37 results on '"Ciliberto D"'
Search Results
2. P637: FRONTLINE THERAPY CLL WITHOUT 17P DEL/P53 ABERRATIONS: SYSTEMATIC REVIEW AND BAYESIAN NETWORK META-ANALYSIS
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Caridà, G., primary, Ciliberto, D., additional, Pelaia, G., additional, Staropoli, N., additional, Siciliano, M. A., additional, Calandruccio, N. D., additional, Toscano, R., additional, and Rossi, M., additional
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- 2022
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3. GOLFIG chemo-immunotherapy in metastatic colorectal cancer (mCRC) patients: A fifteen year retrospective analysis
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Correale, P., primary, Staropoli, N., additional, Pastina, P., additional, Giannicola, R., additional, Botta, C., additional, Francini, E., additional, Ridolfi, L., additional, Mini, E., additional, Ciliberto, D., additional, Agostino, R.M., additional, Strangio, A., additional, Azzarello, D., additional, Nardone, V., additional, Falzea, A., additional, Tassone, P., additional, Giordano, A., additional, Pirtoli, L., additional, Francini, G., additional, and Tagliaferri, P.S., additional
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- 2019
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4. 1204P - GOLFIG chemo-immunotherapy in metastatic colorectal cancer (mCRC) patients: A fifteen year retrospective analysis
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Correale, P., Staropoli, N., Pastina, P., Giannicola, R., Botta, C., Francini, E., Ridolfi, L., Mini, E., Ciliberto, D., Agostino, R.M., Strangio, A., Azzarello, D., Nardone, V., Falzea, A., Tassone, P., Giordano, A., Pirtoli, L., Francini, G., and Tagliaferri, P.S.
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- 2019
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5. A gene expression inflammatory signature specifically predicts multiple myeloma evolution and patients survival
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Botta, C, primary, Di Martino, M T, additional, Ciliberto, D, additional, Cucè, M, additional, Correale, P, additional, Rossi, M, additional, Tagliaferri, P, additional, and Tassone, P, additional
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- 2016
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6. A systematic review and meta-analysis of randomized trials on the role of targeted therapy in advanced pancreatic cancer
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Ciliberto, D., primary, Staropoli, N., additional, Chiellino, S., additional, Del Giudice, T., additional, Caglioti, F., additional, Tagliaferri, P., additional, and Tassone, P., additional
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- 2015
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7. Role of targeted therapy in ovarian cancer treatment: a systematic review and meta-analysis of randomized trials
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Staropoli, N., primary, Ciliberto, D., additional, Chiellino, S., additional, Del Giudice, T., additional, Caglioti, F., additional, Strangio, A., additional, Salvino, A., additional, Tassone, P., additional, and Tagliaferri, P., additional
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- 2015
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8. GOLFIG Chemo-Immunotherapy in Metastatic Colorectal Cancer Patients. A Critical Review on a Long-Lasting Follow-Up
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Michele Caraglia, Pierpaolo Correale, Rocco Giannicola, Nicoletta Staropoli, Cirino Botta, Pierpaolo Pastina, Antonello Nesci, Nadia Caporlingua, Edoardo Francini, Laura Ridolfi, Enrico Mini, Giandomenico Roviello, Domenico Ciliberto, Rita Maria Agostino, Alessandra Strangio, Domenico Azzarello, Valerio Nardone, Antonella Falzea, Salvatore Cappabianca, Marco Bocchetti, Graziella D'Arrigo, Giovanni Tripepi, Pierfrancesco Tassone, Raffaele Addeo, Antonio Giordano, Luigi Pirtoli, Guido Francini, Pierosandro Tagliaferri, Caraglia M., Correale P., Giannicola R., Staropoli N., Botta C., Pastina P., Nesci A., Caporlingua N., Francini E., Ridolfi L., Mini E., Roviello G., Ciliberto D., Agostino R.M., Strangio A., Azzarello D., Nardone V., Falzea A., Cappabianca S., Bocchetti M., D'Arrigo G., Tripepi G., Tassone P., Addeo R., Giordano A., Pirtoli L., Francini G., Tagliaferri P., Caraglia, M., Correale, P., Giannicola, R., Staropoli, N., Botta, C., Pastina, P., Nesci, A., Caporlingua, N., Francini, E., Ridolfi, L., Mini, E., Roviello, G., Ciliberto, D., Agostino, R. M., Strangio, A., Azzarello, D., Nardone, V., Falzea, A., Cappabianca, S., Bocchetti, M., D'Arrigo, G., Tripepi, G., Tassone, P., Addeo, R., Giordano, A., Pirtoli, L., Francini, G., and Tagliaferri, P.
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0301 basic medicine ,Oncology ,medicine.medical_specialty ,Cancer Research ,Colorectal cancer ,medicine.medical_treatment ,colorectal cancer ,chemotherapy ,lcsh:RC254-282 ,03 medical and health sciences ,0302 clinical medicine ,FOLFOX ,Internal medicine ,Medicine ,Adverse effect ,Original Research ,Chemotherapy ,business.industry ,Hazard ratio ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,medicine.disease ,GOLFIG ,immunotherapy ,metastatic ,phase III clinical trial ,real-world medicine ,Gemcitabine ,Oxaliplatin ,Regimen ,030104 developmental biology ,030220 oncology & carcinogenesis ,business ,medicine.drug - Abstract
Background: GOLFIG is a chemo-immunotherapy regimen established in preclinical models that combines gemcitabine + FOLFOX (fluoropyrimidine backbone coupled to oxaliplatin) poly-chemotherapy with low-dose s. c. recombinant interleukin-2 (rIL-2) and granulocyte-macrophage colony stimulating factor (GM-CSF). Promising antitumor effects in metastatic colorectal cancer (mCRC) patients were obtained in previous phase II and III trials. Here we report the results of 15 years of follow-up. Methods: This is a multi-institutional retrospective analysis including 179 mCRC patients receiving GOLFIG regimen between June 2002 and June 2018. Sixty-two of them received the treatment as frontline (enrolled in the GOLFIG-2 phase III trial) and 117 as second/third line (49 enrolled in the GOLFIG-1 phase II trial and 68 as compassionate use). One hundred twelve patients showed a primary left side and 67 a primary right side; K/N-ras mutational status was available in 74 cases, and an activating mutation was detected in 33. Kaplan–Meier and Cox regression analyses were carried out to relate PFS and OS with different parameters. Results: Overall, we recorded a mean PFS and OS of 15.28 (95% CI: 10.36–20.20) and 24.6 (95% CI: 19.07–30.14) months, respectively, with 14 patients surviving free of progression for 10 years. This regimen, in our updated survey of the GOLFIG-2 trial, confirmed superiority over FOLFOX in terms of PFS (hazard ratio (HR) = 0.58, p = 0.006) with a trend to a longer OS (HR = 0.69, P = 0.06) in the first line. Our analysis also confirmed significant antitumor activity in pre-treated patients, reporting a mean PFS and OS of 12.55 (95% CI: 7.19–17.9) and 20.28 (95% CI: 14.4–26.13) months, respectively. Immune-related adverse events (irAEs) were recorded in 24% of the cases and were related to a longer survival (HR = 0.36; P = 0.0001). Finally, patients' outcome was not correlated to sex, sidedness, and MT-K/N-ras. Conclusions: The GOLFIG regimen is a reliable underestimated therapeutic option in pre-treated mCRC patients and offers a strong rationale to design further trials.
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- 2019
9. Systematic review and meta-analysis on targeted therapy in advanced pancreatic cancer
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Nicoletta Staropoli, Domenico Ciliberto, Silvia Chiellino, Pierosandro Tagliaferri, Pierfrancesco Tassone, Cirino Botta, Ciliberto D., Staropoli N., Chiellino S., Botta C., Tassone P., and Tagliaferri P.
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0301 basic medicine ,Oncology ,medicine.medical_specialty ,Funnel plot ,Endocrinology, Diabetes and Metabolism ,medicine.medical_treatment ,Antineoplastic Agents ,Bioinformatics ,law.invention ,Targeted therapy ,03 medical and health sciences ,0302 clinical medicine ,Randomized controlled trial ,law ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,Humans ,Medicine ,Genetic Predisposition to Disease ,Meta-analysi ,Advanced pancreatic cancer ,Hepatology ,business.industry ,Hazard ratio ,Gastroenterology ,Cancer ,Pancreatic cancer ,Publication bias ,medicine.disease ,Pancreatic Neoplasms ,Clinical trial ,030104 developmental biology ,030220 oncology & carcinogenesis ,Meta-analysis ,Randomized clinical trial ,business ,Signal Transduction ,Pathway - Abstract
Aim A systematic review and meta-analysis from literature has been performed to assess the impact of targeted therapy in advanced pancreatic cancer. Methods By searching different literature databases and major cancer meetings proceedings, data from all randomized clinical trials designed to investigate molecular targeted agents in the treatment of advanced pancreatic cancer were collected. The time-frame between January 2007 and March 2015 was selected. Data on predefined end-points, including overall survival, progression-free survival in terms of Hazard Ratio and response-rate were extracted and analyzed by a random effects model. Pooled data analysis was performed according to the DerSimonian and Laird test. The occurrence of publication bias was investigated through Begg's test by visual inspection of funnel plots. Results Twenty-seven randomized clinical trials for a total of 8205 patients were selected and included in the final analysis. A significant benefit was demonstrated for anti-EGFR agents on overall survival (HR = 0.880; 95% confidence interval (CI) 0.797–0.972; p = 0.011). In the pooled analysis no benefit on overall survival (OS: pooled HR = 0.957; 95%CI 0.900–1.017; p = 0.153), or progression-free survival (PFS: pooled HR = 0.908; 95%CI 0.817–1.010; p = 0.075) for targeted-based therapies as compared to conventional treatments could be demonstrated. No advantage was reported in response-rate (OR for RR = 1.210; 95%CI 0.990–1.478; p = 0.063). Begg's funnel plot showed no evidence of publication bias. Conclusion The use of molecular targeted agents does not translate into clinical benefit. Therefore, our work highlights the need to identify predictive factors for patient selection and rationally designed clinical trials.
