20 results on '"Malaguti, Paola"'
Search Results
2. T-DM1 and brain metastases: Clinical outcome in HER2-positive metastatic breast cancer
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Fabi, Alessandra, Alesini, Daniele, Valle, Enrichetta, Moscetti, Luca, Caputo, Roberta, Caruso, Michele, Carbognin, Luisa, Ciccarese, Mariangela, La Verde, Nicla, Arpino, Grazia, Cannita, Katia, Paris, Ida, Santini, Daniele, Montemurro, Filippo, Russillo, Michelangelo, Ferretti, Gianluigi, Filippelli, Gianfranco, Rossello, Rosalba, Fabbri, Agnese, Zambelli, Alberto, Leonardi, Vita, D’Ottavio, Anna Maria, Nisticò, Cecilia, Stani, Simonetta, Giampaglia, Marianna, Scandurra, Giusy, Catania, Giovanna, Malaguti, Paola, Giannarelli, Diana, and Cognetti, Francesco
- Published
- 2018
- Full Text
- View/download PDF
3. MITO39: Efficacy and Tolerability of Pegylated Liposomal Doxorubicin (PLD)–Trabectedin in the Treatment of Relapsed Ovarian Cancer after Maintenance Therapy with PARP Inhibitors—A Multicenter Italian Trial in Ovarian Cancer Observational Case-Control Study
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Turinetto, Margherita, Ricotti, Andrea, Marchetti, Claudia, Pisano, Carmela, Zamagni, Claudio, Cassani, Chiara, Malaguti, Paola, Baldoni, Alessandra, Scollo, Paolo, Scandurra, Giuseppa, Parisi, Alessandro, Artioli, Grazia, Palaia, Innocenza, Vertechy, Laura, Bergamini, Alice, Picardo, Elisa, Tuninetti, Valentina, Scotto, Giulia, Scambia, Giovanni, and Pignata, Sandro
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THERAPEUTIC use of antineoplastic agents ,DRUG efficacy ,RESEARCH ,DISEASE progression ,HAND-foot syndrome ,OVARIAN tumors ,SCIENTIFIC observation ,CONFIDENCE intervals ,DOXORUBICIN ,RESEARCH methodology ,CASE-control method ,RETROSPECTIVE studies ,GASTROINTESTINAL diseases ,PLATINUM ,BLOOD diseases ,DESCRIPTIVE statistics ,RESEARCH funding ,FATIGUE (Physiology) ,ENZYME inhibitors ,EVALUATION - Abstract
Simple Summary: This multicenter, retrospective analysis had the objective of comparing the efficacy of PLD-Trabectedin in patients who had already been treated with PARP-I (cases) before vs. PARPi-naïve patients (controls). Data from 166 patients were collected, composed of 109 cases and 57 controls. In total, 135 patients were included in our analyses, composing 46 controls and 89 cases. We found a median PFS of 11 months (95% IC 10–12) in the control group vs. 8 months (95% IC 6–9) in the case group (p value 0.0017). The clinical benefit rate was evaluated, with an HR for progression of 2.55 (1.28–5.06) for the case group (p value 0.008) persisting when adjusted for BRCA mutation. The study showed a statistically significant difference in terms of PFS, suggesting that a previous exposure to PARP-i might inhibit the efficacy of PLD-Trabectedin. Regarding tolerability, no remarkable disparity was noted. Objective: While PLD-Trabectedin is an approved treatment for relapsed platinum-sensitive ovarian cancer, its efficacy and tolerability has so far not been tested extensively in patients who progress after poly ADP-ribose polymerase inhibitor (PARPi) treatment. Methodology: This multicenter, retrospective analysis had the objective of comparing patients receiving PLD-Trabectedin after being treated with PARP-I (cases) with PARPi-naïve patients. Descriptive and survival analyses were performed for each