; HR 0.54, 95% CI 0.39-0.74, P < 0.001). Multivariate analysis showed only treatment and Eastern Cooperative Oncology Group performance status (and not age, gender, study centre or previous treatment) were significantly associated with duration of PFS. CONCLUSION Our findings suggest a limited cross-resistance between sorafenib and sunitinib and that the sequence SoSu may result in a longer combined PFS than SuSo. This is the largest retrospective study to date, though its findings are limited in part by the retrospective nature. © 2011 BJU Internationl.


Paglino C.,University of Pavia | Paglino C.,Gruppo Italiano Of Nefro Oncologia Italian Nephro Oncology Group | Procopio G.,Gruppo Italiano Of Nefro Oncologia Italian Nephro Oncology Group | Procopio G.,Italian National Cancer Institute | And 12 more authors.
Anticancer Research | Year: 2013

Background/Aim: the ideal sequence of targeted agents for advanced kidney cancer is still unknown. In the present study we assessed the clinical benefit of two different sequential approaches, namely sorafenib, an inhibitor of mammalian target of rapamycin (mTORi) and sunitinib, or sunitinib (an mTORi) and sorafenib. Patients and Methods: we retrospectively reviewed the outcome of 40 advanced kidney cancer patients treated with one of the two above sequences. Results: a total of 26 patients were treated with the sequence sorafenib-mTORi-sunitinib and 14 with the sequence sunitinib-mTORi-sorafenib. The actuarial overall median progression-free survival (PFS) in the sorafenib-mTORi-sunitinib group and in the sunitinib-mTORi-sorafenib group were 21.9 and 22.8 months, respectively (log-rank test: p=0.928). In the sorafenib-mTORi- sunitinib group, patients in first-, second- and third-line therapy experienced PFS of 11.7, 5.1 and 9.1 months, respectively, while in the sunitinib-mTORi-sorafenib group PFS was 14.4, 4.3, and 3.9 months, respectively. Conclusion: Our results suggest there is no significant difference between the two sequence modalities.


PubMed | a Microbiology Immunology and Virology Unit, Oncology Reference Center and b Epidemiology and Biostatistic Unit
Type: Journal Article | Journal: Biomarkers : biochemical indicators of exposure, response, and susceptibility to chemicals | Year: 2015

To evaluate whether plasma cell-free DNA (cfDNA) was related to clinical outcome in inoperable stage I non-small cell lung cancer (NSCLC) patients undergoing stereotactic body radiotherapy (SBRT).Plasma cfDNA was assessed at baseline, before the last day and 45 days after the end of SBRT, in 22 NSCLC patients. Twenty-two healthy controls were also evaluated.Plasma cfDNA was higher in patients than in controls. An association with unfavourable disease-free survival was found for continuous baseline cfDNA increments (HR=5.9, 95%CI: 1.7-19.8, p=0.04).Plasma cfDNA may be a promising prognostic biomarker in high-risk NSCLC patients.


Grignani G.,Institute for Cancer Research and Treatment | Palmerini E.,Rizzoli Orthopaedic Institute | Stacchiotti S.,IRCCS Foundation National Tumor Institute | Boglione A.,Gradenigo Hospital | And 6 more authors.
Cancer | Year: 2011

BACKGROUND. Chondrosarcoma (CS) is a rare and heterogeneous sarcoma in which, after failure of surgery and radiotherapy, chemotherapy plays only a marginal role. Different molecular pathways have been shown to be activated in CS; in particular, both isoforms of platelet-derived growth factor receptor (PDGFR) are expressed and phosphorylated. These observations prompted investigation of the activity of imatinib mesylate (IM) in patients with advanced CS in a phase 2 trial. METHODS. Between January 2007 and June 2009, patients with metastatic, nonresectable CS were treated with 400 mg of IM administered twice daily until disease progression or unacceptable toxicity. Two criteria determined patient trial eligibility: ≥1 prior line of chemotherapy and immunohistochemical expression of either PDGFR-α or PDGFR-β. The primary objective of the trial was objective response. As secondary objectives, the authors selected progression-free survival (PFS) at 4 months, overall survival, and clinical benefit (EUDRACT number 2006-006446-33). RESULTS. Twenty-six patients were enrolled and all demonstrated PDGFR positivity and phosphorylation. No objective response was demonstrated. The 4-month PFS rate was 31% (95% confidence interval [95% CI], 16%-53%). The median overall survival was 11 months (95% CI, 6 months-15 months). Neither long-lasting freedom from disease progression nor clinical benefit was observed. The IM dose was temporarily reduced in 60%15 of the patients because of toxicity. CONCLUSIONS. IM was found to be relatively well-tolerated, but failed to demonstrate meaningful clinical activity in terms of both objective response and freedom from disease progression. Advanced CS remains an incurable disease, and effective targeted therapies are still awaited. © 2010 American Cancer Society.


Bortolin M.T.,Microbiology Immunology and Virology Unit | Tedeschi R.,Microbiology Immunology and Virology Unit | Bidoli E.,Epidemiology and Biostatistic Unit | Furlan C.,Oncology Reference Center | And 6 more authors.
Biomarkers | Year: 2015

Objective: To evaluate whether plasma cell-free DNA (cfDNA) was related to clinical outcome in inoperable stage I non-small cell lung cancer (NSCLC) patients undergoing stereotactic body radiotherapy (SBRT).Materials and methods: Plasma cfDNA was assessed at baseline, before the last day and 45 days after the end of SBRT, in 22 NSCLC patients. Twenty-two healthy controls were also evaluated.Results: Plasma cfDNA was higher in patients than in controls. An association with unfavourable disease-free survival was found for continuous baseline cfDNA increments (HR = 5.9, 95%CI: 1.7-19.8, p = 0.04).Conclusion: Plasma cfDNA may be a promising prognostic biomarker in high-risk NSCLC patients. © 2015 Taylor & Francis.

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