Stefano Cascinu

Università Politecnica delle Marche, Ancona, The Marches, Italy

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Publications (367)1678.94 Total impact

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    ABSTRACT: A phase Ib/II trial was performed to evaluate safety, tolerability, recommended dose (RD) and efficacy of F16-IL2, a recombinant antibody-cytokine fusion protein, in combination with doxorubicin in patients with solid tumours (phase Ib) and metastatic breast cancer (phase II). Six patient cohorts with progressive solid tumours (n = 19) received escalating doses of F16-IL2 [5-25 Million International Units (MIU) of IL2 equivalent dose] in combination with escalating doses of doxorubicin (0-25mg/m(2)) on day 1, 8 and 15 every 4 weeks. Subsequently, patients with metastatic breast cancer (n = 10) received the drug combination at the RD. Clinical data and laboratory findings were analysed for safety, tolerability, and activity. F16-IL2 could be administered up to 25 MIU, in combination with the RD of doxorubicin (25mg/m(2)). No human anti-fusion protein antibodies (HAFA) response was detected. Pharmacokinetics of F16-IL2 was dose-dependent over the tested range, with half-lives of ca. 13 and ca. 8 hours for cohorts dosed at lower and higher levels, respectively. Toxicities were controllable and reversible, with no combination treatment-related death. After 8 weeks, 57% and 67% disease control rates were observed for Phase I and II, respectively (decreasing to 43% and 33% after 12 weeks), considering 14 and 9 patients evaluable for efficacy. One patient experienced a long lasting partial response (45 weeks), still on-going at exit of study. F16-IL2 can be safely and repeatedly administered at the RD of 25 Mio I.U. in combination with 25mg/m(2) doxorubicin; its safety and activity are currently being investigated in combination with other chemotherapeutics, in order to establish optimal therapy settings.
    Cell adhesion & migration 01/2015; · 3.40 Impact Factor
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    ABSTRACT: RCC is considered an immunogenic tumor with a prominent dysfunctional immune cell infiltrate, unable to control tumor growth. Evasion of immune surveillance, a process defined immune-editing, leads to malignant progression. The striking improvement of knowledge in immunology has led to the identification of immune checkpoints (such as CTLA-4 and PD-1), whose blockage enhances the antitumor immunity. The interaction between PD-1, an inducible inhibitory receptor expressed on lymphocytes and DCs, and PD-L1 ligand, expressed by tumor cells, results in a down-regulation of the T-cell response. Therefore, the PD-1/PD-L1 axis inhibition by targeted-antibodies, increasing the T-cell proliferation and cytotoxicity, represents a promising mechanism to stimulate the anti-tumor activity of the immune system, improving the outcomes of cancer patients. Several PD-1 and PD-L1 inhibitors have been evaluated in different tumor types, showing promising results. The interesting correlation between lymphocytes PD-1 expression and RCC advanced stage, grade and prognosis, as well as the selective PD-L1 expression by RCC tumor cells and its potential association with worse clinical outcomes, have led to the development of new anti PD-1/PD-L1 agents, alone or in combination with anti-angiogenic drugs or other immunotherapeutic approaches, for the treatment of RCC.
    Cancer Treatment Reviews 01/2015; · 6.02 Impact Factor
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    ABSTRACT: We aimed to assess the prognostic role of pretreatment neutrophilia, lymphocytopenia, and neutrophil to lymphocyte ratio (NLR) in patients treated with vascular endothelial growth factor-tyrosine kinase inhibitors (VEGFR-TKIs) for late relapsing (>5 years) metastatic renal cell carcinoma (mRCC). Data were collected from 13 Italian centers involved in the treatment of metastatic RCC. Late relapse was defined as >5 years after initial radical nephrectomy. One hundred fifty-one patients were included in this analysis. Among them, MSKCC risk score was favorable in 68 %, intermediate in 29 %, and poor in 3 %. Fifty-six patients (37 %) had NLR ≥3 at the start of VEGFR-TKI therapy (group A), while 95 had lower NLR (63 %, group B). The median overall survival (OS) was 28.8 months in group A and 68.7 months (95 % confidence interval (CI) 45.3–NA) in group B (p p = 0.03). At multivariate analysis, MSKCC risk group and NLR were independent prognostic factors for both OS and PFS. Pretreatment NLR is an independent prognostic factor for patients with late relapsing mRCC treated with first-line VEGFR-TKIs. A better characterization of baseline immunological impairment may optimize the management of this RCC subpopulation.