group. Results: Data from 166 patients were collected, composed of 109 cases and 57 controls. In total, 135 patients were included in our analyses, composing 46 controls and 89 cases. The median PFS was 11 months (95% IC 10–12) in the control group vs. 8 months (95% IC 6–9) in the case group (p value 0.0017). The clinical benefit rate was evaluated, with an HR for progression of 2.55 (1.28–5.06) for the case group (p value 0.008), persisting when adjusted for BRCA and line with treatment. We compared hematological toxicity, gastro-intestinal toxicity, hand–foot syndrome (HFS), fatigue, and liver toxicity, and no statistically significant disparity was noted, except for HFS with a p value of 0.006. The distribution of G3 and G4 toxicities was also equally represented. Conclusion: The MITO39 study showed a statistically significant difference in terms of PFS, suggesting that previous exposure to PARPi might inhibit the efficacy of PLD-Trabectedin. Regarding tolerability, no remarkable disparity was noted; PLD-Trabectedin was confirmed to be a well-tolerated scheme in both groups. To our knowledge, these are the first data regarding this topic, which we deem to be of great relevance in the current landscape. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
4. Fixed dose-rate gemcitabine infusion as first-line treatment for advanced-stage carcinoma of the pancreas and biliary tree
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Gelibter, Alain, Malaguti, Paola, Di Cosimo, Serena, Bria, Emilio, Ruggeri, Enzo Maria, Carlini, Paolo, Carboni, Fabio, Ettorre, Giuseppe Maria, Pellicciotta, Mario, Giannarelli, Diana, Terzoli, Edmondo, Cognetti, Francesco, and Milella, Michele
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- 2005
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5. Nanoparticle albumin-bound paclitaxel/liposomal-encapsulated doxorubicin in HER2-negative metastatic breast cancer patients.
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Fabi, Alessandra, Ferretti, Gianluigi, Malaguti, Paola, Gasparro, Simona, Nisticò, Cecilia, Arpino, Grazia, Papaldo, Paola, Russillo, Michelangelo, Catania, Giovanna, Schettini, Francesco, Giannarelli, Diana, and Cognetti, Francesco
- Abstract
Aim: To investigate the toxicity of nab-paclitaxel (wNP)/nonpegylated liposome-encapsulated doxorubicin (wNPLD) combination in HER2-negative metastatic breast cancer (MBC) patients as first-line treatment. Materials & methods: Phase I, single-arm study in metastatic breast cancer patients naive to previous chemotherapy for advanced disease. A 3 + 3 dose-escalation design was used to determine the safety. Primary endpoints were the identification of dose-limiting toxicity and maximum tolerated dose. Results: In total, 12 patients (mean age: 52 years; median metastatic sites: 2) were enrolled and 97 cycles were completed. Maximum tolerated dose was wNP + wNPLD 25 mg/m2. The most common adverse events were neutropenia, nausea, diarrhea and mucositis. The objective response rate was 68% (response mean duration: 12.6 months). Conclusion: wNP/wNPLD combination constitutes an active regimen with mild toxicity. [ABSTRACT FROM AUTHOR]
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- 2020
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6. Activity of Eribulin Mesylate in Brain Metastasis from Breast Cancer: A Stone in a Pond?
