36 results on '"Lucrezia Silvestro"'
Search Results
2. Heterogeneous disease and intermittent treatment in metastatic colorectal cancer: A case report
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Alfonso De Stefano, Nicoletta Zanaletti, Antonino Cassata, Lucrezia Silvestro, Anna Nappi, Rossana Casaretti, Carmela Romano, Francesca Foschini, Claudia Cardone, Marco Borrelli, Antonella Petrillo, Alfredo Budillon, Paolo Delrio, and Antonio Avallone
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Cancer Research ,Oncology - Abstract
BackgroundMetastatic colorectal cancer is one of the most common causes of cancer death worldwide. RAS and BRAF mutational analyses are strongly recommended before beginning chemotherapy in the metastatic setting for their predictive role for the efficacy of anti-EGFR monoclonal antibodies. In most of cases, mutational status coincides between primary tumor and metastases. In RAS and BRAF wild-type patients treated with anti-EGFRs, after an induction treatment period, recent evidence supports the role of a maintenance treatment with fluoropyrimidines and anti-EGFRs. However, skin toxicity is the most described and limiting side-effect of maintenance. Moreover, it is described that the continuous administration of these monoclonal antibodies leads to an acquired resistance to anti-EGFRs, with subsequent treatment failure. Intermittent strategy with chemotherapy plus anti-EGFR may help maintain treatment efficacy, delaying resistance.Case presentationIn this case report, we describe the case of a RAS-BRAF wild-type elderly patient undergoing first-line chemotherapy with FOLFOX + panitumumab, reporting response of disease on all metastatic sites except for a node. This node, surgically removed, revealed host BRAF V600 mutant clones. After surgery, patient continued chemotherapy with a stop-and-go strategy continuing to benefit from the same drugs after 4 years since diagnosis, and continuing to achieve response when on treatment, avoiding unacceptable anti-EGFR toxicity. This patient, still alive after 6 years since the diagnosis, represents the case of a good synergy between molecular profiling of disease, surgery, and intermittent treatment.
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- 2023
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3. Safety of ramucirumab in patients with advanced gastric cancer in Europe and North America: A prospective observational registry
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Lucrezia Silvestro, Ferdinando De Vita, Arndt Vogel, Thomas Jens Ettrich, Eric Van Cutsem, Maria Di Bartolomeo, Yulia D'yachkova, Astra M. Liepa, Natalia Smolyakova, Mariusz Lukanowski, and Yu-Jing Huang
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Cancer Research ,Oncology - Abstract
341 Background: The objective was to describe the safety of ramucirumab (Ram) for previously treated advanced gastric cancer under real-world conditions in Europe and North America. Methods: This was a non-interventional, descriptive study of adult patients with advanced gastric or gastroesophageal junction adenocarcinoma whose disease had progressed after first-line chemotherapy (I4T-MC-JVDD). Data collection began in December 2015 and was completed in August 2021. Patients were followed up to 12 months after initiation of Ram. Safety outcomes included adverse events (AEs)/serious AEs (SAEs), and AEs leading to dose adjustment or death. Subgroups of interest were elderly, patients with cardiac comorbidities, hepatic, or renal impairment. Results: 606 patients were classified in 3 cohorts: Ram monotherapy (Ram Mono, N=51); Ram plus paclitaxel (Ram+PTX, N=547); or Ram plus other anti-cancer agents (N=8). Most patients were male (70%), white (97%) and aged ≥65 (55%); 22% of the population was ≥75 years old. Metastatic cancer was reported in 552 patients (96%); primary tumor location was gastric in 417 patients (69%) and in the gastroesophageal junction in 189 patients (31%). Patients were previously treated mainly with platinum (97%) and fluoropyrimidine (96%). Hypertension was the most frequently reported historical medical condition (25%). At baseline, 23% patients had documented cardiac comorbidities, 11% hepatic impairment and 6% renal impairment. The median duration of Ram was 8 weeks (IQR=4.0-10.6) in Ram Mono and 15 weeks (IQR=8.4-26.7) in Ram+PTX. Regardless of causality, 98% of patients experienced ≥1 AE; most commonly fatigue (31%) and abdominal pain (20%) in Ram Mono cohort; and fatigue (46%) and neuropathy (31%) in Ram+PTX cohort. In total, 40% experienced ≥1 AE of special interest; most commonly bleeding/hemorrhage (21% [mainly epistaxis]) and hypertension (11%). In total, 33 patients (5%) died due to AEs that occurred on, or within 90 days of last dose of Ram, 9 (2%) were related to Ram treatment as per physician’s assessment. Conclusions: The observed safety profile of Ram in the real-world setting was manageable and consistent with the established safety profile of Ram identified from clinical trials. No new safety concerns or notable findings were observed overall or in the subgroups of interest. Clinical trial information: ENCEPP/SDPP/9400 . [Table: see text]
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- 2023
4. Multicenter Single-Arm, Two-Stage Phase 2 Study of Panitumumab in Patients With Cetuximab-Refractory Metastatic Colorectal Cancer: The PACER Trial
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Guglielmo Nasti, Chiara Carlomagno, Carmela Romano, Francesco Perrone, Sabino De Placido, Tizana Pia Latiano, Maria Carmela Piccirillo, Domenico Bilancia, Pasqualina Giordano, Lucrezia Silvestro, Oscar Alabiso, Antonio Avallone, Nicola Normanno, Anna Nappi, Alessandro Ottaiano, Alfonso De Stefano, Gerardo Rosati, Evaristo Maiello, Bruno Daniele, Antonino Cassata, Rosario Vincenzo Iaffaioli, Piccirillo, M. C., Avallone, A., Carlomagno, C., Maiello, E., Rosati, G., Alabiso, O., Nasti, G., De Placido, S., Latiano, T. P., Bilancia, D., Ottaiano, A., De Stefano, A., Romano, C., Silvestro, L., Nappi, A., Cassata, A., Giordano, P., Iaffaioli, R. V., Normanno, N., Perrone, F., and Daniele, B.
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Male ,Oncology ,medicine.medical_specialty ,Colorectal cancer ,EGFR ,Resistance ,Cetuximab ,Phases of clinical research ,medicine.disease_cause ,Proto-Oncogene Proteins p21(ras) ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,medicine ,Clinical endpoint ,Humans ,Panitumumab ,Prospective Studies ,Aged ,business.industry ,Gastroenterology ,Response ,Biomarker ,Middle Aged ,medicine.disease ,Rash ,Progression-Free Survival ,Confidence interval ,Drug Resistance, Neoplasm ,030220 oncology & carcinogenesis ,Disease Progression ,Female ,030211 gastroenterology & hepatology ,KRAS ,medicine.symptom ,Colorectal Neoplasms ,business ,RAS ,medicine.drug - Abstract
Purpose: To assess whether panitumumab is active in patients with cetuximab-refractory metastatic colorectal cancer (mCRC). Patients and Methods: Eligible patients had pretreated RAS (renin–angiotensin system) wild-type mCRC that progressed after cetuximab treatment, after having shown either objective response or stable disease. A minimax two-stage design was applied, with progression-free rate at 2 months as the primary end point. At least 12 of 28 and 21 of 41 successes at the first and second stage, respectively, were required for a positive result. Panitumumab 6 mg/kg was provided every 2 weeks, until progression or unacceptable toxicity. Results: Overall, 52 patients with KRAS (Kirsten rat sarcoma viral oncogene) wild-type disease were enrolled, but 11 were found to have mutated disease after all-RAS retesting. Among 41 eligible patients, median time since diagnosis was 38 months, and 71% experienced an objective response to previous cetuximab. First stage was passed with 12 of 28 patients alive without progression at 2 months. At the second stage, 17 of 41 patients were alive without progression at 2 months. At a median follow-up of 21.8 months, 35 patients experienced disease progression, and 26 died. Median progression-free survival was 2.1 months (95% confidence interval, 1.8-3.6) and median overall survival 6.8 months (95% confidence interval, 4.6-16.6). Most of the patients experienced no adverse reactions; 25% of patients had grade 3 rash. Conclusion: According to our study design, panitumumab was not effective in patients with cetuximab-refractory RAS wild-type mCRC. PACER is a phase 2 study aiming to assess whether panitumumab monotherapy is active in patients with cetuximab-refractory metastatic colorectal cancer. Primary end point was 2-month progression-free rate. According to a minimax two-stage design, 28 and 41 patients were required at the two stages, respectively. Panitumumab was shown to be not active at the second stage. The study failed to demonstrate the experimental hypothesis.
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- 2020
5. Percutanous Electrochemotherapy (ECT) in Primary and Secondary Liver Malignancies: A Systematic Review
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Vincenza Granata, Roberta Fusco, Valeria D’Alessio, Igino Simonetti, Francesca Grassi, Lucrezia Silvestro, Raffaele Palaia, Andrea Belli, Renato Patrone, Mauro Piccirillo, and Francesco Izzo
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Clinical Biochemistry - Abstract
The aim of the study was to analyse papers describing the use of Electrochemotherapy (ECT) in local treatment of primary and secondary liver tumours located at different sites and with different histologies. Other Local Ablative Therapies (LAT) are also discussed. Analyses of these papers demonstrate that ECT use is safe and effective in lesions of large size, independently of the histology of the treated lesions. ECT performed better than other thermal ablation techniques in lesions > 6 cm in size and can be safely used to treat lesions distant, close, or adjacent to vital structures. ECT spares vessel and bile ducts, is repeatable, and can be performed between chemotherapeutic cycles. ECT can fill the gap in local ablative therapies due to being lesions too large or localized in highly challenging anatomical sites.
