91 results on '"Frassineti, G. L."'
Search Results
2. Dynamics of RAS/BRAF Mutations in cfDNA from Metastatic Colorectal Carcinoma Patients Treated with Polychemotherapy and Anti-EGFR Monoclonal Antibodies
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Rachiglio, A. M., Forgione, L., Pasquale, R., Barone, Carlo Antonio, Maiello, E., Antonuzzo, L., Cassata, A., Tonini, G., Bordonaro, R., Rosati, G., Zaniboni, Alberto, Lonardi, S., Ferrari, D., Frassineti, G. L., Tamberi, S., Pisconti, S., Di Fabio, F., Roma, C., Orlandi, Armando, Latiano, T., Damato, A., Tortora, Giampaolo, Pinto, C., Normanno, N., Barone C. A., Zaniboni A., Orlandi A. (ORCID:0000-0001-5253-4678), Tortora G. (ORCID:0000-0002-1378-4962), Rachiglio, A. M., Forgione, L., Pasquale, R., Barone, Carlo Antonio, Maiello, E., Antonuzzo, L., Cassata, A., Tonini, G., Bordonaro, R., Rosati, G., Zaniboni, Alberto, Lonardi, S., Ferrari, D., Frassineti, G. L., Tamberi, S., Pisconti, S., Di Fabio, F., Roma, C., Orlandi, Armando, Latiano, T., Damato, A., Tortora, Giampaolo, Pinto, C., Normanno, N., Barone C. A., Zaniboni A., Orlandi A. (ORCID:0000-0001-5253-4678), and Tortora G. (ORCID:0000-0002-1378-4962)
- Abstract
Analysis of plasma-derived cell-free DNA (cfDNA) might allow for the early identification of resistance in metastatic colorectal carcinoma (mCRC) patients receiving anti-EGFR monoclonal antibodies. We tested plasma samples from the Erbitux Metastatic Colorectal Cancer Strategy (ERMES) phase III trial of FOLFIRI+Cetuximab in first-line treatment of RAS/BRAF wild-type mCRC. Samples were collected at baseline (n = 37), at 8 weeks of treatment (n = 32), progressive disease (PD; n = 36) and 3 months after PD (n = 21). cfDNA testing was performed using the IdyllaTM ctKRAS and ctNRAS-BRAF tests and the Oncomine Pan-Cancer Cell-Free Assay. Analysis of basal samples revealed RAS/BRAF mutations in 6/37 cases. A transient RAS positivity not associated with PD was observed at 8 weeks in five cases that showed no mutations at baseline and PD. The frequency of mutant cases increased at PD (33.3%) and decreased again at 3 months after PD (9.5%). The median progression-free survival (mPFS) of patients RAS/BRAF mutant at PD was 7.13 months versus 7.71 months in wild-type patients (p = 0.3892). These data confirm that the occurrence of RAS/BRAF mutations in mCRC patients receiving anti-EGFR agents is relatively frequent. However, the cfDNA dynamics of RAS mutations in patients treated with anti-EGFR agents plus polychemotherapy are complex and might not be directly associated with resistance to treatment.
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- 2022
3. Correction to: Sequential Treatment of Sorafenib–Regorafenib Versus Sorafenib–Physician’s Choice: A Propensity Score-Matched Analysis (Targeted Oncology, (2021), 16, 3, (401-410), 10.1007/s11523-021-00797-3)
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Bang Y., Yoo C., Lonardi S., Kim H. -D., Vivaldi C., Rimini M., Frassineti G. L., Park S. R., Rizzato M. D., Ryu M. -H., Salani F., Rapposelli I. G., Ryoo B. -Y., Zagonel V., Massa V., Valgiusti M., Burgio V., Scartozzi M., Cascinu S., Casadei-Gardini A., Bang, Y., Yoo, C., Lonardi, S., Kim, H. -D., Vivaldi, C., Rimini, M., Frassineti, G. L., Park, S. R., Rizzato, M. D., Ryu, M. -H., Salani, F., Rapposelli, I. G., Ryoo, B. -Y., Zagonel, V., Massa, V., Valgiusti, M., Burgio, V., Scartozzi, M., Cascinu, S., and Casadei-Gardini, A.
- Abstract
The listing of the author names and affiliations, which previously read:.
- Published
- 2021
4. ROS1 rearrangements are uncommon in biliary tract cancers
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Mazzoni F., Petreni P., Vasile E., Panebianco M., Casadei Gardini A., Negri F., Lunghi A., Pillozzi S., Vivaldi C., Gervasi E., Frassineti G. L., Messerini L., Jocolle G., Bisagni A., Antonuzzo L., Rossi G., Mazzoni, F., Petreni, P., Vasile, E., Panebianco, M., Casadei Gardini, A., Negri, F., Lunghi, A., Pillozzi, S., Vivaldi, C., Gervasi, E., Frassineti, G. L., Messerini, L., Jocolle, G., Bisagni, A., Antonuzzo, L., and Rossi, G.
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Molecular target ,Fluorescence in situ hybridization ,Biliary tract cancers ,Biomarker ,Immuno‑ histochemistry ,ROS1 rearrangements ,Articles - Abstract
Biliary tract cancers (BTCs) are a pool of diseases with poor prognosis and there is no orphan drug available. Currently, no molecular targets have been tested as druggable oncogenic drivers. C‑ros oncogene 1 (ROS1) rearrangements have been previously described in various tumors, including BTCs; however, data regarding their incidence and biological significance are controversial. Therefore, a retrospective multi‑ center study was performed to assess the incidence of ROS1 rearrangements in BTCs by means of immunohistochemistry and fluorescence in situ hybridization (FISH). The present study failed to demonstrate ROS1 expression in a multicenter series of 150 cases with BTCs and revealed that D4D6 was the most specific clone compared with other ROS1 primary antibodies, namely PA1‑30318 and EPMGHR2. Notably, nega‑ tive results obtained with D4D6 completely matched to data sorted out by FISH analysis, thus confirming a lack of ROS1 gene rearrangements in BTCs and false positive results when PA1‑30318 and EPMGHR2 clones were used. These results suggest that ROS1 rearrangements may not be targets for molecular therapy of BTCs with specific inhibitors.
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- 2020
5. Effectiveness of bevacizumab added to standard chemotherapy in metastatic colorectal cancer: final results for first-line treatment from the ITACa randomized clinical trial
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Passardi, A., Nanni, O., Tassinari, D., Turci, D., Cavanna, L., Fontana, A., Ruscelli, S., Mucciarini, C., Lorusso, V., Ragazzini, A., Frassineti, G. L., and Amadori, D.
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- 2015
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6. Khorana score and thromboembolic risk in stage II–III colorectal cancer patients: a post hoc analysis from the adjuvant TOSCA trial
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Barni, S, Rosati, G, Lonardi, S, Pella, N, Banzi, M, Zampino, M, Dotti, K, Rimassa, L, Marchetti, P, Maiello, E, Artioli, F, Ferrari, D, Labianca, R, Bidoli, P, Zaniboni, A, Sobrero, A, Iaffaioli, V, De Placido, S, Frassineti, G, Ciarlo, A, Buonadonna, A, Silvestris, N, Piazza, E, Pavesi, L, Moroni, M, Clerico, M, Aglietta, M, Giordani, P, Galli, F, Petrelli, F, Barni S., Rosati G., Lonardi S., Pella N., Banzi M., Zampino M. G., Dotti K. F., Rimassa L., Marchetti P., Maiello E., Artioli F., Ferrari D., Labianca R., Bidoli P., Zaniboni A., Sobrero A., Iaffaioli V., De Placido S., Frassineti G. L., Ciarlo A., Buonadonna A., Silvestris N., Piazza E., Pavesi L., Moroni M., Clerico M., Aglietta M., Giordani P., Galli F., Petrelli F., Barni, S, Rosati, G, Lonardi, S, Pella, N, Banzi, M, Zampino, M, Dotti, K, Rimassa, L, Marchetti, P, Maiello, E, Artioli, F, Ferrari, D, Labianca, R, Bidoli, P, Zaniboni, A, Sobrero, A, Iaffaioli, V, De Placido, S, Frassineti, G, Ciarlo, A, Buonadonna, A, Silvestris, N, Piazza, E, Pavesi, L, Moroni, M, Clerico, M, Aglietta, M, Giordani, P, Galli, F, Petrelli, F, Barni S., Rosati G., Lonardi S., Pella N., Banzi M., Zampino M. G., Dotti K. F., Rimassa L., Marchetti P., Maiello E., Artioli F., Ferrari D., Labianca R., Bidoli P., Zaniboni A., Sobrero A., Iaffaioli V., De Placido S., Frassineti G. L., Ciarlo A., Buonadonna A., Silvestris N., Piazza E., Pavesi L., Moroni M., Clerico M., Aglietta M., Giordani P., Galli F., and Petrelli F.
- Abstract
Background: The risk of venous thromboembolic events (VTE) during adjuvant chemotherapy for colorectal cancer (CRC) is unknown. We aim to evaluate if the Khorana score (KS) can predict this risk, and if it represents a prognostic factor for overall survival (OS) through a post hoc analysis of the phase III TOSCA trial of different durations (3- versus 6-months) of adjuvant chemotherapy. Methods: A logistic regression model was used to test the associations between the risk of VTE and the KS. The results are expressed as odds ratios (OR) with 95% confidence intervals (95% CI). To assess the effect of the KS on OS, multivariable analyses using Cox regression models were performed. The results are expressed as hazard ratios (HR) with 95% CI. Results: Among 1380 CRC patients with available data, the VTE risk (n = 72 events: 5.2%) was similar in the two duration arms (5.5% versus 4.9%), with 0.2% of patients belonging to the high-risk KS group. Rates of VTE were similar in the low- and intermediate-risk groups (4.8% versus 6.4%). KS did not represent an independent predictive factor for VTE occurrence. Chemotherapy duration was not associated with VTE risk. In addition, KS was not prognostic for OS in multivariate analysis (HR: 0.92, 95% CI, 0.63–1.36; p = 0.6835). Conclusions: The use of the KS did not predict VTEs in a low–moderate thromboembolic risk population as CRC. These data did not support the use of KS to predict VTE during adjuvant chemotherapy, and suggest that other risk assessment models should be researched.
