Publications by authors named "Raffaele Addeo"

78 Publications

Sarcomatoid larynx carcinoma differential clinical evolution, on field statistical considerations.

Am J Otolaryngol 2021 May-Jun;42(3):102934. Epub 2021 Jan 27.

Department of Otolaryngology, Pellegrini Hospital, ASL Napoli 1 Centro, Naples, Italy.

Spindle cell larynx carcinoma (SpCC) represents around 3% of laryngeal cancers. It is originated by a single cancer stem cell undergoing epithelial to mesenchymal transition. This explains the aggressiveness, the peculiar resistance to conventional therapy and the frequent relapses. We focused on this particular cancer subset characteristics in patients, in early and advanced stages primarily aiming to define and highlight the differences with Laryngeal Squamous Cell Carcinoma (LSCC) focusing on clinical features, treatments, follow-up and survival in a patient's cohort composed by comparable cases from two subgroups.
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http://dx.doi.org/10.1016/j.amjoto.2021.102934DOI Listing
January 2021

TAS-102 in metastatic colorectal cancer (mCRC): efficacy, tolerability, and quality of life in heavily pretreated elderly patients: a real-life study.

Drugs Context 2020 18;9. Epub 2020 Sep 18.

Department of Surgical, Oncological and Oral Sciences, Section of General and Emergency Surgery, University of Palermo, Palermo, Italy.

Background: TAS-102 is an oral monotherapy, combining trifluridine and tipiracil hydrochloride, indicated for the treatment of pretreated metastatic colorectal cancer (mCRC). The aim of this real-life study is to evaluate the efficacy and safety of TAS-102 in heavily pretreated elderly patients with mCRC whose disease has progressed with standard therapies.

Methods: In this retrospective observational study, we enrolled 50 elderly patients >70 years of age (median age 78 years) with a diagnosis of mCRC who were previously treated or were not considered candidates for treatment with other available therapies. Patients aged >70 years with advanced colorectal cancer and with an ECOG performance status of grade 0 (=18) or grade 1 (=32) were included. Overall survival and progression-free survival were the primary endpoints, whereas objective response rate, tolerability, and quality of life were the secondary endpoints.

Results: Treatment with TAS-102 appeared to be well tolerated and side effects were generally mild, achieving disease control and a benefit on quality of life. The median overall survival was 6.7 (95% CI 5.7-11.3) and the median progression-free survival was 2.1 months (95% CI 1.2-3.2), estimated using the Kaplan-Meier method.

Conclusion: TAS-102 represents a manageable and effective therapeutic opportunity and appeared to be well tolerated with generally mild side effects in elderly patients with mCRC who were heavily pretreated with standard therapies.
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http://dx.doi.org/10.7573/dic.2020-6-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7505119PMC
September 2020

Comparative Study of NGS Platform Ion Torrent Personal Genome Machine and Therascreen Rotor-Gene Q for the Detection of Somatic Variants in Cancer.

High Throughput 2020 Feb 11;9(1). Epub 2020 Feb 11.

Department of Precision Medicine, University of Campania "L. Vanvitelli", 80138 Naples, Italy.

Molecular profiling of a tumor allows the opportunity to design specific therapies which are able to interact only with cancer cells characterized by the accumulation of several genomic aberrations. This study investigates the usefulness of next-generation sequencing (NGS) and mutation-specific analysis methods for the detection of target genes for current therapies in non-small-cell lung cancer (NSCLC), metastatic colorectal cancer (mCRC), and melanoma patients. We focused our attention on EGFR, BRAF, KRAS, and BRAF genes for NSCLC, melanoma, and mCRC samples, respectively. Our study demonstrated that in about 2% of analyzed cases, the two techniques did not show the same or overlapping results. Two patients affected by mCRC resulted in wild-type (WT) for BRAF and two cases with NSCLC were WT for EGFR according to PGM analysis. In contrast, these samples were mutated for the evaluated genes using the therascreen test on Rotor-Gene Q. In conclusion, our experience suggests that it would be appropriate to confirm the WT status of the genes of interest with a more sensitive analysis method to avoid the presence of a small neoplastic clone and drive the clinician to correct patient monitoring.
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http://dx.doi.org/10.3390/ht9010004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7151067PMC
February 2020

GOLFIG Chemo-Immunotherapy in Metastatic Colorectal Cancer Patients. A Critical Review on a Long-Lasting Follow-Up.

Front Oncol 2019 8;9:1102. Epub 2019 Nov 8.

Medical Oncology Unit, Department of Experimental and Clinical Medicine, Magna Graecia University, Catanzaro, Italy.