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- 2023
6. Risk Assessment and Pancreatic Cancer: Diagnostic Management and Artificial Intelligence
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Vincenza Granata, Roberta Fusco, Sergio Venanzio Setola, Roberta Galdiero, Nicola Maggialetti, Lucrezia Silvestro, Mario De Bellis, Elena Di Girolamo, Giulia Grazzini, Giuditta Chiti, Maria Chiara Brunese, Andrea Belli, Renato Patrone, Raffaele Palaia, Antonio Avallone, Antonella Petrillo, and Francesco Izzo
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Cancer Research ,Oncology - Abstract
Pancreatic cancer (PC) is one of the deadliest cancers, and it is responsible for a number of deaths almost equal to its incidence. The high mortality rate is correlated with several explanations; the main one is the late disease stage at which the majority of patients are diagnosed. Since surgical resection has been recognised as the only curative treatment, a PC diagnosis at the initial stage is believed the main tool to improve survival. Therefore, patient stratification according to familial and genetic risk and the creation of screening protocol by using minimally invasive diagnostic tools would be appropriate. Pancreatic cystic neoplasms (PCNs) are subsets of lesions which deserve special management to avoid overtreatment. The current PC screening programs are based on the annual employment of magnetic resonance imaging with cholangiopancreatography sequences (MR/MRCP) and/or endoscopic ultrasonography (EUS). For patients unfit for MRI, computed tomography (CT) could be proposed, although CT results in lower detection rates, compared to MRI, for small lesions. The actual major limit is the incapacity to detect and characterize the pancreatic intraepithelial neoplasia (PanIN) by EUS and MR/MRCP. The possibility of utilizing artificial intelligence models to evaluate higher-risk patients could favour the diagnosis of these entities, although more data are needed to support the real utility of these applications in the field of screening. For these motives, it would be appropriate to realize screening programs in research settings.
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- 2023
7. Precision medicine in gastric cancer
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F. Tuccillo, Lucrezia Silvestro, Antonella Borrelli, Raffaele Palaia, P. Bonelli, and Franco M. Buonaguro
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Oncology ,medicine.medical_specialty ,Microarray ,medicine.medical_treatment ,Phases of clinical research ,Review ,Disease ,Targeted therapy ,Ramucirumab ,03 medical and health sciences ,0302 clinical medicine ,Trastuzumab ,Internal medicine ,medicine ,business.industry ,Precision medicine ,Gastroenterology ,Molecular characterization ,Radiation therapy ,030220 oncology & carcinogenesis ,030211 gastroenterology & hepatology ,Gastric cancer ,business ,Biomarkers ,medicine.drug - Abstract
Gastric cancer (GC) is a complex disease linked to a series of environmental factors and unhealthy lifestyle habits, and especially to genetic alterations. GC represents the second leading cause of cancer-related deaths worldwide. Its onset is subtle, and the majority of patients are diagnosed once the cancer is already advanced. In recent years, there have been innovations in the management of advanced GC including the introduction of new classifications based on its molecular characteristics. Thanks to new technologies such as next-generation sequencing and microarray, the Cancer Genome Atlas and Asian Cancer Research Group classifications have also paved the way for precision medicine in GC, making it possible to integrate diagnostic and therapeutic methods. Among the objectives of the subdivision of GC into subtypes is to select patients in whom molecular targeted drugs can achieve the best results; many lines of research have been initiated to this end. After phase III clinical trials, trastuzumab, anti-Erb-B2 receptor tyrosine kinase 2 (commonly known as ERBB2) and ramucirumab, anti-vascular endothelial growth factor receptor 2 (commonly known as VEGFR2) monoclonal antibodies, were approved and introduced into first- and second-line therapies for patients with advanced/metastatic GC. However, the heterogeneity of this neoplasia makes the practical application of such approaches difficult. Unfortunately, scientific progress has not been matched by progress in clinical practice in terms of significant improvements in prognosis. Survival continues to be low in contrast to the reduction in deaths from many common cancers such as colorectal, lung, breast, and prostate cancers. Although several target molecules have been identified on which targeted drugs can act and novel products have been introduced into experimental therapeutic protocols, the overall approach to treating advanced stage GC has not substantially changed. Currently, surgical resection with adjuvant or neoadjuvant radiotherapy and chemotherapy are the most effective treatments for this disease. Future research should not underestimate the heterogeneity of GC when developing diagnostic and therapeutic strategies aimed toward improving patient survival.
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- 2019
8. Cetuximab, irinotecan and fluorouracile in fiRst-line treatment of immunologically-selected advanced colorectal cancer patients: the CIFRA study protocol
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Francesco Izzo, Anna Maria Trotta, Vittorio Albino, Lucrezia Silvestro, Antonio Avallone, Raffaele Palaia, Gerardo Botti, Monica Capozzi, Paolo Chiodini, Rossana Casaretti, Carmine Picone, Stefania Scala, Nicola Normanno, Mario Tamburini, Andrea Belli, Crescenzo D'Alterio, Anna Maria Rachiglio, Massimiliano Di Marzo, Guglielmo Nasti, Paolo Delrio, Cristin Roma, Anna Nappi, Carmela Romano, Antonella Petrillo, Antonino Cassata, Gianfranco De Feo, Alessandro Ottaiano, Salvatore Tafuto, Maria Napolitano, Alfonso Amore, Alfonso De Stefano, Ugo Pace, Luigi Portella, Ottaiano, A., Scala, S., Normanno, N., Napolitano, M., Capozzi, M., Rachiglio, A. M., Roma, C., Trotta, A. M., D'Alterio, C., Portella, L., Romano, C., Cassata, A., Casaretti, R., Silvestro, L., Nappi, A., Tafuto, S., Avallone, A., De Stefano, A., Tamburini, M., Picone, C., Petrillo, A., Izzo, F., Palaia, R., Albino, V., Amore, A., Belli, A., Pace, U., Di Marzo, M., Chiodini, P., Botti, G., De Feo, G., Delrio, P., and Nasti, G.
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0301 basic medicine ,Oncology ,Cancer Research ,medicine.medical_specialty ,Bevacizumab ,Antibody-dependent cell-mediated cytotoxicity ,Colorectal cancer ,Phase II study ,Cetuximab ,medicine.disease_cause ,Irinotecan ,Fluorouracule ,lcsh:RC254-282 ,03 medical and health sciences ,Study Protocol ,0302 clinical medicine ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,FcγR ,Genetics ,Medicine ,Panitumumab ,Humans ,Epidermal growth factor receptor ,neoplasms ,Colorectal Cancer ,Polymorphism, Genetic ,biology ,business.industry ,Receptors, IgG ,medicine.disease ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,digestive system diseases ,030104 developmental biology ,Treatment Outcome ,030220 oncology & carcinogenesis ,biology.protein ,KRAS ,Fluorouracil ,business ,Colorectal Neoplasms ,medicine.drug - Abstract
Background Combination of chemotherapies (fluoropirimidines, oxaliplatin and irinotecan) with biologic drugs (bevacizumab, panitumumab, cetuximab) have improved clinical responses and survival of metastatic colorectal cancer (mCRC). However, patients’ selection thorough the identification of predictive factors still represent a challange. Cetuximab (Erbitux®), a chimeric monoclonal antibody binding to the Epidermal Growth Factor Receptor (EGFR), belongs to the Immunoglobulins (Ig) grade 1 subclass able to elicite both in vitro and in vivo the Antibody-Dependent Cell-mediated Cytotoxicity (ADCC). ADCC is the cytotoxic killing of antibody-coated target cells by immunologic effectors. The effector cells express a receptor for the Fc portion of these antibodies (FcγR); genetic polymorphisms of FcγR modify the binding affinity with the Fc of IgG1. Interestingly, the high-affinity FcγRIIIa V/V is associated with increased ADCC in vitro and in vivo. Thus, ADCC could partially account for cetuximab activity. Methods/design CIFRA is a single arm, open-label, phase II study assessing the activity of cetuximab in combination with irinotecan and fluorouracile in FcγRIIIa V/V patients with KRAS, NRAS, BRAF wild type mCRC. The study is designed with a two-stage Simon model based on a hypothetical higher response rate (+ 10%) of FcγRIIIa V/V patients as compared to previous trials (about 60%) assuming ADCC as one of the possible mechanisms of cetuximab action. The test power is 95%, the alpha value of the I-type error is 5%. With these assumptions the sample for passing the first stage is 14 patients with > 6 responses and the final sample is 34 patients with > 18 responses to draw positive conclusions. Secondary objectives include toxicity, responses’ duration, progression-free and overall survival. Furthermore, an associated translational study will assess the patients’ cetuximab-mediated ADCC and characterize the tumor microenvironment. Discussion The CIFRA study will determine whether ADCC contributes to cetuximab activity in mCRC patients selected on an innovative immunological screening. Data from the translational study will support results’ interpretation as well as provide new insights in host-tumor interactions and cetuximab activity. Trial registration The CIFRA trial (version 0.0, June 21, 2018) has been registered into the NIH-US National Library of Medicine, ClinicalTrials.gov database with the identifier number (NCT03874062).
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- 2019
9. 18F-FDG PET/CT Is an Early Predictor of Pathologic Tumor Response and Survival After Preoperative Radiochemotherapy with Bevacizumab in High-Risk Locally Advanced Rectal Cancer
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Paolo Delrio, Antonio Avallone, Secondo Lastoria, Francesca Di Gennaro, Fabiana Tatangelo, Biagio Pecori, Vincenza Granata, Alfredo Budillon, Carmela Romano, Antonella Petrillo, Corradina Caracò, Paolo Muto, Francesco Bianco, Alfonso De Stefano, Lucrezia Silvestro, Luigi Aloj, and Gerardo Botti
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Oncology ,medicine.medical_specialty ,PET-CT ,Bevacizumab ,business.industry ,Colorectal cancer ,Surrogate endpoint ,Area under the curve ,Phases of clinical research ,medicine.disease ,030218 nuclear medicine & medical imaging ,03 medical and health sciences ,0302 clinical medicine ,030220 oncology & carcinogenesis ,Internal medicine ,Concomitant ,Medicine ,Radiology, Nuclear Medicine and imaging ,business ,Chemoradiotherapy ,medicine.drug - Abstract
There is an unmet need for predictive biomarkers of the clinical benefit of antiangiogenic drugs. The aim of the present study was to prospectively evaluate the value of (18)F-FDG PET/CT performed during and after preoperative chemoradiotherapy with bevacizumab for the prediction of complete pathologic tumor regression and survival in patients with MRI-defined high-risk locally advanced rectal cancer. Methods: Sixty-one patients treated in a nonrandomized phase II study (BRANCH) with concomitant or sequential (4 d before chemoradiotherapy) administration of bevacizumab with preoperative chemoradiotherapy were included. (18)F-FDG PET/CT was performed at baseline, 11 d after the beginning of chemoradiotherapy (early), and before surgery (late). Metabolic changes were compared with pathologic complete tumor regression (TRG1) versus incomplete tumor regression (TRG2–TRG5), progression-free survival, cancer-specific survival, and overall survival. Receiver-operating-characteristic curves were calculated for those (18)F-FDG PET/CT parameters that significantly correlated with TRG1. Results: Early total-lesion glycolysis and its percentage change compared with baseline (ΔTLG-early) could discriminate TRG1 from TRG2–TRG5. Only receiver-operating-characteristic analysis of ΔTLG-early showed an area under the curve greater than 0.7 (0.76), with an optimal cutoff at 59.5% (80% sensitivity, 71.4% specificity), for identifying TRG1. Late metabolic assessment could not discriminate between the 2 groups. After a median follow-up of 98 mo (range, 77–132 mo), metabolic responders (ΔTLG-early ≥ 59.5%) demonstrated a significantly higher 10-y progression-free survival (89.3% vs. 63.6%, P = 0.02) and cancer-specific survival (92.9% vs. 72.6%, P = 0.04) than incomplete metabolic responders. Conclusion: Our results suggest that early metabolic response can act as a surrogate marker of the benefit of antiangiogenic therapy. The findings provide further support for the use of early (18)F-FDG PET/CT evaluation to predict pathologic response and survival in the preoperative treatment of patients with locally advanced rectal cancer. ΔTLG-early showed the best accuracy in predicting tumor regression and may be particularly useful in guiding treatment-modifying decisions during preoperative chemoradiotherapy based on expected response.