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Catania, Giovanna, Malaguti, Paola, Gasparro, Simona, Cognetti, Francesco, Vidiri, Antonello, and Fabi, Alessandra
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ERIBULIN , *ANTINEOPLASTIC agents , *BONE metastasis , *BRAIN tumors , *BREAST tumors , *CANCER chemotherapy , *DRUG toxicity , *LIVER tumors , *LUNG tumors , *METASTASIS , *SURVIVAL , *DISEASE progression , *PROGNOSIS , *THERAPEUTICS - Abstract
Background: Brain metastases develop in approximately 10–25% of patients with metastatic breast cancer (MBC) and are associated with a very poor prognosis.Case Report: We report the case of a 40-year-old woman with MBC and associated lung, bone, liver, and brain metastases, who experienced a time to progression of several months with eribulin after whole-brain radiotherapy (WBRT), 2 lines of chemotherapy, and 1 line of hormonal therapy, maintaining a good toxicity profile.Discussion: Eribulin, in association with local treatment such as WBRT, can be well tolerated and effective in achieving a long progression-free survival and a good control of brain metastases in patients with MBC who have received multiple lines of treatment. The vascular remodeling properties of eribulin, combined with brain radiotherapy, might facilitate the passage of eribulin across the blood brain barrier, improving brain response.Conclusion: Our anecdotal experience suggests that eribulin may have a potentially beneficial effect on brain metastases while maintaining a good systemic control of the disease in patients with MBC. [ABSTRACT FROM AUTHOR]- Published
- 2018
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7. Palbociclib: efficacious but predictive biomarkers still needed
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Cognetti, Francesco, Malaguti, Paola, and Alesini, Daniele
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- 2016
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8. First-line therapy in HER2 positive metastatic breast cancer: is the mosaic fully completed or are we missing additional pieces?
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Fabi, Alessandra, Malaguti, Paola, Vari, Sabrina, and Cognetti, Francesco
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HER2 gene , *BREAST cancer , *EPIDERMAL growth factor receptors , *TRASTUZUMAB , *BIOMARKERS , *HER2 positive breast cancer , *CANCER treatment - Abstract
The discovery of human epidermal growth factor receptor 2 (HER2) and its role in the biology of breast cancer and the subsequent development of HER2-targeted therapies, have dramatically improved clinical outcomes for women with early-stage and advanced HER2-positive breast cancer (BC). HER-2 targeted therapies represent a major step forward in achieving the goal of delivering individualized targeted therapy for BC, and trastuzumab was the first anti-HER-2 strategy to be approved for treatment of HER-2 positive BC. This review discusses the treatment of metastatic HER2-positive BC and describes efficacy and safety of novel anti-HER2 target therapies in first-line metastatic settings and the future challenges include refining such treatments, reducing toxicity and simultaneously developing innovative therapies. Furthermore, combinations of trastuzumab and drugs targeting the downstream pathway are described. In the next future will be possible to use an ample armamentarium of combination therapies directed against HER2 and key signaling components integrated in the HER network. This approach will allow clinicians to tailor the management of the individual patient on the basis of tumor- specific biomarker profiles. There is an urgent need for prospective biomarker-driven trials to identify patients for whom targeting is cost-effective. [ABSTRACT FROM AUTHOR]
- Published
- 2016
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- View/download PDF
9. Prospective study on nanoparticle albumin-bound paclitaxel in advanced breast cancer: clinical results and biological observations in taxanepretreated patients.
- Author
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Fabi, Alessandra, Giannarelli, Diana, Malaguti, Paola, Ferretti, Gianluigi, Vari, Sabrina, Papaldo, Paola, Nisticò, Cecilia, Caterino, Mauro, De Vita, Roy, Mottolese, Marcella, Iacorossi, Laura, and Cognetti, Francesco
- Published
- 2015
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10. Metronomic oral cyclophosphamide (MOC) in the salvage therapy of heavily treated recurrent ovarian cancer patients: a retrospective, multicenter study.