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- 2016
10. Systemic inflammatory status predict the outcome of k-RAS WT metastatic colorectal cancer patients receiving the thymidylate synthase poly-epitope-peptide anticancer vaccine
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Michele Caraglia, Antonella Fioravanti, Luigi Pirtoli, Pierosandro Tagliaferri, Stefano Lazzi, Claudia Gandolfo, Pierfrancesco Tassone, Rocco Giannicola, Valerio Nardone, Cirino Botta, Nicoletta Staropoli, Antonio Giordano, Silvia Zappavigna, Maria Grazia Cusi, Cristina Ulivieri, Pierpaolo Pastina, Tatiana Cosima Baldari, Domenico Ciliberto, Pierpaolo Correale, Correale, Pierpaolo, Botta, Cirino, Staropoli, Nicoletta, Nardone, Valerio, Pastina, Pierpaolo, Ulivieri, Cristina, Gandolfo, Claudia, Baldari, Tatiana Cosima, Lazzi, Stefano, Ciliberto, Domenico, Giannicola, Rocco, Fioravanti, Antonella, Giordano, Antonio, Zappavigna, Silvia, Caraglia, Michele, Tassone, Pierfrancesco, Pirtoli, Luigi, Cusi, Maria Grazia, Tagliaferri, Pierosandro, Correale P., Botta C., Staropoli N., Nardone V., Pastina P., Ulivieri C., Gandolfo C., Baldari T.C., Lazzi S., Ciliberto D., Giannicola R., Fioravanti A., Giordano A., Zappavigna S., Caraglia M., Tassone P., Pirtoli L., Cusi M.G., and Tagliaferri P.
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0301 basic medicine ,medicine.medical_specialty ,Colorectal cancer ,Thymidylate synthase ,K-ra ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,Overall survival ,Cancer vaccine ,Medicine ,In patient ,K-ras ,Antitumor activity ,biology ,business.industry ,Bio-marker ,University hospital ,medicine.disease ,Predictive value ,Clinical trial ,030104 developmental biology ,Bio-markers ,Oncology ,030220 oncology & carcinogenesis ,biology.protein ,business ,Research Paper - Abstract
// Pierpaolo Correale 1 , Cirino Botta 2 , Nicoletta Staropoli 3 , Valerio Nardone 4 , Pierpaolo Pastina 4 , Cristina Ulivieri 5 , Claudia Gandolfo 6 , Tatiana Cosima Baldari 5 , Stefano Lazzi 7 , Domenico Ciliberto 3 , Rocco Giannicola 1 , Antonella Fioravanti 8 , Antonio Giordano 9 , Silvia Zappavigna 10 , Michele Caraglia 9, 10 , Pierfrancesco Tassone 2, 3, 10 , Luigi Pirtoli 4 , Maria Grazia Cusi 6 and Pierosandro Tagliaferri 3 1 Unit of Medical Oncology, Grand Metropolitan Hospital Bianchi Melacrino Morelli, Reggio-Calabria, Italy 2 Medical Oncology Unit, AUO Mater Domini, Magna Graecia University, Catanzaro, Italy 3 Department of Experimental and Clinical Medicine, Magna Graecia University , Catanzaro, Italy 4 Unit of Radiotherapy, Department of Surgery, Medicine and Neurological Science, Siena University Hospital, Siena, Italy 5 Department of Science of Life, Siena University, Siena, Italy 6 Microbiology and Virology Unit, Department of Medical Biotechnology, Siena University, Siena, Italy 7 Unit of Pathology, Department of Surgery, Medicine and Neurological Science, Siena University Hospital, Siena, Italy 8 Unit of Rheumatology, Department of Clinical Medicine and Immunologic Sciences, University of Siena, Siena, Italy 9 Department of Biotechnology, Temple University, Sbarro Foundation, Philadelphia, Pennsylvania, USA 10 Department of Precision Medicine, University of Campania L. Vanvitelli, Naples, Italy Correspondence to: Pierosandro Tagliaferri, email: tagliaferri@unicz.it Pierpaolo Correale, email: correalep@yahoo.it Keywords: bio-markers; cancer vaccine; colorectal cancer; K-ras; thymidylate synthase Received: August 24, 2017 Accepted: February 21, 2018 Published: April 17, 2018 ABSTRACT TSPP is an anticancer poly-epitope peptide vaccine to thymidylate synthase, recently investigated in the multi-arm phase Ib TSPP/VAC1 trial. TSPP vaccination induced immune-biological effects and showed antitumor activity in metastatic colorectal cancer (mCRC) patients and other malignancies. Progression-free and overall survival of 41 mCRC patients enrolled in the study correlated with baseline levels of CEA, immune-inflammatory markers (neutrophil/lymphocyte ratio, CRP, ESR, LDH, ENA), IL-4 and with post-treatment change in p-ANCA and CD56 dim CD16 bright NKs ( p < 0.04). A subset of 19 patients with activating k-ras mutations showed a different immune-inflammatory response to TSPP as compared to patients with k-ras/wt and a worse outcome in term of PFS ( p = 0.048). In patients with k-ras/mut, inflammatory markers lost their predictive value and their survival directly correlated with the baseline levels of IL17/A over the median value ( p = 0.01). These results provide strong hints for the design of further clinical trials aimed to test TSPP vaccination in mCRC patients.
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- 2018
11. The best strategy for RAS wild-type metastatic colorectal cancer patients in first-line treatment: A classic and Bayesian meta-analysis
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Mariamena Arbitrio, Nicoletta Staropoli, Pierfrancesco Tassone, Domenico Ciliberto, Pierpaolo Correale, Silvia Chiellino, Pierosandro Tagliaferri, Antonella Ierardi, Rossana Ingargiola, F. Caglioti, Cirino Botta, Ciliberto D., Staropoli N., Caglioti F., Chiellino S., Ierardi A., Ingargiola R., Botta C., Arbitrio M., Correale P., Tassone P., and Tagliaferri P.
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0301 basic medicine ,Oncology ,medicine.medical_specialty ,Colorectal cancer ,medicine.medical_treatment ,Bayesian probability ,Sidedness ,Disease-Free Survival ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Humans ,In patient ,Meta-analysi ,Systemic chemotherapy ,Neoplasm Metastasis ,RAS wild-type ,Chemotherapy ,business.industry ,Metastatic colorectal cancer ,Wild type ,Bayes Theorem ,Hematology ,medicine.disease ,Neoadjuvant Therapy ,First line treatment ,Meta-analysis ,Safety profile ,Genes, ras ,030104 developmental biology ,030220 oncology & carcinogenesis ,Colorectal Neoplasms ,business - Abstract
Background: At present, there is uncertainty on the best systemic treatment in first-line setting for RAS wild-type (WT) metastatic colorectal cancer (mCRC) patients. Indeed, several chemotherapy and biologics combinations showed an improvement on survival. We performed a systematic review with a pair-wise and bayesan meta-analysis to rank the best strategy for these patients. Methods: A systematic literature search through March 2017 was performed to evaluate the association between several treatment combinations and overall survival (OS), progression-free survival (PFS), overall response rate (ORR) and toxicity rate (TR) in RAS WT mCRC patients. Data were extracted from studies and pooled using the random-effect model for pair-wise meta-analyses and bayesan model for network meta-analysis (NMA). Results: Eight studies with a total of 2518 individuals were included in the meta-analyses. Pooled analyses for subgroups stratified by type of schedule and tumor location demonstrated that anti-EGFR + doublet had the best OS when compared to doublet ± bevacizumab (0.767; 95%CI, 0.695–0.846; P < 0.0001). This benefit is limited to LSCC when compared to a doublet-based schedule and doublet + bevacizumab (HRs, 0.692; 95%CI, 0.596–0.804; P < 0.001; 0.706; 95%CI, 0.584–0.854; P < 0.001; respectively). No significant differences are detected in PFS, whereas the cetuximab-based regimens showed the highest ORR and TR. In NMA our ranking showed the best performance for FOLFOX + panitumumab. Conclusions: Our study indicates that FOLFOX + panitumumab has the major probability to provide an improvement of survival with a good safety profile in patients with RAS WT mCRC with an added value from selection based on sidedness.
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- 2018
12. Network meta-analysis of randomized trials in multiple myeloma: efficacy and safety in relapsed/refractory patients
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Marco Rossi, Domenico Ciliberto, Pierfrancesco Tassone, Teresa Galeano, Cirino Botta, Nicoletta Staropoli, Pierosandro Tagliaferri, Maria Cucè, Botta C., Ciliberto D., Rossi M., Staropoli N., Cuce M., Galeano T., Tagliaferri P., and Tassone P.
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Oncology ,medicine.medical_specialty ,lenalidomide ,Pharmacology ,law.invention ,03 medical and health sciences ,0302 clinical medicine ,Randomized controlled trial ,law ,Internal medicine ,medicine ,Multiple myeloma ,Lenalidomide ,Lymphoid Neoplasia ,business.industry ,Bortezomib ,Daratumumab ,Hematology ,medicine.disease ,Clinical trial ,multiple myeloma ,Regimen ,network meta-analysi ,Tolerability ,030220 oncology & carcinogenesis ,business ,daratumumab, bortezomib ,030215 immunology ,medicine.drug - Abstract
Despite major therapeutic advancements, multiple myeloma (MM) is still incurable and relapsed/refractory multiple myeloma (RRMM) remains a challenge; the rational choice of the most appropriate regimen in this setting is currently undefined. We performed a systematic review and 2 standard pairwise meta-analyses to evaluate the efficacy of regimens that have been directly compared with bortezomib or immunomodulatory imide drugs (IMiDs) in head-to-head clinical trials and a network meta-analysis (NMA) to determine the relevance of each regimen on the basis of all the available direct and indirect evidence. Sixteen trials were included in the pairwise meta-analyses, and 18 trials were included in the NMA. Pairwise meta-analyses showed that a 3-drug regimen (bortezomib- or IMiD-based) was superior to a 2-drug regimen in progression-free-survival (PFS) and overall response rate (ORR). NMA showed that an IMiD backbone associated with anti-MM monoclonal antibodies (mAbs) (preferably) or proteasome inhibitors had the highest probability of being the most effective regimen with the lowest toxicity. The combination of daratumumab, lenalidomide, and dexamethasone ranked as the first regimen in terms of activity, efficacy, and tolerability according to the average value between surface under the cumulative ranking curve of PFS, overall survival, ORR, complete response rate, and safety. This is the first NMA comparing all currently available regimens evaluated in published randomized trials for the treatment of RRMM, but our results need to be interpreted taking into account differences in their patient populations. Our analysis suggests that IMiDs plus new anti-MM mAb–containing regimens are the most active therapeutic option in RRMM.
