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1.
Hepatol Res ; 51(12): 1229-1241, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34591334

RESUMO

BACKGROUND: Advanced Hepatocarcinoma (HCC) is an important health problem worldwide. Recently, the REFLECT trial demonstrated the non-inferiority of Lenvatinib compared to Sorafenib in I line setting, thus leading to the approval of new first-line standard of care, along with Sorafenib. AIMS AND METHODS: With aim to evaluate the optimal choice between Sorafenib and Lenvatinib as primary treatment in clinical practice, we performed a multicentric analysis with the propensity score matching on 184 HCC patients. RESULTS: The median overall survival (OS) were 15.2 and 10.5 months for Lenvatinib and Sorafenib arm, respectively. The median progression-free survival (PFS) was 7.0 and 4.5 months for Lenvatinib and Sorafenib arm, respectively. Patients treated with Lenvatinib showed a 36% reduction of death risk (p = 0.0156), a 29% reduction of progression risk (p = 0.0446), a higher response rate (p < 0.00001) and a higher disease control rate (p = 0.002). Sorafenib showed to be correlated with more hand-foot skin reaction and Lenvatinib with more hypertension and fatigue. We highlighted the prognostic role of Barcelona Clinic Liver Cancer (BCLC) stage, Eastern Cooperative Oncology Group Performance Status (ECOG-PS), bilirubin, alkaline phosphatase and eosinophils for Sorafenib. Conversely, albumin, aspartate aminotransferase (AST), alkaline phosphatase and Neutrophil-Lymphocyte Ratio (NLR) resulted prognostic in Lenvatinib arm. Finally, we highlighted the positive predictive role of albumin > Normal Value (NV), ECOG > 0, NLR < 3, absence of Hepatitis C Virus positivity, and presence of portal vein thrombosis in favor of Lenvatinib arm. Eosinophil < 50 and ECOG > 0 negatively predicted the response to Sorafenib. CONCLUSION: SLenvatinib showed to better perform in a real-word setting compared to Sorafenib. More researches are needed to validate the predictor factors of response to Lenvatinib rather than Sorafenib.

2.
Tumori ; 107(6): 550-555, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33243068

RESUMO

INTRODUCTION: The association between pancreatic ductal adenocarcinoma (PDAC) and type 2 diabetes mellitus (DM2) has long been evaluated and the role of antidiabetic medications such as metformin has also been investigated. The objective of this study was to examine the association between insulin use and overall survival (OS) in patients with advanced PDAC and DM2. METHODS: We retrospectively collected data from 164 patients, including an exploratory cohort of 96 patients from Medical Oncology Unit, University Hospital and University of Cagliari, Italy, and a validation cohort of 68 patients from Medical Oncology of Modena University Hospital. Patients had metastatic disease and received a first-line gemcitabine-based chemotherapy and, subsequently, a second-line fluoropyrimidines-based chemotherapy. We performed univariate analysis to evaluate correlation between long-term diabetes and overall survival. Then we performed multivariate analysis, adjusting for sex, metastatic sites, Eastern Cooperative Oncology Group Performance Status, Ca19.9 levels, N/L ratio, and lactate dehydrogenase levels at diagnosis, to confirm the independence of the variable. RESULTS: In the exploratory cohort, DM2 was significantly associated with higher median OS at univariate analysis (16 vs 10 months; p = 0.004). This result was confirmed by validation cohort (11 months vs 6 months; p = 0.01). In multivariate analysis, insulin-treated patients compared with non diabetic patients showed a significantly increased survival of 4.6 months (p = 0.03). CONCLUSIONS: Patients with insulin-treated metastatic PDAC showed better OS than non diabetic patients, as demonstrated by both cohorts. The correlation between OS and insulin-treated DM2 should be investigated further through a prospective clinical trial.


Assuntos
Carcinoma Ductal Pancreático/complicações , Carcinoma Ductal Pancreático/mortalidade , Diabetes Mellitus Tipo 2/complicações , Neoplasias Pancreáticas/complicações , Neoplasias Pancreáticas/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Ductal Pancreático/epidemiologia , Carcinoma Ductal Pancreático/patologia , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/epidemiologia , Feminino , Humanos , Hipoglicemiantes/administração & dosagem , Insulina/administração & dosagem , Itália/epidemiologia , Masculino , Pessoa de Meia-Idade , Neoplasias Pancreáticas/epidemiologia , Neoplasias Pancreáticas/patologia , Prognóstico , Vigilância em Saúde Pública , Estudos Retrospectivos , Análise de Sobrevida
3.
HPB (Oxford) ; 23(6): 915-920, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33191108

RESUMO

BACKGROUND AND AIM: The aim of our retrospective study is to evaluate the prognostic significance of aspirin in patients with advanced HCC treated with sorafenib. METHODS: 304 patients with HCC,consecutively treated with sorafenib from May 2007 to September 2018, were included in the clinical study. Of Them 93 patients token aspirin. Progression-free survival (PFS)and overall survival (OS)were estimated with the Kaplan-Meier method and compared with the log-rank test. RESULTS: The concomitant use of sorafenib and aspirin was associated with a median OS of 18.3 months compared to 8.8 months of patients who did not receive aspirin (HR 0.57; P < 0.0001). The concomitant use of sorafenib and aspirin was associated with a median PFS of 7.3 months compared to 3.0 months of patients who did not receive aspirin (HR 0.61; P = 0.0003). In the multivariate analysis, the use of aspirin maintained an independent prognostic value for OS(HR 0.61; P = 0.0013). In second line the concomitant use of regorafenib and aspirin was associated with a median OS of 16.9 months compared to 8.0 months of patients who did not receive aspirin (HR 0.30; P = 0.02). CONCLUSION: Globally, our data seem to suggest that aspirin use may improve the clinical outcome of patients with advanced hepatocellular carcinoma receiving sorafenib and regorafenib.