- Author
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Ferrandina, Gabriella, Corrado, Giacomo, Mascilini, Floriana, Malaguti, Paola, Samaritani, Riccardo, Distefano, Mariagrazia, Masciullo, Valeria, Di Legge, Alessia, Savarese, Antonella, and Scambia, Giovanni
- Subjects
OVARIAN cancer treatment ,CYCLOPHOSPHAMIDE ,SALVAGE therapy ,DRUG efficacy ,MEDICATION safety ,DISEASE relapse ,RETROSPECTIVE studies - Abstract
Background The aim of this multicenter, retrospective study was to evaluate the efficacy and safety of metronomic oral cyclophosphamide (MOC) in heavily treated, relapsed ovarian cancer (ROC) patients. Methods oral cyclophosphamide (Endoxan®, Baxter, Italy) was administered at the dose of 50 mg daily, continuously. Treatment-related toxicity and response to treatment were assessed by the NCI-CTC criteria, and RECIST criteria, respectively. Progression-free (PFS), and overall survival (OS) were also assessed. Results 54 patients were analyzed: 20 patients (37.0%) were considered primarily platinum refractory/resistant, while 34 patients (63.0%) were defined as platinum sensitive; 79.6% of patients had received ≥2 previous lines before starting MOC. The objective response rate (ORR) was 20.4%. Eleven patients (20.4%) experienced stable disease and 8 of them had a response duration ≥6 months. A total of 32 patients (59.2.%) progressed during treatment. Median PFS was 4 months, and the 12-month PFS rate was 19.6%; median OS was 13 months, and the 12-month OS rate was 51.5% . Patients responding to MOC showed a more favorable PFS (median = 17 months) compared to patients with stabilization (median = 6 months) or progression of disease (median = 3 months) (p value = 0.0001). Median OS of responding patients was 30 months compared to 11 months in cases achieving stabilization, or progression of disease (median = 8 months) (p value = 0.0001). Only 1 patient experienced grade 3 anemia. Non-hematological grade 3 toxicity was registered in 2 patients. Conclusions MOC could provide a valid alternative in terms of risk/benefit ratio in the palliative treatment of heavily treated ROC patients. [ABSTRACT FROM AUTHOR]
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- 2014
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11. A Liquid Chromatography-Tandem Mass Spectrometry Method for the Determination of 5-Fluorouracil Degradation Rate by Intact Peripheral Blood Mononuclear Cells.
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Lostia, Alfonso M, Lionetto, Luana, Ialongo, Cristiano, Gentile, Giovanna, Viterbo, Antonella, Malaguti, Paola, Paris, Ida, Marchetti, Luca, Marchetti, Paolo, Blasi, Antonio De, and Simmaco, Maurizio
- Published
- 2009
- Full Text
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12. Unusual liver locations of growing teratoma syndrome in ovarian malignant germ cell tumors
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Lorusso, Domenica, Malaguti, Paola, Trivellizzi, Ilaria Nausica, and Scambia, Giovanni
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- 2011
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13. AXL Receptor in Breast Cancer: Molecular Involvement and Therapeutic Limitations.
- Author
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Falcone, Italia, Conciatori, Fabiana, Bazzichetto, Chiara, Bria, Emilio, Carbognin, Luisa, Malaguti, Paola, Ferretti, Gianluigi, Cognetti, Francesco, Milella, Michele, and Ciuffreda, Ludovica
- Subjects
BREAST cancer ,TUMOR microenvironment ,CANCER invasiveness ,BIOMARKERS ,ONCOGENES ,LIFE expectancy - Abstract
Breast cancer was one of the first malignancies to benefit from targeted therapy, i.e., treatments directed against specific markers. Inhibitors against HER2 are a significant example and they improved the life expectancy of a large cohort of patients. Research on new biomarkers, therefore, is always current and important. AXL, a member of the TYRO-3, AXL and MER (TAM) subfamily, is, today, considered a predictive and prognostic biomarker in many tumor contexts, primarily breast cancer. Its oncogenic implications make it an ideal target for the development of new pharmacological agents; moreover, its recent role as immune-modulator makes AXL particularly attractive to researchers involved in the study of interactions between cancer and the tumor microenvironment (TME). All these peculiarities characterize AXL as compared to other members of the TAM family. In this review, we will illustrate the biological role played by AXL in breast tumor cells, highlighting its molecular and biological features, its involvement in tumor progression and its implication as a target in ongoing clinical trials. [ABSTRACT FROM AUTHOR]
- Published
- 2020
- Full Text
- View/download PDF
14. MITO39: Efficacy and Tolerability of Pegylated Liposomal Doxorubicin (PLD)-Trabectedin in the Treatment of Relapsed Ovarian Cancer after Maintenance Therapy with PARP Inhibitors-A Multicenter Italian Trial in Ovarian Cancer Observational Case-Control Study.