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- 2020
7. Preoperative Chemotherapy and Resection Margin Status in Colorectal Liver Metastasis Patients: A Propensity Score-Matched Analysis
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Solaini, L., Gardini, A., Passardi, A., Mirarchi, M. T., D Acapito, F., La Barba, G., Cucchi, M., Gardini, A. C., Frassineti, G. L., Cucchetti, A., Giorgio Ercolani, Solaini, Leonardo, Gardini, Andrea, Passardi, Alessandro, Mirarchi, Maria Teresa, D'Acapito, Fabrizio, La Barba, Giuliano, Cucchi, Michele, Casadei Gardini, Andrea, Frassineti, Giovanni L, Cucchetti, Alessandro, Ercolani, Giorgio, and Gardini, Andrea Casadei
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Male ,Liver Neoplasms ,Margins of Excision ,Antineoplastic Agents ,Middle Aged ,Neoadjuvant Therapy ,Survival Rate ,Treatment Outcome ,Preoperative chemotherapy, propensity score, colorectal liver metastasis, hepatectomy ,Chemotherapy, Adjuvant ,Chemotherapy ,Hepatectomy ,Humans ,Female ,Aged ,Colorectal Neoplasms ,Propensity Score ,Retrospective Studies ,Adjuvant - Abstract
In this article, we compared the early and long-term outcomes of patients with metastatic colorectal cancer treated with chemotherapy followed by resection with those of patients undergoing surgery first, focusing our analysis on resection margin status. Patients who underwent liver resection with curative intent for colorectal liver metastases from July 2001 to January 2018 were included in the analysis. Propensity score matching was used to reduce treatment allocation bias. The cohort comprised 164 patients; 117 (71.3%) underwent liver resection first, whereas the remaining 47 (28.7%) had preoperative chemotherapy. After a 1:1 ratio of propensity score matching, 47 patients per group were evaluated. A positive resection margin was found in 13 patients in the surgery-first group (25.5%) versus 4 (8.5%) in the preoperative chemotherapy group (P = 0.029). Postmatched logistic regression analysis showed that only preoperative chemotherapy was significantly associated with the rate of positive resection margin (odds ratio 0.24, 95% confidence interval 0.07-0.81; P = 0.022). Median follow-up was 41 months (interquartile range 8-69). Cox proportional hazard regression analysis revealed that only positive resection margin was a significant negative prognostic factor (hazard ratio 2.2, 95% CI 1.18-4.11; P = 0.014). Within the preoperative chemotherapy group, median overall survival was 40 months in R0 patients and 10 months in R1 patients (P = 0.016). Although preoperative chemotherapy in colorectal liver metastasis patients may affect the rate of positive resection margin, its impact on survival seems to be limited. In the present study, the most important prognostic factor was the resection margin status.
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- 2019
8. RT-PCR determination of maspin and mammaglobin B in peripheral blood of healthy donors and breast cancer patients
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Mercatali, L., Valenti, V., Calistri, D., Calpona, S., Rosti, G., Folli, S., Gaudio, M., Frassineti, G. L., Amadori, D., and Flamini, E.
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- 2006
9. Onycholysis secondary to multiple paclitaxel 1-hour infusions: possible role for its vehicle (Cremophor EL)
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De Giorgi, U., Rosti, G., Monti, M., Frassineti, G. L., and Marangolo, M.
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- 2003
10. Intra-arterial chemotherapy for the treatment of liver metastases from colorectal cancer
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Passardi, Alessandro, Calzolari, F, Milandri, C, Giampalma, E, Fabbri, M, Frassineti, G L, Rossi, D, Amadori, D, and Golfieri, R
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- 2001
11. Gemcitabine (G) with Doxorubicin (D) and Paclitaxel (P) in the treatment of stage III-IV breast cancer (BC): a new treatment sequence
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Ibrahim, Toni, Frassineti, G L, Zoli, W, Milandri, C, Nanni, M, Ricotti, L, Rossi, D, and Amadori, D
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- 2001
12. Schedule specific biochemical modulation of 5-fluorouracil in advanced colorectal cancer: A randomized study
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Sobrero, A., Zaniboni, A., Frassineti, G. L., Aschele, C., Guglielmi, A., Giuliani, R., Ravaioli, A., Lanfranco, C., Caroti, C., Arnoldi, E., Barni, S., Gallo, L., Pessi, M. A., Turci, D., Cortesi, E., Grossi, F., Frontini, L., Piazza, E., Bruzzi, P., and Labianca, R.
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- 2000
13. Combined 4-hydroxy-ifosfamide and vinorelbine treatment in established and primary human breast cell cultures
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Ricotti, L., Barzanti, F., Tesei, A., Amadori, D., Gasperi-Campani, A., Frassineti, G. L., and Zoli, W.
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- 2000
14. TEACHING NEW TRICKS TO OLD DRUGS: A HIGHLY ACTIVE, LOW COST REGIMEN FOR FIRST LINE TREATMENT OF ADVANCED COLORECTAL CANCER (CRC).
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Cirillo, M, Recaldin, E, Magarotto, R, Caroti, C, Aschele, C, Labianca, R, Frassineti, G L, Testore, F, Pessi, M A, Turci, D, Grossi, F, Guglielmi, A, and Sobrero, A
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- 2000
15. A phase II study to evaluate LY2603618 in combination with gemcitabine in pancreatic cancer patients
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Laquente, Berta, primary, Lopez-Martin, Jose, additional, Richards, Donald, additional, Illerhaus, Gerald, additional, Chang, David Z., additional, Kim, George, additional, Stella, Philip, additional, Richel, Dirk, additional, Szcylik, Cezary, additional, Cascinu, Stefano, additional, Frassineti, G. L., additional, Ciuleanu, Tudor, additional, Hurt, Karla, additional, Hynes, Scott, additional, Lin, Ji, additional, Lin, Aimee Bence, additional, Von Hoff, Daniel, additional, and Calvo, Emiliano, additional
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- 2017
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16. Activity of endovesical gemcitabine in BCG-refractory bladder cancer patients: a translational study
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Gunelli, R, primary, Bercovich, E, additional, Nanni, O, additional, Ballardini, M, additional, Frassineti, G L, additional, Giovannini, N, additional, Fiori, M, additional, Pasquini, E, additional, Ulivi, P, additional, Pappagallo, G L, additional, Silvestrini, R, additional, and Zoli, W, additional
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- 2007
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17. High-dose sequential chemotherapy (HDSC) with peripheral blood progenitor cells (PBPC) support for high-risk breast cancer (BC)
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Sabbatini, R., primary, Da Prada, G. A., additional, Frassineti, G. L., additional, Aietta, M., additional, Pedrazzoli, P., additional, Maur, M., additional, Zambelli, A., additional, Giovannini, N., additional, Siena, S., additional, Ponchio, L., additional, and Conte, P. F., additional
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- 2007
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18. Adjuvant high-dose dense chemotherapy: Epirubicin-dexrazoxane and paclitaxel with peripheral blood progenitor cell (PBPC) support in high risk stage II-IIIA breast cancer (phase II trial)
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Frassineti, G. L., primary, de Giorgi, U., additional, Giovannini, N., additional, Kopf, B., additional, Flamini, E., additional, Carminati, O., additional, Tassinari, D., additional, Cecconetto, L., additional, Mercatali, L., additional, and Zumaglini, F., additional
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- 2005
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19. Gemcitabine as an endovesical treatment in patients with BCG-refractory superficial bladder carcinoma
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Gunelli, R., primary, Frassineti, G. L., additional, Giovannini, N., additional, Zoli, W., additional, Fiori, M., additional, Amadori, D., additional, Fabbri, P., additional, and Bercovich, E., additional
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- 2005
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20. High-dose dense chemotherapy with epirubicin and paclitaxel with peripheral blood progenitor cell support in women with high-risk stage II-IIIA breast cancer
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Rosti, G., primary, De Giorgi, U., additional, Frassineti, G. L., additional, Ciucci, G., additional, Spinolo, L., additional, Flamini, E., additional, Giovannini, N., additional, Monti, M., additional, Zumaglini, F., additional, and Marangolo, M., additional
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- 2004
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21. Role of biological markers in the clinical outcome of colon cancer
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Nanni, O, primary, Volpi, A, additional, Frassineti, G L, additional, De Paola, F, additional, Granato, A M, additional, Dubini, A, additional, Zoli, W, additional, Scarpi, E, additional, Turci, D, additional, Oliverio, G, additional, Gambi, A, additional, and Amadori, D, additional
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- 2002
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22. 5-fluorouracil modulated by leucovorin, methotrexate and mitomycin: highly effective, low-cost chemotherapy for advanced colorectal cancer
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Sobrero, A, primary, Guglielmi, A, additional, Cirillo, M, additional, Recaldin, E, additional, Frassineti, G L, additional, Aschele, C, additional, Ravaioli, A, additional, Testore, P, additional, Caroti, C, additional, Gallo, L, additional, Pessi, M A, additional, Cortesi, E, additional, Turci, D, additional, Grossi, F, additional, and Labianca, R, additional
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- 2001
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23. Docetaxel and gemcitabine activity in NSCLC cell lines and in primary cultures from human lung cancer
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Zoli, W, primary, Ricotti, L, additional, Susino, M Dal, additional, Barzanti, F, additional, Frassineti, G L, additional, Folli, S, additional, Tesei, A, additional, Bacci, F, additional, and Amadori, D, additional
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- 1999
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24. Schedule-selective biochemical modulation of 5-fluorouracil in advanced colorectal cancer: a multicentric phase II study.
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Aschele, C, Guglielmi, A, Frassineti, GL, Milandri, C, Amadori, D, Labianca, R, Vinci, M, Tixi, L, Caroti, C, Ciferri, E, Verdi, E, Rosso, R, Sobrero, A, and Frassineti, G L
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- 1998
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25. A Phase II Study of Gemcitabine in Patients with Transitional Cell Carcinoma of the Urinary Tract Previously Treated with Platinum
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Lorusso, V., Pollera, C. F., Antimi, M., Luporini, G., Gridelli, C., Frassineti, G. L., Oliva, C., Pacini, M., and Lena, M. De
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- 1998
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26. Preclinical evaluation of the interaction among doxorubicin, paclitaxel and gemcitabine in human breast cancer cell line
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Ricotti, L., Zoli, W., Barzanti, F., Dal Susino, M., Frassineti, G. L., Anna Tesei, Casadei Giunchi, D., and Amadori, D.
27. In vitro schedule-dependent interaction between docetaxel and gemcitabine in human gastric cancer cell lines
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Ricotti, L., Tesei, A., Paola, F., Paola Ulivi, Frassineti, G. L., Milandri, C., Amadori, D., and Zoli, W.
28. In vitro schedule-dependent interactions between the multitargeted antifolate LY231514 and gemcitabine in human colon adenocarcinoma cell lines
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Anna Tesei, Ricotti, L., Paola, F., Amadori, D., Frassineti, G. L., and Zoli, W.
29. Lonidamine in modulation of response to adriamycin in advanced breast cancer. Preliminary results
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Frassineti, G. L., Nanni, O., Lombardi, A., Milandri, C., Ferrari, M., Matteis, A., GIORGIO MUSTACCHI, Cariello, S., Mascia, V., Santoro, A., and Amadori, D.
30. Italian results of the PRECONNECT study: safety and efficacy of trifluridine/tipiracil in metastatic colorectal cancer
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Livio Blasi, Mario Spione, Francesca Bergamo, Francesco Di Costanzo, Marie Georges Besse, Carlo Barone, Patrizia Racca, Francesco Giuliani, Tiziana Latiano, Emiliano Tamburini, Alberto Zaniboni, Giuseppe Tonini, Carlo Garufi, Maria Di Bartolomeo, Roberto Bordonaro, Alfredo Falcone, Giovanni Luca Frassineti, Nicola Personeni, Maria Banzi, Erika Martinelli, Zaniboni, A., Barone, C. A., Banzi, M. C., Bergamo, F., Blasi, L., Bordonaro, R., Bartolomeo, M. D., Costanzo, F. D., Frassineti, G. L., Garufi, C., Giuliani, F., Latiano, T. P., Martinelli, E., Personeni, N., Racca, P., Tamburini, E., Tonini, G., Besse, M. G., Spione, M., and Falcone, A.