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- 2016
13. Immunotherapy of colorectal cancer: New perspectives after a long path
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Luigi Pirtoli, Rossana Ingargiola, Michele Caraglia, Silvia Zappavigna, Pierpaolo Pastina, Pierpaolo Correale, Domenico Ciliberto, Pierfrancesco Tassone, Pierosandro Tagliaferri, Cirino Botta, Correale, Pierpaolo, Botta, Cirino, Ciliberto, Domenico, Pastina, Pierpaolo, Ingargiola, Rossana, Zappavigna, Silvia, Tassone, Pierfrancesco, Pirtoli, Luigi, Caraglia, Michele, Tagliaferri, Pierosandro, Correale P., Botta C., Ciliberto D., Pastina P., Ingargiola R., Zappavigna S., Tassone P., Pirtoli L., Caraglia M., and Tagliaferri P.
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0301 basic medicine ,Oncology ,medicine.medical_specialty ,Bevacizumab ,Colorectal cancer ,medicine.medical_treatment ,Immunology ,colorectal cancer ,thymidylate synthase ,chemotherapy ,Cancer Vaccines ,03 medical and health sciences ,0302 clinical medicine ,Costimulatory and Inhibitory T-Cell Receptors ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Animals ,Humans ,Panitumumab ,Immunology and Allergy ,Molecular Targeted Therapy ,immune-modulating strategie ,Immunotherapy, metastatic colorectal cancer, monoclonal antibodies, target therapy ,Cetuximab ,business.industry ,target therapy ,metastatic colorectal cancer ,carcinoembryonic antigen ,Antibodies, Monoclonal ,Cancer ,Combination chemotherapy ,immune-modulating strategies ,Immunotherapy ,medicine.disease ,Combined Modality Therapy ,030104 developmental biology ,030220 oncology & carcinogenesis ,Cancer vaccine ,monoclonal antibodies ,Colorectal Neoplasms ,business ,cancer vaccine ,medicine.drug - Abstract
Although significant therapeutic improvement has been achieved in the last 10 years, the survival of metastatic colorectal cancer patients remains in a range of 28 to 30 months. Presently, systemic treatment includes combination chemotherapy with oxaliplatin and/or irinotecan together with a backbone of 5-fluorouracil/levofolinate, alone or in combination with monoclonal antibodies to VEGFA (bevacizumab) or EGF receptor (cetuximab and panitumumab). The recent rise of immune checkpoint inhibitors in the therapeutic scenario has renewed scientific interest in the investigation of immunotherapy in metastatic colorectal cancer patients. According to our experience and view, here, we review the immunological strategies investigated for the treatment of this disease, including the use of tumor target-specific cancer vaccines, chemo-immunotherapy and immune checkpoint inhibitors.
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- 2016
14. Is ovarian cancer a targetable disease? A systematic review and meta-analysis and genomic data investigation
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Cirino Botta, Angela Salvino, Sandro Pignata, Nicoletta Staropoli, F. Caglioti, Domenico Ciliberto, Alessandra Strangio, Silvia Chiellino, Teresa Del Giudice, Simona Gualtieri, Pierfrancesco Tassone, Pierosandro Tagliaferri, Staropoli N., Ciliberto D., Chiellino S., Caglioti F., Del Giudice T., Gualtieri S., Salvino A., Strangio A., Botta C., Pignata S., Tassone P., and Tagliaferri P.
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0301 basic medicine ,Oncology ,medicine.medical_specialty ,Time Factors ,Bevacizumab ,medicine.medical_treatment ,Angiogenesis Inhibitors ,Disease-Free Survival ,Targeted therapy ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Risk Factors ,Ovarian cancer ,Internal medicine ,Biomarkers, Tumor ,Odds Ratio ,medicine ,Humans ,Meta-analysi ,Molecular Targeted Therapy ,Precision Medicine ,Systemic chemotherapy ,Ovarian Neoplasms ,business.industry ,Patient Selection ,Hazard ratio ,Cancer ,medicine.disease ,Carboplatin ,meta-analysis ,Clinical trial ,Treatment Outcome ,030104 developmental biology ,chemistry ,Drug Resistance, Neoplasm ,030220 oncology & carcinogenesis ,Meta-analysis ,Disease Progression ,Systematic review ,Female ,Personalized medicine ,business ,Research Paper ,Signal Transduction ,medicine.drug - Abstract
// Nicoletta Staropoli 1, * , Domenico Ciliberto 1, * , Silvia Chiellino 1 , Francesca Caglioti 1 , Teresa Del Giudice 1 , Simona Gualtieri 1 , Angela Salvino 1 , Alessandra Strangio 1 , Cirino Botta 1 , Sandro Pignata 2 , Pierfrancesco Tassone 1, * , Pierosandro Tagliaferri 1, * 1 Department of Experimental and Clinical Medicine, Magna Graecia University, Catanzaro, Italy 2 Department of Gynecologic and Urologic Oncology, Fondazione Pascale, National Cancer Institute of Naples, Naples, Italy * These authors have contributed equally to this work Correspondence to: Pierosandro Tagliaferri, email: tagliaferri@unicz.it Keywords: ovarian cancer, targeted therapy, systemic chemotherapy, systematic review, meta-analysis Received: May 01, 2016 Accepted: September 25, 2016 Published: October 13, 2016 ABSTRACT Objectives: The current gold-standard for the first-line treatment in IIIb/IV stages of epithelial ovarian cancer (EOC) is the combination of carboplatin and paclitaxel plus bevacizumab in some countries. In the era of personalized medicine, there is still uncertainty on the impact of several molecularly targeted agents, which have been investigated for the management of this disease. To shed light on the actual role of targeted therapy in EOC, a systematic review and meta-analysis was performed. Methods: Clinical trials were selected by searching “Pubmed” database and abstracts from major cancer meetings within the time-frame of January 2004-June 2015. The endpoints were survival outcome and response rate (RR). Hazard ratios (HRs) of survival outcomes, with confidence intervals and odds-ratios (ORs) of RR, were extracted from retrieved studies and used for current analysis. Meta-analysis was carried out by random effect model. Results: 30 randomized trials for a total of 10,530 patients were selected and included in the final analysis. A benefit in terms of OS (pooled HR 0.915; 95%CI 0.840-0.997; p =0.043), particularly for anti-angiogenetic agents (HR 0.872; 95%CI 0.761-1.000; p =0.049), has been demonstrated for targeted therapy. Moreover, a significant advantage in platinum-resistant subgroup in term of PFS (HR 0.755; 95%CI 0.624-0.912; p =0.004) was found. Conclusions: This systematic review and meta-analysis provide the first evidence that targeted therapy is potentially able to translate into improved survival of EOC patients, with a major role played by anti-angiogenetic drugs. The role of target therapy is underlined in the platinum-resistant setting that represents the “pain in the neck” in EOC management.
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- 2016
15. A systematic review and meta-analysis of randomized trials on the role of targeted therapy in the management of advanced gastric cancer: Evidence does not translate?
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F. Caglioti, Lucia Fiorillo, Francesco Mendicino, Pierosandro Tagliaferri, Cirino Botta, Domenico Ciliberto, Pierfrancesco Tassone, Nicoletta Staropoli, Silvia Chiellino, Simona Gualtieri, Antonina Maria De Angelis, Michele Caraglia, Ciliberto D., Staropoli N., Caglioti F., Gualtieri S., Fiorillo L., Chiellino S., De Angelis A.M., Mendicino F., Botta C., Caraglia M., Tassone P., Tagliaferri P., Ciliberto, Domenico, Staropoli, Nicoletta, Caglioti, Francesca, Gualtieri, Simona, Fiorillo, Lucia, Chiellino, Silvia, De Angelis, Antonina Maria, Mendicino, Francesco, Botta, Cirino, Caraglia, Michele, Tassone, Pierfrancesco, and Tagliaferri, Pierosandro
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Oncology ,Cancer Research ,medicine.medical_specialty ,Receptor, ErbB-2 ,medicine.medical_treatment ,Angiogenesis Inhibitors ,Bioinformatics ,Targeted therapy ,law.invention ,Randomized controlled trial ,Targeted pathway ,Stomach Neoplasm ,law ,Stomach Neoplasms ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Humans ,Meta-analysi ,Molecular Targeted Therapy ,Systemic chemotherapy ,Survival analysis ,Randomized Controlled Trials as Topic ,Pharmacology ,Antineoplastic Combined Chemotherapy Protocol ,business.industry ,Cancer ,Advanced gastric cancer ,medicine.disease ,Survival Analysis ,ErbB Receptors ,Angiogenesi ,Pooled analysis ,Tolerability ,Meta-analysis ,Clinical Study ,Molecular Medicine ,Receptor, Epidermal Growth Factor ,Survival Analysi ,Randomized clinical trial ,business ,Gastric cancer ,Angiogenesis Inhibitor ,Human - Abstract
It is still uncertain if targeted therapy-based regimens in advanced gastric cancer actually produce survival benefit. To shed light on this important question, we performed a systematic review and meta-analyses on each relevant targeted-pathway. By searching literature databases and proceedings of major cancer meetings in the time-frame 2005–2014, 22 randomized clinical trials exploring targeted therapy for a total of 7022 advanced gastric cancer patients were selected and included in the final analysis. Benefit was demonstrated for antiangiogenic agents in terms of overall survival (HR 0.759; 95%CI 0.655–0.880; p < 0.001). Conversely no benefit was found for EGFR pathway (HR 1.077; 95%CI 0.847–1.370; p = 0.543). Meta-analysis of HER-2 pathway confirmed improvement in terms of survival outcome, already known for this class of drugs (HR 0.823; 95%CI 0.722–0.939; p = 0.004). Pooled analysis demonstrated a significant survival benefit (OS: HR 0.823; PFS: HR 0.762) with acceptable tolerability profile for targeted-based therapies as compared to conventional treatments. This finding conflicts with the outcome of most individual studies, probably due to poor trial design or patients selection. In conclusion, our findings demonstrate a significant survival benefit for targeted therapy in its whole, which can be ascribed to anti-angiogenic and anti-HER2 agents.
