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1.
JCO Oncol Pract ; 17(8): e1162-e1169, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-33621121

RESUMO

PURPOSE: Measuring and tracking quality of care is highly relevant in today's health care. The Quality Oncology Practice Initiative (QOPI) program is a referral for evaluating oncology practices worldwide. Excellence and Quality in Oncology Foundation, a collaboration of oncology experts from major Spanish hospitals involved in cancer treatment, reached an agreement with QOPI to include Spanish hospitals in this program. METHODS: We analyzed the results of the QOPI Core module measures from 19 Spanish hospitals over nine rounds (from fall 2015 to fall 2019). RESULTS: Of the 19 hospitals, 15 completed more than one round; none participated in all nine (two hospitals participated in eight rounds). The highest scores were for pathology report confirming malignancy, documenting a plan of care for moderate or severe pain and chemotherapy dose, and chemotherapy administered to patients with metastatic solid tumor with performance status undocumented. Measures regarding a summary of chemotherapy treatment, tobacco use cessation counseling, and assessment of patient emotional well-being were among the lowest scored measures. Six of the 15 practices that participated repeatedly achieved a better score in their last round compared with their first. Overall, scores of Spanish hospitals improved from 67.79% in fall 2015 to 68.91% in fall 2019. CONCLUSION: To our knowledge, this is the first study to evaluate QOPI scores in Spain. There was high variability in scores, with quality of care improving with repeated participation in some hospitals, but worsening in others. Excellence and Quality in Oncology Foundation will support practices to increase their participation to improve oncology care and implement strategies that address the areas for improvement.


Assuntos
Oncologia , Neoplasias , Humanos , Neoplasias/terapia , Espanha
2.
JCO Oncol Pract ; 16(3): e298-e305, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32160482

RESUMO

PURPOSE: Several frameworks have been developed to define and quantify the value of oncologic therapies and to support decision making; however, they define treatment value mainly in terms of clinical benefit. As part of its mission to improve oncologic care, the ECO Foundation (Excellence and Quality in Oncology) directed this pilot study aimed at developing a reflective multicriteria decision analysis (MCDA)-based framework for evaluating and positioning oncologic drugs in the clinical setting. METHODS: The framework was developed following Evidence and Value: Impact on Decision-Making methodology, and literature was reviewed to identify relevant criteria. The selected criteria were then presented to a group of experts composed of 9 clinical oncologists who assessed each criterion for inclusion in the framework and suggested modifications in their definition and/or response scale. The framework was tested in 2 case studies (abemaciclib for advanced or metastatic hormone receptor-positive, human epidermal growth factor receptor 2-negative breast cancer and TAS-102 for metastatic colorectal cancer) to validate the proposed framework; this was followed by a discussion of the results. RESULTS: Eight of the 15 criteria presented to the experts were included in the framework: disease severity, unmet needs, comparative efficacy, comparative safety/tolerability, treatment intent, comparative treatment cost, comparative other medical costs, and quality of evidence. Framework validation in 2 drug cases resulted in similar value scores, although they were based on different contributing criteria and resulted in different clinical recommendations. CONCLUSION: We developed and validated a reflective MCDA framework for the assessment and positioning of oncologic therapies in Spain. Additional work is needed to create a manual for practical decision making in the clinical setting.


Assuntos
Técnicas de Apoio para a Decisão , Oncologia/normas , Humanos
3.
J Pain Res ; 12: 2349-2358, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31534359

RESUMO

PURPOSE: There is a lack of standards for the diagnosis, assessment and management of breakthrough cancer pain (BTcP). La Fundación ECO (the Foundation for Excellence and Quality in Oncology) commissioned a study to establish a consensus and lay the foundations for the appropriate management of BTcP in oncology patients. PATIENTS AND METHODS: A modified Delphi survey comprising two rounds was used to gather and analyze data, which was conducted over the Internet. Each statement that reached a consensus with the respondents was defined as a median consensus score (MED) of ≥7, and agreement among panelists as an interquartile range (IQR) of ≤3. RESULTS: In total, 69 medical oncologists responded, with a broad consensus that BTcP implied exacerbations of high-intensity pain, as opposed to moderate pain. Furthermore, they concurred that appropriate diagnostic equipment is needed, and that rapid-onset fentanyl formulations should be the preferred treatment for BTcP management. The panelists agreed that a lack of appropriate information and training to attend to patients, as well as limited patient visitation rights, were barriers to effective BTcP management. Regarding gaps in detected knowledge, the panelists were unsure of the measures necessary to assess the burden of the disease on the patient's quality of life and associated medication costs. Alongside this, there was a lack of awareness of the technical specifics of the different formulations of rapid-onset fentanyl. CONCLUSION: These results represent the current status of BTcP management. They may inform recommendations and provide a framework for future research.