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safety ,Male ,0301 basic medicine ,Cancer Research ,medicine.medical_specialty ,Pyrrolidines ,Colorectal cancer ,Trifluridine ,colorectal cancer ,Context (language use) ,Neutropenia ,trifluridine/tipiracil ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Quality of life ,real life ,Internal medicine ,medicine ,Humans ,Neoplasm Metastasis ,Adverse effect ,Aged ,Tipiracil ,Performance status ,business.industry ,International Agencies ,General Medicine ,Middle Aged ,Prognosis ,medicine.disease ,Survival Rate ,Drug Combinations ,030104 developmental biology ,Italy ,Oncology ,chemistry ,030220 oncology & carcinogenesis ,Quality of Life ,Female ,Colorectal Neoplasms ,business ,Thymine ,Follow-Up Studies ,medicine.drug - Abstract
The international PRECONNECT Phase IIIb study demonstrated safety and efficacy of trifluridine/tipiracil in the management of patients with metastatic colorectal cancer. Post-hoc analyses in a national context are important because of the differences in disease management across countries. Post-hoc safety and efficacy analyses in the PRECONNECT Italian patient subset were conducted. Patients' quality of life was assessed from baseline to end of treatment. In Italy, 161 patients were enrolled. The median age was 64 years, with a performance status of 0–1. The most common hematological drug-related adverse events ≥grade 3 were neutropenia (41.0%) and anemia (13.7%). The median progression-free survival was reached at 3.0 months, with a disease control rate of 28.6%. The Quality of Life Questionnaire Core 30 score improved in 25.4% of the patients. Safety, efficacy and quality of life results confirmed trifluridine/tipiracil as a feasible and favorable treatment option for metastatic colorectal cancer patients.
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- 2021
31. Sequential Treatment of Sorafenib–Regorafenib Versus Sorafenib–Physician’s Choice: A Propensity Score-Matched Analysis
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Hyung-Don Kim, Caterina Vivaldi, Francesca Salani, Martina Valgiusti, Ilario Giovanni Rapposelli, Changhoon Yoo, Stefano Cascinu, Yeonghak Bang, Baek-Yeol Ryoo, Min-Hee Ryu, Giovanni Luca Frassineti, Sook Ryun Park, Valentina Burgio, Sara Lonardi, Mario Domenico Rizzato, Margherita Rimini, Valentina Massa, Mario Scartozzi, Andrea Casadei-Gardini, Vittorina Zagonel, Bang, Y., Yoo, C., Lonardi, S., Kim, H. -D., Vivaldi, C., Rimini, M., Frassineti, G. L., Park, S. R., Rizzato, M. D., Ryu, M. -H., Salani, F., Rapposelli, I. G., Ryoo, B. -Y., Zagonel, V., Massa, V., Valgiusti, M., Burgio, V., Scartozzi, M., Cascinu, S., and Casadei-Gardini, A.
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Male ,0301 basic medicine ,Oncology ,Sorafenib ,Cancer Research ,medicine.medical_specialty ,Carcinoma, Hepatocellular ,Pyridines ,Population ,Placebo ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Internal medicine ,Regorafenib ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Humans ,Pharmacology (medical) ,Propensity Score ,education ,Survival analysis ,Retrospective Studies ,Univariate analysis ,education.field_of_study ,business.industry ,Phenylurea Compounds ,Liver Neoplasms ,Retrospective cohort study ,digestive system diseases ,030104 developmental biology ,chemistry ,030220 oncology & carcinogenesis ,Propensity score matching ,Female ,business ,medicine.drug - Abstract
Background: Regorafenib has been shown to improve clinical outcomes compared to placebo, becoming a standard second-line therapy for sorafenib-progressed and -tolerated hepatocellular carcinoma (HCC) patients. Objective: We performed a multicentre, retrospective study in Italy and Korea to evaluate the effectiveness of the treatment sequence sorafenib–regorafenib compared with sorafenib and physician’s choice in a real-life setting. Patients and Methods: A propensity score model was developed to control the results for baseline variable imbalances between the arm treated with sorafenib and regorafenib (S–R) and the arm treated with sorafenib and physician’s choice (S–P). Survival analysis was conducted on the matched population. Results: After the application of propensity score matching, we analysed 99 patients in the arm treated with S–R and 99 patients in the arm treated with S–P. For the S–R group, the median overall survival was 22.2 months (95% CI 17.1–27.4), compared to 17.9 months (95% CI 15.1–50.0) for the S–P group. The results of the univariate analysis showed a 31% reduction of death risk for patients treated with S–R (p = 0.0382) compared to patients treated with S–P. Interaction tests highlighted the predictive role of alpha-fetoprotein (AFP), neutrophil-to-lymphocyte ratio (NLR), and extrahepatic spread. Conclusion: This study provides additional proof of the superiority of the S–R treatment over the S–P treatment approach in advanced HCC patients from a real-life setting.
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- 2021
32. Evolving pancreatic cancer treatment: From diagnosis to healthcare management
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Michele Milella, Claudio Bassi, Ugo Boggi, Oronzo Brunetti, Alessandro Cavaliere, Stefano Crippa, Ferdinando De Vita, Massimo Falconi, Giovanni Luca Frassineti, Elisa Giommoni, Marina Macchini, Giuseppe Malleo, Nicola Silvestris, Antonella Tudisco, Enrico Vasile, Michele Reni, Milella, Michele, Bassi, Claudio, Boggi, Ugo, Brunetti, Oronzo, Cavaliere, Alessandro, Crippa, Stefano, De Vita, Ferdinando, Falconi, Massimo, Frassineti, Giovanni Luca, Giommoni, Elisa, Macchini, Marina, Malleo, Giuseppe, Silvestris, Nicola, Tudisco, Antonella, Vasile, Enrico, Reni, Michele, Milella, M., Bassi, C., Boggi, U., Brunetti, O., Cavaliere, A., Crippa, S., De Vita, F., Falconi, M., Frassineti, G. L., Giommoni, E., Macchini, M., Malleo, G., Silvestris, N., Tudisco, A., Vasile, E., and Reni, M.
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Patient-reported outcomes ,Prognosi ,Locally advanced pancreatic cancer ,Carcinoma ,Hematology ,Prognosis ,Adjuvant chemotherapy ,Borderline Resectable pancreatic cancer ,Healthcare management ,Neoadjuvant chemotherapy ,Pancreatic ductal adenocarcinoma ,Delivery of Health Care ,Humans ,Neoadjuvant Therapy ,Carcinoma, Pancreatic Ductal ,Pancreatic Neoplasms ,Oncology ,Pancreatic Ductal ,Patient-reported outcome ,Human - Abstract
The prognosis of pancreatic ductal adenocarcinoma is still the worst among solid tumors. In this review, a panel of experts addressed the main unanswered questions about the clinical management of this disease, with the aim of providing practical decision support for physicians. On the basis of the evidence available from the literature, the main topics concerning pancreatic cancer are discussed: the diagnosis, as the need for a pathological characterization and the role for germ-line and somatic molecular profiling; the therapeutic management of resectable disease, as the role of upfront surgery or neoadjuvant chemotherapy, the post-operative restaging and the optimal timing foradjuvant chemotherapy, the management of the borderline resectable and locally advanced disease; the metastatic disease and the role of surgery for the management of patients with isolated metastasis and the use of biomarkers of metastatic potential; the role of supportive care and the healthcare management of pancreatic ductal adenocarcinoma.
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- 2022
33. Upfront FOLFOXIRI plus bevacizumab and reintroduction after progression versus mFOLFOX6 plus bevacizumab followed by FOLFIRI plus bevacizumab in the treatment of patients with metastatic colorectal cancer (TRIBE2): a multicentre, open-label, phase 3, randomised, controlled trial
- Author
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Chiara Cremolini, Carlotta Antoniotti, Daniele Rossini, Sara Lonardi, Fotios Loupakis, Filippo Pietrantonio, Roberto Bordonaro, Tiziana Pia Latiano, Emiliano Tamburini, Daniele Santini, Alessandro Passardi, Federica Marmorino, Roberta Grande, Giuseppe Aprile, Alberto Zaniboni, Sabina Murgioni, Cristina Granetto, Angela Buonadonna, Roberto Moretto, Salvatore Corallo, Stefano Cordio, Lorenzo Antonuzzo, Gianluca Tomasello, Gianluca Masi, Monica Ronzoni, Samantha Di Donato, Chiara Carlomagno, Matteo Clavarezza, Giuliana Ritorto, Andrea Mambrini, Mario Roselli, Samanta Cupini, Serafina Mammoliti, Elisabetta Fenocchio, Enrichetta Corgna, Vittorina Zagonel, Gabriella Fontanini, Clara Ugolini, Luca Boni, Alfredo Falcone, Filippo Guglielmo Maria De Braud, Evaristo Maiello, Giovanni Luca Frassineti, Teresa Gamucci, Francesco Di Costanzo, Luca Gianni, Patrizia Racca, Giacomo Allegrini, Alberto Sobrero, Massimo Aglietta, Enrico Cortesi, Domenico Cristiano Corsi, Alberto Ballestrero, Andrea Bonetti, Francesco Di Clemente, Enzo Ruggeri, Fortunato Ciardiello, Marco Benasso, Stefano Vitello, Saverio Cinieri, Stefania Mosconi, Nicola Silvestris, Antonio Frassoldati, Samantha Cupini, Alessandro Bertolini, Giampaolo Tortora, Carmelo Bengala, Daris Ferrari, Antonia Ardizzoia, Carlo Milandri, Silvana Chiara, Gianpiero Romano, Stefania Miraglia, Laura Scaltriti, Francesca Pucci, Livio Blasi, Silvia Brugnatelli, Luisa Fioretto, Angela Stefania Ribecco, Raffaella Longarini, Michela Frisinghelli, Maria Banzi, Cremolini, C., Antoniotti, C., Rossini, D., Lonardi, S., Loupakis, F., Pietrantonio, F., Bordonaro, R., Latiano, T. P., Tamburini, E., Santini, D., Passardi, A., Marmorino, F., Grande, R., Aprile, G., Zaniboni, A., Murgioni, S., Granetto, C., Buonadonna, A., Moretto, R., Corallo, S., Cordio, S., Antonuzzo, L., Tomasello, G., Masi, G., Ronzoni, M., Di Donato, S., Carlomagno, C., Clavarezza, M., Ritorto, G., Mambrini, A., Roselli, M., Cupini, S., Mammoliti, S., Fenocchio, E., Corgna, E., Zagonel, V., Fontanini, G., Ugolini, C., Boni, L., Falcone, A., De Braud, F. G. M., Maiello, E., Frassineti, G. L., Gamucci, T., Di Costanzo, F., Gianni, L., Racca, P., Allegrini, G., Sobrero, A., Aglietta, M., Cortesi, E., Corsi, D. C., Ballestrero, A., Bonetti, A., Di Clemente, F., Ruggeri, E., Ciardiello, F., Benasso, M., Vitello, S., Cinieri, S., Mosconi, S., Silvestris, N., Frassoldati, A., Bertolini, A., Tortora, G., Bengala, C., Ferrari, D., Ardizzoia, A., Milandri, C., Chiara, S., Romano, G., Miraglia, S., Scaltriti, L., Pucci, F., Blasi, L., Brugnatelli, S., Fioretto, L., Ribecco, A. S., Longarini, R., Frisinghelli, M., and Banzi, M.