- Author
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Turinetto M, Ricotti A, Marchetti C, Pisano C, Zamagni C, Cassani C, Malaguti P, Baldoni A, Scollo P, Scandurra G, Parisi A, Artioli G, Palaia I, Vertechy L, Bergamini A, Picardo E, Tuninetti V, Scotto G, Scambia G, Pignata S, and Valabrega G
- Abstract
Objective: While PLD-Trabectedin is an approved treatment for relapsed platinum-sensitive ovarian cancer, its efficacy and tolerability has so far not been tested extensively in patients who progress after poly ADP-ribose polymerase inhibitor (PARPi) treatment., Methodology: This multicenter, retrospective analysis had the objective of comparing patients receiving PLD-Trabectedin after being treated with PARP-I (cases) with PARPi-naïve patients. Descriptive and survival analyses were performed for each group., Results: Data from 166 patients were collected, composed of 109 cases and 57 controls. In total, 135 patients were included in our analyses, composing 46 controls and 89 cases. The median PFS was 11 months (95% IC 10-12) in the control group vs. 8 months (95% IC 6-9) in the case group ( p value 0.0017). The clinical benefit rate was evaluated, with an HR for progression of 2.55 (1.28-5.06) for the case group ( p value 0.008), persisting when adjusted for BRCA and line with treatment. We compared hematological toxicity, gastro-intestinal toxicity, hand-foot syndrome (HFS), fatigue, and liver toxicity, and no statistically significant disparity was noted, except for HFS with a p value of 0.006. The distribution of G3 and G4 toxicities was also equally represented., Conclusion: The MITO39 study showed a statistically significant difference in terms of PFS, suggesting that previous exposure to PARPi might inhibit the efficacy of PLD-Trabectedin. Regarding tolerability, no remarkable disparity was noted; PLD-Trabectedin was confirmed to be a well-tolerated scheme in both groups. To our knowledge, these are the first data regarding this topic, which we deem to be of great relevance in the current landscape.
- Published
- 2023
- Full Text
- View/download PDF
15. The immersive experience of virtual reality during chemotherapy in patients with early breast and ovarian cancers: The patient's dream study.
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Fabi A, Fotia L, Giuseppini F, Gaeta A, Falcicchio C, Giuliani G, Savarese A, Taraborelli E, Rossi V, Malaguti P, Giannarelli D, Pugliese P, and Cognetti F
- Abstract
Background: A virtual reality experience (VRE) could represent a viable non-pharmacological intervention to reduce and better manage the main factors of psychophysical distress related to the diagnosis and treatment of cancer., Aim: The "Patient's Dream" study was a two-arm randomized controlled trial conducted at the Regina Elena National Cancer Institute - IRCCS (Rome, Italy) from April 2019 to January 2020 to evaluate VRE impact in patients affected by breast or ovarian cancer. Before starting the first cycle of chemotherapy (CT), patients were randomized to receive the VRE (VRE arm) as "distraction therapy" or to entertain themselves with conventional means (control arm). The primary aims were the assessment of psychological distress, anxiety and quality of life between the two study arms. Secondary endpoints were the perceived time during the first course of CT and the acute and late toxicity., Results: Fourty-four patients were enrolled, 22 patients were randomly assigned to the VRE arm and 22 to the control arm. Collected data underline the absence of prevalent disturbs of anxiety and depression in both groups. Nevertheless, even if the state anxiety values before and after CT decreased in both groups, this reduction was statistically significant over time only in the VRE arm. The duration of therapy perceived by patients undergoing distraction therapy was significantly shorter when compared to the control group. The use of VRE during the first CT cycle appeared to reduce asthenia outcomes., Conclusion: Obtained data suggest that the VRE positively influenced the levels of state anxiety among cancer patients and support the continuous research on VRE as a distraction intervention, with the aim to meet the clinical need for effective nonpharmacologic adjunctive therapies., Clinical Trial Registration: https://clinicaltrials.gov/ct2/show/NCT05234996, identifier NCT05234996., Competing Interests: Authors FG, AG and GG are funders of Twiceout. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Fabi, Fotia, Giuseppini, Gaeta, Falcicchio, Giuliani, Savarese, Taraborelli, Rossi, Malaguti, Giannarelli, Pugliese and Cognetti.)