    Targeted Oncology 01/2015; · 3.46 Impact Factor
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    ABSTRACT: To investigate hypoxia inducible factor-1α's (HIF-1α) immunohistochemical expression in clear cell renal cell carcinoma (ccRCC) treated with radical nephrectomy. One hundred and forty-eight patients were considered from those who underwent radical nephrectomy between 1983 and 1993. Archived materials were retrieved from the Institute of Pathological Anatomy for immunostaining. The features considered on the histological specimens were tumor stage, grade, as well as cellular and vascular HIF-1α expression. All considered parameters were correlated with time to recurrence (TTR) and overall survival (OS). TTR was significantly longer in patients with low cellular HIF-1α expression; patients' survival was higher in those with low HIF-1α expression. Regarding vascular HIF-1α expression, the differences were not statistically significant when considering TTR and OS. On univariate analysis, age, clinical stage and HIF-1α cellular expression showed a significant association with OS. Cellular HIF-1α is an important indicator of prognosis in patients with ccRCC; high HIF-1α expression predicts poor survival. Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.
    Anticancer research 01/2015; 35(1):433-8. · 1.87 Impact Factor
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    ABSTRACT: ABSTRACT The standard of care for patients with local advanced or metastatic urothelial carcinoma is chemotherapy. However, results with this are rather disappointing, and validated prognostic factors and biomarkers of tumor response, which are useful in the decision-making process, are still lacking. PubMed databases were searched for articles published until November 2013. Several promising clinical and biological candidate prognostic factors or markers of tumor response to first- or second-line therapy, such as hemoglobin, performance status, visceral metastasis and ERCC1, hENT1 and EMT markers, have been identified and described in this article. In summary, clinical parameters and molecular profiling could revolutionize the management of local advanced or metastatic urothelial cancer, but an improvement in individualized therapeutic approaches still seems distant.
    Future Oncology 01/2015; 11(1):107-19. · 2.61 Impact Factor
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    ABSTRACT: The aim of the study was to determine the potential role of occupational exposures to chromium (Cr) in the onset of extragonadal germinal embryonal carcinoma. The first two cases of workers in a company with Cr exposure are reported. The published scientific literature regarding the topic in peer-reviewed journals including MEDLINE and CancerLit databases was extensively reviewed. Two young patients who were coworkers in the same company, exposed to Cr, developed extragonadal germinal embryonal carcinomas. One of them also developed angiosarcoma of the mediastinum. To the best of our knowledge these are the first two cases of germinal embryonal carcinoma in patients with occupational exposure to Cr.
    Journal of Toxicology and Environmental Health Part A 01/2015; 78(1):1-6. · 1.83 Impact Factor
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    ABSTRACT: Rectal cancer accounts for a relevant part of colorectal cancer cases, with a mortality of 4-10/100000 per year. The development of locoregional recurrences and the occurrence of distant metastases both influences the prognosis of these patients. In the last two decades, new multimodality strategies have improved the prognosis of locally advanced rectal cancer with a significant reduction of local relapse and an increase in terms of overall survival. Radical surgery still remains the principal curative treatment and the introduction of total mesorectal excision has significantly achieved a reduction in terms of local recurrence rates. The employment of neoadjuvant treatment, delivered before surgery, also achieved an improved local control and an increased sphincter preservation rate in low-lying tumors, with an acceptable acute and late toxicity. This review describes the multidisciplinary management of rectal cancer, focusing on the effectiveness of neoadjuvant chemoradiotherapy and of post-operative adjuvant chemotherapy both in the standard combined modality treatment programs and in the ongoing research to improve these regimens.
    World journal of gastroenterology : WJG. 12/2014; 20(46):17279-17287.