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Male ,0301 basic medicine ,GONO ,Organoplatinum Compounds ,multicentre ,Leucovorin ,Colorectal Neoplasm ,Gastroenterology ,Settore MED/06 ,Antineoplastic Agents, Immunological ,0302 clinical medicine ,Antineoplastic Combined Chemotherapy Protocols ,Neoplasm Metastasis ,FOLFOXIRI ,progression versus mFOLFOX6 plus bevacizumab ,mFOLFOX6 ,metastatic colorectal cancer ,Middle Aged ,TRIBE2 trial ,FOLFIRI plus bevacizumab ,Neoplasm Metastasi ,Bevacizumab ,FOLFOXIRI plus bevacizumab ,triplet FOLFOXIRI ,Oncology ,Fluorouracil ,030220 oncology & carcinogenesis ,Disease Progression ,FOLFIRI ,Female ,metastatic colorectal cancer, triplet FOLFOXIRI , FOLFOXIRI plus bevacizumab, FOLFIRI plus bevacizumab, progression versus mFOLFOX6 plus bevacizumab, TRIBE2 ,Colorectal Neoplasms ,Human ,medicine.drug ,Adult ,medicine.medical_specialty ,Adolescent ,Analogs & derivatives ,open-label ,NO ,Young Adult ,03 medical and health sciences ,Folinic acid ,Internal medicine ,medicine ,cancer ,Humans ,neoplasms ,Aged ,Antineoplastic Combined Chemotherapy Protocol ,Performance status ,business.industry ,Organoplatinum Compound ,randomised controlled ,FOLFOXIRI, bevacizumab, mFOLFOX6, FOLFIRI, metastatic colorectal cancer, TRIBE2 trial, multicentre, open-label, phase 3, randomised controlled, GONO ,Irinotecan ,030104 developmental biology ,phase 3 ,TRIBE2 ,Camptothecin ,business - Abstract
Summary Background The triplet FOLFOXIRI (fluorouracil, leucovorin, oxaliplatin, and irinotecan) plus bevacizumab showed improved outcomes for patients with metastatic colorectal cancer, compared with FOLFIRI (fluorouracil, leucovorin, and irinotecan) plus bevacizumab. However, the actual benefit of the upfront exposure to the three cytotoxic drugs compared with a preplanned sequential strategy of doublets was not clear, and neither was the feasibility or efficacy of therapies after disease progression. We aimed to compare a preplanned strategy of upfront FOLFOXIRI followed by the reintroduction of the same regimen after disease progression versus a sequence of mFOLFOX6 (fluorouracil, leucovorin, and oxaliplatin) and FOLFIRI doublets, in combination with bevacizumab. Methods TRIBE2 was an open-label, phase 3, randomised study of patients aged 18–75 years with an Eastern Cooperative Oncology Group (ECOG) performance status of 2, with unresectable, previously untreated metastatic colorectal cancer, recruited from 58 Italian oncology units. Patients were stratified according to centre, ECOG performance status, primary tumour location, and previous adjuvant chemotherapy. A randomisation system incorporating a minimisation algorithm was used to randomly assign patients (1:1) via a masked web-based allocation procedure to two different treatment strategies. In the control group, patients received first-line mFOLFOX6 (85 mg/m2 of intravenous oxaliplatin concurrently with 200 mg/m2 of leucovorin over 120 min; 400 mg/m2 intravenous bolus of fluorouracil; 2400 mg/m2 continuous infusion of fluorouracil for 48 h) plus bevacizumab (5 mg/kg intravenously over 30 min) followed by FOLFIRI (180 mg/m2 of intravenous irinotecan over 120 min concurrently with 200 mg/m2 of leucovorin; 400 mg/m2 intravenous bolus of fluorouracil; 2400 mg/m2 continuous infusion of fluorouracil for 48 h) plus bevacizumab after disease progression. In the experimental group, patients received FOLFOXIRI (165 mg/m2 of intravenous irinotecan over 60 min; 85 mg/m2 intravenous oxaliplatin concurrently with 200 mg/m2 of leucovorin over 120 min; 3200 mg/m2 continuous infusion of fluorouracil for 48 h) plus bevacizumab followed by the reintroduction of the same regimen after disease progression. Combination treatments were repeated every 14 days for up to eight cycles followed by fluorouracil and leucovorin (at the same dose administered at the last induction cycle) plus bevacizumab maintenance until disease progression, unacceptable adverse events, or consent withdrawal. Patients and investigators were not masked. The primary endpoint was progression-free survival 2, defined as the time from randomisation to disease progression on any treatment given after first disease progression, or death, analysed by intention to treat. Safety was assessed in patients who received at least one dose of their assigned treatment. Study recruitment is complete and follow-up is ongoing. This trial is registered with Clinicaltrials.gov , NCT02339116 . Findings Between Feb 26, 2015, and May 15, 2017, 679 patients were randomly assigned and received treatment (340 in the control group and 339 in the experimental group). At data cut-off (July 30, 2019) median follow-up was 35·9 months (IQR 30·1–41·4). Median progression-free survival 2 was 19·2 months (95% CI 17·3–21·4) in the experimental group and 16·4 months (15·1–17·5) in the control group (hazard ratio [HR] 0·74, 95% CI 0·63–0·88; p=0·0005). During the first-line treatment, the most frequent of all-cause grade 3–4 events were diarrhoea (57 [17%] vs 18 [5%]), neutropenia (168 [50%] vs 71 [21%]), and arterial hypertension (25 [7%] vs 35 [10%]) in the experimental group compared with the control group. Serious adverse events occurred in 84 (25%) patients in the experimental group and in 56 (17%) patients in the control group. Eight treatment-related deaths were reported in the experimental group (two intestinal occlusions, two intestinal perforations, two sepsis, one myocardial infarction, and one bleeding) and four in the control group (two occlusions, one perforation, and one pulmonary embolism). After first disease progression, no substantial differences in the incidence of grade 3 or 4 adverse events were reported between the control and experimental groups, with the exception of neurotoxicity, which was only reported in the experimental group (six [5%] of 132 patients). Serious adverse events after disease progression occurred in 20 (15%) patients in the experimental group and 25 (12%) in the control group. Three treatment-related deaths after first disease progression were reported in the experimental group (two intestinal occlusions and one sepsis) and four in the control group (one intestinal occlusion, one intestinal perforation, one cerebrovascular event, and one sepsis). Interpretation Upfront FOLFOXIRI plus bevacizumab followed by the reintroduction of the same regimen after disease progression seems to be a preferable therapeutic strategy to sequential administration of chemotherapy doublets, in combination with bevacizumab, for patients with metastatic colorectal cancer selected according to the study criteria. Funding The GONO Cooperative Group, the ARCO Foundation, and F Hoffmann–La Roche.
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- 2020
34. Identification of lenvatinib prognostic index via recursive partitioning analysis in advanced hepatocellular carcinoma
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Marianna Silletta, V. Burgio, Gianluca Masi, A. Takata, M.G. Viola, Mario Domenico Rizzato, Kazuto Tajiri, H. Toyoda, M. Scartozzi, Francesca Salani, Syusuke Okamura, Francesco Giuseppe Foschi, Takashi Kumada, G. Astara, I.G. Rapposelli, Fabio Conti, Emiliano Tamburini, Claudia Campani, Kazuhito Kawata, Fabio Marra, A. Forgione, A. Hiraoka, Giovanni Luca Frassineti, R. Tortora, Takuji Torimura, Shigeo Shimose, Masahito Nakano, Masanori Atsukawa, Stefano Cascinu, Andrea Casadei-Gardini, H. Shibata, G.G. Di Costanzo, Caterina Vivaldi, Antonio Pellino, Claudia Angela Maria Fulgenzi, Toshifumi Tada, Eleonora Lai, Fabio Piscaglia, S. Lonardi, Margherita Rimini, Rapposelli, I. G., Shimose, S., Kumada, T., Okamura, S., Hiraoka, A., Di Costanzo, G. G., Marra, F., Tamburini, E., Forgione, A., Foschi, F. G., Silletta, M., Lonardi, S., Masi, G., Scartozzi, M., Nakano, M., Shibata, H., Kawata, K., Pellino, A., Vivaldi, C., Lai, E., Takata, A., Tajiri, K., Toyoda, H., Tortora, R., Campani, C., Viola, M. G., Piscaglia, F., Conti, F., Fulgenzi, C. A. M., Frassineti, G. L., Rizzato, M. D., Salani, F., Astara, G., Torimura, T., Atsukawa, M., Tada, T., Burgio, V., Rimini, M., Cascinu, S., Casadei-Gardini, A., Rapposelli I.G., Shimose S., Kumada T., Okamura S., Hiraoka A., Di Costanzo G.G., Marra F., Tamburini E., Forgione A., Foschi F.G., Silletta M., Lonardi S., Masi G., Scartozzi M., Nakano M., Shibata H., Kawata K., Pellino A., Vivaldi C., Lai E., Takata A., Tajiri K., Toyoda H., Tortora R., Campani C., Viola M.G., Piscaglia F., Conti F., Fulgenzi C.A.M., Frassineti G.L., Rizzato M.D., Salani F., Astara G., Torimura T., Atsukawa M., Tada T., Burgio V., Rimini M., Cascinu S., and Casadei-Gardini A.
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Oncology ,Cancer Research ,medicine.medical_specialty ,lenvatinib prognostic index ,Carcinoma, Hepatocellular ,hepatocellular carcinoma ,recursive partitioning analysis ,Humans ,Phenylurea Compounds ,Prognosis ,Quinolines ,Chemoembolization, Therapeutic ,Liver Neoplasms ,Recursive partitioning ,Prognostic score ,chemistry.chemical_compound ,Internal medicine ,medicine ,Original Research ,business.industry ,Carcinoma ,Treatment options ,Hepatocellular ,medicine.disease ,chemistry ,Hepatocellular carcinoma ,Cohort ,Chemoembolization ,Therapeutic ,Medium Risk ,Lenvatinib ,business - Abstract
Background After the advent of new treatment options for advanced hepatocellular carcinoma (HCC), the identification of prognostic factors is crucial for the selection of the most appropriate therapy for each patient. Patients and methods With the aim to fill this gap, we applied recursive partitioning analysis (RPA) to a cohort of 404 patients treated with lenvatinib. Results The application of RPA resulted in a classification based on five variables that originated a new prognostic score, the lenvatinib prognostic index (LEP) index, identifying three groups: low risk [patients with prognostic nutritional index (PNI) >43.3 and previous trans-arterial chemoembolization (TACE)]; medium risk [patients with PNI >43.3 but without previous TACE and patients with PNI, Highlights • This study shows a new prognostic index (LEP index) for patients undergoing systemic therapy for hepatocellular carcinoma. • LEP index is an easy-to-use tool, based on clinical and laboratory features, that identifies three risk groups. • LEP index may be used to stratify hepatocellular carcinoma patients in order to select the most appropriate treatment.