GOLFIG is a chemo-immunotherapy regimen established in preclinical models that combines gemcitabine + FOLFOX (fluoropyrimidine backbone coupled to oxaliplatin) poly-chemotherapy with low-dose s. c. recombinant interleukin-2 (rIL-2) and granulocyte-macrophage colony stimulating factor (GM-CSF). Promising antitumor effects in metastatic colorectal cancer (mCRC) patients were obtained in previous phase II and III trials. Here we report the results of 15 years of follow-up. This is a multi-institutional retrospective analysis including 179 mCRC patients receiving GOLFIG regimen between June 2002 and June 2018. Sixty-two of them received the treatment as frontline (enrolled in the GOLFIG-2 phase III trial) and 117 as second/third line (49 enrolled in the GOLFIG-1 phase II trial and 68 as compassionate use). One hundred twelve patients showed a primary left side and 67 a primary right side; K/N-ras mutational status was available in 74 cases, and an activating mutation was detected in 33. Kaplan-Meier and Cox regression analyses were carried out to relate PFS and OS with different parameters. Overall, we recorded a mean PFS and OS of 15.28 (95% CI: 10.36-20.20) and 24.6 (95% CI: 19.07-30.14) months, respectively, with 14 patients surviving free of progression for 10 years. This regimen, in our updated survey of the GOLFIG-2 trial, confirmed superiority over FOLFOX in terms of PFS (hazard ratio (HR) = 0.58, = 0.006) with a trend to a longer OS (HR = 0.69, = 0.06) in the first line. Our analysis also confirmed significant antitumor activity in pre-treated patients, reporting a mean PFS and OS of 12.55 (95% CI: 7.19-17.9) and 20.28 (95% CI: 14.4-26.13) months, respectively. Immune-related adverse events (irAEs) were recorded in 24% of the cases and were related to a longer survival (HR = 0.36; = 0.0001). Finally, patients' outcome was not correlated to sex, sidedness, and MT-K/N-ras. The GOLFIG regimen is a reliable underestimated therapeutic option in pre-treated mCRC patients and offers a strong rationale to design further trials.
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http://dx.doi.org/10.3389/fonc.2019.01102DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6857002PMC
November 2019

Clinical and pathological factors predictive of response to neoadjuvant chemotherapy in breast cancer: A single center experience.

Oncol Lett 2019 Oct 7;18(4):3873-3879. Epub 2019 Aug 7.

Division of Medical Oncology, 'San Giovanni Di Dio Hospital', ASL NA2NORD, I-80027 Naples, Italy.

Neoadjuvant chemotherapy (NAC) of breast cancer (BC) improves outcomes, especially in patients with locally advanced and inflammatory cancer. Further insight into clinic-pathological factors influencing outcomes is essential to define the optimal therapeutic strategy for each category of patients and to predict the response to the treatment. In total, 117 patients with BC were treated with NAC with or without trastuzumab between 2010 and 2015. The histologic response to NAC was defined as a pathological complete response (pCR) when there was no evidence of residual invasive tumor in the breast or axillary lymph nodes. Relapse-free survival (RFS) was estimated using the Kaplan-Meier method and compared using log rank analysis. P-value <0.05 was considered statistically significant. The median age of the 117 patients enrolled in the present study was 52 years (age range, 35-85 years). The overall response rate (complete and partial responses) assessed by radiological and pathological evaluation were 76 and 72%, respectively. pCR was achieved in 35 out of 117 patients (~30%). In total, 6 patients (5%) developed progressive disease during chemotherapy. The RFS was 85 months (SE=3; 95% CI 79-91). The median was not reached and the mean follow-up time was 55 months (median 52 months; range 11-100 months). In this time, 20 patients (17%) experienced tumor recurrence. From the univariate analysis, the pathological response was significantly associated with receptor-based subtype, menopausal status and T-stage. From the multivariate analysis by using linear multiple regression and including receptor- menopausal status and T-stage, the model was not significant (P=0.062). However, by using the multiple logistic regression, and including age, pCR was significantly associated with ER+ HER2neg (P=0.006), T2 (P=0.043) and T3 (P=0.018). T-stage, menopausal status and receptor status are significantly associated with the pathological response in patients with inoperable BC treated with NAC.
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http://dx.doi.org/10.3892/ol.2019.10729DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6732960PMC
October 2019

Italian survey on cetuximab-based therapy of elderly patients with metastatic colorectal cancer.

Cancer Chemother Pharmacol 2019 Nov 6;84(5):1089-1096. Epub 2019 Sep 6.

Fullcro S.r.l, Rome, Italy.

Purpose: There is no consensus on the use of cetuximab in elderly patients with metastatic colorectal cancer. To this end, a survey was carried in 17 Italian oncology centers.

Methods: The centers answered a 29-item questionnaire structured as follows: (i) demographic characteristics; (ii) medical history; (iii) assessment of RAS/BRAF mutations and DPD/UGT polymorphism before treatment; (iv) treatment schemes and side effects; (v) geriatric assessment and customization of treatment.

Results: One-third of patients are over 80 years old. The RAS/BRAF mutational status is not primarily evaluated by 17.6% of the centers, while DPD and UGT polymorphism is not evaluated by 82.4% and 76.5% of the centers. The most common therapeutic scheme is cetuximab/FOLFIRI and diarrhea is the main cause of suspension/reduction of treatment. The 70% of centers use systemic tetracyclines for skin toxicity. The 23.5% of the centers do not carry out any geriatric evaluation before the start of the therapy and those who perform it prefer the G8 (70.6%) and VES-13 (29.4%) scales.