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    ABSTRACT: The aim of this study was to compare survival of resected and unresected patients in a large cohort of patients with metastases to the pancreas from renal cell carcinoma (PM-RCC). Data from 16 Italian centers involved in the treatment of metastatic RCC were retrospectively collected. The Kaplan-Meier and log-rank test methods were used to evaluate overall survival (OS). Clinical variables considered were sex, age, concomitant metastasis to other sites, surgical resection of PM-RCC, and time to PM-RCC occurrence. Overall, 103 consecutive patients with radically resected primary tumors were enrolled in the analysis. PM-RCCs were synchronous in only three patients (3 %). In 56 patients (54 %), the pancreas was the only metastatic site, whereas in the other 47 patients, lung (57 %), lymph nodes (28 %), and liver (21 %) were the most common concomitant metastatic sites. Median time for PM-RCC occurrence was 9.6 years (range 0-24 years) after nephrectomy. Surgical resection of PM-RCC was performed in 44 patients (median OS 103 months), while 59 patients were treated with tyrosine kinase inhibitors (TKIs; median OS 86 months) (p = 0.201). At multivariate analysis, Memorial Sloan Kettering Cancer Center risk group was the only independent prognostic factor. None of the other clinical variables, such as age, sex, pancreatic surgery, or the presence of concomitant metastases, were significantly associated with outcome in PM-RCC patients. The presence of PM-RCC is associated with a long survival, and surgical resection does not improve survival in comparison with TKI therapy. However, surgical resection leads to a percentage of disease-free PM-RCC patients.
    Annals of Surgical Oncology 12/2014; · 3.94 Impact Factor
  • Matteo Santoni, Stefano Cascinu, Charles D Mills
    Cellular & molecular immunology 11/2014; · 4.19 Impact Factor
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    ABSTRACT: Background: To assess the predictive role of lactate dehydrogenases (LDH) and fibrinogen (FBG) serum levels in metastatic colorectal cancer (mCRC) patients receiving a first-line bevacizumab-based therapy.Objectives: The aim of the present analysis was to retrospectively evaluate the role of basal and post-treatment LDH and FBG serum levels in predicting the clinical outcome of 139 mCRC patients receiving first-line chemotherapy in combination with bevacizumab.Results: A statistically significant association between high pre-treatment LDH and FBG levels and progressive disease was observed with respect to low basal LDH and FBG patients. Furthermore, median progression-free survival was 7.3 versus 10.8 months and 7.3 versus 9.4 months for high and low LDH and FBG levels, respectively. Within the high LDH group, we observed a statistically significant reduction of LDH mean value compared with pre-treatment values in patients with objective response rate and stable disease.Conclusions: High LDH and FBG levels correlated with prognosis. A significant correlation between bevacizumab-based chemotherapy-induced reduction in LDH serum levels and response to treatment was observed within the high LDH group. These results, if confirmed in larger prospective studies, could be helpful for early identification of patients responsive to bevacizumab-based chemotherapy or candidate to more aggressive treatments.
    Expert Opinion on Biological Therapy 11/2014; · 3.65 Impact Factor
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    ABSTRACT: Although the extended RAS analysis allows a better identification of patients potentially candidates to anti-EGFR monoclonal antibodies, a significant proportion of tumours may still reveals refractory to such a treatment approach. In these latter cases patients are then exposed to unnecessary toxicities without clinical benefit. Among many further biological factors that may have a role in determining resistance/sensitivity to EGFR-inhibitors, the EGFR itself, other members of the HER family (i.e. HER-2 and HER-3) as well as other surface receptors such as the IGF-1 receptor seem of particular interest. Preclinical models have shown that these receptors are biologically connected to each other and that they are able to directly or indirectly influence each other's downstream molecular pathways. In the presence of abnormal expression of these biological determinants, intracellular pathways may consequently become independent from receptor-targeting pharmacological modulations thus making treatment directed against the receptor ineffective. Clinical observations and translational studies seem to confirm these findings. The Authors have reviewed the literature and have selected recent clinical reports focusing on translational research on EGFR itself or on other molecules that may interfere with its pathway. With the aim to offer an effective tool for research and clinical practice, we also discuss on potential future developments.
    Current Drug Targets 11/2014; · 3.60 Impact Factor
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    ABSTRACT: Neuroendocrine prostate cancer (NEPC) is an aggressive variant of prostate cancer that commonly arises in later stages of castration resistant prostate cancer (CRPC) The detection of NEPC has clinical implications as these patients are often treated with platinum chemotherapy rather than with androgen receptor targeted therapies. The poor molecular characterization of NEPC accounts in part for the lack of disease specific therapeutics. Several mechanisms are involved in NE differentiation, including inflammation and autophagy, and may actually represent future therapeutic targets for advanced NEPC patients. Furthermore, a growing body of evidence suggests a potential role of circulating tumor cells in the early diagnosis and treatment of NEPC. Here we summarize the recent findings on NEPC pathogenesis and we discuss the ongoing clinical trials and future perspectives for the treatment of NEPC patients. Copyright © 2014. Published by Elsevier B.V.