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- 2019
10. Randomized intermittent or continuous panitumumab plus FOLFIRI (FOLFIRI/PANI) for first-line treatment of patients (pts) with RAS/BRAF wild-type (wt) metastatic colorectal cancer (mCRC): The IMPROVE study
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Antonio Avallone, Francesco Giuliani, Guglielmo Nasti, Vincenzo Montesarchio, Giuseppe Santabarbara, Silvana Leo, Alfonso De Stefano, Gerardo Rosati, Ivan Lolli, Emiliano Tamburini, Alfredo Colombo, Daniele Santini, Lucrezia Silvestro, Gaetano Facchini, Francesco Mannavola, Antonio Febbraro, Giancarlo Troncone, Alberto F. Sobrero, Diana Giannarelli, and Alfredo Budillon
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Cancer Research ,Oncology - Abstract
3503 Background: Continuous anti-EGFR-based FOLFIRI is a first-line standard of care in pts with RAS/BRAF wt mCRC. The emergence of resistance and treatment-related toxicity limit the efficacy of continuous treatment. Thus, an intermittent strategy could reduce both toxicity and resistance. Methods: This is a prospective, randomized, non-comparative, open-label, multicenter phase II study. Unresectable, previously untreated RAS/BRAF wt mCRC pts, were randomized to a control arm (A) receiving FOLFIRI/PANI continuously until progression or to the experimental arm (B), receiving 8 cycles of the same regimen followed by a treatment free interval. This lasted untill progressive disease, when another treatment period of up to 8 cycles was restarted. This intermittent strategy was continued until progression occurred on treatment. Tumor assessment was always done every 8 weeks in both arms. Pts were stratified for center, ECOG PS (0-1 vs 2), previous adjuvant therapy (yes or no), sidedness (right vs left) and metastatic sites (1 vs ≥ 2). The primary endpoint was the progression-free survival on treatment (PFSOT) at 1 year. Assuming p1=43% PFSOT at 1 year, corresponding to an expected median PFSOT time ≥ 10 months in the experimental arm, and a 5% drop-out rate, a sample size of 68 pts in each arm granted the study a power of 80%, with a type I error of 10% (binomial test) for rejecting the null hypothesis, p0=30%, corresponding to a median PFSOT time of ≤ 7 months. Secondary endpoints were safety, quality of life, OS and response rate (ORR); ctDNA samples were also collected. No formal comparison between the two arms was planned. Results: From May 2018 to June 2021, 137 pts were randomized (69 arm A/68 arm B). Main pts’ characteristics were (arm A/B): males 59/61%; median age 62/66yrs; PS 0 84/72%; right colon 17/15%; previous adjuvant therapy 22/29%; single metastatic site 33/26%. At a median follow-up of 18 months (IQR: 10-26), median PFS OT was 12.6 months (95% CI: 9.0-16.1) in arm A and 17.6 months (95% CI: 7.5-27.8) in arm B with a 1 year PFSOT rate of 51.7% and 61.3%, respectively. ORR (arm A/B) was 64/56%. Median number of FOLFIRI/PANI cycles administered per patient were (arm A/B) 13/12. Main grade 3-4 toxicities were (arm A/B): skin 27/13%, neutropenia 23/22%; diarrhea 13/15%. Conclusions: The primary endpoint of the study was met with the intermittent FOLFIRI-PANI strategy producing a long PFS with a reduced skin toxicity. These data deserve further investigations in a phase III trial. Clinical trial information: NCT04425239.
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- 2022
11. Effect of Bevacizumab in Combination with Standard Oxaliplatin-Based Regimens in Patients with Metastatic Colorectal Cancer: A Randomized Clinical Trial
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Paolo Delrio, Domenico Bilancia, G. Rosati, Lucrezia Silvestro, Chiara Carlomagno, F. Perrone, Luigi Aloj, Gerardo Botti, Antonino Cassata, Anna Nappi, Guglielmo Nasti, Secondo Lastoria, Antonella Petrillo, Fabiana Tatangelo, A. Avallone, Alessandra Leone, Carmela Romano, Elena Di Gennaro, Laura Arenare, Vincenza Granata, Maria Carmela Piccirillo, Alfredo Budillon, Alfonso De Stefano, Valeria Vicario, Francesco Izzo, Ciro Gallo, Avallone, A., Piccirillo, M. C., Nasti, G., Rosati, G., Carlomagno, C., Di Gennaro, E., Romano, C., Tatangelo, F., Granata, V., Cassata, A., Silvestro, L., De Stefano, A., Aloj, L., Vicario, V., Nappi, A., Leone, A., Bilancia, D., Arenare, L., Petrillo, A., Lastoria, S., Gallo, C., Botti, G., Delrio, P., Izzo, F., Perrone, F., and Budillon, A.
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Adult ,Diarrhea ,Male ,medicine.medical_specialty ,Adolescent ,Bevacizumab ,Colorectal Neoplasm ,law.invention ,Young Adult ,Randomized controlled trial ,Interquartile range ,law ,Internal medicine ,medicine ,Clinical endpoint ,Aged ,Antineoplastic Combined Chemotherapy Protocol ,business.industry ,Hazard ratio ,Nausea ,General Medicine ,Middle Aged ,Chemotherapy regimen ,Progression-Free Survival ,Oxaliplatin ,Neoplasm Metastasi ,Treatment Outcome ,Response Evaluation Criteria in Solid Tumors ,Quality of Life ,Female ,Drug-Related Side Effects and Adverse Reaction ,business ,Angiogenesis Inhibitor ,Human ,medicine.drug - Abstract
Importance Although bevacizumab is a standard of care in combination treatments for metastatic colorectal cancer (mCRC), its clinical benefit has been limited. Objective To determine whether sequential scheduling of bevacizumab administration in combination with chemotherapy improves treatment efficacy in patients with mCRC, in keeping with the tumor vascular normalization hypothesis. Design, Setting, and Participants This open-label, randomized clinical phase 3 trial was conducted from May 8, 2012, to December 9, 2015, at 3 Italian centers. Patients aged 18 to 75 years with unresectable, previously untreated, or single line–treated mCRC were recruited. Follow-up was completed December 31, 2019, and data were analyzed from February 26 to July 24, 2020. Interventions Patients received 12 biweekly cycles of standard oxaliplatin-based regimens (modified FOLFOX-6 [levo–folinic acid, fluorouracil, and oxaliplatin]/modified CAPOX [capecitabine and oxaliplatin]) plus bevacizumab administered either on the same day as chemotherapy (standard arm) or 4 days before chemotherapy (experimental arm). Main Outcomes and Measures The primary end point was the objective response rate (ORR) measured with Response Evaluation Criteria in Solid Tumors, version 1.1. Secondary end points included progression-free survival, overall survival, safety, and quality of life (QOL). Results Overall, 230 patients (136 men [59.1%]; median age, 62.3 [interquartile range, 53.3-67.6] years) were randomly assigned to the standard arm (n = 115) or the experimental arm (n = 115). The median duration of follow-up was 68.3 (95% CI, 61.0-70.0) months. No difference in ORR (57.4% [95% CI, 47.8%-66.6%] in the standard arm and 56.5% [95% CI, 47.0-65.7] in the experimental arm;P = .89) or progression-free survival (10.5 [95% CI, 9.1-12.3] months in the standard arm and 11.7 [95% CI, 9.9-12.9] months in the experimental arm;P = .15) was observed. However, the median overall survival was 29.8 (95% CI, 22.5-41.1) months in the experimental arm compared with 24.1 (95% CI, 18.6-29.8) months in the standard arm (adjusted hazard ratio, 0.73; 95% CI, 0.54-0.99;P = .04). Moreover, the experimental arm was associated with a significant reduction in the rate of severe diarrhea (6 [5.3%] vs 19 [16.5%];P = .006) and nausea (2 [1.8%] vs 8 [7.0%];P = .05) and improved physical functioning (mean [SD] change from baseline, 0.65 [1.96] vs −7.41 [2.95] at 24 weeks;P= .02), and constipation scores (mean [SD] change from baseline, −17.2 [3.73] vs −0.62 [4.44];P= .003). Conclusions and Relevance In this randomized clinical trial, sequential administration of bevacizumab plus chemotherapy did not improve ORR, the primary end point. However, the overall survival advantage, fewer adverse effects, and better health-related QOL associated with sequential bevacizumab administration might provide the basis for exploring antiangiogenic combination treatments with innovative perspectives. Trial Registration EudraCT Identifier:2011-004997-27; ClinicalTrials.gov Identifier:NCT01718873
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- 2021
12. Study of Ras Mutations' Prognostic Value in Metastatic Colorectal Cancer: STORIA Analysis
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Nicola Normanno, Alfonso De Stefano, Lucrezia Silvestro, S Facchini, Gerardo Botti, Annabella Di Mauro, Guglielmo Nasti, Antonino Cassata, Monica R. Maiello, Carmela Romano, Anna Nappi, Antonio Avallone, Alessandro Ottaiano, Cristin Roma, Stefania Scala, Paolo Delrio, Fabiana Tatangelo, and Anna Maria Rachiglio
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0301 basic medicine ,Neuroblastoma RAS viral oncogene homolog ,Oncology ,Cancer Research ,medicine.medical_specialty ,Prognostic variable ,Colorectal cancer ,NRAS ,colorectal cancer ,medicine.disease_cause ,Group A ,lcsh:RC254-282 ,survival ,Group B ,Article ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,medicine ,KRAS ,Grading (tumors) ,neoplasms ,business.industry ,medicine.disease ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,digestive system diseases ,Log-rank test ,030104 developmental biology ,030220 oncology & carcinogenesis ,prognosis ,business - Abstract
Background: Colorectal cancer (CRC) is the second most common cause of cancer-specific death in both sexes in Western countries. KRAS mutations occur in about 50% of metastatic CRCs (mCRCs). The prognostic value of specific KRAS mutations still remains unexplored and unclear. Methods: Two hundred and forty KRAS wild-type and 206 KRAS/NRAS mutant consecutive unresectable mCRC patients with PS Eastern Cooperative Oncology Group (ECOG) 0 or 1, aged <, 80 years, and with a life expectancy >, 3 months entered into this study. DNA was extracted from paraffin-embedded formalin-fixed tumour tissues, and it was sequenced with the Oncomine Solid Tumour DNA kit (Thermo Fisher Scientific, Waltham, MA, USA). Data were analysed using the Torrent Suite Software v5.0 (Thermo Fisher Scientific). The primary outcome was the analysis of the prognostic role of different KRAS mutations in terms of overall survival (OS). Results: There were no significant differences among the most prevalent mutations (p.G12D, p.G12V, p.G13D, p.G12A, p.G12C, and p.G12S) in terms of age (<, 65 vs. &ge, 65 years), gender (male vs. female), grading (G1/G2 vs. G3), side of primary tumour (left vs. right), pT, and pN. At the median follow-up of 25.6 months, there were 77 deaths in KRAS-mutated patients and 94 in wild-type patients. Three homogeneous prognostic groups were identified: wild-type patients (group A, median survival: 27.5 months), p.G13D/p.G12A/p.G12V/p.G12D mutants (group B, median survival: 17.3 months), and p.G12C/p.G12S mutants (group C, median survival: 5.0 months, p <, 0.0001 according to Log Rank test). Upon multivariate analysis, metastatic involvement and p.G12C/p.G12S KRAS mutation group C (vs. other mutations) emerged as independent prognostic variables for survival. Conclusions: We show that mutant KRAS is a negative prognostic factor and that p.G12C/p.G12S variants present the worst clinical courses. This information suggests a clear difference among KRAS mutations, and it will be useful to test potentiated and/or innovative therapeutic strategies in p.G12C/p.G12S metastatic CRC patients.