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- 2015
16. Postinfectious Functional Gastrointestinal Disorders in Children: A Multicenter Prospective Study
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Federica Altomare, Francesca Graziano, Mariateresa Sanseviero, Antonio Marseglia, Antonella Falvo, Valentina Talarico, Carlo Di Lorenzo, Elvira Cozza, V. Rutigliano, Domenico Ciliberto, Annamaria Staiano, Daniela Concolino, Elisabetta Gatta, Angelo Campanozzi, Domenica De Venuto, Teresa Gentile, Bianca Virginia Palermo, Licia Pensabene, Silvia Salvatore, A. Ripepi, Rossella Turco, Pensabene, L., Talarico, V., Concolino, D., Ciliberto, D., Campanozzi, A., Gentile, T., Rutigliano, V., Salvatore, S., Staiano, A., Lorenzo, Di, Graziano, C., Palermo, F., Sanseviero, B. V., Altomare, M., Cozza, F., Falvo, E., Marseglia, A., Gatta, A., Venuto, De, Ripepi, D., and Turco, A.
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Male ,medicine.medical_specialty ,Adolescent ,Gastrointestinal Diseases ,medicine.disease_cause ,Infections ,Gastroenterology ,Functional gastrointestinal disorder ,Internal medicine ,Rotavirus ,Surveys and Questionnaires ,medicine ,Humans ,Prospective Studies ,Prospective cohort study ,Child ,Irritable bowel syndrome ,business.industry ,Incidence (epidemiology) ,Incidence ,medicine.disease ,Relative risk ,Child, Preschool ,Pediatrics, Perinatology and Child Health ,Etiology ,Norovirus ,Female ,business ,Follow-Up Studies - Abstract
Objectives To prospectively investigate the occurrence of postinfectious functional gastrointestinal disorders (FGIDs), diagnosed according to the Rome III criteria, in children with acute diarrhea of different infectious etiology. Study design This was a prospective cohort multicenter study. Children 4-17 years of age presenting with acute diarrhea who tested positive for an enteric infection were recruited within 1 month from the episode and matched with control subjects of similar age and sex. Symptoms were evaluated with a validated questionnaire for FGIDs at the time of enrollment in the study and after 3 and 6 months. Results A total of 64 patients (36 boys; median age 5.3 years; age range 4.1-14.1 years) were recruited, 32 subjects in each arm. Infections included rotavirus (56.8%), salmonella (30%), adenovirus (6.6%), norovirus (3.3%), and Giardia lamblia (3.3%). FGIDs were significantly more common in exposed patients compared with controls within 1 month from acute diarrhea (40.6% vs 12.5% [ P = .02, relative risk (RR) = 1.9]), 3 months (53% vs 15.6% [ P = .003, RR = 2.2]), and 6 months (46.8% vs 15.6% [ P = .01, RR = 1.9]) later. No correlation was found between different etiologies, age, or sex, and any type of FGIDs. Among exposed children, abdominal pain–related FGIDs were significantly more frequent compared with controls after 6 months from infection ( P = .04, RR = 1.7). Conclusion This prospective cohort multicenter study supports postinfectious FGIDs as a true entity in children. There seems to be a significant increase in abdominal pain–related FGIDs after acute diarrhea in children within 1 month and 3 and 6 months later.
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- 2015
17. A gene expression inflammatory signature specifically predicts multiple myeloma evolution and patients survival
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Domenico Ciliberto, Pierosandro Tagliaferri, Cirino Botta, Marco Rossi, Pierpaolo Correale, Maria Cucè, Pierfrancesco Tassone, M T Di Martino, Botta C., Di Martino M.T., Ciliberto D., Cuce M., Correale P., Rossi M., Tagliaferri P., and Tassone P.
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0301 basic medicine ,Oncology ,Adult ,Male ,Candidate gene ,medicine.medical_specialty ,Biology ,IFN ,CCL5 ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,medicine ,Humans ,Multiple myeloma ,Aged ,Aged, 80 and over ,Inflammation ,Hematology ,Computational Biology ,Middle Aged ,medicine.disease ,Neoplasm Proteins ,Gene expression profiling ,Gene Expression Regulation, Neoplastic ,myeloma ,030104 developmental biology ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,Immunology ,gene expression ,Disease Progression ,Original Article ,Female ,IL17A ,Bone marrow ,Multiple Myeloma ,Transcriptome ,Monoclonal gammopathy of undetermined significance ,Signal Transduction - Abstract
Multiple myeloma (MM) is closely dependent on cross-talk between malignant plasma cells and cellular components of the inflammatory/immunosuppressive bone marrow milieu, which promotes disease progression, drug resistance, neo-angiogenesis, bone destruction and immune-impairment. We investigated the relevance of inflammatory genes in predicting disease evolution and patient survival. A bioinformatics study by Ingenuity Pathway Analysis on gene expression profiling dataset of monoclonal gammopathy of undetermined significance, smoldering and symptomatic-MM, identified inflammatory and cytokine/chemokine pathways as the most progressively affected during disease evolution. We then selected 20 candidate genes involved in B-cell inflammation and we investigated their role in predicting clinical outcome, through univariate and multivariate analyses (log-rank test, logistic regression and Cox-regression model). We defined an 8-genes signature (IL8, IL10, IL17A, CCL3, CCL5, VEGFA, EBI3 and NOS2) identifying each condition (MGUS/smoldering/symptomatic-MM) with 84% accuracy. Moreover, six genes (IFNG, IL2, LTA, CCL2, VEGFA, CCL3) were found independently correlated with patients’ survival. Patients whose MM cells expressed high levels of Th1 cytokines (IFNG/LTA/IL2/CCL2) and low levels of CCL3 and VEGFA, experienced the longest survival. On these six genes, we built a prognostic risk score that was validated in three additional independent datasets. In this study, we provide proof-of-concept that inflammation has a critical role in MM patient progression and survival. The inflammatory-gene prognostic signature validated in different datasets clearly indicates novel opportunities for personalized anti-MM treatment.
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- 2016
18. The Italian Rare Biliary tract Cancer initiative (IRaBiCa): A multicentric observational study of Gruppo Oncologico dell'Italia Meridionale (GOIM) in collaboration with Gruppo Italiano Colangiocarcinoma (GICO).
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Speranza D, Sapuppo E, Aprile G, Auriemma A, Bergamo F, Bianco R, Bordonaro R, Brandi G, Brunetti O, Carnaghi C, Ciliberto D, Cinieri S, Corallo S, De Vita F, Di Donato S, Ferraù F, Fornaro L, Barucca V, Giommoni E, Lotesoriere C, Luchini C, Masini C, Niger M, Pisconti S, Rapposelli IG, Rimassa L, Rognone C, Rodriquenz MG, Corsini LR, Santin D, Scarpa A, Scartozzi M, Soto Parra H, Tonini G, Tortora G, Tralongo P, and Silvestris N
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- Humans, Italy epidemiology, Retrospective Studies, Female, Male, Bile Duct Neoplasms pathology, Bile Duct Neoplasms therapy, Middle Aged, Aged, Biliary Tract Neoplasms pathology, Biliary Tract Neoplasms therapy, Biliary Tract Neoplasms drug therapy, Cholangiocarcinoma pathology, Cholangiocarcinoma therapy
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Introduction: About 90% of cholangiocarcinomas are adenocarcinomas with glandular or tubular structures lined by epithelial cells, with no bile production and with a variable degree of differentiation, arising in the background of desmoplastic stroma. The remaining 10% is represented by rarer histological variants of which there is little knowledge regarding the biological behavior, molecular characterization, and sensitivity to the various possible therapies, including molecular-based treatments. Such rare tumors are described only in case reports or small retrospective series because of their exclusion from clinical trials. This national initiative, here presented, aims to address the following knowledge gap: a) how much does histological diversity translate into clinical manifestation variety? b) are those chemotherapy regimens, recommended for conventional biliary tract cancers, potentially active in rare variants?Therefore, epidemiological, pathological, and clinical characterization of series of rare biliary histotypes/variants, for which therapeutic and follow-up data are available, will be collected., Methods: An Italian task force on rare tumors of the biliary tract (IRaBiCa) has been created, whose initiative is a multicenter retrospective study involving 34 Italian cancer centers.Clinical data from approximately 100 patients will be collected and analyzed. Continuous variables will be presented as median ± standard deviation, while categorical variables will be expressed in terms of frequency. Kaplan-Maier analyses will be used to compare disease free, progression free and overall survival, according to the different histotypes., Conclusions: We expect to gather novel data on rare histotypes of biliary tract cancer that will be useful to support their molecular and immunological characterization., Competing Interests: Declaration of conflicting interestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: LR reports consulting fees from AstraZeneca, Basilea, Bayer, BMS, Eisai, Exelixis, Genenta, Hengrui, Incyte, Ipsen, IQVIA, Jazz Pharmaceuticals, Lilly, MSD, Nerviano Medical Sciences, Roche, Servier, Taiho Oncology, Zymeworks; lecture fees from AstraZeneca, Bayer, Eisai, Gilead, Incyte, Ipsen, Merck Serono, Roche, Sanofi, Servier; travel expenses from AstraZeneca; research grants (to Institution) from Agios, AstraZeneca, BeiGene, Eisai, Exelixis, Fibrogen, Incyte, Ipsen, Lilly, MSD, Nerviano Medical Sciences, Roche, Zymeworks.NS reports consulting fees from MSD, Bristol Myers Squibb, GSK.MN:Travel expenses from AstraZeneca, speaker honorarium from Accademia della Medicina and Incyte; honoraria from Sandoz, Medpoint SRL, Incyte and Servier for editorial collaboration. Consultant honoraria from EMD Serono, Basilea Pharmaceutica, Incyte, MSD Italia, Servier, Astrazeneca and TaihoAll other authors have nothing to declare
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- 2024
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19. LNA-i-miR-221 activity in colorectal cancer: A reverse translational investigation.