- Published
- 2022
- Full Text
- View/download PDF
16. An update on palonosetron hydrochloride for the treatment of radio/chemotherapy-induced nausea and vomiting.
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Fabi A and Malaguti P
- Subjects
- Animals, Antiemetics administration & dosage, Antiemetics adverse effects, Antiemetics pharmacokinetics, Drug Therapy, Combination, Humans, Isoquinolines administration & dosage, Isoquinolines adverse effects, Isoquinolines pharmacokinetics, Nausea chemically induced, Neurokinin-1 Receptor Antagonists, Palonosetron, Practice Guidelines as Topic, Quinuclidines administration & dosage, Quinuclidines adverse effects, Quinuclidines pharmacokinetics, Radiotherapy adverse effects, Serotonin 5-HT3 Receptor Antagonists administration & dosage, Serotonin 5-HT3 Receptor Antagonists adverse effects, Serotonin 5-HT3 Receptor Antagonists pharmacokinetics, Substance P antagonists & inhibitors, Treatment Outcome, Vomiting chemically induced, Antiemetics therapeutic use, Antineoplastic Agents adverse effects, Isoquinolines therapeutic use, Nausea prevention & control, Quinuclidines therapeutic use, Serotonin 5-HT3 Receptor Antagonists therapeutic use, Vomiting prevention & control
- Abstract
Introduction: Nausea and vomiting are well recognized in different clinical situations, suggesting that no single mechanism is likely to be responsible for their production. Chemotherapy-induced nausea and vomiting (CINV) can have a negative impact on quality of life and this may lead to a refusal of curative therapy or to a decline in palliative benefits offered by cytotoxic treatment. Palonosetron is a new agent in the class of 5-HT3 receptor antagonists (5-HT3RAs), and differs from the other agents by its higher receptor-binding affinity and longer half-life. These pharmacological properties have resulted in improved antiemetic activity in clinical trials, particularly in the treatment of delayed CINV following moderate emetogenic chemotherapy (MEC)., Area Covered: A systematic review of the medical literature was completed to inform this update. MEDLINE, the Cochrane Collaboration Library and meeting materials from ASCO and MASCC were all searched., Expert Opinion: Palonosetron was the only serotonin receptor antagonist approved for prevention of delayed CINV caused by MEC and its use was incorporated in guideline recommendations. To date, several treatment settings such as multiple day chemotherapy require further studies to improve emesis related to therapy.
- Published
- 2013
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17. Epidermal growth factor receptor gene copy number may predict lapatinib sensitivity in HER2-positive metastatic breast cancer.
