National Tumor Institute of Naples

IT Naples, Italy

National Tumor Institute of Naples

IT Naples, Italy
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Perri F.,Medical Oncology Unit | Longo F.,National Tumor Institute of Naples | Giuliano M.,University of Naples Federico II | Giuliano M.,Baylor College of Medicine | And 7 more authors.
Critical Reviews in Oncology/Hematology | Year: 2017

Epigenetic changes are defined as inherited modifications that are not present in DNA sequence. Gene expression is regulated at various levels and not only in response to DNA modifications. Examples of epigenetic control are DNA methylation, histone deacetylation and mi-RNA expression. Methylation of several tumor suppressor gene promoters is responsible for their silencing and thus potentially sustain cancerogenesis. Similarly, histone deacetylation can lead to oncogene activation. mi-RNA are small (18–20 nucleotides) non-coding RNA fragments capable of inhibiting other m-RNA, ultimately altering the balance in oncogene and tumor suppressor gene expression. It has been shown that growth of several tumor types can be stimulated by epigenetic changes in various phases of cancerogenesis, and drugs able to interfere with these mechanisms can have a positive impact on tumor progression. As matter of fact, epigenetic changes are dynamic and can be reversed by epigenetic inhibitors. Recently, methyltransferase and histone deacetylase inhibitors have attracted the attention of researchers and clinicians as they potentially provide alternative therapeutic options in some cancers. Drugs that inhibit DNA methylation or histone deacetylation have been studied for the reactivation of tumor suppressor genes and repression of cancer cell growth. Epigenetic inhibitors work alone or in combination with other therapeutic agents. To date, a number of epigenetic inhibitors have been approved for cancer treatment. The main challenge in the field of epigenetic inhibitors is their lack of specificity. In this review article we describe their mechanisms of action and potential in cancer treatment. © 2017 Elsevier B.V.


Clement P.M.,Catholic University of Leuven | Gauler T.,University of Duisburg - Essen | Machiels J.P.,Catholic University of Leuven | Haddad R.I.,Dana-Farber Cancer Institute | And 16 more authors.
Annals of Oncology | Year: 2016

Background: In the phase III LUX-Head & Neck 1 (LHN1) trial, afatinib significantly improved progression-free survival (PFS) versus methotrexate in recurrent and/or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) patients progressing on/after platinum-based therapy. This report evaluates afatinib efficacy and safety in prespecified subgroups of patients aged ≥65 and <65 years. Patients and methods: Patients were randomized (2:1) to 40 mg/day oral afatinib or 40 mg/m2/week intravenous methotrexate. PFS was the primary end point; overall survival (OS) was the key secondary end point. Other end points included: Objective response rate (ORR), patient-reported outcomes, tumor shrinkage, and safety. Disease control rate (DCR) was also assessed. Results: Of 483 randomized patients, 27% (83 afatinib; 45 methotrexate) were aged ≥65 years (older) and 73% (239 afatinib; 116 methotrexate) <65 years (younger) at study entry. Similar PFS benefit with afatinib versus methotrexate was observed in older {median 2.8 versus 2.3 months, hazard ratio (HR) = 0.68 [95% confidence interval (CI) 0.45-1.03], P = 0.061} and younger patients [2.6 versus 1.6 months, HR = 0.79 (0.62-1.01), P = 0.052]. In older and younger patients, the median OS with afatinib versus methotrexate was 7.3 versus 6.4 months [HR = 0.84 (0.54-1.31)] and 6.7 versus 6.2 months [HR = 0.98 (0.76-1.28)]. ORRs with afatinib versus methotrexate were 10.8% versus 6.7% and 10.0% versus 5.2%; DCRs were 53.0% versus 37.8% and 47.7% versus 38.8% in older and younger patients, respectively. In both subgroups, the most frequent treatment-related adverse events were rash/acne (73%-77%) and diarrhea (70%-80%) with afatinib, and stomatitis (43%) and fatigue (31%-34%) with methotrexate. Fewer treatment-related discontinuations were observed with afatinib (each subgroup 7% versus 16%). A trend toward improved time to deterioration of global health status, pain, and swallowing with afatinib was observed in both subgroups. Conclusions: Advancing age (≥65 years) did not adversely affect clinical outcomes or safety with afatinib versus methotrexate in second-line R/M HNSCC patients. Clinical trial registration: NCT01345682 (ClinicalTrials.gov). © The Author 2016. Published by Oxford University Press on behalf of the European Society for Medical Oncology.