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Ali A, Grillone K, Ascrizzi S, Caridà G, Fiorillo L, Ciliberto D, Staropoli N, Tagliaferri P, Tassone P, and Di Martino MT
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Colorectal cancer (CRC) is one of the most common malignancies and a relevant cause of cancer-related deaths worldwide. Dysregulation of microRNA (miRNA) expression has been associated with the development and progression of various cancers, including CRC. Among them, miR-221 emerged as an oncogenic driver, whose high expression is associated with poor patient prognosis. The present study was conceived to investigate the anti-CRC activity of miR-221 silencing based on early clinical data achieved from a first-in-human study by our group. Going back from bedside to bench, we demonstrated that LNA-i-miR-221 reduces cell viability, induces apoptosis in vitro , and impairs tumor growth in preclinical in vivo models of CRC. Importantly, we disclosed that miR-221 directly targets TP53BP2, which, together with TP53INP1, is known as a positive regulator of the TP53 apoptotic pathway. We found that (1) both these genes are overexpressed following miR-221 inhibition, (2) the strong anti-tumor activity of LNA-i-miR-221 was selectively observed on TP53 wild-type cells, and (3) this activity was reduced in the presence of the TP53-inhibitor Pifitrin-α. Our data pave the way to further investigations on TP53 functionality as a marker predictive of response to miR-221 silencing, which might be relevant for clinical applications., Competing Interests: P.Tagliaferri, M.T.D.M., and P.Tassone are inventors of patents (US 9,404,111 B2; EPO 2943570; C.C.I.A.A. 0001429326) and applied for PCT/IB2023/055010, which are owned by Magna Græcia University, Catanzaro, Italy. All other authors declare no competing interests., (© 2024 The Author(s).)
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- 2024
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20. Identification of ADME genes polymorphic variants linked to trastuzumab-induced cardiotoxicity in breast cancer patients: Case series of mono-institutional experience.
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Staropoli N, Scionti F, Farenza V, Falcone F, Luciano F, Renne M, Di Martino MT, Ciliberto D, Tedesco L, Crispino A, Labanca C, Cucè M, Esposito S, Agapito G, Cannataro M, Tassone P, Tagliaferri P, and Arbitrio M
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- Humans, Female, Middle Aged, Retrospective Studies, Antineoplastic Agents, Immunological adverse effects, Antineoplastic Agents, Immunological pharmacokinetics, Aged, Receptor, ErbB-2 genetics, Receptor, ErbB-2 metabolism, Adult, Trastuzumab adverse effects, Trastuzumab pharmacokinetics, Breast Neoplasms drug therapy, Breast Neoplasms genetics, Cardiotoxicity genetics, Polymorphism, Single Nucleotide
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Background: Long-term survival induced by anticancer treatments discloses emerging frailty among breast cancer (BC) survivors. Trastuzumab-induced cardiotoxicity (TIC) is reported in at least 5% of HER2+BC patients. However, TIC mechanism remains unclear and predictive genetic biomarkers are still lacking. Interaction between systemic inflammation, cytokine release and ADME genes in cancer patients might contribute to explain mechanisms underlying individual susceptibility to TIC and drug response variability. We present a single institution case series to investigate the potential role of genetic variants in ADME genes in HER2+BC patients TIC experienced., Methods: We selected data related to 40 HER2+ BC patients undergone to DMET genotyping of ADME constitutive variant profiling, with the aim to prospectively explore their potential role in developing TIC. Only 3 patients ("case series"), who experienced TIC, were compared to 37 "control group" matched patients cardiotoxicity-sparing. All patients underwent to left ventricular ejection fraction (LVEF) evaluation at diagnosis and during anti-HER2 therapy. Each single probe was clustered to detect SNPs related to cardiotoxicity., Results: In this retrospective analysis, our 3 cases were homogeneous in terms of clinical-pathological characteristics, trastuzumab-based treatment and LVEF decline. We identified 9 polymorphic variants in 8 ADME genes (UGT1A1, UGT1A6, UGT1A7, UGT2B15, SLC22A1, CYP3A5, ABCC4, CYP2D6) potentially associated with TIC., Conclusion: Real-world TIC incidence is higher compared to randomized clinical trials and biomarkers with potential predictive value aren't available. Our preliminary data, as proof of concept, could suggest a predictive role of pharmacogenomic approach in the identification of cardiotoxicity risk biomarkers for anti-HER2 treatment., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)
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- 2024
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21. Genetic Biomarkers of Sorafenib Response in Patients with Hepatocellular Carcinoma.
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Giannitrapani L, Di Gaudio F, Cervello M, Scionti F, Ciliberto D, Staropoli N, Agapito G, Cannataro M, Tassone P, Tagliaferri P, Seidita A, Soresi M, Affronti M, Bertino G, Russello M, Ciriminna R, Lino C, Spinnato F, Verderame F, Augello G, and Arbitrio M
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- Humans, Sorafenib pharmacology, Sorafenib therapeutic use, Vascular Endothelial Growth Factor A metabolism, Niacinamide therapeutic use, Phenylurea Compounds therapeutic use, Genetic Markers, Carcinoma, Hepatocellular drug therapy, Carcinoma, Hepatocellular genetics, Carcinoma, Hepatocellular metabolism, Antineoplastic Agents therapeutic use, Liver Neoplasms drug therapy, Liver Neoplasms genetics, Liver Neoplasms metabolism
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The identification of biomarkers for predicting inter-individual sorafenib response variability could allow hepatocellular carcinoma (HCC) patient stratification. SNPs in angiogenesis- and drug absorption, distribution, metabolism, and excretion (ADME)-related genes were evaluated to identify new potential predictive biomarkers of sorafenib response in HCC patients. Five known SNPs in angiogenesis-related genes, including VEGF-A , VEGF-C , HIF-1a , ANGPT2 , and NOS3 , were investigated in 34 HCC patients (9 sorafenib responders and 25 non-responders). A subgroup of 23 patients was genotyped for SNPs in ADME genes. A machine learning classifier method was used to discover classification rules for our dataset. We found that only the VEGF-A (rs2010963) C allele and CC genotype were significantly associated with sorafenib response. ADME-related gene analysis identified 10 polymorphic variants in ADH1A (rs6811453), ADH6 (rs10008281), SULT1A2/CCDC101 (rs11401), CYP26A1 (rs7905939), DPYD (rs2297595 and rs1801265), FMO2 (rs2020863), and SLC22A14 (rs149738, rs171248, and rs183574) significantly associated with sorafenib response. We have identified a genetic signature of predictive response that could permit non-responder/responder patient stratification. Angiogenesis- and ADME-related genes correlation was confirmed by cumulative genetic risk score and network and pathway enrichment analysis. Our findings provide a proof of concept that needs further validation in follow-up studies for HCC patient stratification for sorafenib prescription.
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- 2024
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22. The impact of PARP inhibitors in the whole scenario of ovarian cancer management: A systematic review and network meta-analysis.
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Staropoli N, Ciliberto D, Luciano F, Napoli C, Costa M, Rossini G, Arbitrio M, Labanca C, Riillo C, Del Giudice T, Crispino A, Salvino A, Galvano A, Russo A, Tassone P, and Tagliaferri P
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- Humans, Female, Bevacizumab therapeutic use, Network Meta-Analysis, Bayes Theorem, Carcinoma, Ovarian Epithelial drug therapy, Poly(ADP-ribose) Polymerase Inhibitors therapeutic use, Ovarian Neoplasms drug therapy, Ovarian Neoplasms genetics
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Background: Carboplatin is still the cornerstone of the first-line treatment in advanced Epithelial Ovarian Cancer (aEOC) management and the clinical response to platinum-derived agents remains the major predictor of long-term outcomes., Patient and Methods: We aimed to identify the best treatment of the aEOC in terms of efficacy and safety, considering all treatment phases. A systematic literature search has been done to compare all treatments in aEOC population. Randomized trials with available survival and safety data published in the 2011-2022 timeframe were enclosed. Only trials reporting the BRCA or HRD (Homologous Recombination Deficiency) status were considered., Data Extraction and Synthesis: A ranking of treatment schedules on the progression-free survival (PFS) endpoint was performed. The random-effect model was used to elaborate and extract data. The Network Meta-Analysis (NMA) by Bayesian model was performed by STATA v17. Data on PFS were extracted in terms of Hazard ratio with relative confidence intervals., Results: This NMA involved 18 trials for a total of 9105 patients. Within 12 treatment groups, we performed 3 different sensitivity analyses including "all comers" Intention to Treat (ITT) population, BRCA-mutated (BRCAm), and HRD subgroups, respectively. Considering the SUCRA-reported cumulative PFS probabilities, we showed that in the ITT population, the inferred best treatment was niraparib plus bevacizumab with a SUCRA of 96.7. In the BRCAm subgroup, the best SUCRA was for olaparib plus chemotherapy (96,9). The HRD population showed an inferred best treatment for niraparib plus bevacizumab (SUCRA 98,4). Moreover, we reported a cumulative summary of PARPi toxicity, in which different 3-4 grade toxicity profiles were observed, despite the PARPi "class effect" in terms of efficacy., Conclusions: Considering all aEOC subgroups, the best therapeutical option was identified as PARPi plus chemotherapy and/or antiangiogenetic agents, suggesting the relevance of combinatory approaches based on molecular profile. This work underlines the potential value of "chemo-free" regimens to prolong the platinum-free interval (PFI)., Competing Interests: Declaration of Competing Interest All authors declare that they have no conflicts of interest., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)
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- 2024
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23. First-line systemic treatment for hepatocellular carcinoma: A systematic review and network meta-analysis.
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Ciliberto D, Caridà G, Staropoli N, Romeo C, Arillotta GM, Napoli C, Gervasi L, Luciano F, Riillo C, Tassone P, and Tagliaferri P
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The rapid development of novel therapeutic options for advanced hepatocellular carcinoma (aHCC) has generated some uncertainty about the rational choice of the systemic upfront treatment. So far, a variety of therapeutic strategies have been investigated, including the combination of immunecheckpoint inhibitors and anti -VEGF. To identify the treatment that should be preferred as front-line approach, we compared the efficacy and toxicity of a variety of therapeutic strategies. With this aim, we performed a systematic review and a meta-analysis of randomized clinical trials. OS, PFS, ORR and tolerability outcomes were considered, and for each outcome the treatment ranking was evaluated by the surface under the cumulative rankings (SUCRAs). Combination of Camrelizumab + Rivoceranib scored the best in OS, followed by Sintilimab + Bevacizumab, whereas Lenvatinib + Pembrolizumab showed higher probability to be the best treatment in PFS and Sintilimab + Bevacizumab performed best in ORR. Finally, Durvalumab is the most tolerated treatment., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)
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- 2023
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24. Pembrolizumab plus lenvatinib in advanced endometrial cancer: case report and systematic review of lung toxicity.