Assuntos
Antineoplásicos , Carcinoma Hepatocelular , Neoplasias Hepáticas , Antineoplásicos/efeitos adversos , Aspirina/efeitos adversos , Carcinoma Hepatocelular/tratamento farmacológico , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Compostos de Fenilureia/efeitos adversos , Piridinas , Estudos Retrospectivos , Sorafenibe/efeitos adversos , Resultado do Tratamento
4.
Crit Rev Oncol Hematol ; 157: 103167, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33271389

RESUMO

Advanced hepatocellular carcinoma (HCC) is the most frequent liver cancer. Immunotherapy has been explored in this disease in order to improve survival outcomes. Nowadays, scientific research is focusing especially on immune checkpoint inhibitors, in particular anti-PD1, anti-PD-L1 and anti-CTLA4 monoclonal antibodies (mAbs), as single-agent or in combination with other immunotherapy agents, target therapies, anti-vascular endothelial growth factor (VEGF) and other agents targeting specific molecular pathways. Other immunotherapy strategies have been assessed or are under investigation in advanced HCC, namely cytokines, adoptive cell therapy, oncolytic virus, cancer vaccines. Each treatment presents specific efficacy and toxicity profiles, strictly related to their mechanism of action and to advanced HCC tumour microenvironment (TME). The aim of this review is to outline the state-of-the-art of immunotherapy in advanced HCC treatment, highlighting data on already investigated treatment strategies, safety and toxicity (including HBV/HCV-related HCC), and ongoing clinical trials focusing on new promising therapeutic weapons.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Anticorpos Monoclonais , Carcinoma Hepatocelular/terapia , Humanos , Fatores Imunológicos , Imunoterapia , Neoplasias Hepáticas/terapia , Microambiente Tumoral
5.
PLoS One ; 15(5): e0232449, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32379785

RESUMO

BACKGROUND AND AIMS: The present study aims to investigate the role of the prognostic nutritional index (PNI) on survival in patients with advanced hepatocellular carcinoma (HCC) treated with sorafenib. METHODS: This multicentric study included a training cohort of 194 HCC patients and three external validation cohorts of 129, 76 and 265 HCC patients treated with Sorafenib, respectively. The PNI was calculated as follows: 10 × serum albumin (g/dL) + 0.005 × total lymphocyte count (per mm3). Univariate and multivariate analyses were performed to investigate the association between the covariates and the overall survival (OS). RESULTS: A PNI cut-off value of 31.3 was established using the ROC analysis. In the training cohort, the median OS was 14.8 months (95% CI 12-76.3) and 6.8 months (95% CI 2.7-24.6) for patients with a high (>31.3) and low (<31.3) PNI, respectively. At both the univariate and the multivariate analysis, low PNI value (p = 0.0004), a 1-unit increase of aspartate aminotransferase (p = 0.0001), and age > 70 years (p< 0.0038) were independent prognostic factors for OS. By performing the same multivariate analysis of the training cohort, the PNI <31.3 versus >31.3 was found to be an independent prognostic factor for predicting OS in all the three validation cohorts. CONCLUSIONS: PNI represents a prognostic tool in advanced HCC treated with first-line Sorafenib. It is readily available and low-cost, and it could be implemented in clinical practice in patients with HCC.


Assuntos
Antineoplásicos/uso terapêutico , Carcinoma Hepatocelular/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Avaliação Nutricional , Sorafenibe/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Hepatocelular/sangue , Carcinoma Hepatocelular/mortalidade , Estudos de Coortes , Feminino , Humanos , Itália/epidemiologia , Estimativa de Kaplan-Meier , Neoplasias Hepáticas/sangue , Neoplasias Hepáticas/mortalidade , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Albumina Sérica/metabolismo
6.
Cancers (Basel) ; 12(5)2020 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-32413973

RESUMO

BACKGROUND: Metastatic CRC (mCRC) is a molecular heterogeneous disease. The aim of this review is to give an overview of molecular-driven treatment of mCRC patients. METHODS: A review of clinical trials, retrospective studies and case reports was performed regarding molecular biomarkers with therapeutic implications. RESULTS: RAS wild-type status was confirmed as being crucial for anti-epidermal growth factor receptor (EGFR) monoclonal antibodies and for rechallenge strategy. Antiangiogenic therapies improve survival in first- and second-line settings, irrespective of RAS status, while tyrosine kinase inhibitors (TKIs) remain promising in refractory mCRC. Promising results emerged from anti-HER2 drugs trials in HER2-positive mCRC. Target inhibitors were successful for BRAFV600E mutant mCRC patients, while immunotherapy was successful for microsatellite instability-high/defective mismatch repair (MSI-H/dMMR) or DNA polymerase epsilon catalytic subunit (POLE-1) mutant patients. Data are still lacking on NTRK, RET, MGMT, and TGF-ß, which require further research. CONCLUSION: Several molecular biomarkers have been identified for the tailored treatment of mCRC patients and multiple efforts are currently ongoing to increase the therapeutic options. In the era of precision medicine, molecular-biology-driven treatment is the key to impro patient selection and patient outcomes. Further research and large phase III trials are required to ameliorate the therapeutic management of these patients.