PubMed | Charite Comprehensive Cancer Center, University of Barcelona, University of Lyon, Dana-Farber Cancer Institute and 14 more.
Type: Journal Article | Journal: Annals of oncology : official journal of the European Society for Medical Oncology | Year: 2016

In the phase III LUX-Head & Neck 1 (LHN1) trial, afatinib significantly improved progression-free survival (PFS) versus methotrexate in recurrent and/or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) patients progressing on/after platinum-based therapy. This report evaluates afatinib efficacy and safety in prespecified subgroups of patients aged 65 and <65 years.Patients were randomized (2:1) to 40 mg/day oral afatinib or 40 mg/m(2)/week intravenous methotrexate. PFS was the primary end point; overall survival (OS) was the key secondary end point. Other end points included: objective response rate (ORR), patient-reported outcomes, tumor shrinkage, and safety. Disease control rate (DCR) was also assessed.Of 483 randomized patients, 27% (83 afatinib; 45 methotrexate) were aged 65 years (older) and 73% (239 afatinib; 116 methotrexate) <65 years (younger) at study entry. Similar PFS benefit with afatinib versus methotrexate was observed in older {median 2.8 versus 2.3 months, hazard ratio (HR) = 0.68 [95% confidence interval (CI) 0.45-1.03], P = 0.061} and younger patients [2.6 versus 1.6 months, HR = 0.79 (0.62-1.01), P = 0.052]. In older and younger patients, the median OS with afatinib versus methotrexate was 7.3 versus 6.4 months [HR = 0.84 (0.54-1.31)] and 6.7 versus 6.2 months [HR = 0.98 (0.76-1.28)]. ORRs with afatinib versus methotrexate were 10.8% versus 6.7% and 10.0% versus 5.2%; DCRs were 53.0% versus 37.8% and 47.7% versus 38.8% in older and younger patients, respectively. In both subgroups, the most frequent treatment-related adverse events were rash/acne (73%-77%) and diarrhea (70%-80%) with afatinib, and stomatitis (43%) and fatigue (31%-34%) with methotrexate. Fewer treatment-related discontinuations were observed with afatinib (each subgroup 7% versus 16%). A trend toward improved time to deterioration of global health status, pain, and swallowing with afatinib was observed in both subgroups.Advancing age (65 years) did not adversely affect clinical outcomes or safety with afatinib versus methotrexate in second-line R/M HNSCC patients.NCT01345682 (ClinicalTrials.gov).


Perri F.,National Tumor Institute of Naples | Muto P.,National Tumor Institute of Naples | Aversa C.,National Tumor Institute of Naples | Daponte A.,National Tumor Institute of Naples | And 3 more authors.
Anti-Cancer Agents in Medicinal Chemistry | Year: 2013

Multidisciplinary team (MDT) is of paramount importance in the approach to patients with head and neck cancer. Its aim is to provide the best diagnostic work-up, tumor staging, and treatment. Furthermore, the prognosis of patients who are managed by MDT is usually better. MDT has a great value in all presentation settings. The role of the pathologist in the team is of utmost importance, in particular with regards to information provided on Human Papilloma Virus (HPV) status, which has a well acknowledged independent prognostic value mainly in oropharyngeal carcinoma. In early stage disease, namely in T1-2 N0 M0 patients, the meetings within the MDT mainly involve surgeons and radiation therapists. Surgery represents the mainstay of treatment, while radiation therapy is a suitable alternative, in particular in patients with advanced age, poor performance status and comorbidities. In locally advanced disease, surgeons, medical oncologists and radiotherapists are the key people, since different approaches have been carried out. In operable patients, adjuvant chemoradiation is indicated when resection margins are involved or close, or in presence of extracapsular nodal spread. Concurrent chemoradiotherapy, preceeded or not by induction chemotherapy, is the favourite approach in this setting when surgery is strictly not indicated. In recurrent/metastatic disease chemotherapy and best supportive care are the main options, although local treatments, such as reirradiation and salvage surgery, are also worth considering. The standard chemotherapy treatment has finally evolved after about 30 years, and strong efforts are being pursued to further improve the outcome, mainly with the addition of new drugs. © 2013 Bentham Science Publishers.


Perri F.,National Tumor Institute of Naples | Ionna F.,National Tumor Institute of Naples | Muto P.,National Tumor Institute of Naples | Buonerba C.,University of Naples Federico II | And 8 more authors.
Anticancer Research | Year: 2013

Background: Cervical metastases from unknown primary tumors are rare and no clear therapeutic options are available. This retrospective analysis aimed to evaluate toxicity and activity of a sequential chemoradiation regimen consisting of induction chemotherapy followed by extendedfield radiotherapy in patients with cervical metastases from unknown primary tumors. Patients and Methods: Patients with cytological or histological diagnosis of latero-cervical lymph-node metastasis from carcinoma with unknown origin treated with sequential chemotherapy (3 cycles of docetaxel and cisplatin, each administered as intravenous infusion at the dose of 75 mg/m2 on day 1, every 21 days) and radiotherapy (cumulative dose of 70 Gy) were included in this study. The radiological response was assessed by central review according to the revised RECIST criteria. Results: Fifteen patients received three cycles of induction chemotherapy with the combination of docetaxel and cisplatin. Patients were subsequently treated with extendedfield radiotherapy. Three complete responses were observed after induction chemotherapy and 13 after the chemoradiation treatment. The overall response rate after chemoradiation, was 93.3% (14 of 15 evaluable patients). One year disease-free-survival was 83.3% (10 of 12 evaluable patients). Treatment was well-tolerated; two cases of grade 4 neutropenia, two of grade 3 mucositis and eight of grade 2 nausea were the worst, most clinically-relevant sideeffects. Conclusion: Induction chemotherapy followed by extended-field radiotherapy showed good activity and manageable toxicity in patients with cervical metastases from unknown primary tumors.