Conclusions: Greater efforts should be made to improve the evaluation of the patient both about mutational and genetic procedures with geriatric evaluation. As for cetuximab in elderly patients, randomized studies are needed to provide guidance to physicians.
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http://dx.doi.org/10.1007/s00280-019-03943-xDOI Listing
November 2019

Biweekly fotemustine schedule for recurrent glioblastoma in the elderly: activity and toxicity assessment of a multicenter study.

CNS Oncol 2019 06 10;8(2):CNS32. Epub 2019 Jul 10.

Neuro Oncology Unit, Fondazione IRCSS 'Carlo Besta', Milano, Italy.

To assess the efficacy and safety of alternative fotemustine administration schedule in elderly patients with recurrent glioblastoma. Patients aged >65 years with recurrent glioblastoma received fotemustine (80 mg/m; days 1, 15, 30, 45 and 60, and subsequently every 4 weeks). Primary end point was progression-free survival (PFS) rate at 6 months. Main secondary end point was safety. 58 patients were enrolled at two centers. PFS at 6 months was 47% (27 patients) and overall response rate was 29%. Median PFS and survival were 6 and 7 months, respectively, and longer in responders versus nonresponders. No grade 3-4 hematological toxicities occurred. The alternative fotemustine administration schedule was an effective and safe treatment for recurrent glioblastoma in elderly patients.
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http://dx.doi.org/10.2217/cns-2019-0004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6713024PMC
June 2019

Efficacy and Safety of Cetuximab plus Radiotherapy in Cisplatin-Unfit Elderly Patients with Advanced Squamous Cell Head and Neck Carcinoma: A Retrospective Study.

Chemotherapy 2019 26;64(1):48-56. Epub 2019 Jun 26.

Department of Translational Medical Sciences, School of Medicine, University of Campania "L. Vanvitelli", Naples, Italy.

Introduction: Concurrent platinum-based chemoradiation currently represents the standard treatment for advanced head and neck cancer (HNC), but it induces a significant toxicity, in particular among elderly patients. Elderly and unfit patients have been underrepresented in clinical trials and there is a need for tailored guidelines.

Methods: A retrospective review of clinical data of HNC patients treated at the Operative Oncology Unit of the San Giovanni di Dio Hospital in Frattamaggiore (Naples, Italy) was performed. At study entry, a comprehensive assessment including absolute contraindications for cisplatin use, as well as comorbidities, socioeconomic status, BMI, and weight loss, was performed. The treatment included high-dose radiotherapy plus weekly cetuximab (initially at a dose of 400 mg/m2of body surface area and thereafter at 250 mg weekly during the whole radiotherapy). The aim of this study was to evaluate the activity and toxicity of this schedule in a series of patients aged older than 69 years.

Results: Between May 30, 2013, and March 30, 2015, sixty-four patients (age range, 69-87 years; median age, 73.7 years; male/female ratio, 46/18) were treated. The overall response rate was 67% in this series of patients. The disease control rate was 76%. Disease progression was recorded in 25% of the patients. The median duration of loco-regional control was 17 months (range, 15.8-17.7 months). PFS was 14.8 months (range, 13.9-15.5 months). The overall survival was 34 months, with a median follow-up of 41.0 months (range, 31.1-36.8 months). The main grade 3/4 adverse events were acne rash in 52% and radiation dermatitis in 32% of the cases.

Conclusion: Cetuximab plus radiotherapy appears to be feasible and active in elderly patients unsuitable for cisplatin treatment. The treatment was supported by a favorable toxicity profile.
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http://dx.doi.org/10.1159/000500714DOI Listing
July 2019

CheckMate 141 trial: all that glitters is not gold.

Expert Opin Biol Ther 2019 03 21;19(3):169-171. Epub 2019 Jan 21.

e Department of Precision Medicine , University of Campania "L. Vanvitelli" , Naples and Biogem , Avellino Italy.

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http://dx.doi.org/10.1080/14712598.2019.1570498DOI Listing
March 2019

Maintenance Therapy with Biweekly Cetuximab: Optimizing Schedule Can Preserve Activity and Improves Compliance in Advanced Head and Neck Cancer.

Oncology 2018 5;95(6):353-359. Epub 2018 Sep 5.

U.O.C. Oncologia, "S. Giovanni di Dio" Hospital, ASLNA2NORD Frattamaggiore, Frattamaggiore, Italy.

Objectives: This study evaluates maintenance cetuximab administered every 2 weeks (q2w) after chemotherapy plus cetuximab as first-line treatment in a series of patients with head and neck squamous cell cancer and compares the results with those obtained in a historical control group of patients receiving weekly cetuximab.

Methods: After chemotherapy plus cetuximab as first-line treatment, in Group A, 36 patients enrolled from October 2016 to November 2017, received biweekly cetuximab, administered at 500 mg/m2. Group B was a control group of patients treated at our institution from August 2015 to September 2016 and received weekly infusion of cetuximab at 250 mg/m2.

Results: Confirmed overall response rates were, respectively, 19% for Group A and 17% for Group B according to intention-to-treat analysis. During the maintenance treatment, median progression-free survival (PFS) and median overall survival (OS) were similar for both groups (PFS, 4.8 and 4.4 months; OS, 9.0 and 7.9 months; in Groups A and B, respectively). The most common adverse events among treated subjects included fatigue, rash, and hypomagnesemia.