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Staropoli N, Salvino A, Falcone F, Farenza V, Costa M, Rossini G, Manti F, Crispino A, Riillo C, Ciliberto D, Arbitrio M, Tassone P, and Tagliaferri P
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Background: The optimal strategy for the treatment of recurrent and/or advanced endometrial cancer is still undefined. Recently, despite the lack of any predictive biomarker, the combination of pembrolizumab with lenvatinib has improved survival outcomes. We here report the long-term management of lung toxicity in a patient with endometrial cancer, and we critically review the current therapeutic options for this disease., Results: A patient with heavily pretreated endometrial cancer took pembrolizumab plus lenvatinib for 1 year, achieving a persistent partial response with a time to treatment failure of 18 months, despite relevant lung toxicity that did not affect the remarkable overall clinical benefit. A systematic review of this combination underlines the efficacy outcome despite toxicity. Interestingly, the literature review on lung toxicity suggested the role of anti-angiogenetic agents in the pathogenesis of lung cavitation, probably related to direct treatment activity, and disclosed a potential radiological sign predictive of the activity of anti-angiogenetic agents., Conclusion: We underline the efficacy of pembrolizumab plus lenvatinib in the current treatment landscape of endometrial cancer, underscoring the relevance of a correct management of toxicity., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Staropoli, Salvino, Falcone, Farenza, Costa, Rossini, Manti, Crispino, Riillo, Ciliberto, Arbitrio, Tassone and Tagliaferri.)
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- 2023
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25. Safety and activity of the first-in-class locked nucleic acid (LNA) miR-221 selective inhibitor in refractory advanced cancer patients: a first-in-human, phase 1, open-label, dose-escalation study.
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Tassone P, Di Martino MT, Arbitrio M, Fiorillo L, Staropoli N, Ciliberto D, Cordua A, Scionti F, Bertucci B, Salvino A, Lopreiato M, Thunarf F, Cuomo O, Zito MC, De Fina MR, Brescia A, Gualtieri S, Riillo C, Manti F, Caracciolo D, Barbieri V, Di Paola ED, Di Francesco AE, and Tagliaferri P
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- Humans, Oligonucleotides therapeutic use, MicroRNAs genetics, MicroRNAs therapeutic use, Neoplasms drug therapy
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Background: We developed a 13-mer locked nucleic acid (LNA) inhibitor of miR-221 (LNA-i-miR-221) with a full phosphorothioate (PS)-modified backbone. This agent downregulated miR-221, demonstrated anti-tumor activity against human xenografts in mice, and favorable toxicokinetics in rats and monkeys. Allometric interspecies scaling allowed us to define the first-in-class LNA-i-miR-221 safe starting dose for the clinical translation., Methods: In this first-in-human, open-label, dose-escalation phase 1 trial, we enrolled progressive cancer patients (aged ≥ 18 years) with ECOG 0-2 into 5 cohorts. The treatment cycle was based on a 30-min IV infusion of LNA-i-miR-221 on 4 consecutive days. Three patients within the first cohort were treated with 2 cycles (8 infusions), while 14 patients were treated with a single course (4 infusions); all patients were evaluated for phase 1 primary endpoint. The study was approved by the Ethics Committee and Regulatory Authorities (EudraCT 2017-002615-33)., Results: Seventeen patients received the investigational treatment, and 16 were evaluable for response. LNA-i-miR-221 was well tolerated, with no grade 3-4 toxicity, and the MTD was not reached. We recorded stable disease (SD) in 8 (50.0%) patients and partial response (PR) in 1 (6.3%) colorectal cancer case (total SD + PR: 56.3%). Pharmacokinetics indicated non-linear drug concentration increase across the dose range. Pharmacodynamics demonstrated concentration-dependent downregulation of miR-221 and upregulation of its CDKN1B/p27 and PTEN canonical targets. Five mg/kg was defined as the recommended phase II dose., Conclusions: The excellent safety profile, the promising bio-modulator, and the anti-tumor activity offer the rationale for further clinical investigation of LNA-i-miR-221 (ClinTrials.Gov: NCT04811898)., (© 2023. The Author(s).)
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- 2023
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26. A Prognostic and Carboplatin Response Predictive Model in Ovarian Cancer: A Mono-Institutional Retrospective Study Based on Clinics and Pharmacogenomics.
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Staropoli N, Arbitrio M, Salvino A, Scionti F, Ciliberto D, Ingargiola R, Labanca C, Agapito G, Iuliano E, Barbieri V, Cucè M, Zuccalà V, Cannataro M, Tassone P, and Tagliaferri P
- Abstract
Carboplatin is the cornerstone of ovarian cancer (OC) treatment, while platinum-response, dependent on interindividual variability, is the major prognostic factor for long-term outcomes. This retrospective study was focused on explorative search of genetic polymorphisms in the Absorption, Distribution, Metabolism, Excretion (ADME) genes for the identification of biomarkers prognostic/predictive of platinum-response in OC patients. Ninety-two advanced OC patients treated with carboplatin-based therapy were enrolled at our institution. Of these, we showed that 72% of patients were platinum-sensitive, with a significant benefit in terms of OS ( p = 0.001). We identified an inflammatory-score with a longer OS in patients with lower scores as compared to patients with the maximum score ( p = 0.001). Thirty-two patients were genotyped for 1931 single nucleotide polymorphisms (SNPs) and five copy number variations (CNVs) by the DMET Plus array platform. Among prognostic polymorphisms, we found a potential role of UGT2A1 both as a predictor of platinum-response ( p = 0.01) and as prognostic of survival ( p = 0.05). Finally, we identified 24 SNPs related to OS. UGT2A1 correlates to an "inflammatory-score" and retains a potential prognostic role in advanced OC. These data provide a proof of concept that warrants further validation in follow-up studies for the definition of novel biomarkers in this aggressive disease.
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- 2022
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27. Avelumab treatment in Italian patients with metastatic Merkel cell carcinoma: experience from an expanded access program.
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Grignani G, Chiarion Sileni V, Pinto C, Depenni R, Fazio N, Galli L, Giuffrida D, Carnaghi C, Ciliberto D, Corsi DC, Queirolo P, Benincasa E, Venturini F, Fazzi G, Costa N, and Ascierto PA
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- Antibodies, Monoclonal therapeutic use, Antibodies, Monoclonal, Humanized, Humans, Italy, Carcinoma, Merkel Cell drug therapy, Skin Neoplasms drug therapy
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Background: The incidence of Merkel cell carcinoma (MCC), a rare form of skin cancer with a poor prognosis, has increased in Italy in recent decades. Avelumab, an anti-programmed death ligand 1 monoclonal antibody, is approved for the treatment of metastatic MCC (mMCC) based on the results of the phase 2 JAVELIN Merkel 200 trial. The global avelumab expanded access program (EAP) was designed to provide compassionate use of avelumab prior to approval for patients with mMCC who had limited treatment options. We report findings from a subgroup of Italian patients enrolled in the avelumab EAP., Methods: Eligible patients had mMCC and progressive disease following ≥ 1 prior line of chemotherapy or were ineligible for chemotherapy or clinical trial participation. Patients received avelumab 10 mg/kg intravenously every 2 weeks. Treating physicians were provided with an initial 3-month supply of avelumab; resupply was permitted if the patient achieved a complete response, partial response, stable disease, or other clinical benefit per physician assessment. Safety and efficacy data for the EAP were reported at the treating physician's discretion., Results: Between April 1, 2016, and September 14, 2018, 109 requests for avelumab were received from Italy, and 102 were approved. All but 1 of the approved patients had received ≥ 1 prior line of therapy. At data cutoff (March 22, 2019), 95 patients had been supplied with avelumab and response data were available for 55 patients. The objective response rate in response-evaluable patients was 29.1%, including 6 patients (10.9%) who achieved a complete response and 10 patients (18.2%) who achieved a partial response; in the total population supplied with avelumab (n = 95), the proportion who had an objective response was 16.8%. The median duration of treatment in responding patients was 9.7 months (range, 3.5-41.7 months). The most frequently reported treatment-related adverse events were infusion-related reaction (single preferred term; n = 3 [3.2%]) and pyrexia (n = 2 [2.1%])., Conclusions: Results from Italian patients enrolled in the avelumab EAP are consistent with the findings of the JAVELIN Merkel 200 trial and confirm the efficacy and safety of avelumab treatment in this population.
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- 2021
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28. GOLFIG Chemo-Immunotherapy in Metastatic Colorectal Cancer Patients. A Critical Review on a Long-Lasting Follow-Up.