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- 2021
35. Effects of Metformin and Vitamin D on Clinical Outcome in Cholangiocarcinoma Patients
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Margherita Rimini, Antonella Argentiero, Giulia Bartolini, Oronzo Brunetti, Nicola Silvestris, Giovanni Luca Frassineti, Andrea Casadei-Gardini, Elisa Sperti, Giulia Rovesti, Laura Bernardini, Francesco Giovannelli, Rosa La Face, Roberto Filippi, Caterina Vivaldi, Giacomo Aimar, Martina Valgiusti, Ilario Giovanni Rapposelli, Luca Aldrighetti, Virginia Quarà, Stefano Cascinu, Elisabetta Fenocchio, Francesco Leone, Silvia Cesario, Francesca Ratti, Lorenzo Fornaro, Kalliopi Andrikou, Casadei-Gardini, A., Filippi, R., Rimini, M., Rapposelli, I. G., Fornaro, L., Silvestris, N., Aldrighetti, L., Aimar, G., Rovesti, G., Bartolini, G., Vivaldi, C., Brunetti, O., Sperti, E., La Face, R., Ratti, F., Andrikou, K., Valgiusti, M., Bernardini, L., Argentiero, A., Fenocchio, E., Frassineti, G. L., Cesario, S., Giovannelli, F., Quara, V., Leone, F., and Cascinu, S.
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Male ,Cancer Research ,medicine.medical_specialty ,Disease-free survival ,medicine.medical_treatment ,Biliary tract cancer ,Chemotherapy ,Cholangiocarcinoma ,Gallbladder cancer ,Metfromin ,Vitamin D ,Bile Duct Neoplasms ,Female ,Follow-Up Studies ,Humans ,Hypoglycemic Agents ,Metformin ,Prognosis ,Retrospective Studies ,Survival Rate ,Vitamins ,Internal medicine ,medicine ,Vitamin D and neurology ,In patient ,Prospective cohort study ,Aspirin ,business.industry ,Vitamin D intake ,General Medicine ,medicine.disease ,Oncology ,business ,medicine.drug - Abstract
Background and Aims: In the last few years, there has been increasing interest in non-cancer medications and their potential anti-cancer activity. Data are not available in cholangiocarcinoma (CCA) patients. The aim of this study is to fill this gap by investigating the potential impact in terms of clinical outcome of the common non-cancer medications. Methods: All consecutive patients with CCAs were retrospectively identified from 7 Italian medical institutions. We investigated the role of intake of vitamin D, aspirin, metformin, statins, and diuretics. Results: A total of 537 patients with CCAs were identified; 197 patients undergoing surgery were evaluated for disease-free survival (DFS), and 509 patients with an advanced stage were evaluated for overall survival (OS). A longer DFS was found in patients with intake of vitamin D versus never users (HR 0.55, 95% CI 0.32–0.92, p = 0.02). In an advanced stage an association with OS was found in patients with intake of metformin versus never users (HR 0.70, 95% CI 0.52–0.93, p = 0.0162), and in patients who have started taking metformin after chemotherapy versus before chemotherapy and never users (HR 0.44, 95% CI 0.26–0.73, p = 0.0016). Conclusions: Our results highlighted that vitamin D intake improves DFS in patients undergoing surgery. Metformin intake after starting chemotherapy can improve the clinical outcome in advanced disease. These results could open up new therapeutic strategies in cholangiocarcinoma patients. We are planning to undertake a prospective study to validate these data.
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- 2021
36. Heterogeneity of Response and Immune System Activity during Treatment with Nivolumab in Hepatocellular Carcinoma: Results from a Single-Institution Retrospective Analysis
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Giovanni Luca Frassineti, Paola Lanuti, Serena De Matteis, Paola Ulivi, Ilario Giovanni Rapposelli, Giulia Bartolini, Martina Valgiusti, Giorgia Marisi, Andrea Casadei-Gardini, Federica Pedica, Stefano Cascinu, Valentina Burgio, Rapposelli, I. G., De Matteis, S., Lanuti, P., Valgiusti, M., Bartolini, G., Ulivi, P., Marisi, G., Pedica, F., Burgio, V., Frassineti, G. L., Cascinu, S., and Casadei-Gardini, A.
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0301 basic medicine ,Oncology ,Cancer Research ,medicine.medical_specialty ,Hepatocellular carcinoma ,medicine.medical_treatment ,Peripheral blood mononuclear cell ,lcsh:RC254-282 ,Article ,03 medical and health sciences ,0302 clinical medicine ,Immune system ,Internal medicine ,medicine ,Single institution ,Pseudoprogression ,neoplasms ,business.industry ,Immunotherapy ,hepatocellular carcinoma ,medicine.disease ,Pattern of response ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,peripheral blood mononuclear cells ,digestive system diseases ,030104 developmental biology ,030220 oncology & carcinogenesis ,Peripheral blood mononuclear cells ,Cohort ,immunotherapy ,Nivolumab ,pattern of response ,business - Abstract
Treatment of hepatocellular carcinoma (HCC) is rapidly evolving, with many new therapeutic options, in particular, immunotherapy (IT) is acquiring a major role, even in combination regimens. Despite these promising results, an important limitation is the lack of prognostic and predictive factors that prevent provision of a tool for patient stratification in order to select the most appropriate strategy. Furthermore, response assessment can be challenging with IT due to peculiar patterns such as mixed responses or pseudoprogression. We analyzed biological and clinical features from the first 10 HCC patients treated with nivolumab in our institution. Analysis of patterns of response in CT assessment revealed complete response in pulmonary lesions, along with heterogeneous behavior in the liver and other organ lesions. Peripheral blood mononuclear cells (PBMC) analysis in the first four patients showed unique alterations in a patient with poor prognosis, both at baseline (lower percentage of effector T cells, higher percentage of natural killer T [NK/T] cells) and during treatment with nivolumab (decrease in nonclassical monocytes, increase in monocytic myeloid-derived suppressor cells [MO-MDSC]), suggesting a possible prognostic role for these features. Although obtained in a small cohort of patients, our results open a new perspective for understanding mechanisms underlying IT outcomes in HCC patients.
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- 2021
37. Prognostic role of a new index (multi inflammatory index) in patients with metastatic colorectal cancer: results from the randomized ITACa trial
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Laura Matteucci, Flavia Pagan, Giulia Bartolini, Alessandro Passardi, Silvia Ruscelli, Manlio Monti, Bernadette Vertogen, Emanuela Scarpi, Giovanni Luca Frassineti, Giulia Rovesti, Martina Valgiusti, Andrea Casadei Gardini, Casadei Gardini, A., Scarpi, E., Valgiusti, M., Monti, M., Ruscelli, S., Matteucci, L., Bartolini, G., Vertogen, B., Pagan, F., Rovesti, G., Frassineti, G. L., and Passardi, A.
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Oncology ,medicine.medical_specialty ,Index (economics) ,Bevacizumab ,Colorectal cancer ,First line ,Inflammation ,bevacizumab ,lcsh:RC254-282 ,neutrophil-to-lymphocyte ratio ,Internal medicine ,medicine ,In patient ,Neutrophil to lymphocyte ratio ,first-line ,Original Research ,business.industry ,metastatic colorectal cancer ,medicine.disease ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,inflammation ,prognosis ,medicine.symptom ,business ,medicine.drug - Abstract
Aims: We created a new index (Multi Inflammatory Index, MII) composed of an inflammatory index [neutrophil-to lymphocyte-ratio (NLR): MII-1; platelet-to-lymphocyte ratio (PLR): MII-2; or systemic immune-inflammation index (SII): MII-3] and C-reactive protein (CRP). Our aim was to evaluate the prognostic and/or predictive capacity of the MII in the randomized ITACa (Italian Trial in Advanced Colorectal Cancer) study on patients with metastatic colorectal cancer undergoing first-line chemotherapy. Methods: Between November 2007 and March 2012, baseline NLR, PLR; SII and CRP were available for 131 patients, 66 receiving chemotherapy plus bevacizumab and 65 receiving chemotherapy alone. Results: Patients with low (Conclusion: All MII indexes appear to be useful as prognostic markers. Trial registration ClinicalTrials.gov identifier: NCT01878422 (registration date: 07/06/2013) https://clinicaltrials.gov/ct2/show/NCT01878422
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- 2020
38. 1H-NMR based serum metabolomics highlights different specific biomarkers between early and advanced hepatocellular carcinoma stages
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Anna Maria Giudetti, Paola Ulivi, Giorgia Marisi, Giulia Rovesti, Giovanni Luca Frassineti, Matteo Canale, Laura Del Coco, Fabio Conti, Andrea Casadei-Gardini, Francesco Giuseppe Foschi, Francesco Paolo Fanizzi, Serena Longo, Casadei Gardini, A., Coco, L. D., Marisi, G., Conti, F., Rovesti, G., Ulivi, P., Canale, M., Frassineti, G. L., Foschi, F. G., Longo, S., Fanizzi, F. P., Giudetti, A. M., Casadei-Gardini, A., and Del Coco, L.
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0301 basic medicine ,Sorafenib ,Oncology ,Cancer Research ,medicine.medical_specialty ,Multivariate analysis ,Hepatocellular carcinoma ,Metabolomic ,lcsh:RC254-282 ,Article ,03 medical and health sciences ,radiofrequency ,0302 clinical medicine ,Metabolomics ,Internal medicine ,medicine ,Metabolome ,NMR ,OPLS-DA ,Radiofrequency ,Pathological ,business.industry ,hepatocellular carcinoma ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,medicine.disease ,metabolomics ,digestive system diseases ,Pathophysiology ,Glutamine ,030104 developmental biology ,030220 oncology & carcinogenesis ,sorafenib ,business ,medicine.drug - Abstract
The application of non-targeted serum metabolomics profiling represents a noninvasive tool to identify new clinical biomarkers and to provide early diagnostic differentiation, and insight into the pathological mechanisms underlying hepatocellular carcinoma (HCC) progression. In this study, we used proton Nuclear Magnetic Resonance (1H-NMR) Spectroscopy and multivariate data analysis to profile the serum metabolome of 64 HCC patients, in early (n = 28) and advanced (n = 36) disease stages. We found that 1H-NMR metabolomics profiling could discriminate early from advanced HCC patients with a cross-validated accuracy close to 100%. Orthogonal partial least squares discriminant analysis (OPLS-DA) showed significant changes in serum glucose, lactate, lipids and some amino acids, such as alanine, glutamine, 1-methylhistidine, lysine and valine levels between advanced and early HCC patients. Moreover, in early HCC patients, Kaplan&ndash, Meier analysis highlighted the serum tyrosine level as a predictor for overall survival (OS). Overall, our analysis identified a set of metabolites with possible clinical and biological implication in HCC pathophysiology.
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- 2020
39. Multicenter prospective study of angiogenesis polymorphism validation in HCC patients treated with sorafenib. An INNOVATE study protocol
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Giorgio de Stefano, Arianna Lanzi, Oronzo Brunetti, Daniele Bruno, Francesca Negri, Luca Faloppi, Umberto Vespasiani Gentilucci, Flavia Pagan, Giovanni Luca Frassineti, Marianna Silletta, Mario Scartozzi, Vittorina Zagonel, Daniele Santini, Andrea Casadei Gardini, Luchino Chessa, Vincenzo Dadduzio, Giorgia Marisi, Francesco Giuseppe Foschi, Stefano Cascinu, Emiliano Tamburini, Nicola Silvestris, Gianluca Masi, Lorenzo Calvetti, Giorgio Ercolani, Caterina Vivaldi, Chiara Caparello, Alessandro Leonetti, Giuseppe Aprile, N. Farella, Emanuela Scarpi, Davide Tassinari, Jody Corbelli, Gardini, A. C., Faloppi, L., Aprile, G., Brunetti, O., Caparello, C., Corbelli, J., Chessa, L., Bruno, D., Ercolani, G., Leonetti, A., De Stefano, G., Farella, N., Foschi, F. G., Lanzi, A., Dadduzio, V., Marisi, G., Masi, G., Negri, F. V., Pagan, F., Santini, D., Scarpi, E., Silletta, M., Silvestris, N., Tamburini, E., Tassinari, D., Vivaldi, C., Gentilucci, U. V., Zagonel, V., Calvetti, L., Cascinu, S., Frassineti, G. L., and Scartozzi, M.