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- 2020
13. Randomized phase II study of valproic acid in combination with bevacizumab and oxaliplatin/fluoropyrimidine regimens in patients with
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María Roca, Emiliano Tamburini, Rossana Casaretti, Maria Carmela Piccirillo, Nicola Maurea, Antonella Petrillo, Paolo Delrio, Antonio Avallone, Lucrezia Silvestro, A. Cassata, Anna Nappi, Carmela Romano, Alfredo Budillon, Gerardo Botti, Carlo Vitagliano, Pasquale Aprea, Fabiana Tatangelo, Francesco Giuliani, Francesco Perrone, Alfonso De Stefano, Filomena Calabrese, Ernesta Cavalcanti, Piera Maiolino, Valeria Vicario, Francesco Izzo, Gerardo Rosati, Alessandra Leone, Vincenza Granata, and Elena Di Gennaro
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Oncology ,Anti vegf ,medicine.medical_specialty ,Valproic Acid ,Bevacizumab ,epigenetics ,business.industry ,Colorectal cancer ,Phases of clinical research ,KRAS mutation ,colorectal cancer ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,medicine.disease ,lcsh:RC254-282 ,Oxaliplatin ,Study Protocol ,anti-VEGF ,Internal medicine ,Medicine ,In patient ,Epigenetics ,business ,predictive biomarker ,medicine.drug - Abstract
Background:Despite effective treatments, metastatic colorectal cancer (mCRC) prognosis is still poor, mostly in RAS-mutated tumors, thus suggesting the need for novel combinatorial therapies. Epigenetic alterations play an important role in initiation and progression of cancers, including CRC. Histone-deacetylase inhibitors (HDACi) have shown activity in combination with chemotherapy in the treatment of solid tumors. Owing to its HDACi activity and its safe use for epileptic disorders, valproic acid (VPA) is a good candidate for anticancer therapy that we have largely explored preclinically translating our findings in currently ongoing clinical studies. We have shown in CRC models that HDACi, including VPA, induces synergistic antitumor effects in combination with fluoropyrimidines. Furthermore, unpublished results from our group demonstrated that VPA induces differentiation and sensitization of CRC stem cells to oxaliplatin. Moreover, preclinical and clinical data suggest that HDACi may prevent/reverse anti-angiogenic resistance.Methods/Design:A randomized, open-label, two-arm, multicenter phase-II study will be performed to explore whether the addition of VPA to first line bevacizumab/oxaliplatin/fluoropyrimidine regimens (mFOLFOX-6/mOXXEL) might improve progression-free survival (PFS) in RAS-mutated mCRC patients. A sample size of 200 patients was calculated under the hypothesis that the addition of VPA to chemotherapy/bevacizumab can improve PFS from 9 to 12 months, with one-sided alpha of 0.20 and a power of 0.80. Secondary endpoints are overall survival, objective response rate, metastases resection rate, toxicity, and quality of life. Moreover, the study will explore several prognostic and predictive biomarkers on blood samples, primary tumors, and on resected metastases.Discussion:The “Revolution” study aims to improve the treatment efficacy of RAS-mutated mCRC through an attractive strategy evaluating the combination of VPA with standard cancer treatment. Correlative studies could identify novel biomarkers and could add new insight in the mechanism of interaction between VPA, fluoropyrimidine, oxaliplatin, and bevacizumab.Trial Registration:EudraCT: 2018-001414-15; ClinicalTrials.gov identifier: NCT04310176
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- 2020
14. Integration of stereotactic radiotherapy in the treatment of metastatic colorectal cancer patients: a real practice study with long-term outcome and prognostic factors
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Valerio Scotti, Alessandro Ottaiano, Valeria Vicario, Lucrezia Silvestro, Alfonso De Stefano, Monica Capozzi, Chiara De Divitiis, Guglielmo Nasti, Anna Nappi, Antonino Cassata, Salvatore Tafuto, Carmen Romano, Rossana Casaretti, Massimiliano Berretta, and Antonio Avallone
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Oncology ,medicine.medical_specialty ,Colorectal cancer ,medicine.medical_treatment ,colorectal cancer ,Standardized uptake value ,Stereotactic radiation therapy ,chemotherapy ,medicine.disease_cause ,radiation therapy ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,medicine ,Fluorodeoxyglucose ,business.industry ,metastatic colorectal cancer ,medicine.disease ,Primary tumor ,Radiation therapy ,Response Evaluation Criteria in Solid Tumors ,030220 oncology & carcinogenesis ,030211 gastroenterology & hepatology ,KRAS ,Clinical Research Paper ,Chemotherapy ,Metastatic colorectal cancer ,business ,medicine.drug - Abstract
// Alessandro Ottaiano 1, * , Valerio Scotti 2, * , Chiara De Divitiis 3 , Monica Capozzi 3 , Carmen Romano 3 , Antonino Cassata 3 , Rossana Casaretti 3 , Lucrezia Silvestro 3 , Anna Nappi 3 , Valeria Vicario 3 , Alfonso De Stefano 3 , Salvatore Tafuto 3 , Massimiliano Berretta 4 , Guglielmo Nasti 1 and Antonio Avallone 3 1 Department of Abdominal Oncology, SSD–Innovative Therapies for Abdominal Metastases, Istituto Nazionale Tumori di Napoli G. Pascale IRCCS, National Cancer Institute, 80131, Naples, Italy 2 San Rossore Clinic, Viale delle Cascine, 56122, Pisa, Italy 3 Department of Abdominal Oncology, Experimental Clinical Oncology, Istituto Nazionale Tumori di Napoli G. Pascale IRCCS, National Cancer Institute, 80131, Naples, Italy 4 Department of Medical Oncology, CRO Aviano, National Cancer Institute, 33081, Aviano, Italy * These authors have contributed equally to this work Correspondence to: Guglielmo Nasti, email: g.nasti@istitutotumori.na.it , ale.otto@libero.it Keywords: colorectal cancer; radiation therapy; chemotherapy; metastatic colorectal cancer Received: April 26, 2018 Accepted: June 23, 2018 Published: October 16, 2018 ABSTRACT Background: There are very few clinical or prognostic studies on the role of SRT (Stereotactic Radiation Therapy) in the continuum of care of metastatic colorectal cancer (mCRC) patients. Patients and methods: Patients affected by oligo-mCRC were treated with SRT before or after front-line standard treatments. SRT was delivered according to a risk-adapted protocol. Total body CT (Computed Tomography) scan was done before therapy and every three months thereafter. The radiologic responses to therapy were evaluated by RECIST (Response Evaluation Criteria In Solid Tumors). FDG-PET (FluoroDeoxyGlucose - Positron Emission Tomography) was done before and after SRT; metabolic responses were evaluated by using the EORTC (European Organization for Research and Treatment of Cancer) criteria. The Kaplan-Meier product limit method was applied to graph Overall Survival (OS) and Progression-Free Survival (PFS). Results: Forty-seven patients were included. Twenty-one patients had disease limited to lungs, 9 to lung and liver, 7 only to liver, 10 to multiple sites. The median prescription SRT dose was 60 Gy per organ in 3 fractions (median biological effective dose of 180 Gy). The reduction of delta SUVmax (maximum Standardized Uptake Value) correlated with the local control (p
- Published
- 2018
15. P-198 Prevalence of deleterious DPYD variants in patients with gastrointestinal malignancies: Real-world data from a single institution in Italy
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Giuseppe Viscardi, M. Di Bonito, C. Romano, A. De Stefano, Claudia Cardone, Lucrezia Silvestro, N. Zanaletti, Francesca Collina, I. Di Giovanni, A. Avallone, M. Brogna, A. Cassata, Rossana Casaretti, and Anna Nappi
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medicine.medical_specialty ,Oncology ,business.industry ,Internal medicine ,medicine ,DPYD ,In patient ,Hematology ,Single institution ,business ,Real world data - Published
- 2021
16. P-269 Lenvatinib in hepatocellular carcinoma: QoL surveys and radiological imaging markers predicting clinical outcome in patients with hepatocellular carcinoma treated with lenvatinib as first-line treatment (SULENVA-HCC)
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A. De Stefano, F. Calabrese, F. Lzzo, Lucrezia Silvestro, Mauro Piccirillo, Carmela Romano, N. Zanaletti, A. Cassata, A. Avallone, Rossana Casaretti, Anna Nappi, and Francesco Fiore
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Oncology ,medicine.medical_specialty ,business.industry ,Hematology ,medicine.disease ,First line treatment ,chemistry.chemical_compound ,chemistry ,Hepatocellular carcinoma ,Internal medicine ,medicine ,In patient ,Lenvatinib ,business ,Radiological imaging - Published
- 2020
17. Funds Reimbursement of High-Cost Drugs in Gastrointestinal Oncology: An Italian Real Practice 1 Year Experience at the National Cancer Institute of Naples
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Monica Capozzi, Chiara De Divitiis, Alessandro Ottaiano, Tramontano Teresa, Maurizio Capuozzo, Piera Maiolino, Gerardo Botti, Salvatore Tafuto, Antonio Avallone, The Abdominal Oncology Group, Rossana Casaretti, Antonino Cassata, Anna Nappi, Guglielmo Nasti, Carmela Romano, and Lucrezia Silvestro
