Publications (30)255.61 Total impact
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Article: Atypical Multiple Ileum Metastases of Renal Cell Carcinoma.
Journal of Gastrointestinal Cancer 01/2013; -
Article: Antiangiogenic therapy of colorectal cancer: state of the art, challenges and new approaches.
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ABSTRACT: Advanced colorectal cancer is the first tumor type for which an antiangiogenic agent, namely bevacizumab, has been approved by the Food and Drug Administration for therapy in humans; it has been in use since February 2004. This review paper summarizes and discusses the results obtained with this agent and highlights the main open or controversial issues on antiangiogenic therapy, taking into account that the clinical results obtained are below the expectations, particularly in the adjuvant setting.The International journal of biological markers 12/2012; · 1.48 Impact Factor -
Article: The paradigm of personalized therapy in oncology.
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ABSTRACT: INTRODUCTION: Currently, anticancer therapy is mainly based on histology and on giving the same treatment to presumed homogeneous patients. The switch from histology-driven therapy to molecular clinical oncology is correlated with a better understanding of the 'molecular taxonomy' of each tumor that can provide us with targets for specific drugs. Cancer therapy is moving irreversibly towards personalized therapy that benefits selected patients. Once the potential therapeutic targets are identified, the availability of predictive biomarkers is the key element and their prospective evaluation should be a parallel component of the clinical evaluation of a new drug. AREAS COVERED: The state of the art in clinical results of personalized therapy. The authors discuss the finding that, in patients with advanced disease, a limited number of targeted agents improve overall survival, whilst the majority only have an effect on response rate and/or time to tumor progression, with efficacy limited in time due to acquired resistance. EXPERT OPINION: The mechanisms leading to resistance are related to tumor cell heterogeneity and in part explained by the cancer stem cell model and genetic instability. The steps toward the optimization of tailored therapy need validated predictive biomarkers, pharmacogenetics analysis and a close collaboration between bench and bedside.Expert opinion on therapeutic targets 11/2011; 16 Suppl 1:S7-16. · 3.72 Impact Factor -
Article: Primary nongestational choriocarcinoma of the uterine cervix.
Journal of Clinical Oncology 01/2011; 29(11):e301-2. · 18.37 Impact Factor -
Article: Pharmacogenetics in breast cancer: focus on hormone therapy, taxanes, trastuzumab and bevacizumab.
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ABSTRACT: Breast cancer is the most common female cancer, with more than one million new patients diagnosed annually worldwide. The great heterogeneity, in terms of prognosis and outcome, within patients with the same clinical and pathological characteristics may limit the potential for personalized therapy. Most of the cytotoxic agents and new targeted agents have a narrow therapeutic index and the administration of an equal dose may result in a wide range of toxicities as well as to different antitumor efficacy. Inter-subject variability in drug toxicity and response is common during treatment, so that individualization of treatments is an important issue. Pharmacogenetics is the study of how inter-individual variations in the DNA sequence of specific genes may affect drug response and toxicity. This article highlights the clinical use of determination of polymorphisms of important human drug-metabolizing cytochrome P450s, ABCB1, IgG fragment C receptors and vascular endothelial growth factor, which are responsible of the large inter-individual variability in drug metabolism and clearance of the agents commonly used in breast cancer treatment, such as tamoxifen, aromatase inhibitors, taxanes, trastuzumab and bevacizumab.Expert Opinion on Investigational Drugs 04/2010; 19 Suppl 1:S41-50. · 5.27 Impact Factor -
Article: Bisphosphonate-related osteonecrosis of the jaw and left thumb.
Journal of Clinical Oncology 10/2009; 27(35):e242-3. · 18.37 Impact Factor -
Article: Is hypothyroidism a clinically relevant toxicity of tyrosine kinase inhibitors?
Thyroid: official journal of the American Thyroid Association 06/2009; 19(5):539-40. · 2.60 Impact Factor -
Article: Hypothyroidism related to tyrosine kinase inhibitors: an emerging toxic effect of targeted therapy.