Perri F.,National Tumor Institute of Naples | Muto P.,National Tumor Institute of Naples | Argenone A.,National Tumor Institute of Naples | Ionna F.,National Tumor Institute of Naples | And 5 more authors.
Oncology (Switzerland) | Year: 2013

Objectives: To replace 5-fluorouracil with capecitabine within a trial of induction chemotherapy followed by cetuximab plus radiotherapy (RT) in patients with locally advanced (LA) squamous cell carcinoma of the head and neck (SCCHN). Also, to replace cisplatin with cetuximab after induction chemotherapy. Methods: Docetaxel and cisplatin were given at 75 mg/m2, while capecitabine was initially given at 500 mg/m2 twice a day and subsequently escalated. The maximum tolerated dose was used for the phase II study. Results: Seven patients were enrolled. At dose level 1, two dose-limiting toxicities were observed in the first 4 patients (grade 4 neutropenia and grade 3 diarrhea). In both patients, capecitabine was withdrawn and toxicities resolved. Dose escalation was halted and a lower capecitabine dose (750 mg/m2 daily) was selected. Two complete responses and five partial responses were observed after induction chemotherapy. Four patients were evaluable for response after cetuximab-RT (3 complete response and 1 partial response). Conclusion: Combined chemoradiotherapy is still the gold standard in LA SCCHN and no studies currently support the use of early induction chemotherapy. Our study did not contribute toward addressing this issue since it was discontinued early because of toxicity. Copyright © 2013 S. Karger AG, Basel.


PubMed | National Tumor Institute of Naples
Type: Journal Article | Journal: World journal of clinical cases | Year: 2014

Nasopharyngeal carcinoma is rare in western countries, accounting for less than 1% of all malignancies. Despite prognosis is satisfactory for newly diagnosed, non-metastatic disease, management of recurrent disease is challenging, with a survival expectancy of approximately 6 mo with the use of chemotherapy as the sole salvage treatment. We report a case of recurrent nasopharyngeal carcinoma treated with a combination of chemotherapy, radiotherapy and surgery in the context of a multidisciplinary approach. A durable complete response was achieved.


PubMed | National Tumor Institute of Naples
Type: Journal Article | Journal: Head & neck | Year: 2015

Head and neck squamous cell carcinoma (HNSCC) is strongly associated with alcohol and tobacco consumption. Lately, the incidence of human papillomavirus (HPV)-related tumors has shown a significant increase, and HPV-related tumors show distinctive features if compared with the HPV-negative counterpart. Locally advanced HNSCC can be treated with concomitant chemoradiotherapy, but early recurrences sometimes occur. Relapses are often related to an intrinsic radioresistance of the tumors. Alterations in intracellular pathways, primarily involved in cell proliferation, apoptosis, and DNA repair, can lead to radioresistance. Preclinical and clinical evidence highlighted that 3 main pathways, including the epidermal growth factor receptor (EGFR), the phosphotidylinositol-3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR), and the p53 signaling cascades, play a crucial role in radioresistance development. A future approach may consist in the association of radiotherapy (RT) and selective inhibition of the key pathways involved in radioresistance. Phase I, II, and III clinical trials are currently testing these novel treatment strategies.


To replace 5-fluorouracil with capecitabine within a trial of induction chemotherapy followed by cetuximab plus radiotherapy (RT) in patients with locally advanced (LA) squamous cell carcinoma of the head and neck (SCCHN). Also, to replace cisplatin with cetuximab after induction chemotherapy.Docetaxel and cisplatin were given at 75 mg/m(2), while capecitabine was initially given at 500 mg/m(2) twice a day and subsequently escalated. The maximum tolerated dose was used for the phase II study.Seven patients were enrolled. At dose level 1, two dose-limiting toxicities were observed in the first 4 patients (grade 4 neutropenia and grade 3 diarrhea). In both patients, capecitabine was withdrawn and toxicities resolved. Dose escalation was halted and a lower capecitabine dose (750 mg/m(2) daily) was selected. Two complete responses and five partial responses were observed after induction chemotherapy. Four patients were evaluable for response after cetuximab-RT (3 complete response and 1 partial response).Combined chemoradiotherapy is still the gold standard in LA SCCHN and no studies currently support the use of early induction chemotherapy. Our study did not contribute toward addressing this issue since it was discontinued early because of toxicity.

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