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Oncology ,medicine.medical_specialty ,gastro-intestinal cancers ,targeted drugs ,Pharmacist ,Public expenditure ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,medicine ,030212 general & internal medicine ,Medical prescription ,multidisciplinary team ,Reimbursement ,Health policy ,Government ,business.industry ,lcsh:Public aspects of medicine ,030503 health policy & services ,Medical record ,Public health ,Public Health, Environmental and Occupational Health ,lcsh:RA1-1270 ,Brief Research Report ,managed entry agreements ,reimbursement ,Public Health ,0305 other medical science ,business - Abstract
Introduction: The therapeutic scenario of Oncology is enriching of innovative agents which are determining an increase in public expenditure because of their high cost. In Italy, a web-based government Registry is used to monitor the clinical use of these drugs and, in later phases, to obtain funds reimbursement according to specific economic agreements with companies. Methods: A health policy expert Pharmacist was included in the multidisciplinary team of the Department of Abdominal Oncology of the National Cancer Institute (NCI) of Naples "G. Pascale Foundation" in order to improve the management of the Registry for oncologic drugs monitoring. Pharmacist activities were: basal data registration, prescription appropriateness, drug request, response monitoring, toxicity reporting, follow-up, reimbursement request. These activities were conducted in strict interrelation with clinicians. The source of data were medical records and a web-based national reimbursement platform. The analysis of the economic impact of this strategy was descriptive and it was indicated as resources recovery comparing 2 years: 2015 vs. 2016. The currency reference used was the Euro (€). Results: A total of 932 patients were followed-up and registered, 365 treatments are ongoing at the Department of Abdominal Oncology (NCI of Naples, Italy). The most prescribed biologic drug in advanced gastrointestinal cancers was bevacizumab. Compared to the year 2015, in 2016 we recorded a strong increase of reimbursements: EUR 881.712,42 vs. EUR 214.554,98. Conclusions: We suggest that the reimbursement process can be improved when a health policy reimbursement professional Pharmacist is integrated in the multidisciplinary team along with clinicians.
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- 2018
18. A prognostic model comprising pT stage, N status, and the chemokine receptors CXCR4 and CXCR7 powerfully predicts outcome in neoadjuvant resistant rectal cancer patients
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Chiara Carlomagno, Paolo Delrio, Fabiana Tatangelo, Maria Napolitano, Francesco Paolo D'Armiento, Laura Cella, Roberto Pacelli, Rosario Vincenzo Iaffaioli, Alessia Pelella, Biagio Pecori, Antonio Avallone, Crescenzo D'Alterio, Lucrezia Silvestro, F. Bianco, and Stefania Scala
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Oncology ,Cancer Research ,medicine.medical_specialty ,Colorectal cancer ,business.industry ,medicine.medical_treatment ,medicine.disease ,CXCR4 ,Metastasis ,Chemokine receptor ,Internal medicine ,Concomitant ,medicine ,Immunohistochemistry ,Stage (cooking) ,business ,Adjuvant - Abstract
Despite the optimization of the local treatment of advanced rectal cancer (LARC), combination of preoperative chemoradiotherapy (CRT) and surgery, approximately one third of patients will develop distant metastases. Since the chemokine receptor CXCR4 has been implicated in metastasis development and prognosis in colorectal cancer, the role of the entire axis CXCR4-CXCL12-CXCR7 was evaluated to identify high relapse risk rectal cancer patients. Tumor specimens of 68 LARC patients undergoing surgery after neoadjuvant-CRT were evaluated for CXCR4, CXCR7, and CXCL12 expression through immunohistochemistry. Multivariable prognostic model was developed using classical prognostic factors along with chemokine receptor expression profiles. High CXCR4 correlated with a shorter relapse-free survival (RFS) (p = 0.0006) and cancer specific survival (CSS) (p = 0.0004). Concomitant high CXCR4-negative/low CXCR7 or high CXCR4-negative/low CXCL12 significantly impaired RFS (p = 0.0003 and p = 0.0043) and CSS (p = 0.0485 and p = 0.0026). High CXCR4/N+ identified the worst prognostic category for RFS (p < 0.0001) and CSS (p = 0.0003). The optimal multivariable predictive model for RFS was a five-variable model consisting of gender, pT stage, N status, CXCR4, and CXCR7 (AUC = 0.92, 95% CI = 0.77–0.98). The model is informative and supportive for adjuvant treatment and identifies CXCR4 as a new therapeutic target in rectal cancer.© 2013 UICC
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- 2014
19. Gastrointestinal Non Colorectal Cancer. Do Elderly Patients Need a Specific Management?
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Salvatore Tafuto, Alessandro Ottaiano, Guglielmo Nasti, Carmela Romano, Rossana Casaretti, Massimo Montano, A. Cassata, Massimiliano Berretta, Antonio Avallone, Lucrezia Silvestro, and Rosario Vincenzo Iaffaioli
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Oncology ,Cancer Research ,medicine.medical_specialty ,medicine.medical_treatment ,Target therapy ,Elderly ,Stomach Neoplasms ,Gastro ,Internal medicine ,Pancreatic cancer ,medicine ,Humans ,Chemotherapy ,Geriatric Assessment ,Aged ,Pharmacology ,business.industry ,Palliative Care ,Cancer ,medicine.disease ,humanities ,Pancreatic Neoplasms ,Gastric cancer ,Clinical trial ,Radiation therapy ,Non colorectal ,Quality of Life ,Molecular Medicine ,business - Abstract
Background: Elderly patients (65 years and over) develop often, sometimes predominantly , esophageal, gastro esophageal junction, gastric and pancreatic cancer (gastrointestinal non colorectal cancer). Most clinical trials exclude elderly patients from accrual considering aging a potential risk factor. In fact an elderly patient can develop greater toxicity than a younger patient from oncologic treatments (chemotherapy, radiotherapy, target therapies) due to a worse function of vital organs. Methods: We analyzed the current scientific literature, searching articles since 1990, about gastrointestinal non colorectal cancer in elderly patients, to establish if they need a specific management, different from younger patients. Results: Data from analyzed studies, both gastro esophageal and pancreatic cancer, are contradictory. In some reports elderly patients don’t seem to bring greater toxicity than younger. Other trials consider that dose-adjustment to renal function is need in elderly patients, but these trials are very few. Other trials may include several biases such as accrual of “only fit” elderly patients. Conclusions: It is very important in elderly patients with higher risk of toxicity, to distinguish the aim of cancer treatment: is it curative or palliative? Furthermore, in this type of patients the most important target is probably maintaining the quality of life especially in gastric and pancreatic cancer that often started as advanced disease. For these valuation chronological age alone is not sufficient. Another very important factor in elderly cancer patients is the geriatric assessment including not only age but also functional, social and mental status.
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- 2013
20. Targeting thymidylate synthase in colorectal cancer: critical re-evaluation and emerging therapeutic role of raltitrexed
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Elena Di Gennaro, Antonio Avallone, Alfredo Budillon, Vincenzo Rosario Iaffaioli, and Lucrezia Silvestro
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Oncology ,Antimetabolites, Antineoplastic ,medicine.medical_specialty ,Colorectal cancer ,Thiophenes ,Disease ,Pharmacology ,Thymidylate synthase ,Drug Administration Schedule ,Folinic acid ,Internal medicine ,Humans ,Medicine ,Pharmacology (medical) ,In patient ,Enzyme Inhibitors ,Cardiotoxicity ,biology ,business.industry ,Thymidylate Synthase ,General Medicine ,medicine.disease ,Anticancer drug ,Quinazolines ,biology.protein ,Fluorouracil ,Colorectal Neoplasms ,business ,Raltitrexed ,medicine.drug - Abstract
5-fluorouracil continues to be the cornerstone of treatment for colorectal cancer. Although fluoropyrimidines are generally considered as well-tolerated drugs, severe toxicities can be a major clinical problem, and the recommended prolonged infusion of 5-fluorouracil provokes discomfort in patients. Raltitrexed (Tomudex), a quinazoline analogue of folinic acid, is a selective and direct thymidylate synthase (TS) inhibitor with a convenient 3-weekly schedule of administration.In this review, through critical insight into the mechanism of action and main clinical experiences, the authors suggest the necessity to reconsider raltitrexed as a valuable anticancer drug and as a suitable option for colorectal cancer. The authors highlight its emerging therapeutic role in clinical practice for patients with fluoropyrimidine-induced cardiotoxicity or a significant history of cardiac disease.This review discusses if TS could still be a relevant target for colorectal cancer in the era of molecular therapy and if raltitrexed should still be considered a drug with a life-threatening toxicity. Furthermore, this review discusses the principal combination clinical experiences of raltitrexed and its emerging therapeutic role in clinical practice as a suitable option for colorectal cancer patients with fluoropyrimidine-induced cardiotoxicity or a significant history of cardiac disease.