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ABSTRACT: Despite their inherent selectivity, targeted therapies such as tyrosine kinase inhibitors (TKIs) can cause unusual adverse effects. Sunitinib and sorafenib are multitargeted TKIs that have been demonstrated to induce hypothyroidism and thyroid dysfunction. Retrospective studies indicate that sunitinib can induce hypothyroidism in 53-85% of patients, and in prospective studies this complication has been reported in 36-71% of patients. Sorafenib has been reported to be responsible for hypothyroidism in 18% of patients with metastatic renal-cell carcinoma. Furthermore, imatinib and sunitinib seem to increase the requirement of levothyroxine in hypothyroid patients. The management of thyroid dysfunction and possible related symptoms, such as fatigue, represents a challenge to oncologists. We propose a diagnostic and therapeutic algorithm for the management of TKI-related hypothyroidism. Prospective trials are needed to define the incidence of overt and subclinical hypothyroidism and thyroid dysfunction during therapy with sunitinib, sorafenib and potentially other TKIs. The safety and efficacy, and optimal dosing and timing of starting replacement therapy in patients affected by TKI-related hypothyroidism need accurate appraisal and should be evaluated prospectively in appropriately designed trials.Nature Reviews Clinical Oncology 05/2009; 6(4):219-28. · 11.96 Impact Factor -
Article: Systemic treatment of gastric cancer.
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ABSTRACT: Treatment of gastric cancer is improved over the past years, but unanswered questions remain regarding the efficacy of systemic treatments in adjuvant, neoadjuvant and metastatic setting. It has not been definitively demonstrated the efficacy of adjuvant chemotherapy, that should not be adopted as a standard approach to localized gastric cancer. On the contrary, compelling evidence in support of perioperative chemotherapy with ECF regimen has been recently provided by the MAGIC trial, although many criticisms have been moved to this study. For metastatic setting, a recent meta-analysis showed a small, but significant survival benefit for combination vs single agent chemotherapy, and the V-325 trial demonstrated the superiority of a docetaxel containing regimen (DCF) over a doublet (CF). Finally, the results of ongoing clinical trials on a number of new molecular-targeted drugs should confirm their role in gastric cancer.Critical reviews in oncology/hematology 10/2008; 70(3):216-34. · 5.27 Impact Factor -
Article: Anti-VEGF therapy: the search for clinical biomarkers.
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ABSTRACT: Despite the large diffusion and rapid development of anti-VEGF therapy in clinical practice and in contrast to the consolidated evidence with imatinib and trastuzumab that demonstrated a direct correlation between pre-treatment target expression and drug activity, it is very difficult, at present, to identify validated and useful biomarkers to monitor the efficacy of these compounds and to appropriately select patients most likely to benefit from such treatments. However, emerging data suggest that this is not presently feasible for antiangiogenic drugs. Although tumoral and/or circulating VEGF levels have been associated with tumor progression and/or poor prognosis, to date, there is no validated evidence suggesting their role as potential predictive biomarkers of response to anti-VEGF therapy. Recently, many studies have documented promising results with the evaluation of circulating endothelial cells and/or progenitors, and the use of several imaging techniques, such as dynamic contrast-enhanced MRI, PET, dynamic CT scan and functional ultrasound. These preliminary data need a validation in larger prospective trials.Expert Review of Molecular Diagnostics 06/2008; 8(3):301-14. · 4.86 Impact Factor -
Chapter: Challenges of Antiangiogenic Therapy of Tumors
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ABSTRACT: After the approval of the first antiangiogenic agent, bevacizumab, in February 2004, a humanized monoclonal antibody anti-vascular endothelial growth factor (VEGF), this category of new anticancer drugs expanded rapidly. At the end of 2006, the U.S. Food and Drug Administration (FDA) approved bevacizumab for therapy of advanced colorectal and non-small cell lung cancers (except squamous cell histotype), sunitinib for advancedrefractory renal cancer and for imatinib-resistant gastro- intestinal stromal tumors (GISTs), and sorafenib for recurrent advanced kidney cancer. Twelve antiangiogenic drugs entered Phase III trials and at least another 15-20 are under evaluation in Phase I-II studies. Such a rapid clinical development of inhibitors of angiogenesis with different pharmacodynamic and pharmacokinetic characteristics opens a number of challenges, including: the identification of targets of choice; the optimal therapeutic strategy; the rational selection of the patients; proper study-design of clinical trials as well as the monitoring of drug efficacy; management of toxicity; and, finally, the determination of the disease stage to obtain the best benefit. All the above relevant issues are presented and discussed in this chapter.12/2007: pages 461-475; -
Article: Skin acrometastases in squamous cell carcinoma of the tongue.