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Male ,Vascular Endothelial Growth Factor A ,0301 basic medicine ,Oncology ,Cancer Research ,Hepatocellular carcinoma ,Angiogenesis ,VEGF receptors ,Trial ,0302 clinical medicine ,Prospective Studies ,Prospective cohort study ,Neovascularization, Pathologic ,biology ,ENOS ,Angiopoietin 2 ,Liver Neoplasms ,General Medicine ,Sorafenib ,VEGF ,030220 oncology & carcinogenesis ,eNOS ,Female ,Hypoxia-Inducible Factor 1 ,Biomarkers ,medicine.drug ,medicine.medical_specialty ,Disease free survival ,Carcinoma, Hepatocellular ,Standard of care ,Adolescent ,Nitric Oxide Synthase Type III ,Antineoplastic Agents ,Polymorphism, Single Nucleotide ,Disease-Free Survival ,Angiopoietin-2 ,03 medical and health sciences ,Internal medicine ,medicine ,Humans ,neoplasms ,business.industry ,medicine.disease ,digestive system diseases ,Receptors, Vascular Endothelial Growth Factor ,030104 developmental biology ,biology.protein ,business - Abstract
Introduction: Although sorafenib is the upfront standard of care for advanced hepatocellular carcinoma (HCC), molecular predictors of efficacy have not been identified yet. In the ALICE-1 study, rs2010963 of VEGF-A and VEGF-C proved to be independent predictive factors for progression-free survival (PFS) and overall survival (OS) in multivariate analysis. The ALICE-1 study results were confirmed in the ALICE-2 study, in which VEGF and VEGFR SNPs were analyzed. In the ePHAS study we analyzed the SNPs of eNOS. In univariate analysis, patients homozygous for an eNOS haplotype (HT1: T-4b at eNOS-786/eNOS VNTR) had significantly shorter median PFS and OS than those with other haplotypes. These data were confirmed in the validation set. Methods: This nonpharmacological, interventional, prospective multicenter study aims to determine whether eNOS, HIF-1, VEGF, Ang2 and VEGFR polymorphisms play a role in predicting the objective response rate, PFS, and OS of advanced HCC patients treated with sorafenib. The study will involve 160 advanced HCC patients with Child-Pugh class A disease. The primary aim is to validate the prognostic or predictive roles of eNOS, Ang2, HIF-1, VEGF and VEGFR polymorphisms in relation to the clinical outcome (PFS) of HCC patients treated with sorafenib. Conclusions: Overall, our data may suggest that polymorphism analysis of the VEGF, VEGFR-2, HIF and eNOS genes can identify HCC patients who are more likely to benefit from sorafenib.
- Published
- 2018
40. Chemoradiotherapy (Gemox Plus Helical Tomotherapy) for Unresectable Locally Advanced Pancreatic Cancer: A Phase II Study
- Author
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Flavia Pagan, Giorgio Ercolani, Antonino Romeo, Giovanni Luca Frassineti, Fabio Ferroni, Andrea Casadei Gardini, G. Ghigi, Elisa Neri, Giuliano La Barba, Martina Valgiusti, Andrea Casadei-Gardini, Elisabetta Parisi, Alessandro Passardi, Emanuela Scarpi, Alessandro Passardi, Emanuela Scarpi, Elisa Neri, Elisabetta Parisi, Giulia Ghigi, Giorgio Ercolani, Andrea Gardini, Giuliano La Barba, Flavia Pagan, Andrea Casadei-Gardini, Martina Valgiusti, Fabio Ferroni, Giovanni Luca Frassineti, Antonino Romeo, Passardi, A., Scarpi, E., Neri, E., Parisi, E., Ghigi, G., Ercolani, G., Gardini, A., La Barba, G., Pagan, F., Casadei-Gardini, A., Valgiusti, M., Ferroni, F., Frassineti, G. L., and Romeo, A.
- Subjects
0301 basic medicine ,Cancer Research ,medicine.medical_specialty ,medicine.medical_treatment ,pancreatic cancer ,GemOx ,lcsh:RC254-282 ,Article ,03 medical and health sciences ,0302 clinical medicine ,Laparotomy ,Pancreatic cancer ,GEMOX ,Neoadjuvant therapy ,Radiotherapy ,medicine ,neoadjuvant therapy ,radiotherapy ,business.industry ,Explorative laparotomy ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,medicine.disease ,Gemcitabine ,Surgery ,Oxaliplatin ,Regimen ,030104 developmental biology ,Oncology ,030220 oncology & carcinogenesis ,business ,Chemoradiotherapy ,medicine.drug - Abstract
The aim of the study was to evaluate the safety and efficacy of a new chemo-radiotherapy regimen for patients with locally advanced pancreatic cancer (LAPC). Patients were treated as follows: gemcitabine 1000 mg/m2 on day 1, and oxaliplatin 100 mg/m2 on day 2, every two weeks (GEMOX regimen) for 4 cycles, 15 days off, hypofractionated radiotherapy (35 Gy in 7 fractions in 9 consecutive days), 15 days off, 4 additional cycles of GEMOX, restaging. From April 2011 to August 2016, a total of 42 patients with non resectable LAPC were enrolled. Median age was 67 years (range 41&ndash, 75). Radiotherapy was well tolerated and the most frequently encountered adverse events were mild to moderate nausea and vomiting, abdominal pain and fatigue. In total, 9 patients underwent surgical laparotomy (5 radical pancreatic resection 1 thermoablation and 3 explorative laparotomy), 1 patient became operable but refused surgery. The overall resectability rate was 25%, while the R0 resection rate was 12.5%. At a median follow-up of 50 months, the median progression-free survival and overall survival were 9.3 (95% CI 6.2&ndash, 14.9) and 15.8 (95% CI 8.2&ndash, 23.4) months, respectively. The results demonstrate the feasibility of a new chemo-radiotherapy regimen as a potential treatment for unresectable LAPC.
- Published
- 2019
41. Assessment of Ramucirumab plus paclitaxel as switch maintenance versus continuation of first-line chemotherapy in patients with advanced HER-2 negative gastric or gastroesophageal junction cancers: The ARMANI phase III trial
- Author
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Marta Caporale, Salvatore Corallo, Alberto Gianluigi Luporini, Andrea Spallanzani, Michele Basso, Maria Di Bartolomeo, Mario Scartozzi, Federica Morano, Evaristo Maiello, Davide Tassinari, Andrea Bonetti, Graziella Pinotti, Filippo de Braud, Saverio Cinieri, Sergio Bracarda, Giovanni Gerardo Cardellino, Alessandro Bertolini, Claudio Verusio, Gianluca Tomasello, Hector Soto Parra, Alberto Zaniboni, Giampaolo Tortora, Samantha Di Donato, Sara Lonardi, Vincenzo Catalano, Francesco Di Costanzo, Raffaella Longarini, Libero Ciuffreda, Ferdinando De Vita, Francesco Giuliani, Maria Antista, Lorenza Rimassa, Rossana Berardi, Filippo Pietrantonio, Monica Niger, Stefano Tamberi, Lorenzo Fornaro, Giorgio V. Scagliotti, Giovanni Luca Frassineti, Di Bartolomeo, M., Niger, M., Morano, F., Corallo, S., Antista, M., Tamberi, S., Lonardi, S., Di Donato, S., Berardi, R., Scartozzi, M., Cardellino, G. G., Di Costanzo, F., Rimassa, L., Luporini, A. G., Longarini, R., Zaniboni, A., Bertolini, A., Tomasello, G., Pinotti, G., Scagliotti, G., Tortora, G., Bonetti, A., Spallanzani, A., Frassineti, G. L., Tassinari, D., Giuliani, F., Cinieri, S., Maiello, E., Verusio, C., Bracarda, S., Catalano, V., Basso, M., Ciuffreda, L., De Vita, F., Parra, H. S., Fornaro, L., Caporale, M., De Braud, F., and Pietrantonio, F.
- Subjects
0301 basic medicine ,Oncology ,Male ,Cancer Research ,Receptor, ErbB-2 ,medicine.medical_treatment ,chemistry.chemical_compound ,Study Protocol ,ErbB-2 ,0302 clinical medicine ,Quality of life ,Monoclonal ,Antineoplastic Combined Chemotherapy Protocols ,Clinical endpoint ,Antibodies, Monoclonal ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,Clinical trial ,First line ,Maintenance ,Metastatic gastric cancer ,Ramucirumab ,Drug Administration Schedule ,Esophagogastric Junction ,Female ,Humans ,Maintenance Chemotherapy ,Paclitaxel ,Progression-Free Survival ,Quality of Life ,Stomach Neoplasms ,Treatment Outcome ,030220 oncology & carcinogenesis ,Receptor ,medicine.drug ,Human ,medicine.medical_specialty ,Antibodies, Monoclonal, Humanized ,lcsh:RC254-282 ,Antibodies ,03 medical and health sciences ,Stomach Neoplasm ,Internal medicine ,Genetics ,medicine ,Chemotherapy ,Antineoplastic Combined Chemotherapy Protocol ,business.industry ,Oxaliplatin ,Regimen ,030104 developmental biology ,chemistry ,business - Abstract
Platinum/fluoropyrimidine regimens are the backbone of first-line chemotherapy for advanced gastric cancer (AGC). However response rates to first line chemotherapy range from 30 to 50% and disease progression occurs after 4–6 cycles. The optimal duration of first-line therapy is still unknown and its continuation until disease progression represents the standard. However this strategy is often associated with cumulative toxicity and rapid development of drug resistance. Moreover, only about 40% of AGC pts. are eligible for second-line treatment. This is a randomized, open-label, multicenter phase III trial. It aims at assessing whether switch maintenance to ramucirumab plus paclitaxel will extend the progression-free survival (PFS) of subjects with HER-2 negative AGC who have not progressed after 3 months of a first-line with a platinum/fluoropyrimidine regimen (either FOLFOX4, mFOLFOX6 or XELOX). The primary endpoint is to compare Progression-Free Survival (PFS) of patients in ARM A (switch maintenance to ramucirumab and placlitaxel) versus ARM B (continuation of the same first-line therapy with oxaliplatin/fluoropyrimidine). Secondary endpoints are: overall survival, time-to-treatment failure, overall response rate, duration of response, percentage of patients that will receive a second line therapy according to arm treatment, safety, quality of life. Exploratory studies including Next-Generation Sequencing (NGS) in archival tumor tissues are planned in order to identify potential biomarkers of primary resistance and prognosis. The ARMANI study estimates if patients treated with early swich with ramucirumab plus paclitaxel received benefit when compared to those treated with continuation of first line therapy. The hypothesis is that the early administration of an active, non-cross resistant second-line regimen such as ramucirumab plus paclitaxel may prolong the time in which patients are progression-free, and consequently have a better quality of life. Moreover, this strategy may rescue all those subjects that become ineligible for second-line therapy due to the rapid deterioration of health status after the first disease progression. ARMANI is registered at ClinicalTrials.gov ( NCT02934464 , October 17, 2016) and EudraCT(2016–001783-12, April 202,016).