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- 2013
21. Metastatic Colorectal Cancer: Role of Target Therapies and Future Perspectives
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Francesco Fiorica, Guglielmo Nasti, Anna Nappi, Chiara De Divitiis, Carmela Romano, Massimiliano Berretta, Alessandro Ottaiano, Salvatore Tafuto, Rossana Casaretti, Lucrezia Silvestro, Lara Alessandrini, and Antonino Cassata
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0301 basic medicine ,Oncology ,Cancer Research ,medicine.medical_specialty ,Colorectal cancer ,Population ,Rectum ,Antineoplastic Agents ,Disease ,Target therapy ,03 medical and health sciences ,Therapeutic approach ,chemistry.chemical_compound ,0302 clinical medicine ,Internal medicine ,Drug Discovery ,Medicine ,Humans ,Anti-EGFR ,Anti-VEGF drugs ,Monoclonal antibodies ,Treatment ,Epidermal growth factor receptor ,Molecular Targeted Therapy ,Precision Medicine ,education ,Pharmacology ,education.field_of_study ,biology ,business.industry ,Cancer ,medicine.disease ,Prognosis ,Neoplasm Proteins ,Vascular endothelial growth factor ,030104 developmental biology ,medicine.anatomical_structure ,chemistry ,030220 oncology & carcinogenesis ,Immunology ,biology.protein ,business ,Colorectal Neoplasms - Abstract
Today, we are experiencing a real cultural revolution in the therapeutic approach to cancer of the colon - rectum, that by orphan disease, it is now becoming an important paradigm of scientific innovations and concepts. Survival of patients with metastatic colorectal cancer (m-CRC) has been significantly improved with the introduction of the monoclonal antibodies that have as target the vascular endothelial growth factor (VEGF) and the epidermal growth factor receptor (EGFR). The PD-1/PD-L1 pathway in cancer is implicated in tumors escaping immune destruction. This pathway is up -regulated in many tumours. Blockade of this pathway with anti-PD-1 and anti-PD-L1 agents has led to remarkable clinical responses in patients affected by many different types of cancer. The aim of this review is to evaluate the effects of addiction of biological agents to standard chemotherapy in the treatment of m-CRC. We can say that, among the various treatment options, the challenge of the future will be a better selection of the population, to ensure the best possible benefit from treatment with anti-VEGF drugs or anti-EGFR and a careful and customized planning of the therapeutic strategy for each patient.
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- 2016
22. Indications for Systemic Chemotherapy
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A. Avallone, Rosario Vincenzo Iaffaioli, Carmela Romano, Rossana Casaretti, Salvatore Tafuto, Lucrezia Silvestro, Chiara De Divitiis, Alessandro Ottaiano, Anna Nappi, Antonino Cassata, and G. Nasti
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medicine.medical_specialty ,Chemotherapy ,Systemic chemotherapy ,business.industry ,Colorectal cancer ,medicine.medical_treatment ,medicine.disease ,Total mesorectal excision ,medicine.anatomical_structure ,Quality of life ,medicine ,Radiology ,Presentation (obstetrics) ,business ,Mesentery ,Pelvis - Abstract
Local recurrence (LR) after curative surgery is a critical problem for patients with colorectal cancer (CRC). Over the last two decades, oncologic treatment results for primary rectal cancer have improved due to refinements in neoadjuvant chemotherapy, radiation, and surgery. Nevertheless, there is still a 5–10% rate of LR, threatening the survival and quality of life of affected patients [1]. LR is best defined as any tumor recurring within the true pelvis, including neorectum, mesentery, pelvic viscera, pelvic sidewall structures, and bone. Due to variability of anatomy and clinical presentation, detection, staging, and clinical management are complex. About half of all LRs are limited to the pelvis and can be considered for curative re-excision [2] (Table 6.1).
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- 2016
23. Diabetes and Body Mass Index Are Associated with Neuropathy and Prognosis in Colon Cancer Patients Treated with Capecitabine and Oxaliplatin Adjuvant Chemotherapy
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Maurizio Capuozzo, Vincenzo Quagliariello, Monica Capozzi, Lucrezia Silvestro, Alessandro Ottaiano, Guglielmo Nasti, Antonio Avallone, Salvatore Tafuto, Carmela Romano, Antonino Cassata, Stefania Scala, Rossana Casaretti, Vincenzo Rosario Iaffaioli, Anna Nappi, Piera Maiolino, and Chiara De Divitiis
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Oncology ,Adult ,Male ,Cancer Research ,medicine.medical_specialty ,Organoplatinum Compounds ,Colorectal cancer ,medicine.medical_treatment ,Kaplan-Meier Estimate ,Body Mass Index ,Capecitabine ,Diabetes Complications ,03 medical and health sciences ,0302 clinical medicine ,Diabetes mellitus ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Humans ,Obesity ,Aged ,Chemotherapy ,business.industry ,Neurotoxicity ,Peripheral Nervous System Diseases ,General Medicine ,Middle Aged ,medicine.disease ,Prognosis ,Oxaliplatin ,Chemotherapy, Adjuvant ,030220 oncology & carcinogenesis ,Chronic Disease ,Colonic Neoplasms ,Female ,Neoplasm Recurrence, Local ,business ,Body mass index ,Adjuvant ,030217 neurology & neurosurgery ,medicine.drug ,Follow-Up Studies - Abstract
Background: There are few background data on the impact of clinical factors on neurotoxicity and prognosis in patients treated with adjuvant capecitabine and oxaliplatin (CAPOX) chemotherapy. Methods: 102 stage II high-risk and stage III colorectal cancer patients were treated for 6 months with adjuvant CAPOX, then they were followed up. Associations between clinical variables, metabolic syndrome components, smoking and neurotoxicity were evaluated by the χ2 test. The Kaplan-Meier product limit method was applied to graph disease-free survival (DFS). Univariate analysis was done with the log-rank test. Cox's proportional hazards regression was used to analyze the effect of several risk factors on DFS. Results: Significant associations were found between diabetes (p < 0.001), BMI (p = 0.01) and the occurrence of chronic neurotoxicity. After a median follow-up of 46 months, 14 patients (13.7%) had suffered recurrence. An analysis of the prognostic factors for DFS showed that prognosis is unfavorable for patients with high lymph-nodal involvement (HR: 5.23, p = 0.0007), diabetes (HR: 4.86; p = 0.03) and a BMI ≥25 (HR: 3.69, p = 0.002). Discussion: Common mediators in diabetes and obesity could be involved in peripheral neuropathy and in stimulating micro-metastases. Further studies are necessary to explain this interesting connection between diabetes, obesity and colon cancer.
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- 2015
24. A multicentre, randomized phase 3 study on the optimization of the combination of bevacizumab with mFOLFOX/OXXEL in patients with metastatic colorectal cancer (mCRC)
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F. Perrone, Salvatore Tafuto, Mauro Piccirillo, Guglielmo Nasti, Paolo Delrio, Domenico Bilancia, A. Cassata, Secondo Lastoria, Alfredo Budillon, Lucrezia Silvestro, Alessandro Ottaiano, A. De Stefano, E. Di Gennaro, G. Rosati, Chiara Carlomagno, A. Avallone, Ciro Gallo, Francesco Izzo, Carmela Romano, and F. Bianco
- Subjects
Oncology ,medicine.medical_specialty ,Bevacizumab ,business.industry ,Colorectal cancer ,Phases of clinical research ,Hematology ,medicine.disease ,Internal medicine ,medicine ,In patient ,business ,medicine.drug - Published
- 2017
25. Preoperative nivolumab in patients(pts) with locally advanced colon cancer (T3 or T4): A window-of-opportunity study (NICOLE)
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Paolo Delrio, Lucrezia Silvestro, Guglielmo Nasti, A. Cassata, Secondo Lastoria, Ernesta Cavalcanti, Anna Nappi, Fabiana Tatangelo, Carmela Romano, P.A. Ascierto, A. De Stefano, Alfredo Budillon, Rossana Casaretti, Alessandro Ottaiano, Jérôme Galon, Piera Maiolino, Antonella Petrillo, E. Di Gennaro, A. Avallone, and Diana Giannarelli
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Oncology ,medicine.medical_specialty ,Window of opportunity ,business.industry ,Colorectal cancer ,Locally advanced ,Hematology ,medicine.disease ,Internal medicine ,Medicine ,In patient ,Nivolumab ,business - Published
- 2018
26. Survival analysis of a multicentre, randomized phase 3 study on the optimization of the combination of bevacizumab with FOLFOX/OXXEL in patients with metastatic colorectal cancer (mCRC)
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Francesco Izzo, Ugo Pace, Salvatore Tafuto, Rossana Casaretti, Lucrezia Silvestro, A. De Stefano, F. Bianco, Guglielmo Nasti, Mauro Piccirillo, A. Cassata, G. Rosati, Chiara Carlomagno, C. Gallo, Carmela Romano, Paolo Delrio, A. Avallone, E. De Gennaro, Domenico Bilancia, Vittorio Albino, Secondo Lastoria, Alfredo Budillon, and Alessandro Ottaiano
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Oncology ,medicine.medical_specialty ,Bevacizumab ,business.industry ,Colorectal cancer ,Phases of clinical research ,Hematology ,medicine.disease ,FOLFOX ,Internal medicine ,medicine ,In patient ,business ,Survival analysis ,medicine.drug - Published
- 2018
27. Update survival analysis from a multicenter, randomized phase 3 study on the optimization of the combination of bevacizumab with FOLFOX/OXXEL in patients with metastatic colorectal cancer (mCRC)
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Guglielmo Nasti, Antonella Petrillo, Valeria Vicario, Francesco Izzo, Paolo Delrio, Lucrezia Silvestro, Domenico Bilancia, Alfonso De Stefano, Ciro Gallo, Salvatore Tafuto, Chiara Carlomagno, Antonino Cassata, F. Bianco, Vincenza Granata, Secondo Lastoria, Alfredo Budillon, Antonio Avallone, Carmen Romano, Maria Carmela Piccirillo, and Gerardo Rosati
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Oncology ,Cancer Research ,medicine.medical_specialty ,Chemotherapy ,Bevacizumab ,medicine.drug_class ,Colorectal cancer ,business.industry ,medicine.medical_treatment ,Growth factor ,Phases of clinical research ,Monoclonal antibody ,medicine.disease ,digestive system diseases ,FOLFOX ,Internal medicine ,medicine ,business ,Survival analysis ,medicine.drug - Abstract
3562Background: Bevacizumab is a humanized anti-vascular endothelial growth factor (VEGF) monoclonal antibody, approved in combination with chemotherapy in the treatment of mCRC. It has been hypoth...