7.
Front Oncol ; 10: 601240, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33585218

RESUMO

Hepatocellular carcinoma (HCC) is the typical inflammation-induced neoplasia. It often prospers where a chronic liver disease persists, thus leading a strong rationale for immune therapy. Several immune-based treatments, including immune checkpoint inhibitors (ICI), cytokines, adoptive cell transfer, and vaccines, have been tested in the treatment of HCC. In this review, we summarize the role of the ICI in HCC patients in various sets of treatment. As for advanced HCC, the anti-Programmed cell Death protein 1 (PD1) antibodies and the anti-Cytotoxic T-Lymphocyte Antigen 4 (CTLA-4) antibodies have been examined in patients with enthusiastic results in phase I-II-III studies. Overall, this led the Food and Drug Administration (FDA) to approve pembrolizumab, nivolumab, and nivolumab + ipilimumab in the second-line setting. The anti- Programmed Death-Ligand 1 (PDL-1) antibodies have also been evaluated. Thanks to the results obtained from phase III IMbrave study, atezolizumab + bevacizumab is now the standard of care in the first-line advanced setting of HCC. As for localized HCC, the putative immunological effect of locoregional therapies led to evaluate the combination strategy with ICI. This way, chemoembolization, ablation with radiofrequency, and radioembolization combined with ICI are currently under study. Likewise, the study of adjuvant immunotherapy following surgical resection is underway. In addition, the different ICI has been studied in combination with other ICI as well as with multikinase inhibitors and anti-angiogenesis monoclonal antibody. The evidence available suggests that combining systemic therapies and locoregional treatments with ICI may represent an effective strategy in this context.

8.
Front Physiol ; 9: 1294, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30294279

RESUMO

Cancer-related anemia (CRA) is a common sign occurring in more than 30% of cancer patients at diagnosis before the initiation of antineoplastic therapy. CRA has a relevant influence on survival, disease progression, treatment efficacy, and the patients' quality of life. It is more often detected in patients with advanced stage disease, where it represents a specific symptom of the neoplastic disease, as a consequence of chronic inflammation. In fact, CRA is characterized by biological and hematologic features that resemble those described in anemia associated to chronic inflammatory disease. Proinflammatory cytokine, mainly IL-6, which are released by both tumor and immune cells, play a pivotal action in CRA etiopathogenesis: they promote alterations in erythroid progenitor proliferation, erythropoietin (EPO) production, survival of circulating erythrocytes, iron balance, redox status, and energy metabolism, all of which can lead to anemia. The discovery of hepcidin allowed a greater knowledge of the relationships between immune cells, iron metabolism, and anemia in chronic inflammatory diseases. Additionally, chronic inflammation influences a compromised nutritional status, which in turn might induce or contribute to CRA. In the present review we examine the multifactorial pathogenesis of CRA discussing the main and novel mechanisms by which immune, nutritional, and metabolic components affect its onset and severity. Moreover, we analyze the status of the art and the perspective for the treatment of CRA. Notably, despite the high incidence and clinical relevance of CRA, controlled clinical studies testing the most appropriate treatment for CRA are scarce, and its management in clinical practice remains challenging. The present review may be useful to indicate the development of an effective approach based on a detailed assessment of all factors potentially involved in the pathogenesis of CRA. This mechanism-based approach is essential for clinicians to plan a safe, targeted, and successful therapy, thereby promoting a relevant amelioration of patients' quality of life.

9.
Target Oncol ; 11(5): 593-603, 2016 10.
Artigo em Inglês | MEDLINE | ID: mdl-27184491

RESUMO

The encouraging results in immunotherapy for melanoma also led the way for translational and clinical research about immune-related mechanisms possibly relevant for gastrointestinal tumours. It is in fact now evident that the immune checkpoint modulation and in particular cell-mediated immune-response through programmed cell death-1 (PD-1) and the cytotoxic T-lymphocyte antigen-4 (CTLA4) receptors along with the regulatory T cells activity all have a relevant role in gastrointestinal cancers as well. This review aims to explore the state of the art of immunotherapy for gastrointestinal tumours, deepening recent scientific evidence regarding anti PD-1/PDL-1 and anti CTLA4 monoclonal antibodies, peptide based vaccine, DNA based vaccine, and pulsed dendritic cells, either alone or in combination with other antineoplastic medical therapy and locoregional treatments. Considering the non-negligible toxicity profile deriving from such a treatment approach, predictive biomarkers of response to immunotherapy in gastrointestinal cancer are also urgently needed in order to better select the patients' group with the highest likelihood of benefit.


Assuntos
Neoplasias Gastrointestinais/imunologia , Imunoterapia/métodos , Terapia de Alvo Molecular/métodos , Humanos
10.
Future Oncol ; 11(19): 2697-2710, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26376740

RESUMO

The present review aimed at discussing the impact, pathogenesis and therapeutic approaches of muscle wasting, which is a major clinical feature of cancer-related cachexia syndrome. The pathogenesis of muscle wasting in cancer cachexia lies in a discrepancy between anabolic and catabolic pathways mediated by chronic inflammation. Effective interventions specifically aimed at hampering muscle loss and enhancing muscle function are still lacking. Promising agents include anti-inflammatory, orexigenic and anabolic drugs, alongside with nutritional supplements that influence the STAT3 and PI3K/Akt/mTOR pathways involved in muscle wasting. Personalized physical activity combined with pharmacological and nutritional support hold promise. A greater understanding of the pathogenetic processes of cancer cachexia-related muscle wasting will enable the development of an early and effective targeted mechanism-based multimodal approach.