- Published
- 2019
42. Impact of Metformin Use and Diabetic Status During Adjuvant Fluoropyrimidine-Oxaliplatin Chemotherapy on the Outcome of Patients with Resected Colon Cancer: A TOSCA Study Subanalysis
- Author
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Vincenzo Adamo, Sabino De Placido, Luigi Cavanna, Evaristo Maiello, Sandro Barni, Francesca Galli, Claudio Vernieri, M. Nicolini, Massimo Aglietta, Sara Lonardi, Maria Di Bartolomeo, Laura Ferrari, Emiliano Tamburini, Azzurra Damiani, Maria Giulia Zampino, Rosario Vincenzo Iaffaioli, Francesco Leonardi, Gerardo Rosati, Katia Fiorella Dotti, F. Galli, Paolo Marchetti, Paolo Giordani, Giovanni Lo Re, Alberto Zaniboni, Roberto Labianca, Maria Antista, Tosca Investigators, A. Ciarlo, Maria Banzi, Lorenzo Pavesi, Paolo Bidoli, Giovanni Luca Frassineti, Maria Chiara Tronconi, S. Ferrario, Stefania Gori, Daris Ferrari, Marina Faedi, Mario Clerico, Angela Buonadonna, Saverio Cinieri, Vernieri, C., Galli, F., Ferrari, L., Marchetti, P., Lonardi, S., Maiello, E., Iaffaioli, R. V., Zampino, M. G., Zaniboni, A., De Placido, S., Banzi, M., Damiani, A., Ferrari, D., Rosati, G., Labianca, R. F., Bidoli, P., Frassineti, G. L., Nicolini, M., Pavesi, L., Tronconi, M. C., Buonadonna, A., Ferrario, S., Re, G. L., Adamo, V., Tamburini, E., Clerico, M., Giordani, P., Leonardi, F., Barni, S., Ciarlo, A., Cavanna, L., Gori, S., Cinieri, S., Faedi, M., Aglietta, M., Antista, M., Dotti, K. F., Di Bartolomeo, M., Vernieri, C, Galli, F, Ferrari, L, Marchetti, P, Lonardi, S, Maiello, E, Iaffaioli, R, Zampino, M, Zaniboni, A, De Placido, S, Banzi, M, Damiani, A, Ferrari, D, Rosati, G, Labianca, R, Bidoli, P, Frassineti, G, Nicolini, M, Pavesi, L, Tronconi, M, Buonadonna, A, Ferrario, S, Re, G, Adamo, V, Tamburini, E, Clerico, M, Giordani, P, Leonardi, F, Barni, S, Ciarlo, A, Cavanna, L, Gori, S, Cinieri, S, Faedi, M, Aglietta, M, Antista, M, Dotti, K, and Di Bartolomeo, M
- Subjects
Aged ,Antineoplastic Agents, Chemotherapy, Adjuvant, Colonic Neoplasms, Diabetes Mellitus, Type 2, Female, Fluorouracil, Humans, Hypoglycemic Agents, Male, Metformin, Middle Aged, Oxaliplatin, Risk Factors ,0301 basic medicine ,Oncology ,Male ,Cancer Research ,medicine.medical_specialty ,endocrine system diseases ,Colorectal cancer ,colon cancer (CC) ,radical surgery ,Antineoplastic Agents ,03 medical and health sciences ,0302 clinical medicine ,Type 2 diabetes mellitus (T2DM), colon cancer (CC), metformin, radical surgery, TOSCA study ,Risk Factors ,Diabetes mellitus ,Internal medicine ,Gastrointestinal Cancer ,medicine ,Adjuvant therapy ,Humans ,Hypoglycemic Agents ,Prospective cohort study ,Cancer staging ,business.industry ,Hazard ratio ,nutritional and metabolic diseases ,Middle Aged ,medicine.disease ,Metformin ,Oxaliplatin ,Type 2 diabetes mellitus (T2DM) ,030104 developmental biology ,TOSCA study ,colon cancer ,Diabetes Mellitus, Type 2 ,Chemotherapy, Adjuvant ,030220 oncology & carcinogenesis ,Colonic Neoplasms ,Female ,Fluorouracil ,business ,medicine.drug - Abstract
Background Type 2 diabetes mellitus (T2DM) is associated with increased risk of colon cancer (CC), whereas metformin use seems to be protective. However, the impact of metformin use on the risk of death or disease recurrence after radical surgery for CC remains uncertain. Materials and Methods This is a substudy conducted in patients with high-risk stage II or stage III CC randomized in the TOSCA trial, which compared 3 versus 6 months of fluoropyrimidine-oxaliplatin adjuvant chemotherapy. Objective of the study was to investigate the impact of metformin exposure during adjuvant chemotherapy on overall survival (OS) and relapse-free survival (RFS). We also evaluated the impact of T2DM or metformin dosage on clinical outcomes. Results Out of 3,759 patients enrolled in the TOSCA trial, 133 patients with diabetes (9.2%) and 1,319 without diabetes (90.8%) were recruited in this study. After excluding 13 patients with diabetes without information on metformin exposure, 76 patients with T2DM (63.3%) were defined as metformin users and 44 (36.7%) as metformin nonusers. After a median follow-up of 60.4 months, 26 (21.7%) patients relapsed and 16 (13.3%) died. Metformin use was neither associated with OS (adjusted hazard ratio [HR], 1.51; 95% confidence interval [CI], 0.48–4.77; p = .4781) nor with RFS (HR, 1.56; 95% CI, 0.69–3.54; p = .2881). Similarly, we found no association between T2DM or metformin dosage and OS or RFS. Conclusions Metformin use and T2DM did not impact on OS or RFS in patients with resected CC treated with adjuvant fluoropyrimidine-oxaliplatin chemotherapy. Larger studies and longer follow-up are required to clarify the potential efficacy of metformin in improving the prognosis of patients with CC. Implications for Practice The role of the antidiabetic drug metformin in colon cancer prevention and treatment is highly debated. While low-dose metformin reduced the incidence of colorectal adenomas in two prospective studies, its effect in patients with already established colon cancer remains unclear. In this study, the potential impact of metformin on the survival of resected colon cancer patients who received adjuvant chemotherapy was investigated in the context of the TOSCA study. We did not find any association between metformin use or dosages and patient survival. Prospective studies are required to draw definitive conclusions about metformin impact on colon cancer recurrence and survival.
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- 2018
43. Treatment of squamous cell carcinoma of the anal canal: A new strategies with anti-EGFR therapy and immunotherapy
- Author
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C. Casadei, Martina Valgiusti, Paola Rosetti, Giovanni Luca Frassineti, Alessandro Passardi, Silvia Ruscelli, Lorenzo Fornaro, A. Casadei Gardini, Manlio Monti, Flavia Pagan, Casadei Gardini, A., Passardi, A., Fornaro, L., Rosetti, P., Valgiusti, M., Ruscelli, S., Monti, M., Casadei, C., Pagan, F., and Frassineti, G. L.
- Subjects
0301 basic medicine ,Oncology ,medicine.medical_specialty ,Combination therapy ,medicine.medical_treatment ,Cetuximab ,Antineoplastic Agents ,Pembrolizumab ,03 medical and health sciences ,0302 clinical medicine ,Anal cancer ,Anti-EGFR ,Immunotherapy ,Nivolumab ,Panitumumab ,Hematology ,Internal medicine ,medicine ,Humans ,business.industry ,Standard treatment ,Therapies, Investigational ,Antibodies, Monoclonal ,Anal canal ,medicine.disease ,Anus Neoplasms ,Combined Modality Therapy ,Radiation therapy ,ErbB Receptors ,030104 developmental biology ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,Carcinoma, Squamous Cell ,business ,medicine.drug - Abstract
The incidence of squamous cell carcinoma of the anal canal (SCAC) is increasing in both sexes but the standard treatment remains that of 20 years ago. However, interesting data have recently emerged on the use of anti-epidermal growth factor receptor (EGFR) agents and immunotherapy in advanced disease. Thus, new avenues of research are opening up that will hopefully lead to more effective therapeutic strategies. We provide an overview of the latest studies published on this tumor and discuss the possible future therapeutic options for combination therapy, anti-EGFR treatment and radiotherapy.
- Published
- 2018
44. Treatment of squamous cell carcinoma of the anal canal (SCCA): A new era?
- Author
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Martina Valgiusti, A. Casadei Gardini, Alessandro Passardi, Giovanni Luca Frassineti, Casadei Gardini, Andrea, Valgiusti, M., Passardi, A., and Frassineti, G. L.
- Subjects
0301 basic medicine ,Oncology ,medicine.medical_specialty ,business.industry ,Hematology ,Anal canal ,medicine.disease ,Anus neoplasms ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,Internal medicine ,medicine ,Carcinoma ,Basal cell ,Radiology ,business - Abstract
N/A
- Published
- 2017
45. A phase II study to evaluate LY2603618 in combination with gemcitabine in pancreatic cancer patients
- Author
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George P. Kim, David Z. Chang, Daniel D. Von Hoff, Philip J. Stella, Berta Laquente, Karla Hurt, Tudor Ciuleanu, Cezary Szcylik, Jose A. Lopez-Martin, Scott M. Hynes, Aimee Bence Lin, Dirk J. Richel, Emiliano Calvo, Giovanni Luca Frassineti, Ji Lin, Donald A. Richards, Gerald Illerhaus, Stefano Cascinu, Oncology, Cancer Center Amsterdam, CCA - Cancer Treatment and Quality of Life, Laquente, B., Lopez-Martin, J., Richards, D., Illerhaus, G., Chang, D. Z., Kim, G., Stella, P., Richel, D., Szcylik, C., Cascinu, S., Frassineti, G. L., Ciuleanu, T., Hurt, K., Hynes, S., Lin, J., Lin, A. B., Hoff, D., and Calvo, E.