Conclusion: Maintenance therapy with simplified biweekly cetuximab is a convenient, effective, and well-tolerated regimen in patients with recurrent and/or metastatic head and neck squamous cell carcinoma.
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http://dx.doi.org/10.1159/000492153DOI Listing
December 2018

Exemestane and Everolimus combination treatment of hormone receptor positive, HER2 negative metastatic breast cancer: A retrospective study of 9 cancer centers in the Campania Region (Southern Italy) focused on activity, efficacy and safety.

Mol Clin Oncol 2018 Sep 16;9(3):255-263. Epub 2018 Jul 16.

Division of Medical Oncology, Department of Precision Medicine, University of Campania 'Luigi Vanvitelli', I-80131 Naples, Italy.

Exemestane (Exe) in combination with Everolimus (Eve) represents an important treatment option for patients diagnosed with hormone receptor positive (HR+), human epidermal growth factor receptor 2 negative (HER2-) metastatic breast cancer (MBC), which was previously treated with non-steroidal aromatase inhibitors (NSAI). Data from unselected populations may be useful for defining the optimal therapeutic algorithm within a clinical setting. Data from 264 HR+, HER2-MBC patients who received Exe-Eve treatment in combination, following the failure of NSAIs was retrospectively analyzed. Different lines of endocrine treatment (ET) were investigated to evaluate the efficacy and toxicity of the treatment within the 'everyday clinical practice' population. The disease control rate (DCR) was 73.1%, with no statistically significant difference among the different settings. At a median follow-up of 42 months, the median progression free survival (PFS) was 11.6, 9.7 and 7.5 months for patients treated with Exe-Eve as first, second or third line therapy, respectively. There was a statistically significant correlation with younger age, no previous adjuvant chemotherapy (CT), no previous adjuvant endocrine therapy (ET), HT duration ≥36 months, involvement of liver and/or lung, no prior CT for metastatic disease and PS=0 at the start of treatment. The median overall survival (OS) was 33.0 months; at a median follow-up of 67 months, the median OS was 43.1, 31.7 and 27.9 months in patients treated with Exe-Eve in first, second or third line therapy, respectively. On multivariate analysis, diabetes and previous CT for metastatic disease were revealed to correlate with a worse outcome. Conversely, the presence of mucositis was significantly associated with long-term survival. Overall, Exe-Eve was typically well tolerated and the majority toxicities were G1 or 2, while treatment discontinuation due to unacceptable toxicity was only required in 5.7% of patients. Despite the limitations due to the observational nature of this study, the findings suggest that treatment with Exe-Eve is an active and safe therapeutic option for endocrine-sensitive MBC patients in a real-world clinical setting, regardless of treatment lines.
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http://dx.doi.org/10.3892/mco.2018.1672DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6109668PMC
September 2018

Adenoid cystic carcinoma of the larynx in a 70-year-old patient: A case report.

Oncol Lett 2018 Sep 18;16(3):2783-2788. Epub 2018 Jun 18.

Department of Neuroscience, Reproductive and Odontostomatological Science, Ear Nose and Throat Unit, University of Naples 'Federico II', I-80131 Naples, Italy.

Adenoid cystic carcinoma (ACC) is a relatively rare tumor that accounts for <1% of all head and neck malignancies. Laryngeal localization of ACC, which is most commonly hypoglottic, is relatively rare, occurring in 0.07-0.25% of all laryngeal tumors. ACC is characterized as a slow-growing tumor with a high recurrence rate, which often causes dyspnea and hoarseness. ACC exhibits a propensity for perineural invasion and thus, patients may experience pain as a late symptom of the disease. Distant metastasis occurs in 35-50% of cases and the lungs are the most common site of metastasis. Tumors are usually diagnosed by physical examination with fiberoscopy and computed tomography of the neck and chest, due to the high rate of lung metastases. The standard therapy for ACC is surgery followed by radiotherapy. In this study, a 70-year-old patient presented with laryngeal ACC, who underwent total laryngectomy with bilateral neck dissection and adjuvant radiotherapy, is presented. Follow-up examination performed 2 years after surgery revealed no evidence of locoregional recurrence or distant metastases. Previously published literature regarding ACC of the larynx was also reviewed.
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http://dx.doi.org/10.3892/ol.2018.8976DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6096139PMC
September 2018

Metastatic HPV-related oropharyngeal carcinoma cured with chemoradiotherapy: importance of pretherapy biomolecular assessment.

Clin Case Rep 2018 01 24;6(1):56-62. Epub 2017 Nov 24.

Institute of Biostructure and Bioimaging National Council of Research Naples Italy.

Pretherapy assessment has a crucial role in the management of advanced oropharyngeal carcinoma. The case report represents an example of how translational research may help to optimize the therapeutic options and to choose a well-shaped therapy adapted to the tumor and the patient.
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http://dx.doi.org/10.1002/ccr3.1107DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5771910PMC
January 2018

Locally advanced paranasal sinus carcinoma: A study of 30 patients.