11.
Clin Nutr ; 31(2): 176-82, 2012 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-22047681

RESUMO

BACKGROUND & AIMS: A phase III, randomized non-inferiority study was carried out to compare a two-drug combination (including nutraceuticals, i.e. antioxidants) with carnitine + celecoxib ± megestrol acetate for the treatment of cancer-related anorexia/cachexia syndrome (CACS): the primary endpoints were increase of lean body mass (LBM) and improvement of total daily physical activity. Secondary endpoint was: increase of physical performance tested by grip strength and 6-min walk test. METHODS: Sixty eligible patients were randomly assigned to: arm 1, L-carnitine 4 g/day + Celecoxib 300 mg/day or arm 2, L-carnitine 4 g/day + celecoxib 300 mg/day + megestrol acetate 320 mg/day, all orally. All patients received as basic treatment polyphenols 300 mg/day, lipoic acid 300 mg/day, carbocysteine 2.7 g/day, Vitamin E, A, C. Treatment duration was 4 months. Planned sample size was 60 patients. RESULTS: The results did not show a significant difference between tre atment arms in both primary and secondary endpoints. Analysis of changes from baseline showed that LBM (by dual-energy X-ray absorptiometry and by L3 computed tomography) increased significantly in both arms as well as physical performance assessed by 6MWT. Toxicity was quite negligible and comparable between arms. CONCLUSIONS: The results of the present study showed a non-inferiority of arm 1 (two-drug combination) vs arm 2 (two-drug combination + megestrol acetate). Therefore, this simple, feasible, effective, safe, low cost with favorable cost-benefit profile, two-drug approach could be suggested in the clinical practice to implement CACS treatment.


Assuntos
Anorexia/tratamento farmacológico , Caquexia/tratamento farmacológico , Carnitina/uso terapêutico , Acetato de Megestrol/uso terapêutico , Neoplasias/complicações , Pirazóis/uso terapêutico , Sulfonamidas/uso terapêutico , Absorciometria de Fóton , Idoso , Idoso de 80 Anos ou mais , Anorexia/complicações , Apetite , Caquexia/complicações , Celecoxib , Terapia Combinada , Combinação de Medicamentos , Determinação de Ponto Final , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/tratamento farmacológico , Cooperação do Paciente , Qualidade de Vida , Resultado do Tratamento
12.
J Mol Med (Berl) ; 88(7): 677-86, 2010 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-20339829

RESUMO

Obesity is considered the most important risk and prognostic factor for estrogen-dependent breast cancer in postmenopausal women. Adipokines, in particular leptin, are at the center of the etiopathogenetic mechanisms by which obesity and related metabolic disorders influence breast cancer risk and its prognosis. The present prospective observational study aims to investigate the relationship between body mass index (BMI), serum levels of leptin and proinflammatory cytokines, and breast cancer prognostic factors. In the study, 98 postmenopausal and 82 premenopausal patients with ER-positive breast cancer participated. During the same study period, 221 control subjects were simultaneously recruited. Women underwent baseline measurements pre-operatively, before any surgical and systemic treatments. Pathologic characteristics of tumors were abstracted from pathology reports. Leptin and proinflammatory cytokines were assayed in stored fasting blood specimens. In postmenopausal breast cancer patients, BMI, leptin, and interleukin-6 significantly correlated with pathological tumor classification (pT) and TNM stage. Multivariate regression analysis showed that BMI and leptin, but not interleukin-6, were independent predictive variables of pT and TNM stage. Our results seem to suggest a twofold role of leptin in the etiopathogenesis of postmenopausal estrogen-positive breast cancer. Indeed, leptin reflects the total amount of fat mass, which correlates to aromatase activity and subsequent estrogens levels. Further studies are warranted to clarify the role of leptin and interleukin-6 in breast carcinogenesis and identify new therapeutic options, beyond the use of aromatase inhibitors, acting selectively on adipokine-driven pathways.


Assuntos
Índice de Massa Corporal , Neoplasias da Mama/sangue , Neoplasias da Mama/patologia , Leptina/sangue , Pós-Menopausa , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/imunologia , Feminino , Humanos , Interleucina-6/sangue , Interleucina-6/imunologia , Pessoa de Meia-Idade , Pré-Menopausa , Prognóstico , Estudos Prospectivos , Fator de Necrose Tumoral alfa/sangue , Fator de Necrose Tumoral alfa/imunologia , Adulto Jovem
13.
J Cell Mol Med ; 13(9B): 3951-9, 2009 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-18624749