- Subjects
Male ,0301 basic medicine ,Oncology ,Cancer Research ,LY2603618 ,Phases of clinical research ,Deoxycytidine ,chemistry.chemical_compound ,0302 clinical medicine ,Antineoplastic Combined Chemotherapy Protocols ,Quimioteràpia ,Medicine ,Pancreas cancer ,Cancer ,Aged, 80 and over ,education.field_of_study ,gemcitabine ,Common Terminology Criteria for Adverse Events ,Middle Aged ,phase II ,Prognosis ,Phase II ,Survival Rate ,Pyrazines ,030220 oncology & carcinogenesis ,Female ,Research Article ,medicine.drug ,Adult ,medicine.medical_specialty ,CHK1 ,Population ,Adenocarcinoma ,Neutropenia ,03 medical and health sciences ,Internal medicine ,Pancreatic cancer ,Genetics ,Humans ,cancer ,Chemotherapy ,education ,Survival rate ,Càncer de pàncrees ,Aged ,Neoplasm Staging ,business.industry ,Phenylurea Compounds ,medicine.disease ,Gemcitabine ,Pancreatic Neoplasms ,030104 developmental biology ,chemistry ,business ,Follow-Up Studies - Abstract
The aim of this study was to determine whether checkpoint kinase 1 inihibitor (CHK1), LY2603618, and gemcitabine prolong overall survival (OS) compared to gemcitabine alone in patients with unresectable pancreatic cancer. Patients with Stage II-IV locally advanced or metastatic pancreatic cancer were randomized (2:1) to either 230 mg of LY2603618/1000 mg/m2 gemcitabine combined or 1000 mg/m2 gemcitabine alone. OS was assessed using both a Bayesian augment control model and traditional frequentist analysis for inference. Progression-free survival (PFS), overall response rate (ORR), duration of response, pharmacokinetics (PK), and safety (Common Terminology Criteria for Adverse Events [AEs] v 3.0) were also evaluated. Ninety-nine patients (n = 65, LY2603618/gemcitabine; n = 34, gemcitabine) were randomized (intent-to-treat population). The median OS (months) was 7.8 (range, 0.3–18.9) with LY2603618/gemcitabine and 8.3 (range, 0.8-19.1+) with gemcitabine. Similarly, in a Bayesian analysis, the study was not positive since the posterior probability that LY2603618/gemcitabine was superior to gemcitabine in improving OS was 0.3, which did not exceed the prespecified threshold of 0.8. No significant improvements in PFS, ORR, or duration of response were observed. Drug-related treatment-emergent AEs in both arms included nausea, thrombocytopenia, fatigue, and neutropenia. The severity of AEs with LY2603618/gemcitabine was comparable to gemcitabine. The LY2603618 exposure targets (AUC(0-∞) ≥21,000 ng∙hr/mL and Cmax ≥2000 ng/mL) predicted for maximum pharmacodynamic response were achieved after 230 mg of LY2603618. LY2603618/gemcitabine was not superior to gemcitabine for the treatment of patients with pancreatic cancer. NCT00839332 . Clinicaltrials.gov. Date of registration: 6 February 2009
- Published
- 2017
46. Treatment of squamous cell carcinoma of the anal canal (SCCA): a new era?
- Author
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Gardini, A. Casadei, Valgiusti, M., Passardi, A., and Frassineti, G. L.
- Subjects
- *
CANCER treatment , *SQUAMOUS cell carcinoma , *ANAL cancer treatment - Published
- 2017
- Full Text
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47. Phase II study of capecitabine-based concomitant chemoradiation followed by durvalumab as a neoadjuvant strategy in locally advanced rectal cancer: the PANDORA trial.
- Author
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Grassi E, Zingaretti C, Petracci E, Corbelli J, Papiani G, Banchelli I, Valli I, Frassineti GL, Passardi A, Di Bartolomeo M, Pietrantonio F, Gelsomino F, Carandina I, Banzi M, Martella L, Bonetti AV, Boccaccino A, Molinari C, Marisi G, Ugolini G, Nanni O, and Tamberi S
- Subjects
- Humans, Capecitabine pharmacology, Capecitabine therapeutic use, Prospective Studies, Chemoradiotherapy adverse effects, Diarrhea chemically induced, Transaminases therapeutic use, Neoadjuvant Therapy, Rectal Neoplasms drug therapy, Rectal Neoplasms pathology
- Abstract
Background: This study investigated the efficacy of chemoradiotherapy (CRT) followed by durvalumab as neoadjuvant therapy of locally advanced rectal cancer., Patients and Methods: The PANDORA trial is a prospective, phase II, open-label, single-arm, multicenter study aimed at evaluating the efficacy and safety of preoperative treatment with durvalumab (1500 mg every 4 weeks for three administrations) following long-course radiotherapy (RT) plus concomitant capecitabine (5040 cGy RT in 25-28 fractions over 5 weeks and capecitabine administered at 825 mg/m
2 twice daily). The primary endpoint was the pathological complete response (pCR) rate; secondary endpoints were the proportion of clinical complete remissions and safety. The sample size was estimated assuming a null pCR proportion of 0.15 and an alternative pCR proportion of 0.30 (α = 0.05, power = 0.80). The proposed treatment could be considered promising if ≥13 pCRs were observed in 55 patients (EudraCT: 2018-004758-39; NCT04083365)., Results: Between November 2019 and August 2021, 60 patients were accrued, of which 55 were assessable for the study's objectives. Two patients experienced disease progression during treatment. Nineteen out of 55 eligible patients achieved a pCR (34.5%, 95% confidence interval 22.2% to 48.6%). Regarding toxicity related to durvalumab, grade 3 adverse events (AEs) occurred in four patients (7.3%) (diarrhea, skin toxicity, transaminase increase, lipase increase, and pancolitis). Grade 4 toxicity was not observed. In 20 patients (36.4%), grade 1-2 AEs related to durvalumab were observed. The most common were endocrine toxicity (hyper/hypothyroidism), dermatologic toxicity (skin rash), and gastrointestinal toxicity (transaminase increase, nausea, diarrhea, constipation)., Conclusion: This study met its primary endpoint showing that CRT followed by durvalumab could increase pCR with a safe toxicity profile. This combination is a promising, feasible strategy worthy of further investigation., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)- Published
- 2023
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48. Identification of lenvatinib prognostic index via recursive partitioning analysis in advanced hepatocellular carcinoma.
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Rapposelli IG, Shimose S, Kumada T, Okamura S, Hiraoka A, Di Costanzo GG, Marra F, Tamburini E, Forgione A, Foschi FG, Silletta M, Lonardi S, Masi G, Scartozzi M, Nakano M, Shibata H, Kawata K, Pellino A, Vivaldi C, Lai E, Takata A, Tajiri K, Toyoda H, Tortora R, Campani C, Viola MG, Piscaglia F, Conti F, Fulgenzi CAM, Frassineti GL, Rizzato MD, Salani F, Astara G, Torimura T, Atsukawa M, Tada T, Burgio V, Rimini M, Cascinu S, and Casadei-Gardini A
- Subjects
- Humans, Phenylurea Compounds, Prognosis, Quinolines, Carcinoma, Hepatocellular drug therapy, Chemoembolization, Therapeutic, Liver Neoplasms drug therapy
- Abstract
Background: After the advent of new treatment options for advanced hepatocellular carcinoma (HCC), the identification of prognostic factors is crucial for the selection of the most appropriate therapy for each patient., Patients and Methods: With the aim to fill this gap, we applied recursive partitioning analysis (RPA) to a cohort of 404 patients treated with lenvatinib., Results: The application of RPA resulted in a classification based on five variables that originated a new prognostic score, the lenvatinib prognostic index (LEP) index, identifying three groups: low risk [patients with prognostic nutritional index (PNI) >43.3 and previous trans-arterial chemoembolization (TACE)]; medium risk [patients with PNI >43.3 but without previous TACE and patients with PNI <43.3, albumin-bilirubin (ALBI) grade 1 and Barcelona Clinic Liver Cancer stage B (BCLC-B)]; high risk [patients with PNI <43.3 and ALBI grade 2 and patients with PNI <43.3, albumin-bilirubin (ALBI) grade 1 and Barcelona Clinic Liver Cancer stage C (BCLC-C)]. Median overall survival was 29.8 months [95% confidence interval (CI) 22.8-29.8 months] in low risk patients (n = 128), 17.0 months (95% CI 15.0-24.0 months) in medium risk (n = 162) and 8.9 months (95% CI 8.0-10.7 months) in high risk (n = 114); low risk hazard ratio (HR) 1 (reference group), medium risk HR 1.95 (95% CI 1.38-2.74), high risk HR 4.84 (95% CI 3.16-7.43); P < 0.0001. The LEP index was validated in a cohort of 127 Italian patients treated with lenvatinib. While the same classification did not show a prognostic value in a cohort of 311 patients treated with sorafenib, we also show a possible predictive role in favor of lenvatinib in the low risk group., Conclusions: LEP index is a promising, easy-to-use tool that may be used to stratify patients undergoing systemic treatment of advanced HCC., Competing Interests: Disclosure The authors have declared no conflicts of interest. Data sharing Data are available upon reasonable request., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)
- Published
- 2021
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49. Microbiological evaluation of environmental cleanliness in haematopoietic cell transplant patient rooms: implementing JACIE standards.
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Zeneli A, Petrini M, Foca F, Bernabini M, Ronconi S, Montalti S, Pancisi E, Soldati V, Golinucci M, Frassineti GL, and Altini M
- Subjects
- Air Microbiology, Disease Reservoirs, Environmental Microbiology, Environmental Monitoring methods, Equipment Contamination, Humans, Hygiene standards, Infection Control legislation & jurisprudence, Patient Isolation, Risk Assessment, Cross Infection prevention & control, Hematopoietic Stem Cell Transplantation, Infection Control methods, Patients' Rooms standards
- Abstract
Background: Environmental hygiene is one of the most important strategies to prevent hospital-acquired infections by reducing pathogens in haematopoietic cell transplant (HCT) patient rooms. This study was designed in response to JACIE requirements for microbiological monitoring, and aimed to assess environmental hygiene in protective isolation rooms., Methods: Environmental cleanliness was assessed by measuring microbial loads in at-rest and operational conditions sampled from target surfaces, and in passive and active air from rooms occupied by patients with different grades of neutropenia. The study also evaluated whether microbial loads were influenced by isolation precautions., Results: The failure rate of cleanliness on target surfaces in at-rest conditions was 0% compared with 37% for surfaces and 13% for passive and active air samples in operational conditions. Differences in failure rates were observed in the rooms of patients with different levels of neutropenia (P=0.036 for surfaces, 0.028% for passive air). No relationship was found between infections and microbial loads., Conclusions: Microbiological assessment integrated with an enhanced monitoring programme for hospital hygiene provides invaluable information to drive infection control policies in HCT patients. These results highlight the need to set and validate strict standards for the assessment of cleanliness in a clinical setting., (Copyright © 2019 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.)
- Published
- 2020
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50. Treatment of squamous cell carcinoma of the anal canal: A new strategies with anti-EGFR therapy and immunotherapy.
- Author
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Casadei Gardini A, Passardi A, Fornaro L, Rosetti P, Valgiusti M, Ruscelli S, Monti M, Casadei C, Pagan F, and Frassineti GL
- Subjects
- Anus Neoplasms pathology, Carcinoma, Squamous Cell pathology, Cetuximab administration & dosage, Combined Modality Therapy, Humans, Therapies, Investigational methods, Antibodies, Monoclonal administration & dosage, Antineoplastic Agents administration & dosage, Anus Neoplasms therapy, Carcinoma, Squamous Cell therapy, ErbB Receptors antagonists & inhibitors, Immunotherapy methods
- Abstract
The incidence of squamous cell carcinoma of the anal canal (SCAC) is increasing in both sexes but the standard treatment remains that of 20 years ago. However, interesting data have recently emerged on the use of anti-epidermal growth factor receptor (EGFR) agents and immunotherapy in advanced disease. Thus, new avenues of research are opening up that will hopefully lead to more effective therapeutic strategies. We provide an overview of the latest studies published on this tumor and discuss the possible future therapeutic options for combination therapy, anti-EGFR treatment and radiotherapy., (Copyright © 2018 Elsevier B.V. All rights reserved.)
- Published
- 2018
- Full Text
- View/download PDF
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