- Author
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Fabi A, Merola R, Ferretti G, Di Benedetto A, Antoniani B, Ercolani C, Nisticò C, Papaldo P, Ciccarese M, Sperduti I, Vici P, Marino M, Gori S, Botti C, Malaguti P, Cognetti F, and Mottolese M
- Subjects
- Adult, Aged, Biomarkers metabolism, Breast Neoplasms pathology, Drug Resistance, Neoplasm, Female, Gene Dosage, Humans, Lapatinib, Middle Aged, Neoplasm Metastasis, Proportional Hazards Models, Prospective Studies, Protein Kinase Inhibitors pharmacology, ROC Curve, Receptor, ErbB-2 metabolism, Regression Analysis, Antineoplastic Agents pharmacology, Breast Neoplasms drug therapy, ErbB Receptors genetics, Quinazolines pharmacology
- Abstract
Objective: Lapatinib, a dual HER2/EGFR tyrosine kinase inhibitor (TKI), associated to capecitabine represents the treatment of choice in HER2-positive metastatic breast cancer (BC) patients in progression after trastuzumab-based therapy. Though lapatinib-based therapy prolongs the time to progression, its efficacy is often limited by the development of drug resistance. It is aimed to evaluate novel biomarkers predictive of lapatinib response, we analyzed EGFR protein and gene status in a series of 50 metastatic HER2-positive BC patients., Methods: Lapatinib was given at 1250 mg/day continuously and capecitabine at 2000 mg/m(2)/day every 3 weeks. EGFR protein expression and gene copy number (GCN) were assessed by immunohistochemistry and FISH, respectively. Receiver operating curve (ROC) analysis identified the value of > 3.36 EGFR copies/nucleus as the cut-off point able to discriminate responders versus non-responders., Results: A statistical significant correlation between EGFR GCN value > 3.36 and response to lapatinib (p = 0.01) was found. Cox regression analysis further supported these findings evidencing that HER2 score 3+ and EGFR GCN increase are positive predictor factors of lapatinib response., Conclusions: Though further investigations are needed to confirm these findings, EGFR GCN could be a suitable screening to identify the subset of BC patients particularly responsive to the dual TKI lapatinib.
- Published
- 2013
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18. The Mammalian target of rapamycin inhibitors in breast cancer: current evidence and future directions.
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Malaguti P, Vari S, Cognetti F, and Fabi A
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- Clinical Trials as Topic, Drug Resistance, Neoplasm genetics, Estrogens metabolism, Everolimus, Female, Humans, Molecular Targeted Therapy, Phosphatidylinositol 3-Kinases metabolism, Proto-Oncogene Proteins c-akt metabolism, Receptor, ErbB-2 metabolism, Sirolimus analogs & derivatives, Sirolimus therapeutic use, Breast Neoplasms drug therapy, Breast Neoplasms metabolism, Breast Neoplasms pathology, Neoplasms, Hormone-Dependent metabolism, Neoplasms, Hormone-Dependent pathology, Neoplasms, Hormone-Dependent therapy, TOR Serine-Threonine Kinases antagonists & inhibitors, TOR Serine-Threonine Kinases genetics, TOR Serine-Threonine Kinases metabolism
- Abstract
Mammalian target of rapamycin (mTOR) is a crucial mediator of tumor progression and may be a promising target in a significant proportion of patients with breast cancer. More specifically, the phosphatidylinositol-3-kinase (PI3K)/protein kinase B (AKT)/mTOR pathway plays a critical role in multiple cellular functions including metabolism, proliferation, growth and survival. This pathway is higly active in many types of cancer and is linked to resistance to many types of therapy. Direct blockade of the mTOR pathway is a new area in breast cancer therapy, with the potential to modulate growth factor- and estrogen-dependent and estrogen-independent pathways, which contribute to the pathogenesis and progression of tumors. Thus, inhibitors of mTOR are of interest as potential therapeutic agents for patients with breast cancer, everolimus and temsirolimus being the main representatives of this category. This review of the literature analyzes the available data emerging from trials and evaluates the efficacy and safety of mTOR inhibitors in all subtypes of breast cancer.
- Published
- 2013
19. [Pharmacogenomics and chemotherapy].