RESUMO

The progression of the neoplastic disease is characterized by specific alterations of energy metabolism and by symptoms like fatigue, anorexia, nausea, anaemia, immunodepression and poor performance status (PS). The main cause of these symptoms and metabolic abnormalities is the chronic action of proinflammatory cytokines released both by tumour and immune cells. The present study aimed to assess the relationship between markers of inflammation (C-Reactive Protein, Fibrinogen, proinflammatory cytokines) and energy metabolic status (BMI, leptin, oxidative stress) according to clinical parameters in 104 ovarian cancer patients at different stage and, moreover, to evaluate prospectively the changes of these parameters in accordance to tumour response in a subgroup of 70 advanced stage ovarian cancer patients. Advanced stage and poor PS were associated to high-grade inflammation and impaired energy metabolism. Among inflammatory mediators, interleukin (IL)-6 had a central role as predictive factor of leptin, reactive oxygen species and glutathione peroxidase. In turn, leptin considered the key marker of the nutritional status and energy metabolism, was independently determined from stage and IL-6, not only from BMI. Moreover, the evaluation of the changes of these parameters during the course of the neoplastic disease in the subgroup of advanced ovarian cancer patients clearly unveils the central role of IL-6 and leptin as early markers of the metabolic alterations and symptoms associated to disease progression in advanced stage ovarian cancer. Their assessment should be included in monitoring disease outcome, especially when cancer is no longer curable and quality of life becomes the primary endpoint.


Assuntos
Regulação Neoplásica da Expressão Gênica , Interleucina-6/metabolismo , Leptina/metabolismo , Neoplasias Ovarianas/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Metabolismo Energético , Feminino , Glutationa Peroxidase/metabolismo , Humanos , Inflamação , Leptina/biossíntese , Pessoa de Meia-Idade , Neoplasias Ovarianas/patologia , Espécies Reativas de Oxigênio , Resultado do Tratamento
14.
Crit Rev Oncol Hematol ; 70(1): 83-91, 2009 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-18723369

RESUMO

Aim of the present phase II non-randomized study was to verify whether palonosetron might be able to prevent acute and especially delayed CINV for either HEC or MEC, starting from the second chemotherapy cycle, in patients who had failed to respond to a different antiemetic 5-HT(3) antagonist during the first cycle. Stratification factor was age <65 years vs. > or =65 years of patients included. Forty-seven cancer patients (23 elderly and 24 non-elderly) scheduled to receive HEC or MEC regimens who had experienced CINV grade 3-4 during the first chemotherapy course and for whom the same course of chemotherapy regimen was further scheduled were enrolled. Complete response (CR) and complete control (CC) rates for the acute, delayed and overall phases of CINV were not significantly different between elderly and non-elderly patients. Palonosetron was safe: only grade 1-2 toxicities were observed with a peak of 12.9% for asthenia with no significant difference between elderly and non-elderly patients. In conclusion, single dose palonosetron (250 microg) should be considered a safe and effective second generation 5-HT(3) antagonist in the prevention of nausea and vomiting induced by HEC or MEC, irrespective of patients' age.


Assuntos
Antieméticos/uso terapêutico , Dexametasona/uso terapêutico , Isoquinolinas/uso terapêutico , Náusea/prevenção & controle , Quinuclidinas/uso terapêutico , Antagonistas da Serotonina/uso terapêutico , Vômito/prevenção & controle , Doença Aguda , Adulto , Idoso , Idoso de 80 Anos ou mais , Antieméticos/administração & dosagem , Antineoplásicos/efeitos adversos , Antineoplásicos/uso terapêutico , Dexametasona/administração & dosagem , Feminino , Humanos , Isoquinolinas/administração & dosagem , Isoquinolinas/efeitos adversos , Masculino , Pessoa de Meia-Idade , Náusea/induzido quimicamente , Neoplasias/tratamento farmacológico , Palonossetrom , Quinuclidinas/administração & dosagem , Quinuclidinas/efeitos adversos , Antagonistas da Serotonina/administração & dosagem , Vômito/induzido quimicamente
15.
Crit Rev Oncol Hematol ; 66(1): 75-83, 2008 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-18164209

RESUMO

OBJECTIVES: To establish a correlation between a specific MGA category, an appropriate preventively established treatment and clinical outcome in a population of elderly cancer patients. The ultimate goal was to verify whether the appropriate treatment given to elderly cancer patients according to their MGA category could translate into a better clinical outcome assessed as clinical response and toxicity, i.e whether this process might achieve a clinically meaningful impact. PATIENTS AND METHODS: We carried out a phase II open, prospective non-randomized study in 75 elderly cancer patients (lung, head and neck, colorectal, gynecologic and breast) hospitalized at the Department of Medical Oncology, University of Cagliari, Italy. All patients underwent MGA evaluation and were assigned to three different categories: fit, intermediate and frail. Thereafter, an appropriate preventively established treatment was administered and the clinical outcome was assessed. The clinical outcome after 3 month treatment was defined on the basis of objective clinical response and toxicity. The difference of clinical outcome in the MGA categories was assessed by ANOVA test. Moreover, the correlation between MGA category and the clinical outcome (clinical response and toxicity) was assessed by Spearman's correlation test. RESULTS: A better clinical response was observed in fit patients as compared both to intermediate and frail patients. Treatment toxicity was comparable in the different MGA categories. The correlation analysis between MGA category, clinical response to treatment and toxicity showed that there was a significant direct correlation with clinical response and no correlation with toxicity. Overall, the regression analysis showed that MGA was predictive of clinical outcome, in the sense that it is truly predictive for clinical response and no predictive for toxicity. CONCLUSION: Our study demonstrates that the MGA, although time-consuming, is a useful and cost-benefit effective tool to appropriately select elderly cancer patients to be treated effectively in terms of a survival advantage and those who would benefit mainly in terms of improvement of quality of life. Moreover, the treatment preventively established for each MGA category was shown to be adequate and accomplished the most appropriate performances in terms of effectiveness and toxicity.