Oncol Lett 2017 Mar 11;13(3):1338-1342. Epub 2017 Jan 11.

Institute of Biostructure and Bioimaging, National Council of Research, I-80128 Naples, Italy.

Sinonasal carcinomas (SNcs) are rare neoplasms arising from the paranasal sinuses and nasal cavity. Although these tumours have a heterogeneous histology, they are commonly diagnosed as a locally advanced disease and are associated with a poor prognosis. The present retrospective study reviewed 30 patients with locally advanced SNc, who were treated with surgery followed by chemoradiotherapy or radiotherapy, or radiotherapy with or without concomitant chemotherapy between January 1999 and January 2013 at the Department of Radiation Therapy, University of Naples 'Federico II' (Naples, Italy). A total of 19 patients were treated with upfront surgery followed by adjuvant radio- or chemoradiotherapy (group A), while the remaining 11 patients received exclusive radiotherapy with or without concomitant chemotherapy (group B). Concurrent cisplatin-based chemotherapy (100 mg/m, days 1, 22 and 43 for 3 cycles) was administered to 34% of patients in group A and 55% of patients in group B. At a median follow-up of 31 months, 33.3% of patients were alive. Cause-specific survival (CSS) and progression-free survival (PFS) times were 32 and 12 months, respectively. No difference in CSS rate was observed between the two treatment groups. Univariate analysis determined that disease stage was the only factor that significantly affected CSS (P=0.002) and PFS (P=0.0001) rates. Acute and chronic toxicities were mild, with only 23.3% of patients reporting G1-2 side effects and no treatment-related blindness. The present study reported moderate activity and efficacy of surgery followed by adjuvant radio- or chemoradiotherapy, and exclusive radiotherapy with or without chemotherapy in this poor prognosis category of patients.
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http://dx.doi.org/10.3892/ol.2017.5598DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5403341PMC
March 2017

A new frontier for targeted therapy in NSCLC: clinical efficacy of pembrolizumab in the inhibition of programmed cell death 1 (PD-1).

Authors:
Raffaele Addeo

Expert Rev Anticancer Ther 2017 03 8;17(3):199-201. Epub 2017 Feb 8.

a U.O.C. Oncologia , ASL NA2 NORD , Frattamaggiore , Italy.

Non-small-cell lung cancer (NSCLC) is the main pathological type among lung cancers, and it is often diagnosed at an advanced stage of the disease when it is no longer amenable to curative treatments. During recent decades, the survival rate for lung cancer patients has improved significantly in only those whose tumours harbour a driver mutation. Immune checkpoint inhibition is a promising therapeutic strategy for lung cancer. The Keynote 024 is randomized, open-label, international, phase III study to evaluate the efficacy of pembrolizumab, an antibody directed to programmed death 1 (PD-1), an immune checkpoint inhibitor, compared with platinum-based chemotherapy in patients with previously untreated advanced NSCLC and PD-L1 expression in at least 50% of the tumour cells. Pembrolizumab treatment achieved statistically significant clinical benefits in terms of progression free survival, overall survival and objective responses. The high quality of data and the novelty of the information obtained created the conditions for a new standard of care driven by the expression of PD-L1.
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http://dx.doi.org/10.1080/14737140.2017.1286986DOI Listing
March 2017

Adherence and safety of regorafenib for patients with metastatic colorectal cancer: observational real-life study.

Future Oncol 2017 Feb 26;13(5):415-423. Epub 2016 Oct 26.

U.O. Oncologia, ASL NA2 NORD, Frattamaggiore, Italy.

Aim: In this prospective multicenter real-life observational cohort study, we investigated the acceptance, adherence and safety of regorafenib, in the treatment of metastatic colorectal cancer patients.

Patients & Methods: A total of 136 patients were recruited at six oncological hospital sites in southern Italy. The adherence to the treatment was measured with patient-completed medication diaries, physician interviews and pill counts.

Results: We found a statistically significant improvement of therapy adhesion by the acceptance questionnaire. The Eastern Cooperative Oncology Group performance status, the level of acceptance, the educational level and the concomitant usage of oral medications influenced the adherence to the treatment.

Conclusion: Patients' level of education, concomitant other oral medications and patients' general clinical condition may influence the adherence to regorafenib.
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http://dx.doi.org/10.2217/fon-2016-0421DOI Listing
February 2017

The strange connection between epidermal growth factor receptor tyrosine kinase inhibitors and dapsone: from rash mitigation to the increase in anti-tumor activity.

Curr Med Res Opin 2016 11 11;32(11):1839-1848. Epub 2016 Aug 11.

a Department of Biochemistry, Biophysics and General Pathology , Second University of Naples , Naples , Italy.