    Biochimica et Biophysica Acta (BBA) - Reviews on Cancer 11/2014; 1846(2):630-637. · 7.58 Impact Factor
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    ABSTRACT: In November 1964, the recently founded American Society of Clinical Oncology (ASCO) held its first national meeting in Chicago (IL, USA). Only 51 members attended the conference. At the 2014 ASCO meeting, more than 30,000 healthcare professionals gathered together in the same city to attend this prime scientific conference. The many passionate attendees not only wanted to celebrate ASCO's 50th anniversary, but they also wanted to share the results of milestone clinical and translational research and, most notably, to consider future avenues of progress against cancer. In this report, the most significant advances in both clinical and translational research presented at the 2014 ASCO plenary session and oral abstract sessions will be discussed, specifically focusing on breast and colorectal carcinomas. Both of these are among the leading causes of cancer-related deaths. Many of the results presented significantly contribute to building a pipeline of novel treatment options. Moreover, these results will soon have an impact on clinical practice and may help medical oncologists move their research forward.
    Future Oncology 11/2014; 10(12):1901-1906. · 2.61 Impact Factor
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    ABSTRACT: 2014 Genitourinary Cancers Symposium San Francisco, CA, USA, 30 January-1 February 2014 The American Society of Clinical Oncology symposium dedicated to genitourinary tumors represents an unmissable opportunity for the whole oncology community with a special interest in the diagnosis and treatment of genitorurinary tract malignancies, in particular kidney and prostate tumors. The 2014 Genitourinary Cancers Symposium focused attention on the need to find a personalized therapy for metastatic renal cell carcinoma and castration-resistant prostate cancer patients. The development of biomarkers for tumor response and/or resistance will represent a major step in this context and has been the focus of several researches at the symposium.
    Future Oncology 11/2014; 10(14):2103-6. · 2.61 Impact Factor
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    ABSTRACT: Measures of prognosis for cancer patients are typically evaluated at the time of diagnosis. However, this study assessed the changes in 2-year CS rates after first-line chemotherapy for metastatic UC.Patients and Methods Conditional overall survival and CPFS probability were estimated using the Kaplan–Meier method. Adjusted survival functions were stratified according to age groups (< 70 years vs. ≥ 70 years), sex, Eastern Cooperative Oncology Group (ECOG) performance status (PS; ECOG PS ≤ 2 vs. ECOG PS > 2), pretreatment Hb levels (< 12 mg/dL vs. ≥ 12 mg/dL) and pretreatment NLR (< 3 vs. ≥ 3). Pairs of CS curves were compared using the Mantel–Haenszel log-rank test.ResultsTwo hundred ninety-eight patients were included in this analysis, 233 were male, and their median age was 69 years. First-line median overall survival and progression-free survival were 10.7 months (95% confidence interval [CI], 9.6-12.6) and 6.0 months (95% CI, 5.5-7.1), respectively. CPFS and COS showed an increasing trend in the population considered (b = 0.35; P < .001 and b = 0.79; P < .001, respectively). A significant increase in terms of COS and CPFS trends was identified in patients with age < 70 years (P = .02 and P = .005, respectively) and pretreatment NLR ≤ 3 (P = .05 and P < .001, respectively). Patients with Hb levels < 12 g/dL showed a significantly poorer 2-year COS.Conclusion The conditional probability of survival at 2 years from the start of first-line chemotherapy for advanced UC changes over time according to clinical characteristics.
    Clinical Genitourinary Cancer 10/2014; · 1.69 Impact Factor
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    ABSTRACT: Totally implantable central venous accesses (port-a-cath) are often used for chemotherapy administration or prolonged intravenous infusions in cancer patients. Local and systemic complications may occur both during and after placement of port-a-cath despite the well-established techniques for its placement and care. Out of other catheter-related local complications, thrombosis and infections represent the most common. Complications related to central venous catheter may be associated with infusion of both conventional chemotherapy and molecularly targeted therapy. Incidence and nature of complications of central venous catheter have been well established for long-term chemotherapy. However, very sparse data exists on the incidence of complications of molecularly targeted therapies administered through a central venous catheter. Hence, we decided to retrospectively analyze the local complications of a central venous catheter in patients receiving molecularly targeted therapy and conventional chemotherapy, respectively.