Journal of Clinical Oncology 08/2007; 25(19):2847-8. · 18.37 Impact Factor -
Article: Targeted therapy of breast cancer.
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ABSTRACT: Breast cancer is the most frequent tumor of women. The development of effective adjuvant therapy based on postoperative administration of short-term chemotherapy (4-6 months) or long-term hormone therapy (5 years) or both, significantly improved survival of patients. However, therapy of adjuvant/metastatic disease is still palliative with a very low probability to induce complete remission and definitive cure of disease. The relevant efforts of basic research to identify the key and selective molecular alterations, which sustain breast cancer growth and progression allowed the possibility to develop specific molecular target treatments. Trastuzumab, a humanized monoclonal antibody to HER-2, is the first molecular targeting agent approved for therapy of metastatic breast cancer, capable to significantly improve clinical outcome in combination with cytotoxic therapy. Recent preliminary data from randomized, prospective, clinical trials suggest that trastuzumab decreases the risk of early recurrence by 50% in patients with HER-2-positive disease. Other novel targeted treatments are in clinical evaluation, including antiangiogenic compounds (Bevacizumab, sunitinib, vatalanib, and others) and bi-functional drugs such as lapatinib (anti Her-2 and EGFR agent) showing promising activity. This review provides an updated overview of the status of development of targeted therapy in breast cancer, as well as the challenges related to the rational use of molecular targeting agents.Current pharmaceutical design 02/2007; 13(5):497-517. · 4.41 Impact Factor -
Article: Trastuzumab in combination with gemcitabine and vinorelbine as second-line therapy for HER-2/neu overexpressing metastatic breast cancer.
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ABSTRACT: The aim of this study was to evaluate the safety and efficacy of combined treatment with trastuzumab (T), gemcitabine (gem) and vinorelbine (vin) as second-line therapy for HER-2 overexpressing metastatic breast cancer, pretreated with anthracyclines and/or taxanes and/or trastuzumab. Eligible patients had HER-2/neu-positive disease (IHC 2+ or 3+), performance status (PS) <or=2 and normal L-VEF. Patients were treated with weekly T (4 mg/kg on day 0, then 2 mg/kg), in combination with gem (800 mg/m(2)) and vin (25 mg/m(2)) on days 1 and 8, every 21 days. Patients were restaged every 3 cycles. A total of 30 patients (median age, 58 years; range, 41-74) were enrolled in the study. Fifteen patients were HER-2 3+ and 26 (86.7%) presented >or=2 metastatic sites. Of the patients, 7 (23.3%) had received trastuzumab as first-line therapy. Treatment was well-tolerated with grade 4 neutropenia in 6 patients, grade 3 thrombocytopenia and grade 3 anemia in 1 patient, and grade 3 asthenia in 4 patients. Fifteen patients obtained an objective response (response rate, 50%; C.I. 95%, range, 31.3-68.7%). Among the patients with HER-2/neu 3+, the response rate was 73.3%. Noteworthy were 4 objective responses observed in patients with brain metastasis. Also, 7 patients had stable disease (23.3%). Median progression-free survival was 7 months (range 5-10), and median overall survival was 15 months (range 5-33). T-gem-vin is a safe and active regimen in this subgroup of patients with poor prognosis, and the efficacy of such a schedule was particularly satisfactory in patients with HercepTest 3+.Oncology Reports 09/2006; 16(2):393-8. · 1.84 Impact Factor -
Article: Anti-angiogenic and anti-HER therapy.