The presence of an aberrantly activated epidermal growth factor receptor (EGFR) in many epithelial tumors, due to its overexpression, activating mutations, gene amplification and/or overexpression of receptor ligands, represent the fundamental basis underlying the use of EGFR tyrosine kinase inhibitors (EGFR-TKIs). Drugs inhibiting the EGFR have different mechanisms of action; while erlotinib and gefitinib inhibit the intracellular tyrosine kinase, monoclonal antibodies like cetuximab and panitumumab bind the extracellular domain of the EGFR both activating immunomediated anti-cancer effect and inhibiting receptor function. On the other hand, interleukin-8 has tumor promoting as well as neo-angiogenesis enhancing effects and several attempts have been made to inhibit its activity. One of these is based on the use of the old sulfone antibiotic dapsone that has demonstrated several interleukin-8 system inhibiting actions. Erlotinib typically gives a rash that has recently been proven to come out via up-regulated keratinocyte interleukin-8 synthesis with histological features reminiscent of typical neutrophilic dermatoses. In this review, we report experimental evidence that shows the use of dapsone to improve quality of life in erlotinib-treated patients by ameliorating rash as well as short-circuiting a growth-enhancing aspect of erlotinib based on increased interleukin-8 secretion.
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http://dx.doi.org/10.1080/03007995.2016.1211522DOI Listing
November 2016

Hepatocellular carcinoma: Will novel targeted drugs really impact the next future?

World J Gastroenterol 2016 Jul;22(27):6114-26

Liliana Montella, Raffaele Addeo, Salvatore Del Prete, Medical Oncology Unit, "San Giovanni di Dio" Hospital, Frattamaggiore, 80027 Naples, Italy.

Cancer treatment has been revolutionized by the advent of new molecular targeted and immunotherapeutic agents. Identification of the role of tumor angiogenesis changed the understanding of many tumors. After the unsuccessful results with chemotherapy, sorafenib, by interfering with angiogenic pathways, has become pivotal in the treatment of hepatocellular carcinoma. Sorafenib is the only systemic treatment to show a modest but statistically significant survival benefit. All novel drugs and strategies for treatment of advanced hepatocellular carcinoma must be compared with the results obtained with sorafenib, but no new drug or drug combination has yet achieved better results. In our opinion, the efforts to impact the natural history of the disease will be directed not only to drug development but also to understanding the underlying liver disease (usually hepatitis B virus- or hepatitis C virus-related) and to interrupting the progression of cirrhosis. It will be important to define the role and amount of mutations in the complex pathogenesis of hepatocellular carcinoma and to better integrate locoregional and systemic therapies. It will be important also to optimize the therapeutic strategies with existing chemotherapeutic drugs and new targeted agents.
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http://dx.doi.org/10.3748/wjg.v22.i27.6114DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4945973PMC
July 2016

Pembrolizumab: the value of PDL1 biomarker in head and neck cancer.

Expert Opin Biol Ther 2016 09 21;16(9):1075-8. Epub 2016 Jul 21.

c Merck Sharp Dohme , Department of Oncology , Milan , Italy.

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http://dx.doi.org/10.1080/14712598.2016.1211635DOI Listing
September 2016

Concomitant cetuximab and radiation therapy: A possible promising strategy for locally advanced inoperable non-melanoma skin carcinomas.

Mol Clin Oncol 2016 Apr 27;4(4):467-471. Epub 2016 Jan 27.

Oncology Unit, 'San Giovanni di Dio' Hospital, A.S.L. Napoli 2 Nord, I-80027 Frattamaggiore (NA), Italy.

Non-melanoma skin cancers (NMSCs) include a heterogeneous group of malignancies arising from the epidermis, comprising squamous cell carcinoma (SCC), basal cell carcinoma (BCC), Merkel cell carcinoma and more rare entities, including malignant pilomatrixoma and sebaceous gland tumours. The treatment of early disease depends primarily on surgery. In addition, certain patients present with extensive local invasion or metastasis, which renders these tumours surgically unresectable. Improving the outcome of radiotherapy through the use of concurrent systemic therapy has been demonstrated in several locally advanced cancer-treatment paradigms. Recently, agents targeting the human epidermal growth factor receptor (EGFR) have exhibited a consolidated activity in phase II clinical trials and case series reports. Cetuximab is a monoclonal antibody that binds to and completely inhibits the EGFR, which has been revealed to be up-regulated in a variety of SCCs, including NMSCs. The present review aimed to summarize the role of anti-EGFR agents in the predominant types of NMSC, including SCC and BCC, and focuses on the cetuximab-based studies, highlighting the biological rationale of this therapeutic option. In addition, the importance of the association between cetuximab and radiotherapy for locally advanced NMSC is discussed.
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http://dx.doi.org/10.3892/mco.2016.746DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4812109PMC
April 2016

Natural History of Non-Small-Cell Lung Cancer with Bone Metastases.

Sci Rep 2015 Dec 22;5:18670. Epub 2015 Dec 22.

Department of Medical Oncology, Institute for Cancer Research &Treatment (IRCC), Candiolo, Torino, Italy.