5.
Clin Cancer Res ; 24(11): 2517-2529, 2018 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-29581135

RESUMO

Purpose: This study aimed to identify biomarkers of resistance to endocrine therapy in estrogen receptor-positive (ER+) breast cancers treated with prolonged neoadjuvant letrozole.Experimental Design: We performed targeted DNA and RNA sequencing in 68 ER+ breast cancers from patients treated with preoperative letrozole (median, 7 months).Results: Twenty-four tumors (35%) exhibited a PEPI score ≥4 and/or recurred after a median of 58 months and were considered endocrine resistant. Integration of the 47 most upregulated genes (log FC > 1, FDR < 0.03) in letrozole-resistant tumors with transcription-binding data showed significant overlap with 20 E2F4-regulated genes (P = 2.56E-15). In patients treated with the CDK4/6 inhibitor palbociclib before surgery, treatment significantly decreased expression of 24 of the 47 most upregulated genes in letrozole-resistant tumors, including 18 of the 20 E2F4 target genes. In long-term estrogen-deprived ER+ breast cancer cells, palbociclib also downregulated all 20 E2F4 target genes and P-RB levels, whereas the ER downregulator fulvestrant or paclitaxel only partially suppressed expression of this set of genes and had no effect on P-RB. Finally, an E2F4 activation signature was strongly associated with resistance to aromatase inhibitors in the ACOSOG Z1031B neoadjuvant trial and with an increased risk of relapse in adjuvant-treated ER+ tumors in METABRIC.Conclusions: In tumors resistant to prolonged neoadjuvant letrozole, we identified a gene expression signature of E2F4 target activation. CDK4/6 inhibition suppressed E2F4 target gene expression in estrogen-deprived ER+ breast cancer cells and in patients' ER+ tumors, suggesting a potential benefit of adjuvant CDK4/6 inhibitors in patients with ER+ breast cancer who fail to respond to preoperative estrogen deprivation. Clin Cancer Res; 24(11); 2517-29. ©2018 AACR.


Assuntos
Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Resistencia a Medicamentos Antineoplásicos , Fator de Transcrição E2F4/genética , Inibidores de Proteínas Quinases/uso terapêutico , Receptores de Estrogênio/genética , Idoso , Idoso de 80 Anos ou mais , Inibidores da Aromatase/uso terapêutico , Biomarcadores Tumorais , Neoplasias da Mama/metabolismo , Linhagem Celular Tumoral , Proliferação de Células , Biologia Computacional/métodos , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/genética , Fator de Transcrição E2F4/metabolismo , Feminino , Perfilação da Expressão Gênica , Humanos , Letrozol/uso terapêutico , Pessoa de Meia-Idade , Mutação , Inibidores de Proteínas Quinases/farmacologia , Receptores de Estrogênio/metabolismo , Retratamento , Transcriptoma
6.
J Acad Nutr Diet ; 116(12): 1914-1924.e6, 2016 12.
Artigo em Inglês | MEDLINE | ID: mdl-27373727

RESUMO

BACKGROUND: Diet is a key modifiable risk for many chronic diseases, but it remains unclear whether dietary patterns from one study sample are generalizable to other independent populations. OBJECTIVE: The primary objective of this study was to assess whether data-driven dietary patterns from one study sample are applicable to other populations. The secondary objective was to assess the validity of two criteria of pattern similarity. METHODS: Six dietary patterns-Western (n=3), Mediterranean, Prudent, and Healthy- from three published studies on breast cancer were reconstructed in a case-control study of 973 breast cancer patients and 973 controls. Three more internal patterns (Western, Prudent, and Mediterranean) were derived from this case-control study's own data. STATISTICAL ANALYSIS: Applicability was assessed by comparing the six reconstructed patterns with the three internal dietary patterns, using the congruence coefficient (CC) between pattern loadings. In cases where any pair met either of two commonly used criteria for declaring patterns similar (CC ≥0.85 or a statistically significant [P<0.05] Pearson correlation), then the true similarity of those two dietary patterns was double-checked by comparing their associations to risk for breast cancer, to assess whether those two criteria of similarity are actually reliable. RESULTS: Five of the six reconstructed dietary patterns showed high congruence (CC >0.9) to their corresponding dietary pattern derived from the case-control study's data. Similar associations with risk for breast cancer were found in all pairs of dietary patterns that had high CC but not in all pairs of dietary patterns with statistically significant correlations. CONCLUSIONS: Similar dietary patterns can be found in independent samples. The P value of a correlation coefficient is less reliable than the CC as a criterion for declaring two dietary patterns similar. This study shows that diet scores based on a particular study are generalizable to other populations.