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ABSTRACT: The recent completion of the human genome sequence provided the basis and the tools to better understand the cellular biological complexity in both healthy and disease conditions, such as human cancer. In recent years, the improvement in biological and molecular knowledge enabled us to identify new targets and innovative drugs, allowing the beginning of new therapeutic strategies based on the so called "target oriented therapies".Biomedecine [?] Pharmacotherapy 08/2006; 60(6):263-5. · 2.00 Impact Factor -
Article: Is tailored therapy feasible in oncology?
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ABSTRACT: Tailored therapy aims to cure a patient who suffers from a specific disease with an effective and safe drug, based on the complex interactions among patient's characteristics, disease physiopathology and drug metabolism. Genomic and proteomic technologies represent promising new useful tools to understand cancer biology and molecular basis of interindividual differences of anticancer drugs efficacy. Genomic profiling seems to be able to re-classifying cancer into new molecular and prognostic homogeneous subgroups. By individual polymorphisms it is possible to identify the patients at higher risk for severe toxicity from those that may gain benefit from a particular treatment. The clinical use of targeted therapy is hampered by several questions, including: optimal biological dose, availability of surrogate biomarkers predictive of activity, schedule of administration, tumor histotype and stage to treat and modalities of combination with chemo/radiotherapy. In addition, further efforts are needed to improve the reliability of genomic and proteomic technologies. These unsolved issues presently make tailored therapy an open challenge.Critical Reviews in Oncology/Hematology 02/2006; 57(1):79-101. · 4.41 Impact Factor -
Article: Multiorganic dissemination of a colorectal signet ring cell carcinoma with fulminant clinical course.
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ABSTRACT: Mucinous colorectal cancer with signet ring cell aspects is a rare form of adenocarcinoma representing about 2-5% of large bowel neoplasms. The tumor frequently presents with late-stage or peritoneal spreading. It can often affect young patients and diffusely infiltrate through all layers of the intestinal wall. Local recurrence and distant metastases are common in spite of surgical operation and adjuvant treatment, conditioning a poor prognosis. At the present, early diagnosis and complete resection are the most important approaches to improve the outcome. In our report we describe a case of a 41-yr-old patient with very aggressive untreated metastatic colorectal signet ring cell carcinoma. The fulminant tumor progression was really unexpected and misled every possible medical interpretation, leading to rapid worsening of the patient's clinical conditions and no chance for chemotherapy treatment. The tumor mimicked the picture observed in the acute leukemia, developing diffuse infiltration in all serosal membranes, liver, lung, kidneys, multiple lymph nodes, and meninges, as revealed by the post-mortem medical report.International Journal of Gastrointestinal Cancer 02/2006; 37(1):49-54. -
Article: A complete atrioventricular block secondary to myocardial metastases of lung cancer. A case report.
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ABSTRACT: A metastatic involvement of the heart is an uncommon phenomenon in clinical practice; it is more frequent in patients with end-stage disease and a wide tumor spread. The clinical diagnosis is very difficult because there are no early symptoms and most often, the presence of metastases in other sites, such as lung and lymph nodes, may determine a misunderstanding of the clinical picture. We report the case of a young male (44 years old) with a complete atrioventricular block due to metastatic myocardial involvement from a primary occult lung cancer. The first symptom of the disease was a syncopal spell. In spite of permanent pacemaker implantation, the patient died suddenly and unexpectedly after 3 days. Autopsy revealed an anaplastic carcinoma of the right lung hilus. The myocardium was invaded by numerous metastatic nodules, particularly in the interventricular septum and in the left ventricular wall.Italian heart journal: official journal of the Italian Federation of Cardiology 12/2005; 6(11):931-2. -
Article: Angiogenic inhibitors: a new therapeutic strategy in oncology.