    Supportive Care Cancer 10/2014; · 2.50 Impact Factor
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    ABSTRACT: Pancreatic ductal adenocarcinoma (PDAC), which accounts for more than 90% of all pancreatic tumours, is a devastating malignancy with an extremely poor prognosis, as shown by a 1-year survival rate of around 18% for all stages of the disease. The low survival rates associated with PDAC primarily reflect the fact that tumours progress rapidly with few specific symptoms and are thus at an advanced stage at diagnosis in most patients. As a result, there is an urgent need to develop accurate markers of pre-invasive pancreatic neoplasms in order to facilitate prediction of cancer risk and to help diagnose the disease at an earlier stage. However, screening for early diagnosis of prostate cancer remains challenging and identifying a highly accurate, low-cost screening test for early PDAC for use in clinical practice remains an important unmet need. More effective therapies are also crucial in PDAC, since progress in identifying novel therapies has been hampered by the genetic complexity of the disease and treatment remains a major challenge. Presently, the greatest step towards improved treatment efficacy has been made in the field of palliative chemotherapy by introducing FOLFIRINOX (folinic acid, 5-fluorouracil, irinotecan and oxaliplatin) and gemcitabine/nab-paclitaxel. Strategies designed to raise the profile of PDAC in research and clinical practice are a further requirement in order to ensure the best treatment for patients. This article proposes a number of approaches that may help to accelerate progress in treating patients with PDAC, which, in turn, may be expected to improve the quality of life and survival for those suffering from this devastating disease.
    Pancreatology 10/2014; · 2.50 Impact Factor
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    ABSTRACT: Aim: SIADH may be related to several causes (pulmonary disorders, CNS disturbances, drugs and chemotherapeutic agents), but in the majority of cases it is caused by malignancies. This observational study aimed to analyze treatments and outcome of SIADH in cancer pts. Methods: This study includes 69 consecutive cancer pts who experienced SIADH between 2010 and 2014 in 22 Italian Cancer Centers. Data on clinico-pathology, anticancer and SIADH treatments were recorded and statistically analized. Results: M/F ratio was 47/22, median age was 67 years (range 37-83). Primary tumor was lung cancer in 50 pts (SCLC in 39), while it was GI cancer in 8 pts. Fifty-eight pts were hospitalized due to SIADH, HN at admission was ≤130 mEq/l in 94.3%. Median duration of hospitalization was 13 days (range 3-90). 31 pts received tolvaptan for SIADH treatment (group A); other treatments included hypertonic saline solutions, diuretics, fluids restriction (group B). Group A included a significant higher N° of lung cancer pts (77.4% vs 68.4%) with metastatic disease (80.6% vs 76.3%). Moreover pts in group A had more severe HN at admission: serum sodium was ≤130 mEq/l in 96.7% pts and <120 mEq/l in 48% of pts, while in group B it was ≤130 mEq/l in 66.6% of pts and <120 mEq/l in 42.9%. Median sodium at the beginning of tolvaptan was 120 mEq/l (range 110-130), in group B it was 117 mEq/l (range 109-132). In group A 13 pts started tolvaptan 15 mg/daily, 4 started with 30 mg and 14 with 7.5 mg. No toxicity due to tolvaptan was observed in 25 pts, 6 experienced dry mouth. In 19 pts a dose change was required: in 4 it was increased to 30 mg/daily, while in the remaining 15 it was decreased to 7.5 mg every other day. HN improvement with tolvaptan was observed in all cases. Lenght of hospitalization was significantly longer in pts not receiving tolvaptan (15 days, range 4-100, vs 12 days, range 3-53 in pts receiving tolvaptan vs 8 days, range 1-41 in pts receiving tolvaptan since start of tolvaptan, p = 0.002). Severity of HN and not obtaining its correction correlated with lenght of stay and with overall survival (p < 0.05). Conclusions: To our knowledge this is the largest study analyzing SIADH in cancer pts to demonstrate that HN due to SIADH may result in a prolongation of hospitalization and in a worse overall survival when not adequately corrected and that tolvaptan represents an effective treatment potentially improving both. Disclosure: All authors have declared no conflicts of interest.