Assuntos
Neoplasias da Mama/epidemiologia , Dieta Saudável , Dieta Mediterrânea , Dieta Ocidental , Estudos de Casos e Controles , Bases de Dados Factuais , Feminino , Humanos , Modelos Teóricos , Fatores de Risco , Espanha
7.
J Natl Compr Canc Netw ; 14(5): 553-8, 2016 05.
Artigo em Inglês | MEDLINE | ID: mdl-27160233

RESUMO

BACKGROUND: The quality of cancer care has become a priority for health care systems. The goal of this research was to develop a set of evidence-based quality indicators (QIs) for organization, palliative care, and colorectal, breast, and lung cancers for introducing a system of benchmarking in Spain. METHODS: A comprehensive evidence-based literature search was performed to identify potential QIs. An expert panel (the health care quality promotion group) of 9 oncologists identified indicators and evaluated them. A Delphi process involving 58 physicians was used to rank QIs by clinical relevance (validity). The expert panel then evaluated the selected indicators in terms of the feasibility of measuring them in Spanish hospitals, their usefulness for comparisons, their degree of clinical relevance, and their sensitivity to the impact of health care improvements. RESULTS: From the literature review, 99 potential QIs were identified. The Delphi process shortened the list to 72 QIs. A final set of 57 QIs was established by the health care quality promotion group: 12 related to organizational issues, 11 to colorectal cancer, 11 to breast cancer, 12 to lung cancer, and 11 to palliative care. This final set included structure (n=2), process (n=36), and outcome (n=19) indicators. CONCLUSIONS: A set of QIs has been developed using a validated Delphi method, meaning that we can be confident of their validity, feasibility, sensitivity, and acceptability. These QIs are to serve as the basis of a strategy for benchmarking across oncology services in Spanish hospitals and should enable us to assure and improve the quality of cancer care.


Assuntos
Técnica Delphi , Neoplasias/terapia , Indicadores de Qualidade em Assistência à Saúde/tendências , Idoso , Humanos , Espanha
8.
Melanoma Res ; 26(3): 278-83, 2016 06.
Artigo em Inglês | MEDLINE | ID: mdl-26958991

RESUMO

Adjuvant interferon-α2b (IFN-α2b) has been studied extensively in clinical trials, but there have been few studies of real-world use. The aim of this study is to describe the IFN-α2b real-world patterns in patients with high-risk melanoma in Spain. This was a retrospective and multicentre chart review study of an unselected cohort of patients with melanoma at high risk for relapse (stage IIB/IIC/III) treated with IFN-α2b. Patterns were assessed in terms of dose and compliance to planned treatment. A survival analysis was carried out for the full population and according to Kirkwood scheme compliance and the presence of ulceration. Of 327 patients treated with IFN-α2b, 318 received a high-dose regimen following the standard Kirkwood scheme; thus, patterns are described for this regimen. A total of 121 (38%) and 88 (28%) patients had at least one dose reduction during the induction and maintenance phases, respectively. Dose delay was required in fewer than 10% of patients. A total of 78, 40 and 38% of the patients completed the induction phase, maintenance phase and completed treatment, respectively. The median progression-free and overall survival for the full population were 3.2 and 10.5 years, respectively. There were no differences in progression-free survival and overall survival according to Kirkwood scheme compliance and the presence of ulceration. The most frequent adverse events were neutropenia (31%) and fatigue (30%). High-dose IFN-α2b is the most frequently used regimen in Spain as an adjuvant systemic treatment for high-risk melanoma. Despite poor compliance, in this retrospective study, IFN-α2b treatment provided a benefit consistent with that described previously.