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ABSTRACT: Angiogenesis is a multistep, complex and tightly regulated process that is necessary for tumor growth and metastasis. Based on data of preclinical models, several antiangiogenic compounds has been shown to modify activated tumor endothelium, which suggests that these compounds can improve cytotoxic drug delivery. Such agents have entered clinical trials as single agents or in combination with cytotoxic drugs, and have shown promising antitumor activity. The pharmacodynamic and pharmacokinetic characteristics of antiangiogenic drugs are reviewed here. Most of the early clinical testing of these agents was conducted in patients with advanced disease resistant to standard therapies. Phase III trials compared the efficacy of standard chemotherapy alone with standard chemotherapy in combination with an experimental angiogenesis inhibitor. Although some of these studies were negative or controversial, recent studies validated in large clinical trials with an anti-vascular endothelial growth factor antibody demonstrated significant clinical benefit and renewed enthusiasm for this therapeutic strategy. This review describes the clinical studies of antiangiogenic agents and highlights the challenges related to choosing appropriate strategies for the selection of patients, study design and choice of appropriate endpoints for the studies' development.Nature Clinical Practice Oncology 12/2005; 2(11):562-77. · 8.00 Impact Factor -
Article: Combined therapy with weekly irinotecan, infusional 5-fluorouracil and the selective COX-2 inhibitor rofecoxib is a safe and effective second-line treatment in metastatic colorectal cancer.
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ABSTRACT: The purpose of this study was to determine the tolerability and activity of rofecoxib (Vioxx; Merck & Co., Inc., Whitehouse Station, NJ, http://www.merck.com) combined with weekly irinotecan (Camptosar; Pfizer Pharmaceuticals, New York, http://www.pfizer.com) and infusional 5-fluorouracil (5-FU) as second-line therapy in metastatic colorectal cancer (MCRC). Enrolled patients had previously treated metastatic disease, were aged > or =18 to < or =75 years, and had adequate performance status. A cycle of treatment consisted of i.v. irinotecan on days 1, 8, 15, and 22, rofecoxib at an oral dose of 50 mg/day, and infusional 5-FU at a fixed dose of 200 mg/m(2) per day for 5 weeks followed by 3 weeks of therapy with rofecoxib alone. In the dose-finding study, the starting dose of irinotecan was 87.5 mg/m(2) and further dose escalations were planned by increments of 12.5 mg/m(2) up to 125 mg/m(2). Forty-eight consecutive patients were enrolled in the study. Among the 15 cases enrolled in the dose-finding study, one patient experienced grade 3 reversible diarrhea as the dose-limiting toxicity, at the fourth dose level tested. Therefore, the dose of irinotecan for the phase II study was 125 mg/m(2), and 33 patients were enrolled and received a total of 75 cycles. Hematological side effects were moderate, with grade 4 neutropenia recorded in only two patients. The most common nonhematological toxicity was diarrhea, occurring in 25 patients (75.8%) and considered to be of grade 3 in 12 patients (36.4%). Sixteen patients achieved partial responses (48.5%; 95% confidence interval [CI], 30.8%-66.5%), and another 10 patients (30.3%) had stable disease. The median time to progression was 7 months (95% CI, 5-12) and the median overall survival (OS) was 18 months; the 1-year estimated OS rate was 69.4%. The unique schedule tested in this study is feasible, is well-tolerated, and has promising activity in patients with MCRC after progression on oxaliplatin (Eloxatin; Sanofi-Synthelabo Inc., New York, http://www.sanofi-synthelabo.us)-based chemotherapy.The Oncologist 11/2005; 10(9):710-7. · 3.91 Impact Factor
Top co-authors
Top Journals
Institutions
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2005–2013
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A.C.O. San Filippo Neri
Roma, Latium, Italy
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2008
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CRO Centro di Riferimento Oncologico di Aviano
Aviano, Friuli Venezia Giulia, Italy
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