We conducted a large, multicenter, retrospective survey aimed to explore the impact of tumor bone involvement in Non-Small Cell Lung Cancer.Data on clinical-pathology, skeletal outcomes and bone-directed therapies for 661 deceased patients with evidence of bone metastasis were collected and statistically analyzed. Bone metastases were evident at diagnosis in 57.5% of patients. In the remaining cases median time to bone metastases appearance was 9 months. Biphosphonates were administered in 59.6% of patients. Skeletal-related events were experienced by 57.7% of patients; the most common was the need for radiotherapy. Median time to first skeletal-related event was 6 months. Median survival after bone metastases diagnosis was 9.5 months and after the first skeletal-related event was 7 months. We created a score based on four factors used to predict the overall survival from the diagnosis of bone metastases: age >65 years, non-adenocarcinoma histology, ECOG Performance Status >2, concomitant presence of visceral metastases at the bone metastases diagnosis. The presence of more than two of these factors is associated with a worse prognosis.This study demonstrates that patients affected by Non-Small Cell Lung Cancer with bone metastases represent a heterogeneous population in terms of risk of skeletal events and survival.
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http://dx.doi.org/10.1038/srep18670DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4687045PMC
December 2015

Metronomic oral vinorelbine in advanced breast cancer and non-small-cell lung cancer: current status and future development.

Future Oncol 2016 Feb 19;12(3):373-87. Epub 2015 Nov 19.

Department of Clinical & Experimental Medicine, Division of Pharmacology, University of Pisa, 56126 Pisa, Italy.

Metronomic chemotherapy (mCT), a frequent administration of low-dose chemotherapy, allows prolonged treatment duration and minimizes the toxicity of standard-dose chemotherapy. mCT has multiple actions against cancer cells including inhibition of angiogenesis and modulation of the immune system. A number of studies lend support to the clinical efficacy of mCT in advanced breast cancer and non-small-cell lung cancer. However, further evidence is necessary to describe the optimal use of mCT and to identify suitable patients. Oral vinorelbine has emerged as a promising metronomic treatment in patients with metastatic breast cancer and non-small-cell lung cancer and is the only orally available microtubule-targeting agent. This paper reviews current evidence on metronomic oral vinorelbine, discusses its management and defines a suitable patient profile on the basis of a workshop of Italian experts.
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http://dx.doi.org/10.2217/fon.15.306DOI Listing
February 2016

MicroRNA-423-5p Promotes Autophagy in Cancer Cells and Is Increased in Serum From Hepatocarcinoma Patients Treated With Sorafenib.

Mol Ther Nucleic Acids 2015 Mar 17;4:e233. Epub 2015 Mar 17.

Department of Biochemistry, Biophysics and General Pathology, Second University of Naples, Naples, Italy.

Hepatocellular carcinoma (HCC) is the third cause of cancer-related deaths worldwide. Sorafenib is the only approved drug for patients with advanced HCC but has shown limited activity. microRNAs (miRs) have been involved in several neoplasms including HCC suggesting their use or targeting as good tools for HCC treatment. The purpose of this study was to identify novel approaches to sensitize HCC cells to sorafenib through miRs. miR-423-5p was validated as positive regulator of autophagy in HCC cell lines by transient transfection of miR and anti-miR molecules. miR-423-5p expression level was evaluated by real-time polymerase chain reaction (PCR) in sera collected from 39 HCC patients before and after treatment with sorafenib. HCC cells were cotreated with sorafenib and miR-423-5p and the effects on cell cycle, apoptosis, and autophagy were evaluated. Secretory miR-423-5p was upregulated both in vitro and in vivo by sorafenib treatment and its increase was correlated with response to therapy since 75% of patients in which an increase of secretory miR423-5p was found were in partial remission or stable disease after 6 moths from the beginning of therapy. HCC cells transfected with miR-423-5p showed an increase of cell percentage in S-phase of cell cycle paralleled by a similar increase of autophagic cells evaluated at both fluorescence activated cell sorter (FACS) and transmission electron microscopy. Our results suggest the miR423-5p can be used as a useful tool to predict response to sorafenib in HCC patients and is involved in autophagy regulation in HCC cells.
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http://dx.doi.org/10.1038/mtna.2015.8DOI Listing
March 2015

The role of immunotherapy in solid tumors: report from the Campania Society of Oncology Immunotherapy (SCITO) meeting, Naples 2014.

J Transl Med 2014 Oct 21;12:291. Epub 2014 Oct 21.

Unit of Oncology, A.O.R.N. dei COLLI "Ospedali Monaldi-Cotugno-CTO", Naples, Italy.

The therapeutic approach to advanced or metastatic solid tumors, either with chemotherapy or targeted therapies, is mainly palliative. Resistance to chemotherapy occurs very frequently and is one of the most important reasons for disease progression. Immunotherapy has the potential to mount an ongoing, dynamic immune response that can kill tumor cells for an extended time after the conventional therapy has been administered. Such a long-lasting response is potentially able to completely eradicate tumor cells, rather than producing only a temporary killing of cells. The most promising immune-based treatments are monoclonal antibodies that act as checkpoint inhibitors (e.g. ipilimumab and nivolumab), adoptive cell therapy (e.g. T-cells expressing chimeric antigen receptors) and vaccines (e.g. sipuleucel-T). Ipilimumab is currently approved for the treatment of metastatic melanoma and sipuleucel-T is approved for advanced prostate cancer. There is great interest in immunotherapy in other solid tumors, potentially used alone or in a multimodal fashion with chemotherapy and/or biological drugs. In this paper, we review recent advances in immuno-oncology in solid malignancies (except melanoma) as were discussed at the inaugural meeting of the Campania Society of Oncology Immunotherapy (SCITO).
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http://dx.doi.org/10.1186/s12967-014-0291-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4209076PMC
October 2014

Pharmacogenetics of methotrexate in pediatric hematological neoplasm treatment: does it need a personalized regimen based on MTHFR polymorphisms?