Assuntos
Interferon-alfa/administração & dosagem , Melanoma/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Quimioterapia Adjuvante , Estudos de Coortes , Feminino , Humanos , Interferon alfa-2 , Masculino , Melanoma/mortalidade , Melanoma/patologia , Melanoma/cirurgia , Pessoa de Meia-Idade , Estudos Retrospectivos , Análise de Sobrevida , Adulto Jovem
9.
PLoS One ; 10(5): e0126096, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25978407

RESUMO

BACKGROUND: According to the "World Cancer Research Fund" and the "American Institute of Cancer Research" (WCRF/AICR) one in four cancer cases could be prevented through a healthy diet, weight control and physical activity. OBJECTIVE: To explore the association between the WCRF/AICR recommendations and risk of breast cancer. METHODS: During the period 2006 to 2011 we recruited 973 incident cases of breast cancer and 973 controls from 17 Spanish Regions. We constructed a score based on 9 of the WCRF/AICR recommendations for cancer prevention:: 1)Maintain adequate body weight; 2)Be physically active; 3)Limit the intake of high density foods; 4)Eat mostly plant foods; 5)Limit the intake of animal foods; 6)Limit alcohol intake; 7)Limit salt and salt preserved food intake; 8)Meet nutritional needs through diet; S1)Breastfeed infants exclusively up to 6 months. We explored its association with BC by menopausal status and by intrinsic tumor subtypes (ER+/PR+ & HER2-; HER2+; ER&PR-&HER2-) using conditional and multinomial logistic models respectively. RESULTS: Our results point to a linear association between the degree of noncompliance and breast cancer risk. Taking women who met 6 or more recommendations as reference, those meeting less than 3 showed a three-fold excess risk (OR=2.98(CI95%:1.59-5.59)), especially for postmenopausal women (OR=3.60(CI95%:1.24;10.47)) and ER+/PR+&HER2- (OR=3.60(CI95%:1.84;7.05)) and HER2+ (OR=4.23(CI95%:1.66;10.78)) tumors. Noncompliance of recommendations regarding the consumption of foods and drinks that promote weight gain in premenopausal women (OR=2.24(CI95%:1.18;4.28); p for interaction=0.014) and triple negative tumors (OR=2.93(CI95%:1.12-7.63)); the intake of plant foods in postmenopausal women (OR=2.35(CI95%:1.24;4.44)) and triple negative tumors (OR=3.48(CI95%:1.46-8.31)); and the alcohol consumption in ER+/PR+&HER2- tumors (OR=1.52 (CI95%:1.06-2.19)) showed the strongest associations. CONCLUSION: Breast cancer prevention might be possible by following the "World Cancer Research Fund" and the "American Institute of Cancer Research" recommendations, even in settings like Spain, where a high percentage of women already comply with many of them.


Assuntos
Neoplasias da Mama/epidemiologia , Academias e Institutos , Adolescente , Adulto , Idoso , Estudos de Casos e Controles , Ingestão de Energia , Comportamento Alimentar , Feminino , Humanos , Estilo de Vida , Pessoa de Meia-Idade , Espanha/epidemiologia , Estados Unidos , Adulto Jovem
10.
BMC Urol ; 15: 15, 2015 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-25887442

RESUMO

BACKGROUND: More than 429,000 patients worldwide are diagnosed with bladder cancer each year and muscle-invasive bladder cancer has an especially poor outcome. The median age at diagnosis is over 70 years, and many patients also have a substantial number of age-associated impairments that need to be considered when planning therapeutic interventions. CASE PRESENTATION: Here, we report the case of a 63-year-old man with a cT3b urothelial carcinoma which was surgically removed. No neoadjuvant or adjuvant chemotherapy was administered. After 18 months a lung metastasis was confirmed and resected but no chemotherapy was given after surgery. Twelve months later, the patient relapsed and was treated with a combination of gemcitabine and cisplatin and after a decline in renal function the treatment was changed to a combination of carboplatin and gemcitabine which resulted in a partial response which lasted 8 months. Following this vinflunine was administered as a second line treatment. Here we review the evidence available in the literature regarding the suitability of different treatment options for managing muscle-invasive bladder cancer at each step of the case presentation. CONCLUSION: Bladder cancer treatment requires a multidisciplinary approach. Although, depending on the clinical characteristics of the patient, there are some controversial points in the management of this pathology we hope that the scientific data and the clinical trials reviewed in this case report, can help to guide physicians to make more rational decisions regarding the management of these patients.