- Published
- 2018
28. Phase 1/2 study of valproic acid and short-course radiotherapy plus capecitabine as preoperative treatment in low-moderate risk rectal cancer-V-shoRT-R3 (Valproic acid - short RadioTherapy - rectum 3rd trial)
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Ernesta Cavalcanti, Vincenzo Rosario Iaffaioli, Giovanni Maria Romano, Gennaro Daniele, Maria Carmela Piccirillo, Massimo Montano, Antonella Petrillo, Francesco Perrone, Piera Maiolino, Secondo Lastoria, Luigi Aloj, Fabiana Tatangelo, F. Bianco, Gerardo Botti, Ciro Gallo, Elena Di Gennaro, P. Marone, Alfredo Budillon, Paolo Delrio, Massimo Di Maio, Valentina D’Angelo, Antonio Avallone, Corradina Caracò, Paolo Muto, Nicola Maurea, Biagio Pecori, Lucrezia Silvestro, Cinzia Granata, Manuela Terranova Barberio, María Roca, Avallone, A, Piccirillo, Mc, Delrio, P, Pecori, B, Di Gennaro, E, Aloj, L, Tatangelo, F, D'Angelo, V, Granata, C, Cavalcanti, E, Maurea, N, Maiolino, P, Bianco, F, Montano, M, Silvestro, L, Terranova Barberio, M, Roca, M, Di Maio, M, Marone, P, Botti, G, Petrillo, A, Daniele, G, Lastoria, S, Iaffaioli, Vr, Romano, G, Caracò, C, Muto, P, Gallo, Ciro, Perrone, F, and Budillon, A.
- Subjects
Oncology ,Male ,Cancer Research ,Colorectal cancer ,medicine.medical_treatment ,Valproic acid (VPA) ,Thymidylate synthase ,Deoxycytidine ,chemistry.chemical_compound ,Study Protocol ,HDAC inhibitors ,Antineoplastic Combined Chemotherapy Protocols ,Rectal cancer ,FDG-PET ,biology ,Middle Aged ,Combined Modality Therapy ,Fluorouracil ,Research Design ,Female ,medicine.drug ,Adult ,medicine.medical_specialty ,Short-course radiotherapy (SCRT) ,Adolescent ,Preoperative chemo-radiotherapy ,Capecitabine ,Young Adult ,Internal medicine ,Preoperative Care ,medicine ,Genetics ,Humans ,Thymidine phosphorylase ,Short-course radiotherapy ,Aged ,Chemotherapy ,Radiotherapy ,business.industry ,Rectal Neoplasms ,Valproic Acid ,medicine.disease ,Radiation therapy ,chemistry ,biology.protein ,business - Abstract
Background: Locally advanced rectal cancer (LARC) is a heterogeneous group of tumors where a risk-adapted therapeutic strategy is needed. Short-course radiotherapy (SCRT) is a more convenient option for LARC patients than preoperative long-course RT plus capecitabine. Histone-deacetylase inhibitors (HDACi) have shown activity in combination with RT and chemotherapy in the treatment of solid tumors. Valproic acid (VPA) is an anti-epileptic drug with HDACi and anticancer activity. In preclinical studies, our group showed that the addition of HDACi, including VPA, to capecitabine produces synergistic antitumour effects by up-regulating thymidine phosphorylase (TP), the key enzyme converting capecitabine to 5-FU, and by downregulating thymidylate synthase (TS), the 5-FU target. Methods/Design: Two parallel phase-1 studies will assess the safety of preoperative SCRT (5 fractions each of 5 Gy, on days 1 to 5) combined with (a) capecitabine alone (increasing dose levels: 500–825 mg/m2/bid), on days 1–21, or (b) capecitabine as above plus VPA (oral daily day −14 to 21, with an intra-patient titration for a target serum level of 50–100 microg/ml) followed by surgery 8 weeks after the end of SCRT, in low-moderate risk RC patients. Also, a randomized phase-2 study will be performed to explore whether the addition of VPA and/or capecitabine to preoperative SCRT might increase pathologic complete tumor regression (TRG1) rate. A sample size of 86 patients (21-22/arm) was calculated under the hypothesis that the addition of capecitabine or VPA to SCRT can improve the TRG1 rate from 5% to 20%, with one-sided alpha = 0.10 and 80% power. Several biomarkers will be evaluated comparing normal mucosa with tumor (TP, TS, VEGF, RAD51, XRCC1, Histones/proteins acetylation, HDAC isoforms) and on blood samples (polymorphisms of DPD, TS, XRCC1, GSTP1, RAD51 and XRCC3, circulating endothelial and progenitors cells; PBMCs-istones/proteins acetylation). Tumor metabolism will be measured by 18FDG-PET at baseline and 15 days after the beginning of SCRT. Discussion: This project aims to improve the efficacy of preoperative treatment of LARC and to decrease the inconvenience and the cost of standard long-course RT. Correlative studies could identify both prognostic and predictive biomarkers and could add new insight in the mechanism of interaction between VPA, capecitabine and RT. EudraCT Number: 2012-002831-28. Trial registration: ClinicalTrials.gov number, NCT01898104
- Published
- 2014
29. Targeting HER2 as a therapeutic strategy for breast cancer: a paradigmatic shift of drug development in oncology
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Luca Malorni, Mario Giuliano, Angela Esposito, F. Caputo, L. Zinno, S. De Placido, M. De Laurentiis, Lucrezia Silvestro, Antonio Giordano, Giuseppe Cancello, R. Pennacchio, Emilia Montagna, Antonello Accurso, DE LAURENTIIS, Michelino, Cancello, G, Zinno, L, Montagna, E, Malorni, L, Esposito, A, Pennacchio, R, Silvestro, L, Giuliano, Mario, Giordano, A, Caputo, F, Accurso, A, and DE PLACIDO, Sabino
- Subjects
Oncology ,medicine.medical_specialty ,Paclitaxel ,Receptor, ErbB-2 ,medicine.medical_treatment ,Breast Neoplasms ,Docetaxel ,Antibodies, Monoclonal, Humanized ,Vinorelbine ,Targeted therapy ,Capecitabine ,Breast cancer ,Trastuzumab ,HER2 ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Animals ,Humans ,Anthracyclines ,skin and connective tissue diseases ,neoplasms ,business.industry ,Antibodies, Monoclonal ,Hematology ,medicine.disease ,Metastatic breast cancer ,Gemcitabine ,Tamoxifen ,Drug development ,Female ,Taxoids ,business ,medicine.drug - Abstract
Targeted therapies are causing a dramatic change in cancer drug development. Trastuzumab, a humanised recombinant monoclonal antibody that recognizes the extracellular domain of HER2 trans-membrane protein, is among the first target-specific drugs that have been licensed for clinical use and its development represents a model of integration of new agents with classical treatment strategies. In preclinical models, trastuzumab has demonstrated a marked antiproliferative effect and a synergistic action with several chemotherapeutic agents. Monotherapy trials indicate that trastuzumab is active as a single agent in HER2 positive patients, is well tolerated, and is associated with preservation of quality of life (QoL). Furthermore, as first line therapy for metastatic breast cancer overexpressing HER2 receptor, the addition of trastuzumab to taxane-based chemotherapy significantly increased rate of objective response, time to disease progression and survival when compared with chemotherapy alone. Trastuzumab has shown important activity when used with many chemotherapeutic agents such as platinum salts, gemcitabine, vinorelbine and capecitabine and liposomal anthracyclines. Various trials are now ongoing to optimize the use of trastuzumab and to investigate its role in the adjuvant and in the neo-adjuvant setting.
- Published
- 2005
30. Optimization of the combination of bevacizumab with FOLFOX/OXXEL in patients with metastatic colorectal cancer (mCRC): the multicentre, randomized phase 3 study OBELICS
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Secondo Lastoria, P. Del Rio, Domenico Bilancia, G. Rosati, Chiara Carlomagno, F. Perrone, A. Avallone, F. Bianco, A. De Stefano, Guglielmo Nasti, A. Cassata, Carmela Romano, Alessandro Ottaiano, Francesco Izzo, Mauro Piccirillo, E. Di Gennaro, Alfredo Budillon, Lucrezia Silvestro, Salvatore Tafuto, and Ciro Gallo
- Subjects
0301 basic medicine ,Oncology ,medicine.medical_specialty ,Bevacizumab ,business.industry ,Colorectal cancer ,Phases of clinical research ,Hematology ,medicine.disease ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,FOLFOX ,030220 oncology & carcinogenesis ,Internal medicine ,medicine ,In patient ,business ,medicine.drug - Published
- 2017
31. A prognostic model comprising pT stage, N status, and the chemokine receptors CXCR4 and CXCR7 powerfully predicts outcome in neoadjuvant resistant rectal cancer patients
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Crescenzo, D'Alterio, Antonio, Avallone, Fabiana, Tatangelo, Paolo, Delrio, Biagio, Pecori, Laura, Cella, Alessia, Pelella, Francesco Paolo, D'Armiento, Chiara, Carlomagno, Franco, Bianco, Lucrezia, Silvestro, Roberto, Pacelli, Maria, Napolitano, Rosario Vincenzo, Iaffaioli, and Stefania, Scala
- Subjects
Male ,Receptors, CXCR ,Receptors, CXCR4 ,Rectal Neoplasms ,Chemoradiotherapy ,Kaplan-Meier Estimate ,Middle Aged ,Prognosis ,Immunohistochemistry ,Radiation Tolerance ,Chemokine CXCL12 ,Disease-Free Survival ,Neoadjuvant Therapy ,ROC Curve ,Drug Resistance, Neoplasm ,Area Under Curve ,Biomarkers, Tumor ,Humans ,Female ,Neoplasm Recurrence, Local ,Aged ,Neoplasm Staging ,Proportional Hazards Models - Abstract
Despite the optimization of the local treatment of advanced rectal cancer (LARC), combination of preoperative chemoradiotherapy (CRT) and surgery, approximately one third of patients will develop distant metastases. Since the chemokine receptor CXCR4 has been implicated in metastasis development and prognosis in colorectal cancer, the role of the entire axis CXCR4-CXCL12-CXCR7 was evaluated to identify high relapse risk rectal cancer patients. Tumor specimens of 68 LARC patients undergoing surgery after neoadjuvant-CRT were evaluated for CXCR4, CXCR7, and CXCL12 expression through immunohistochemistry. Multivariable prognostic model was developed using classical prognostic factors along with chemokine receptor expression profiles. High CXCR4 correlated with a shorter relapse-free survival (RFS) (p = 0.0006) and cancer specific survival (CSS) (p = 0.0004). Concomitant high CXCR4-negative/low CXCR7 or high CXCR4-negative/low CXCL12 significantly impaired RFS (p = 0.0003 and p = 0.0043) and CSS (p = 0.0485 and p = 0.0026). High CXCR4/N+ identified the worst prognostic category for RFS (p0.0001) and CSS (p = 0.0003). The optimal multivariable predictive model for RFS was a five-variable model consisting of gender, pT stage, N status, CXCR4, and CXCR7 (AUC = 0.92, 95% CI = 0.77-0.98). The model is informative and supportive for adjuvant treatment and identifies CXCR4 as a new therapeutic target in rectal cancer.