Assuntos
Avaliação Geriátrica , Neoplasias/terapia , Atividades Cotidianas , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Neoplasias/psicologia , Estudos Prospectivos , Resultado do Tratamento
16.
Cancer Epidemiol Biomarkers Prev ; 15(5): 1030-4, 2006 May.
Artigo em Inglês | MEDLINE | ID: mdl-16702388

RESUMO

PURPOSE: To test the efficacy and safety of an integrated treatment based on a pharmaconutritional support, antioxidants, and drugs, all given orally, in a population of advanced cancer patients with cancer-related anorexia/cachexia and oxidative stress. PATIENTS AND METHODS: An open early-phase II study was designed according to the Simon two-stage design. The integrated treatment consisted of diet with high polyphenols content (400 mg), antioxidant treatment (300 mg/d alpha-lipoic acid + 2.7 g/d carbocysteine lysine salt + 400 mg/d vitamin E + 30,000 IU/d vitamin A + 500 mg/d vitamin C), and pharmaconutritional support enriched with 2 cans per day (n-3)-PUFA (eicosapentaenoic acid and docosahexaenoic acid), 500 mg/d medroxyprogesterone acetate, and 200 mg/d selective cyclooxygenase-2 inhibitor celecoxib. The treatment duration was 4 months. The following variables were evaluated: (a) clinical (Eastern Cooperative Oncology Group performance status); (b) nutritional [lean body mass (LBM), appetite, and resting energy expenditure]; (c) laboratory [proinflammatory cytokines and leptin, reactive oxygen species (ROS) and antioxidant enzymes]; (d) quality of life (European Organization for Research and Treatment of Cancer QLQ-C30, Euro QL-5D, and MFSI-SF). RESULTS: From July 2002 to January 2005, 44 patients were enrolled. Of these, 39 completed the treatment and were assessable. Body weight increased significantly from baseline as did LBM and appetite. There was an important decrease of proinflammatory cytokines interleukin-6 (IL-6) and tumor necrosis factor-alpha, and a negative relationship worthy of note was only found between LBM and IL-6 changes. As for quality of life evaluation, there was a marked improvement in the European Organization for Research and Treatment of Cancer QLQ-C30, Euro QL-5D(VAS), and multidimensional fatigue symptom inventory-short form scores. At the end of the study, 22 of the 39 patients were "responders" or "high responders." The minimum required was 21; therefore, the treatment was effective and more importantly was shown to be safe. CONCLUSION: The efficacy and safety of the treatment have been shown by the study; therefore, a randomized phase III study is warranted.


Assuntos
Anorexia/dietoterapia , Caquexia/dietoterapia , Suplementos Nutricionais , Neoplasias/complicações , Apoio Nutricional/métodos , Adulto , Idoso , Anorexia/etiologia , Ácido Ascórbico/administração & dosagem , Caquexia/etiologia , Carbocisteína/administração & dosagem , Celecoxib , Ácidos Docosa-Hexaenoicos/administração & dosagem , Feminino , Humanos , Modelos Lineares , Masculino , Medroxiprogesterona/administração & dosagem , Pessoa de Meia-Idade , Estresse Oxidativo , Pirazóis/administração & dosagem , Estatísticas não Paramétricas , Sulfonamidas/administração & dosagem , Ácido Tióctico/administração & dosagem , Resultado do Tratamento , Vitamina A/administração & dosagem , Vitamina E/administração & dosagem
17.
Nutrition ; 22(2): 136-45, 2006 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-16459226

RESUMO

OBJECTIVE: Fatigue is a multidimensional symptom that is described in terms of perceived energy, mental capacity, and psychological status: it can impair daily functioning and lead to negative effects on quality of life. It is one of the most common side effects of chemotherapy and radiotherapy. In recent studies, l-carnitine (LC) supplementation has been demonstrated to be able to improve fatigue symptoms in patients with cancer. METHODS: In the present study we tested the efficacy and safety of LC supplementation in a population of patients who had advanced cancer and developed fatigue, high blood levels of reactive oxygen species, or both. As outcome measures we evaluated fatigue and quality of life in relation to oxidative stress, nutritional status, and laboratory variables, mainly levels of reactive oxygen species, glutathione peroxidase, and proinflammatory cytokines. From March to July 2004, 12 patients who had advanced tumors (50% at stage IV) at different sites were enrolled (male-to-female ratio 2:10, mean age 60 y, range 42-73). Patients were only slightly anemic (hemoglobin 10.9 g/dL) and hemoglobin levels did not change after treatment. LC was administered orally at 6 g/d for 4 wk. All patients underwent antineoplastic treatment during LC supplementation. RESULTS: Fatigue, as measured by the Multidimensional Fatigue Symptom Inventory-Short Form, decreased significantly, particularly for the General and Physical scales, and for quality of life in each subscale of quality of life in relation to oxidative stress. Nutritional variables (lean body mass and appetite) increased significantly after LC supplementation. Levels of reactive oxygen species decreased and glutathione peroxidase increased but not significantly. Proinflammatory cytokines did not change significantly. CONCLUSION: Improvement of symptoms with respect to fatigue and quality of life in relation to oxidative stress may be explained mainly by an increase in lean body mass, which may be considered the most important nutritional or functional parameter in assessing the cachectic state of patients. In this view, fatigue with related symptoms can well be considered an important constituent of cancer-related anorexia cachexia syndrome.