Expert Rev Hematol 2014 Oct;7(5):517-9

Department of Woman, Children and General and Specialized Surgery, Second University of Naples, Via L. De Crecchio n 2 - 80138 Naples, Italy.

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http://dx.doi.org/10.1586/17474086.2014.960386DOI Listing
October 2014

Natural history of malignant bone disease in hepatocellular carcinoma: final results of a multicenter bone metastasis survey.

PLoS One 2014 29;9(8):e105268. Epub 2014 Aug 29.

Medical Oncology, A.O. "Ospedali Riuniti Marche Nord", Presidio S. Salvatore, Pesaro, Italy.

Background: Bone is an uncommon site of metastasis in patients with advanced hepatocellular carcinoma (HCC). Therefore, there are few studies concerning the natural history of bone metastasis in patients with HCC.

Patients And Methods: Data on clinicopathology, survival, skeletal-related events (SREs), and bone-directed therapies for 211 deceased HCC patients with evidence of bone metastasis were statistically analyzed.

Results: The median age was 70 years; 172 patients were male (81.5%). The median overall survival was 19 months. The median time to the onset of bone metastasis was 13 months (22.2% at HCC diagnosis); 64.9% patients had multiple bone metastases. Spine was the most common site of bone metastasis (59.7%). Most of these lesions were osteolytic (82.4%); 88.5% of them were treated with zoledronic acid. At multivariate analysis, only the Child Score was significantly correlated with a shorter time to diagnosis of bone metastases (p = 0.001, HR = 1.819). The median survival from bone metastasis was 7 months. At multivariate analysis, HCC etiology (p = 0.005), ECOG performance status (p = 0.002) and treatment with bisphosphonate (p = 0.024) were associated with shorter survival after bone disease occurrence. The site of bone metastasis but not the number of bone lesions was associated with the survival from first skeletal related event (SRE) (p = 0.021) and OS (p = 0.001).

Conclusions: This study provides a significant improvement in the understanding the natural history of skeletal disease in HCC patients. An early and appropriate management of these patients is dramatically needed in order to avoid subsequent worsening of their quality of life.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0105268PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4149423PMC
May 2015

Squamous cell carcinoma of the tongue in a female with advanced breast cancer: A case report of an elderly patient presenting with two types of cancer.

Oncol Lett 2014 Jul 28;8(1):235-237. Epub 2014 Apr 28.

Department of Clinical Otology, ENT Clinic, 'Federico II' University, Naples 80131, Italy.

Elderly patients with cancer are frequently undertreated as they are considered to be unfit for treatment due to inaccurate estimations of the operative risk. In the current study, the case of an 81-year-old female smoker with advanced breast cancer is presented. The patient had received numerous cycles of chemo- and hormonal therapy and the cancer only progressed locally. After six years, the patient developed a second type of cancer; a moderately differentiated squamous cell carcinoma of the tongue. The patient refused any local treatment and she received supportive care only. There is currently a lack of data regarding the molecular mechanisms of second primary cancers as well as other delayed outcomes following cancer treatment. Therefore, it is proposed that chemotherapy may promote the presentation of the second cancer as a result of immunosuppression.
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http://dx.doi.org/10.3892/ol.2014.2097DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4063625PMC
July 2014

Erlotinib: early clinical development in brain cancer.

Expert Opin Investig Drugs 2014 Jul 16;23(7):1027-37. Epub 2014 May 16.

ASL NA2 NORD, Oncology Unit , Frattamaggiore , Italy.

Introduction: Glioblastoma (GBM) is the most common brain cancer in adults. It is also, unfortunately, the most aggressive type and the least responsive to therapy. Overexpression of EGFR and/or EGFRvIII is frequently found in GBM and is frequently associated with the more malignant phenotype of the disease and a poor clinical outcome. EGFR-targeted therapy represents a promising anti-GBM therapy. Two EGFR kinase inhibitors, gefitinib and erlotinib have been tested in clinical trials for malignant gliomas. However, the clinical efficacy of EGFR-targeted therapy has been only modest in GBM patients.

Areas Covered: The authors provide an evaluation of erlotinib as a potential therapy for GBM. The authors highlight experiences drawn from clinical trials and discuss the challenges, which include the insufficient penetration through the blood-brain barrier (BBB) and chemoresistance.

Expert Opinion: Malignant brain tumours have a very complex signalling network that is not only driven by EGFR. This complexity dictates tumour sensitivity to EGFR-targeted therapies. Alternative kinase signalling pathways may be involved in parallel with the inhibited target, so that a single target's inactivation is not sufficient to block downstream oncogenic signalling. The use of nanocarriers offers many opportunities, such as the release of the drug to specific cells or tissues, together with the ability to overcome different biological barriers, like the BBB.
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http://dx.doi.org/10.1517/13543784.2014.918950DOI Listing
July 2014