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- 2013
32. PACER – A multicentre, single-arm, two-stage, phase 2 study of panitumumab in patients with cetuximab-refractory metastatic colorectal cancer (mCRC)
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C. Chiara, F. Perrone, A. De Stefano, Lucrezia Silvestro, Guglielmo Nasti, Domenico Bilancia, Mauro Piccirillo, Carmela Romano, Emiddio Barletta, Alessandro Ottaiano, G. Daniele, G. Rosati, Nicola Normanno, Oscar Alabiso, Matilde Lambiase, A. Avallone, Rosario Vincenz Iaffaioli, Evaristo Maiello, Bruno Daniele, and Tiziana Latiano
- Subjects
Oncology ,medicine.medical_specialty ,Cetuximab ,Colorectal cancer ,business.industry ,Phases of clinical research ,Hematology ,medicine.disease ,Refractory ,Internal medicine ,medicine ,Panitumumab ,In patient ,Stage (cooking) ,business ,medicine.drug - Published
- 2016
33. Prospective observational pilot study on the BTcP evaluation in cancer patients
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A. Cassata, Rossana Casaretti, Guglielmo Nasti, Rosario Vincenz Iaffaioli, Salvatore Tafuto, Carmela Romano, Alessandro Ottaiano, Anna Nappi, A. Avallone, and Lucrezia Silvestro
- Subjects
medicine.medical_specialty ,Oncology ,business.industry ,Internal medicine ,Medicine ,Cancer ,Observational study ,Hematology ,business ,medicine.disease - Published
- 2016
34. Early FDG PET response assessment of preoperative radiochemotherapy in locally advanced rectal cancer: correlation with long-term outcome
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Biagio Pecori, Nigel Scott, Secondo Lastoria, Massimo Montano, Fabiana Tatangelo, Antonio Avallone, Francesca Di Gennaro, Alfredo Budillon, Lucrezia Silvestro, Paolo Delrio, Corradina Caracò, Luigi Aloj, and Rossana Casaretti
- Subjects
Adult ,Male ,medicine.medical_specialty ,Colorectal cancer ,medicine.medical_treatment ,Standardized uptake value ,Fluorodeoxyglucose F18 ,medicine ,Humans ,Radiology, Nuclear Medicine and imaging ,Aged ,Neoplasm Staging ,Chemotherapy ,medicine.diagnostic_test ,business.industry ,Rectal Neoplasms ,Remission Induction ,General Medicine ,Chemoradiotherapy ,Middle Aged ,medicine.disease ,Total mesorectal excision ,Oxaliplatin ,Treatment Outcome ,Positron emission tomography ,Positron-Emission Tomography ,Preoperative Period ,Female ,Radiology ,Neoplasm Recurrence, Local ,Radiopharmaceuticals ,business ,Raltitrexed ,medicine.drug - Abstract
The aim of the present study is to prospectively evaluate the prognostic value of previously defined [(18)F]2-fluoro-2-deoxy-D-glucose positron emission tomography (FDG PET) criteria of early metabolic response in patients with locally advanced rectal cancer (LARC) after long-term follow-up.Forty-two patients with poor prognosis LARC underwent three biweekly courses of chemotherapy with oxaliplatin, raltitrexed and 5-fluorouracil modulated by levofolinic acid during pelvic radiotherapy. FDG PET studies were performed before and 12 days after the beginning of the chemoradiotherapy (CRT) treatment. Total mesorectal excision (TME) was carried out 8 weeks after completion of CRT. A previously identified cutoff value of ≥52 % reduction of the baseline mean FDG standardized uptake value (SUV(mean)) was applied to differentiate metabolic responders from non-responders and correlated to tumour regression grade (TRG) and survival.Twenty-two metabolic responders showed complete (TRG1) or subtotal tumour regression (TRG2) and demonstrated a statistically significantly higher 5-year relapse-free survival (RFS) compared with the 20 non-responders (86 vs 55 %, p = .014) who showed TRG3 and TRG4 pathologic responses. A multivariate analysis demonstrated that early ∆SUV(mean) was the only pre-surgical parameter correlated to the likelihood of recurrence (p = .05).This study is the first prospective long-term evaluation demonstrating that FDG PET is not only an early predictor of pathologic response but is also a valuable prognostic tool. Our results indicate the potential of FDG PET for optimizing multidisciplinary management of patients with LARC.
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- 2012
35. Taxane-based combinations as adjuvant chemotherapy of early breast cancer: a meta-analysis of randomized trials
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Diego D'Agostino, Lucrezia Silvestro, Rossella Lauria, Giuseppe Cancello, Valeria Forestieri, Sabino De Placido, Agnese Montanino, Angelo Raffaele Bianco, Carmen Criscitiello, Gennaro Limite, Michele De Laurentiis, Antonio Giordano, Emilia Montagna, Roberta Pennacchio, Angela Esposito, Mario Giuliano, DE LAURENTIIS, Michelino, Cancello, G., D'Agostino, D., Giuliano, Mario, Giordano, A., Montagna, E., Lauria, Rossella, Forestieri, Valeria, Esposito, A., Silvestro, L., Pennacchio, R., Criscitiello, C., Montanino, A., Limite, Gennaro, Bianco, ANGELO RAFFAELE, and DE PLACIDO, Sabino
- Subjects
Oncology ,Cancer Research ,medicine.medical_specialty ,Anthracycline ,Paclitaxel ,Breast Neoplasms ,Docetaxel ,Disease-Free Survival ,law.invention ,Breast cancer ,Randomized controlled trial ,law ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Humans ,Anthracyclines ,Randomized Controlled Trials as Topic ,Gynecology ,Taxane ,business.industry ,Hazard ratio ,medicine.disease ,Clinical trial ,Chemotherapy, Adjuvant ,Meta-analysis ,Female ,Taxoids ,business ,medicine.drug - Abstract
Purpose We conducted a meta-analysis of randomized trials that evaluated the efficacy of incorporating taxanes into anthracycline-based regimens for early breast cancer (EBC). We aimed to determine whether this approach improves disease-free survival (DFS) and overall survival (OS) and whether benefits are maintained across relevant patient subgroups. Methods Studies were retrieved by searching the PubMed database and the proceedings of major conferences. We extracted hazard ratios (HR) and 95% CIs for DFS and OS from each trial and obtained pooled estimates using an inverse-variance model. Results Thirteen studies were included in the meta-analysis (N = 22,903 patients). The pooled HR estimate was 0.83 (95% CI, 0.79 to 0.87; P < .00001) for DFS and 0.85 (95% CI, 0.79 to 0.91; P < .00001) for OS. Risk reduction was not influenced by the type of taxane, by estrogen receptor (ER) expression, by the number of axillary metastases (N1 to 3 v N4+), or by the patient's age/menopausal status. Sensitivity analysis showed that taxanes given in combination with anthracyclines, unlike sequential administration, did not significantly improve OS. However, the test for interaction showed that HR did not differ between the two schedules (P = .54). Taxane administration resulted in an absolute 5-year risk reduction of 5% for DFS and 3% for OS. Conclusion The addition of a taxane to an anthracycline-based regimen improves the DFS and OS of high-risk EBC patients. The DFS benefit was independent of ER expression, degree of nodal involvement, type of taxane, age/menopausal status of patient, and administration schedule.
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- 2008
36. Central nervous system metastases in a cohort of metastatic breast cancer patients treated with trastuzumab
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M. De Laurentiis, Angela Esposito, Emilia Montagna, Giuseppe Cancello, Rossella Lauria, Diego D'Agostino, Valeria Forestieri, Antonello Accurso, Lucrezia Silvestro, S. De Placido, E., Montagna, G., Cancello, D., D'Agostino, Lauria, Rossella, Forestieri, Valeria, A., Esposito, L., Silvestro, Accurso, Antonello, DE PLACIDO, Sabino, and DE LAURENTIIS, Michelino
- Subjects
CA15-3 ,Oncology ,Adult ,Cancer Research ,medicine.medical_specialty ,Receptor, ErbB-2 ,Antineoplastic Agents ,Breast Neoplasms ,macromolecular substances ,Kaplan-Meier Estimate ,Toxicology ,Antibodies, Monoclonal, Humanized ,Central Nervous System Neoplasms ,Cohort Studies ,Breast cancer ,Trastuzumab ,Internal medicine ,Medicine ,Humans ,Pharmacology (medical) ,skin and connective tissue diseases ,neoplasms ,Aged ,Proportional Hazards Models ,Retrospective Studies ,Pharmacology ,business.industry ,Proportional hazards model ,Antibodies, Monoclonal ,Retrospective cohort study ,Middle Aged ,medicine.disease ,Prognosis ,Metastatic breast cancer ,Cohort ,Female ,business ,medicine.drug ,Cohort study - Abstract
BACKGROUND: Several analyses suggest an increase of brain metastases in HER2 over-expressing breast cancers treated with trastuzumab as compared to historical series of unselected patients. PATIENTS AND METHODS: We analyzed the incidence of central nervous system (CNS) metastases in 78 patients with HER2 over-expressing breast cancer treated with trastuzumab between July 2000 and June 2006 at the Oncology Department of University Federico II in Naples. We also characterized and compared patients with and without CNS involvement. RESULTS: The median follow-up was 35.3 months (95\%CI 26.3-44); median overall survival was 56 months (95\%CIs 46-nr); 5 patients showed CNS involvement before trastuzumab therapy while 31 developed CNS metastases during trastuzumab treatment. The median overall survival after CNS metastases was 25.4 months (95\%CIs 15.2-nr); patients with CNS lesions showed worse overall survival than patients without CNS lesions (39.1 vs. 75 months, p = 0.005). CONCLUSION: CNS metastases are common events in patients with metastatic HER2 over-expressing breast cancer treated with trastuzumab; the impact on survival is detrimental even if survival after CNS metastases is longer than historical reports. Appropriate investigation of the role of CNS imaging screening and the prophylactic treatment strategies for CNS represents a priority research in this setting.
- Published
- 2007
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