Assuntos
Antineoplásicos/efeitos adversos , Carnitina/uso terapêutico , Fadiga/tratamento farmacológico , Estado Nutricional , Estresse Oxidativo/efeitos dos fármacos , Qualidade de Vida , Complexo Vitamínico B/uso terapêutico , Adulto , Idoso , Antineoplásicos/uso terapêutico , Carnitina/efeitos adversos , Citocinas/metabolismo , Suplementos Nutricionais , Fadiga/etiologia , Feminino , Glutationa Peroxidase/efeitos dos fármacos , Glutationa Peroxidase/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/tratamento farmacológico , Neoplasias/fisiopatologia , Espécies Reativas de Oxigênio/metabolismo , Segurança , Resultado do Tratamento , Complexo Vitamínico B/efeitos adversos
18.
Cancer Epidemiol Biomarkers Prev ; 13(10): 1651-9, 2004 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-15466983

RESUMO

OBJECTIVE: Cancer-related anorexia/cachexia syndrome and oxidative stress play a key role in the progression and outcome of neoplastic disease. PATIENTS AND METHODS: On the basis of our previously published studies and clinical experience, we have developed an innovative approach consisting of diet with high polyphenol content (400 mg), p.o. pharmaconutritional support enriched with n - 3 fatty acids (eicosapentaenoic acid and docosahexaenoic acid) 2 cans (237 mL each) per day, medroxiprogesterone acetate 500 mg/d, antioxidant treatment with alpha-lipoic acid 300 mg/d plus carbocysteine lysine salt 2.7 g/d plus vitamin E 400 mg/d plus vitamin A 30,000 IU/d plus vitamin C 500 mg/d, and selective cyclooxygenase-2 inhibitor Celecoxib 200 mg/d. The treatment is administered for 16 weeks. The following variables are evaluated: (a) clinical variables (stage and Eastern Cooperative Oncology Group performance status); (b) nutritional variables (lean body mass, appetite, and resting energy expenditure); (c) laboratory variables (serum levels of proinflammatory cytokines, C-reactive protein, and leptin and blood levels of reactive oxygen species and antioxidant enzymes); and (d) quality of life variables (European Organization for Research and Treatment of Cancer QLQ-C30, EQ-5Dindex, and EQ-5DVAS). A phase II nonrandomized study has been designed to enroll 40 patients with advanced cancer at different sites with symptoms of cancer-related anorexia/cachexia syndrome and oxidative stress. RESULTS: As of January 2004, 28 patients have been enrolled: 25 patients were evaluable and 14 of them have completed the treatment (20 patients have completed 2 months of treatment). As for clinical response, five patients improved, three patients remained unchanged, and six patients worsened. The Eastern Cooperative Oncology Group performance status (grade) 1 remained unchanged. As for nutritional/functional variables, the lean body mass increased significantly at 2 and 4 months. As for laboratory variables, reactive oxygen species decreased significantly and proinflammatory cytokines interleukin-6 and tumor necrosis factor-alpha decreased significantly. As for quality of life, it comprehensively improved after treatment. CONCLUSIONS: The treatment has been shown to be effective for clinical response, increase of lean body mass, decrease of reactive oxygen species and proinflammatory cytokines, and improvement of quality of life. The treatment has been shown to be safe with good compliance of patients. The study is in progress (14 further patients will be included).


Assuntos
Anorexia/dietoterapia , Anorexia/fisiopatologia , Caquexia/dietoterapia , Caquexia/fisiopatologia , Suplementos Nutricionais , Neoplasias/complicações , Estresse Oxidativo , Espécies Reativas de Oxigênio , Adulto , Idoso , Antioxidantes/uso terapêutico , Feminino , Flavonoides/uso terapêutico , Nível de Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Estado Nutricional , Fenóis/uso terapêutico , Polifenóis , Qualidade de Vida , Síndrome , Resultado do Tratamento
19.
J Exp Ther Oncol ; 3(4): 205-19, 2003.
Artigo em Inglês | MEDLINE | ID: mdl-14567291