- Author
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Paris I, Cappellini GC, Malaguti P, Bassanelli M, and Marchetti P
- Subjects
- Animals, Antimetabolites, Antineoplastic metabolism, Antimetabolites, Antineoplastic therapeutic use, Antimetabolites, Antineoplastic toxicity, Antineoplastic Agents metabolism, Camptothecin analogs & derivatives, Camptothecin metabolism, Camptothecin toxicity, Cisplatin, Dihydrouracil Dehydrogenase (NADP), Enzyme Inhibitors toxicity, Fluorouracil metabolism, Fluorouracil toxicity, Genotype, Irinotecan, Neoplasms mortality, Polymorphism, Genetic, Survival Analysis, Taxoids therapeutic use, Thymidylate Synthase genetics, Time Factors, Antineoplastic Agents therapeutic use, Antineoplastic Agents, Phytogenic toxicity, Drug Resistance, Neoplasm, Neoplasms drug therapy, Pharmacogenetics, Toxicology
- Abstract
Genetic factors could alter drug metabolism and activity and could predict drug toxicity and/or efficacy. Several chemotherapy agents are administered in different schedules for the treatment of different cancer histotypes. The most used drug in the treatment of gastro-intestinal, head and neck and breast neoplasms is the 5-fluorouracil (5-FU). Capecitabine is a prodrug of 5-FU. Cisplatin based chemotherapy is administered in the treatment of lung, genitourinary tract, head and neck, occult neoplasms, mesothelioma and melanoma. Taxanes are used in lung, breast, head and neck, genitourinary tract neoplasms and sarcomas. Determination of polymorphisms in metabolizing enzymes before the administration of chemotherapy could offer new strategies for optimizing the treatment of individual patients.
- Published
- 2010
20. Pilot study of celecoxib and infusional 5-fluorouracil as second-line treatment for advanced pancreatic carcinoma.
- Author
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Milella M, Gelibter A, Di Cosimo S, Bria E, Ruggeri EM, Carlini P, Malaguti P, Pellicciotta M, Terzoli E, and Cognetti F
- Subjects
- Adenocarcinoma pathology, Adult, Aged, Antineoplastic Combined Chemotherapy Protocols adverse effects, Carcinoembryonic Antigen blood, Carcinoembryonic Antigen drug effects, Celecoxib, Disease Progression, Female, Fluorouracil administration & dosage, Fluorouracil adverse effects, Humans, Infusions, Intravenous, Male, Middle Aged, Pancreatic Neoplasms pathology, Pilot Projects, Pyrazoles, Sulfonamides administration & dosage, Sulfonamides adverse effects, Treatment Outcome, Adenocarcinoma drug therapy, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Pancreatic Neoplasms drug therapy
- Abstract
Background: Cyclooxygenase-2 (COX-2) is up-regulated frequently and may constitute a promising therapeutic target in patients with pancreatic ductal adenocarcinoma (PDAC)., Methods: Patients with advanced PDAC who had progressive disease after gemcitabine-based chemotherapy were eligible for this pilot study. Treatment was comprised of oral celecoxib (400 mg twice daily) and protracted intravenous (i.v.) infusion 5-fluorouracil (5-FU) (200 mg/m(2) per day), both given continuously for a maximum of 9 treatment months, in the absence of disease progression or unacceptable toxicity. Patients were examined weekly for toxicity and were restaged every 6-8 weeks for tumor assessment., Results: Seventeen patients entered the study. Asymptomatic transaminase elevation was the most common toxicity and reached NCI-CTC (version 3.0) Grade 3-4 in 4 of 133 treatment weeks. No other hematologic or nonhematologic toxicity > Grade 2 was observed. Four patients discontinued celecoxib due to upper gastrointestinal tract toxicity. Two confirmed partial responses (durations of 23 weeks and 68 weeks, respectively) and 2 patients with stable disease (durations of 10 weeks and 13 weeks, respectively) were observed for an overall response rate of 12% (95% confidence interval, 0-27%) in the intent-to-treat population. A significant decrease (> or = 50%) in serum CA 19.9 levels was observed in 3 of 9 evaluable patients. The median time to disease progression was 8 weeks, and the median overall survival was 15 weeks., Conclusions: The combination of oral celecoxib and 5-FU by protracted i.v. infusion was found to be feasible and well tolerated, and was capable of inducing durable objective responses, even in patients with far advanced, gemcitabine-resistant/refractory PDAC. Further exploration of COX-2 inhibitor/fluropyrimidine combinations is warranted., (Copyright 2004 American Cancer Society.)
- Published
- 2004
- Full Text
- View/download PDF
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