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Caraglia M, Correale P, Giannicola R, Staropoli N, Botta C, Pastina P, Nesci A, Caporlingua N, Francini E, Ridolfi L, Mini E, Roviello G, Ciliberto D, Agostino RM, Strangio A, Azzarello D, Nardone V, Falzea A, Cappabianca S, Bocchetti M, D'Arrigo G, Tripepi G, Tassone P, Addeo R, Giordano A, Pirtoli L, Francini G, and Tagliaferri P
- Abstract
Background: GOLFIG is a chemo-immunotherapy regimen established in preclinical models that combines gemcitabine + FOLFOX (fluoropyrimidine backbone coupled to oxaliplatin) poly-chemotherapy with low-dose s. c. recombinant interleukin-2 (rIL-2) and granulocyte-macrophage colony stimulating factor (GM-CSF). Promising antitumor effects in metastatic colorectal cancer (mCRC) patients were obtained in previous phase II and III trials. Here we report the results of 15 years of follow-up. Methods: This is a multi-institutional retrospective analysis including 179 mCRC patients receiving GOLFIG regimen between June 2002 and June 2018. Sixty-two of them received the treatment as frontline (enrolled in the GOLFIG-2 phase III trial) and 117 as second/third line (49 enrolled in the GOLFIG-1 phase II trial and 68 as compassionate use). One hundred twelve patients showed a primary left side and 67 a primary right side; K/N-ras mutational status was available in 74 cases, and an activating mutation was detected in 33. Kaplan-Meier and Cox regression analyses were carried out to relate PFS and OS with different parameters. Results: Overall, we recorded a mean PFS and OS of 15.28 (95% CI: 10.36-20.20) and 24.6 (95% CI: 19.07-30.14) months, respectively, with 14 patients surviving free of progression for 10 years. This regimen, in our updated survey of the GOLFIG-2 trial, confirmed superiority over FOLFOX in terms of PFS (hazard ratio (HR) = 0.58, p = 0.006) with a trend to a longer OS (HR = 0.69, P = 0.06) in the first line. Our analysis also confirmed significant antitumor activity in pre-treated patients, reporting a mean PFS and OS of 12.55 (95% CI: 7.19-17.9) and 20.28 (95% CI: 14.4-26.13) months, respectively. Immune-related adverse events (irAEs) were recorded in 24% of the cases and were related to a longer survival (HR = 0.36; P = 0.0001). Finally, patients' outcome was not correlated to sex, sidedness, and MT-K/N-ras. Conclusions: The GOLFIG regimen is a reliable underestimated therapeutic option in pre-treated mCRC patients and offers a strong rationale to design further trials., (Copyright © 2019 Caraglia, Correale, Giannicola, Staropoli, Botta, Pastina, Nesci, Caporlingua, Francini, Ridolfi, Mini, Roviello, Ciliberto, Agostino, Strangio, Azzarello, Nardone, Falzea, Cappabianca, Bocchetti, D'Arrigo, Tripepi, Tassone, Addeo, Giordano, Pirtoli, Francini and Tagliaferri.)
- Published
- 2019
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29. The Era of PARP inhibitors in ovarian cancer: "Class Action" or not? A systematic review and meta-analysis.
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Staropoli N, Ciliberto D, Del Giudice T, Iuliano E, Cucè M, Grillone F, Salvino A, Barbieri V, Russo A, Tassone P, and Tagliaferri P
- Subjects
- Female, Humans, Prognosis, Ovarian Neoplasms drug therapy, Poly (ADP-Ribose) Polymerase-1 antagonists & inhibitors, Poly(ADP-ribose) Polymerase Inhibitors therapeutic use
- Abstract
Introduction: Carboplatin is the milestone of epithelial ovarian cancer (EOC) treatment, thus response to platinum is the major prognostic factor. Among platinum-sensitive patients, 40% carry a germline or somatic BRCA1/2 mutation. In this scenario a new class of drugs, the PARP inhibitors (PARPis), produced a significant improvement in long-term disease control. In order to make an aggregate evaluation of the impact of these agents, we performed a systematic review and meta-analysis., Patients and Methods: Clinical trials were selected by searching "Pubmed" database and abstracts from major cancer meetings. We considered the January 2008 - April 2018 time frame. Progression free survival (PFS) was the primary end-point, toxicities were secondary end-points. Hazard ratios (HRs) of PFS, with confidence intervals, and risk ratios of grade 3-4 toxicity rates, were extracted from retrieved studies and included in the current analysis. Meta-analysis was carried out by the fixed and random effect models. We conducted this meta-analysis to also compare indirectly the efficacy of different PARPis in EOC patients., Results: Five randomized trials for a total of 1839 patients were selected and included in the final analysis. In particular, we evaluated a BRCA-mutant cohort (871 patients) with a pooled HR 0.25 (95%CI 0.21-0.31) and the BRCA-wild type cohort (836 patients) with a pooled HR 0.41 (95%CI 0.31-0.55), respectively. Regarding safety profile, no significant differences were detected in all grade toxicities, however, taking into account 3-4 grade toxicities and SAEs (severe adverse events), we show that rucaparib-treated patients reported major abdominal pain events, while niraparib-treated patients were associated with the highest percentage of haematological toxicities, hypothesizing a drug effect for the safety analysis. In the indirect comparisons, significant differences were not detected on PFS for the different agents., Conclusions: We confirm a significant benefit in survival outcome of PARPis for EOC patients with a "class effect" on the bases of narrow CI and indirect comparisons in the different groups. Therefore, we underline that this strategy is of special value in BRCA-mutated patients because genetic testing allows best patient selection for all PARPis with the added value of individualized prevention in familiars., (Copyright © 2018 Elsevier B.V. All rights reserved.)
- Published
- 2018
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30. The best strategy for RAS wild-type metastatic colorectal cancer patients in first-line treatment: A classic and Bayesian meta-analysis.
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Ciliberto D, Staropoli N, Caglioti F, Chiellino S, Ierardi A, Ingargiola R, Botta C, Arbitrio M, Correale P, Tassone P, and Tagliaferri P
- Subjects
- Antineoplastic Combined Chemotherapy Protocols therapeutic use, Bayes Theorem, Colorectal Neoplasms genetics, Disease-Free Survival, Humans, Neoplasm Metastasis, Colorectal Neoplasms pathology, Colorectal Neoplasms therapy, Genes, ras physiology, Neoadjuvant Therapy methods
- Abstract
Background: At present, there is uncertainty on the best systemic treatment in first-line setting for RAS wild-type (WT) metastatic colorectal cancer (mCRC) patients. Indeed, several chemotherapy and biologics combinations showed an improvement on survival. We performed a systematic review with a pair-wise and bayesan meta-analysis to rank the best strategy for these patients., Methods: A systematic literature search through March 2017 was performed to evaluate the association between several treatment combinations and overall survival (OS), progression-free survival (PFS), overall response rate (ORR) and toxicity rate (TR) in RAS WT mCRC patients. Data were extracted from studies and pooled using the random-effect model for pair-wise meta-analyses and bayesan model for network meta-analysis (NMA)., Results: Eight studies with a total of 2518 individuals were included in the meta-analyses. Pooled analyses for subgroups stratified by type of schedule and tumor location demonstrated that anti-EGFR + doublet had the best OS when compared to doublet ± bevacizumab (0.767; 95%CI, 0.695-0.846; P < 0.0001). This benefit is limited to LSCC when compared to a doublet-based schedule and doublet + bevacizumab (HRs, 0.692; 95%CI, 0.596-0.804; P < 0.001; 0.706; 95%CI, 0.584-0.854; P < 0.001; respectively). No significant differences are detected in PFS, whereas the cetuximab-based regimens showed the highest ORR and TR. In NMA our ranking showed the best performance for FOLFOX + panitumumab., Conclusions: Our study indicates that FOLFOX + panitumumab has the major probability to provide an improvement of survival with a good safety profile in patients with RAS WT mCRC with an added value from selection based on sidedness., (Copyright © 2018 Elsevier B.V. All rights reserved.)
- Published
- 2018
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31. Systemic inflammatory status predict the outcome of k-RAS WT metastatic colorectal cancer patients receiving the thymidylate synthase poly-epitope-peptide anticancer vaccine.
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Correale P, Botta C, Staropoli N, Nardone V, Pastina P, Ulivieri C, Gandolfo C, Baldari TC, Lazzi S, Ciliberto D, Giannicola R, Fioravanti A, Giordano A, Zappavigna S, Caraglia M, Tassone P, Pirtoli L, Cusi MG, and Tagliaferri P
- Abstract
TSPP is an anticancer poly-epitope peptide vaccine to thymidylate synthase, recently investigated in the multi-arm phase Ib TSPP/VAC1 trial. TSPP vaccination induced immune-biological effects and showed antitumor activity in metastatic colorectal cancer (mCRC) patients and other malignancies. Progression-free and overall survival of 41 mCRC patients enrolled in the study correlated with baseline levels of CEA, immune-inflammatory markers (neutrophil/lymphocyte ratio, CRP, ESR, LDH, ENA), IL-4 and with post-treatment change in p-ANCA and CD56
dim CD16bright NKs ( p < 0.04). A subset of 19 patients with activating k-ras mutations showed a different immune-inflammatory response to TSPP as compared to patients with k-ras/wt and a worse outcome in term of PFS ( p = 0.048). In patients with k-ras/mut, inflammatory markers lost their predictive value and their survival directly correlated with the baseline levels of IL17/A over the median value ( p = 0.01). These results provide strong hints for the design of further clinical trials aimed to test TSPP vaccination in mCRC patients., Competing Interests: CONFLICTS OF INTEREST All the authors declare no conflicts of interest- Published
- 2018
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32. Network meta-analysis of randomized trials in multiple myeloma: efficacy and safety in relapsed/refractory patients.
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Botta C, Ciliberto D, Rossi M, Staropoli N, Cucè M, Galeano T, Tagliaferri P, and Tassone P
- Abstract
Despite major therapeutic advancements, multiple myeloma (MM) is still incurable and relapsed/refractory multiple myeloma (RRMM) remains a challenge; the rational choice of the most appropriate regimen in this setting is currently undefined. We performed a systematic review and 2 standard pairwise meta-analyses to evaluate the efficacy of regimens that have been directly compared with bortezomib or immunomodulatory imide drugs (IMiDs) in head-to-head clinical trials and a network meta-analysis (NMA) to determine the relevance of each regimen on the basis of all the available direct and indirect evidence. Sixteen trials were included in the pairwise meta-analyses, and 18 trials were included in the NMA. Pairwise meta-analyses showed that a 3-drug regimen (bortezomib- or IMiD-based) was superior to a 2-drug regimen in progression-free-survival (PFS) and overall response rate (ORR). NMA showed that an IMiD backbone associated with anti-MM monoclonal antibodies (mAbs) (preferably) or proteasome inhibitors had the highest probability of being the most effective regimen with the lowest toxicity. The combination of daratumumab, lenalidomide, and dexamethasone ranked as the first regimen in terms of activity, efficacy, and tolerability according to the average value between surface under the cumulative ranking curve of PFS, overall survival, ORR, complete response rate, and safety. This is the first NMA comparing all currently available regimens evaluated in published randomized trials for the treatment of RRMM, but our results need to be interpreted taking into account differences in their patient populations. Our analysis suggests that IMiDs plus new anti-MM mAb-containing regimens are the most active therapeutic option in RRMM., Competing Interests: Conflict-of-interest disclosure: The authors declare no competing financial interests.
- Published
- 2017
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33. Is ovarian cancer a targetable disease? A systematic review and meta-analysis and genomic data investigation.