RESUMO

We carried out an open, non-randomized phase II study including all patients treated with whatever chemotherapy or combined modality regimen for whatever cancer who were in clinical objective response (complete response, CR, or partial response, PR) or stable disease (SD). The treatment consisted of administration of recombinant interleukin-2 (rIL-2) at a dose of 1.8 MIU subcutaneously three times/week (every other day) for the first 2 weeks of every month plus medroxyprogesterone acetate (MPA) 500 mg/day every other day plus antioxidant agents alpha-lipoic acid 300 mg/day and N-acetyl cysteine 1800 mg/day or carbocysteine lysine salt oral solution 2.7 g/day. The treatment was administered for 1 year except when progression of disease occurred. The primary study endpoints were to define clinical outcome, i.e. duration of response, survival (overall survival, OS and progression-free survival, PFS), the toxicity profile, and the evaluation of quality of life (QL). As secondary endpoints, we measured the changes of lymphocyte count, serum levels of proinflammatory cytokines, IL-2, C-reactive protein (CRP) and leptin, blood levels of reactive oxygen species (ROS) and antioxidant enzymes (glutathione peroxidase, GPx and superoxide dismertase, SOD). From July 1998 to June 2003, 42 patients were enrolled in the study (M/F ratio, 39/3; mean age, 62.5 years). Twenty (47.6%) patients were elderly (> 65 years). The majority of patients had either head and neck cancer or lung cancer, 88% had locally advanced or metastatic disease at diagnosis, and 76% had ECOG 0. Forty patients were previously treated with chemotherapy (27 also with radiotherapy), two with IL-2 and interfiron (IFN), one with endocrine therapy and one with only surgery. We obtained an objective response to maintenance treatment of 50%. Median duration of response was 19 months and median PFS was 33 months. Median duration of maintenance treatment was 12 months, median follow-up duration from diagnosis to June 2003 was 40 months, and median follow-up duration from study entry to June 2003 was 17 months. The median overall survival has not been reached. Toxicity was negligible. As for QL, a significant improvement of cognitive functions was observed, whereas all other functioning and symptom scales did not change significantly. As for laboratory parameters, absolute lymphocyte count increased significantly, IL-6, IL-1 beta, tumor necrosis factor-alpha, CRP, and fibrinogen decreased significantly whereas IL-2 and leptin increased significantly after treatment. ROS decreased significantly, whereas GPx increased significantly after treatment. Patients alive at study end showed a significant increase in absolute lymphocyte count, IL-2, leptin, and GPx and a significant decrease of proinflammatory cytokines, CRP, fibrinogen, and ROS, whereas patients who died before study end exhibited only a significant increase in absolute lymphocyte count, IL-2, and GPx and a significant decrease of ROS. Long-term combined maintenance therapy with rIL-2 + MPA + antioxidant agents is feasible, has a very low toxicity, and results in the improvement of clinical outcome, QL, and laboratory parameters.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Antioxidantes/uso terapêutico , Neoplasias/tratamento farmacológico , Qualidade de Vida , Acetilcisteína/uso terapêutico , Adulto , Idoso , Antioxidantes/metabolismo , Proteína C-Reativa/análise , Citocinas/sangue , Quimioterapia Combinada , Feminino , Sequestradores de Radicais Livres/uso terapêutico , Humanos , Interleucina-2/administração & dosagem , Leptina/sangue , Contagem de Linfócitos , Masculino , Acetato de Medroxiprogesterona/administração & dosagem , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias/sangue , Neoplasias/patologia , Taxa de Sobrevida , Ácido Tióctico/uso terapêutico , Resultado do Tratamento
20.
Oncol Rep ; 10(3): 759-66, 2003.
Artigo em Inglês | MEDLINE | ID: mdl-12684655

RESUMO

The purpose of the study was to assess response rate, clinical outcome, organ/function preservation and toxicity in head and neck cancer patients treated with induction chemotherapy followed by concomitant chemoradiotherapy and, when necessary, limited surgery. The study was a phase II non-randomized trial. Induction chemotherapy consisted of 6 weekly doses of carboplatin at AUC of 2 and docetaxel 30 mg/m(2) (1 h) followed by 5 cycles of docetaxel 25 mg/m(2)/day 1, 5-FU 600 mg/m(2) c.i. days 1-5, hydroxyurea 500 mg orally every 12 h for 11 and concomitant twice daily radiation therapy at 150 cGy/fraction given every other week per 5 cycles (TFHX), for a total radiation dose of 75 Gy. 13 cis-retinoic acid was administered for chemoprevention and systematic prophylaxis of mucositis with systemic amifostine and local GM-CSF was administered to all patients during TFHX. Conservative surgical resection was reserved to patients with no optimal response (PR > or =70%), whereas radical surgery was performed as salvage treatment. Thirteen patients (mean age 54.9 years, range 44-62; 12/13 site oropharynx, all stage IV) were enrolled: 31% of patients had ECOG performance status (PS) 0 and 69% had PS 1. Response to induction chemotherapy was analyzed in 12 patients: 2/12 (16.7%) achieved a partial response (PR) for an overall response (ORR) of 16.7%, 10/12 (83.3%) achieved stable disease (SD). TFHX was administered to 7 patients: 2 patients (28.6%) had complete remission (CR), 1 patient (14.3%) had PR for an ORR of 42.9%, 3 patients (42.8%) had SD and 1 patient (14.3%) had PD. At the completion of TFHX, 1 patient underwent local therapy. The toxicity was mild and consisted in: grade 3/4 neutropenia (7.7%), anemia (23.1%), diarrhea (15.4%), mucositis (7.7%), neurotoxicity (7.7%) during induction chemotherapy. During TFHX only 42.8% of grade 3/4 mucositis was observed. All patients spared organ/function. In conclusion, this regimen has been found feasible for its acceptable toxicity, particularly mucositis. However, the overall response rate and the data on survival were not satisfactory.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Neoplasias de Cabeça e Pescoço/radioterapia , Adulto , Amifostina/administração & dosagem , Carboplatina/administração & dosagem , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/radioterapia , Terapia Combinada , Citocinas/sangue , Docetaxel , Feminino , Fator Estimulador de Colônias de Granulócitos e Macrófagos/administração & dosagem , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Hidroxiureia/administração & dosagem , Leptina/sangue , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Terapia de Salvação , Taxoides/administração & dosagem , Resultado do Tratamento , Tretinoína/administração & dosagem
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