    09/2014; 25:517-541.
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    ABSTRACT: Increased neutrophil-to-lymphocyte ratio (NLR), an index of systemic inflammation, is associated with poor outcome for various types of cancers. We assessed the role on outcome prediction of NLR at baseline and persistent during first-line chemotherapy in patients with advanced urothelial cancer.
    Annals of Surgical Oncology 09/2014; · 3.94 Impact Factor
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    ABSTRACT: Background: Triple-negative breast cancers (TNBC) are characterized by aggressive tumour biology resulting in a poor prognosis. Androgen receptor (AR) is one of newly emerging biomarker in TNBC. In recent years, ARs have been demonstrated to play an important role in the genesis and in the development of breast cancer, although their prognostic role is still debated. In the present study, we explored the correlation of AR expression with clinical, pathological and molecular features and its impact on prognosis in early TNBC. Patients and Methods: ARs were considered positive in case of tumors with >10% nuclear-stained. Survival distribution was estimated by the Kaplan Meier method. The univariate and multivariate analyses were performed. The difference among variables were calculated by chi-square test. Results: 81 TNBC patients diagnosed between January 2006 and December 2011 were included in the analysis. Slides were stained immunohistochemically for estrogen and progesterone receptors, HER-2, Ki-67, ALDH1, e-cadherin and AR. Of the 81 TNBC samples, 18.8% showed positive immunostaining for AR, 23.5% and 44.4% of patients were negative for e-cadherin and ALDH1, respectively. Positive AR immunostaining was inversely correlated with a higher Ki-67 (p < 0.0001) and a lympho-vascular invasion (p = 0.01), but no other variables. Univariate survival analysis revealed that AR expression was not associated with disease-free survival (p = 0.72) or overall survival (p = 0.93). Conclusions: The expression of AR is associated with some biological features of TNBC, such as Ki-67 and lympho-vascular invasion; nevertheless the prognostic significance of AR was not documented in our analysis. However, since ARs are expressed in a significant number of TNBC, prospective studies in order to determine the biological mechanisms and their potential role as novel treatment target.
    Cancers. 09/2014; 6(3):1351-1362.

Publication Stats

5k Citations
1,678.94 Total Impact Points

Institutions

  • 1970–2014
    • Università Politecnica delle Marche
      • Chair of Medical Oncology
      Ancona, The Marches, Italy
  • 2013
    • Azienda Ospedaliero Universitaria Ancona
      Ancona, The Marches, Italy
  • 2001–2013
    • University Hospital of Parma
      • Reparto di Oncologia medica
      Parma, Emilia-Romagna, Italy
  • 1989–2013
    • Ospedali Riuniti di Bergamo
      Bérgamo, Lombardy, Italy
  • 2012
    • LIUCBM Libera Università Campus Bio-Medico di Roma
      • Unit of Medical Oncology
      Roma, Latium, Italy
  • 2007–2012
    • Azienda Ospedaliero - Universitaria "Ospedali Riuniti" Trieste
      Trst, Friuli Venezia Giulia, Italy
  • 2004–2006
    • Azienda Ospedaliera Ospedali Riuniti Papardo Piemonte
      Messina, Sicily, Italy
  • 2005
    • Kanazawa Medical University
      • Department of Surgery II
      Kanazawa-shi, Ishikawa-ken, Japan
  • 2003
    • University-Hospital of Padova
      Padua, Veneto, Italy
  • 1999–2003
    • Università degli Studi di Messina
      • • Dipartimento di Scienze Radiologiche
      • • Dipartimento di Medicina Clinica e Sperimentale
      Messina, Sicily, Italy
    • Azienda Ospedaliera Bianchi-Melacrino-Morelli di Reggio Calabria
      Reggio di Calabria, Calabria, Italy
  • 1997–2003
    • Università degli Studi di Siena
      Siena, Tuscany, Italy
  • 1993–1997
    • Azienda Ospedaliera San Carlo Borromeo Milano
      • Division of Medical Oncology
      Milano, Lombardy, Italy