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Staropoli N, Ciliberto D, Chiellino S, Caglioti F, Giudice TD, Gualtieri S, Salvino A, Strangio A, Botta C, Pignata S, Tassone P, and Tagliaferri P
- Subjects
- Biomarkers, Tumor genetics, Disease Progression, Disease-Free Survival, Drug Resistance, Neoplasm, Female, Humans, Odds Ratio, Ovarian Neoplasms genetics, Ovarian Neoplasms metabolism, Ovarian Neoplasms mortality, Patient Selection, Precision Medicine, Risk Factors, Signal Transduction drug effects, Time Factors, Treatment Outcome, Angiogenesis Inhibitors therapeutic use, Biomarkers, Tumor metabolism, Molecular Targeted Therapy methods, Ovarian Neoplasms drug therapy
- Abstract
Objectives: The current gold-standard for the first-line treatment in IIIb/IV stages of epithelial ovarian cancer (EOC) is the combination of carboplatin and paclitaxel plus bevacizumab in some countries. In the era of personalized medicine, there is still uncertainty on the impact of several molecularly targeted agents, which have been investigated for the management of this disease. To shed light on the actual role of targeted therapy in EOC, a systematic review and meta-analysis was performed., Methods: Clinical trials were selected by searching "Pubmed" database and abstracts from major cancer meetings within the time-frame of January 2004-June 2015. The endpoints were survival outcome and response rate (RR). Hazard ratios (HRs) of survival outcomes, with confidence intervals and odds-ratios (ORs) of RR, were extracted from retrieved studies and used for current analysis. Meta-analysis was carried out by random effect model., Results: 30 randomized trials for a total of 10,530 patients were selected and included in the final analysis. A benefit in terms of OS (pooled HR 0.915; 95%CI 0.840-0.997; p=0.043), particularly for anti-angiogenetic agents (HR 0.872; 95%CI 0.761-1.000; p=0.049), has been demonstrated for targeted therapy. Moreover, a significant advantage in platinum-resistant subgroup in term of PFS (HR 0.755; 95%CI 0.624-0.912; p=0.004) was found., Conclusions: This systematic review and meta-analysis provide the first evidence that targeted therapy is potentially able to translate into improved survival of EOC patients, with a major role played by anti-angiogenetic drugs. The role of target therapy is underlined in the platinum-resistant setting that represents the "pain in the neck" in EOC management.
- Published
- 2016
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34. Immunotherapy of colorectal cancer: new perspectives after a long path.
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Correale P, Botta C, Ciliberto D, Pastina P, Ingargiola R, Zappavigna S, Tassone P, Pirtoli L, Caraglia M, and Tagliaferri P
- Subjects
- Animals, Colorectal Neoplasms immunology, Combined Modality Therapy, Humans, Molecular Targeted Therapy, Antibodies, Monoclonal therapeutic use, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Cancer Vaccines immunology, Colorectal Neoplasms therapy, Costimulatory and Inhibitory T-Cell Receptors immunology, Immunotherapy methods
- Abstract
Although significant therapeutic improvement has been achieved in the last 10 years, the survival of metastatic colorectal cancer patients remains in a range of 28 to 30 months. Presently, systemic treatment includes combination chemotherapy with oxaliplatin and/or irinotecan together with a backbone of 5-fluorouracil/levofolinate, alone or in combination with monoclonal antibodies to VEGFA (bevacizumab) or EGF receptor (cetuximab and panitumumab). The recent rise of immune checkpoint inhibitors in the therapeutic scenario has renewed scientific interest in the investigation of immunotherapy in metastatic colorectal cancer patients. According to our experience and view, here, we review the immunological strategies investigated for the treatment of this disease, including the use of tumor target-specific cancer vaccines, chemo-immunotherapy and immune checkpoint inhibitors.
- Published
- 2016
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35. Systematic review and meta-analysis on targeted therapy in advanced pancreatic cancer.
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Ciliberto D, Staropoli N, Chiellino S, Botta C, Tassone P, and Tagliaferri P
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- Antineoplastic Combined Chemotherapy Protocols, Genetic Predisposition to Disease, Humans, Pancreatic Neoplasms genetics, Signal Transduction drug effects, Antineoplastic Agents therapeutic use, Pancreatic Neoplasms drug therapy
- Abstract
Aim: A systematic review and meta-analysis from literature has been performed to assess the impact of targeted therapy in advanced pancreatic cancer., Methods: By searching different literature databases and major cancer meetings proceedings, data from all randomized clinical trials designed to investigate molecular targeted agents in the treatment of advanced pancreatic cancer were collected. The time-frame between January 2007 and March 2015 was selected. Data on predefined end-points, including overall survival, progression-free survival in terms of Hazard Ratio and response-rate were extracted and analyzed by a random effects model. Pooled data analysis was performed according to the DerSimonian and Laird test. The occurrence of publication bias was investigated through Begg's test by visual inspection of funnel plots., Results: Twenty-seven randomized clinical trials for a total of 8205 patients were selected and included in the final analysis. A significant benefit was demonstrated for anti-EGFR agents on overall survival (HR = 0.880; 95% confidence interval (CI) 0.797-0.972; p = 0.011). In the pooled analysis no benefit on overall survival (OS: pooled HR = 0.957; 95%CI 0.900-1.017; p = 0.153), or progression-free survival (PFS: pooled HR = 0.908; 95%CI 0.817-1.010; p = 0.075) for targeted-based therapies as compared to conventional treatments could be demonstrated. No advantage was reported in response-rate (OR for RR = 1.210; 95%CI 0.990-1.478; p = 0.063). Begg's funnel plot showed no evidence of publication bias., Conclusion: The use of molecular targeted agents does not translate into clinical benefit. Therefore, our work highlights the need to identify predictive factors for patient selection and rationally designed clinical trials., (Copyright © 2016 IAP and EPC. Published by Elsevier India Pvt Ltd. All rights reserved.)
- Published
- 2016
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36. Postinfectious functional gastrointestinal disorders in children: a multicenter prospective study.
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Pensabene L, Talarico V, Concolino D, Ciliberto D, Campanozzi A, Gentile T, Rutigliano V, Salvatore S, Staiano A, and Di Lorenzo C
- Subjects
- Adolescent, Child, Child, Preschool, Female, Follow-Up Studies, Gastrointestinal Diseases epidemiology, Humans, Incidence, Infections epidemiology, Male, Prospective Studies, Surveys and Questionnaires, Gastrointestinal Diseases etiology, Infections complications
- Abstract
Objectives: To prospectively investigate the occurrence of postinfectious functional gastrointestinal disorders (FGIDs), diagnosed according to the Rome III criteria, in children with acute diarrhea of different infectious etiology., Study Design: This was a prospective cohort multicenter study. Children 4-17 years of age presenting with acute diarrhea who tested positive for an enteric infection were recruited within 1 month from the episode and matched with control subjects of similar age and sex. Symptoms were evaluated with a validated questionnaire for FGIDs at the time of enrollment in the study and after 3 and 6 months., Results: A total of 64 patients (36 boys; median age 5.3 years; age range 4.1-14.1 years) were recruited, 32 subjects in each arm. Infections included rotavirus (56.8%), salmonella (30%), adenovirus (6.6%), norovirus (3.3%), and Giardia lamblia (3.3%). FGIDs were significantly more common in exposed patients compared with controls within 1 month from acute diarrhea (40.6% vs 12.5% [P = .02, relative risk (RR) = 1.9]), 3 months (53% vs 15.6% [P = .003, RR = 2.2]), and 6 months (46.8% vs 15.6% [P = .01, RR = 1.9]) later. No correlation was found between different etiologies, age, or sex, and any type of FGIDs. Among exposed children, abdominal pain-related FGIDs were significantly more frequent compared with controls after 6 months from infection (P = .04, RR = 1.7)., Conclusion: This prospective cohort multicenter study supports postinfectious FGIDs as a true entity in children. There seems to be a significant increase in abdominal pain-related FGIDs after acute diarrhea in children within 1 month and 3 and 6 months later., (Copyright © 2015 Elsevier Inc. All rights reserved.)
- Published
- 2015
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37. A systematic review and meta-analysis of randomized trials on the role of targeted therapy in the management of advanced gastric cancer: Evidence does not translate?
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Ciliberto D, Staropoli N, Caglioti F, Gualtieri S, Fiorillo L, Chiellino S, De Angelis AM, Mendicino F, Botta C, Caraglia M, Tassone P, and Tagliaferri P
- Subjects
- Angiogenesis Inhibitors therapeutic use, Antineoplastic Combined Chemotherapy Protocols adverse effects, Antineoplastic Combined Chemotherapy Protocols therapeutic use, ErbB Receptors antagonists & inhibitors, Humans, Randomized Controlled Trials as Topic, Receptor, ErbB-2 antagonists & inhibitors, Stomach Neoplasms epidemiology, Stomach Neoplasms mortality, Survival Analysis, Molecular Targeted Therapy methods, Stomach Neoplasms drug therapy
- Abstract
It is still uncertain if targeted therapy-based regimens in advanced gastric cancer actually produce survival benefit. To shed light on this important question, we performed a systematic review and meta-analyses on each relevant targeted-pathway. By searching literature databases and proceedings of major cancer meetings in the time-frame 2005-2014, 22 randomized clinical trials exploring targeted therapy for a total of 7022 advanced gastric cancer patients were selected and included in the final analysis. Benefit was demonstrated for antiangiogenic agents in terms of overall survival (HR 0.759; 95%CI 0.655-0.880; p < 0.001). Conversely no benefit was found for EGFR pathway (HR 1.077; 95%CI 0.847-1.370; p = 0.543). Meta-analysis of HER-2 pathway confirmed improvement in terms of survival outcome, already known for this class of drugs (HR 0.823; 95%CI 0.722-0.939; p = 0.004). Pooled analysis demonstrated a significant survival benefit (OS: HR 0.823; PFS: HR 0.762) with acceptable tolerability profile for targeted-based therapies as compared to conventional treatments. This finding conflicts with the outcome of most individual studies, probably due to poor trial design or patients selection. In conclusion, our findings demonstrate a significant survival benefit for targeted therapy in its whole, which can be ascribed to anti-angiogenic and anti-HER2 agents.
- Published
- 2015
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