Assuntos
Carcinoma de Células de Transição/secundário , Carcinoma de Células de Transição/cirurgia , Cistectomia/métodos , Neoplasias Pulmonares/secundário , Neoplasias Pulmonares/cirurgia , Recidiva Local de Neoplasia/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Biópsia por Agulha , Carcinoma de Células de Transição/patologia , Quimioterapia Adjuvante , Seguimentos , Humanos , Imuno-Histoquímica , Neoplasias Pulmonares/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica/patologia , Recidiva Local de Neoplasia/diagnóstico , Estadiamento de Neoplasias , Radiografia , Medição de Risco , Fatores de Tempo , Resultado do Tratamento
11.
Int J Clin Oncol ; 20(3): 480-9, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25011497

RESUMO

BACKGROUND: Based on previous results obtained with non-pegylated liposomal-encapsulated doxorubicin (TLC-D99) together with paclitaxel and trastuzumab in patients with human epidermal growth factor receptor 2 (HER2)-positive locally advanced or metastatic breast cancer (BC), a similar regimen was evaluated in the neoadjuvant setting in a prospectively selected series of consecutive patients with clinical stage II-III BC. Primary and secondary objectives included the rate of pathologic complete response (pCR), safety, and predictive factors of pCR. METHODS: Patients received six cycles of TLC-D99 (50 mg/m(2) every 3 weeks), paclitaxel (80 mg/m(2) weekly) and trastuzumab (4 mg/kg initial dose and 2 mg/kg weekly). All patients underwent surgery after treatment. pCR was defined as the absence of invasive cancer cells in the breast and the axilla. RESULTS: Sixty-two patients with a median age of 46.6 years were analyzed. Stage IIIA was diagnosed in 43.5% of patients and 14.5% had inflammatory BC. Conservative surgery was performed in 46.8% of the patients and pCR was achieved in 63% (95% CI 50.5-75.5). Patients with estrogen receptor (ER)-negative tumors presented a significantly higher pCR rate than patients with ER-positive tumors (74.4 vs 43.5%; P = 0.028). Forty-five patients (72.6%) completed study treatment and 80.6% received at least five treatment cycles. No patients developed congestive heart failure and 14.5% of patients showed a ≥ 10 % decrease in the left ventricular ejection fraction. CONCLUSION: The triple combination therapy assessed is effective and safe, offering a high pCR rate in patients with HER2-positive BC.


Assuntos
Adenocarcinoma/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Adenocarcinoma/metabolismo , Adulto , Idoso , Neoplasias da Mama/metabolismo , Doxorrubicina/administração & dosagem , Doxorrubicina/análogos & derivados , Feminino , Humanos , Pessoa de Meia-Idade , Terapia Neoadjuvante , Paclitaxel/administração & dosagem , Polietilenoglicóis/administração & dosagem , Receptor ErbB-2/metabolismo , Indução de Remissão , Trastuzumab/administração & dosagem , Resultado do Tratamento , Adulto Jovem
12.
Clin Transl Oncol ; 13(9): 664-71, 2011 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-21865138

RESUMO

BACKGROUND: The purpose of this study was (a) to evaluate the association between cigarette smoking and the prevalence of distal colorectal polyps and adenocarcinoma and (b) to analyse genetic alterations representing different molecular pathways of the colorectal carcinogenesis. METHODS: A total of 623 asymptomatic male (mean age: 53 years; 50-65) car factory workers were included. Information on smoking habits and other lifestyle factors were collected followed by a 60 cm colonoscopy. APC and KRAS mutations and microsatellite status were determined in colorectal lesions (colorectal carcinoma (CRC), hyperplastic (HP) and adenomatous polyps (AP)). Data were analysed using unconditional multiple logistic regression models. RESULTS: Smokers had a higher prevalence of AP (OR 2.1; 95% CI 1.2-3.6; p<0.05) and HP (OR 5.4; 95% CI 2.6- 11.1; p<0.05). No differences in CRC were observed. There was a dose-response relationship with the number of cigarettes smoked. The risk of developing AP or HP decreased after smoking cessation, even among heavy smokers (≥20 packs/year). KRAS mutations were more prevalent among smokers AP (OR 5.6; 95% CI 1.6-20.4; p=0.007). There was a trend of positive association with APC mutations (OR 3.5; 95% CI 0.9-4.4; p=0.096). APC and KRAS mutations were found in 36% and 61% of the HP of smokers, but were absent in non-smokers (p=0.89 and 0.78, respectively). There were no differences in MSI between smokers and non-smokers. CONCLUSIONS: Cigarette smoking is associated with a higher risk of developing both HP and AP and a higher prevalence of mutations in APC and KRAS.


Assuntos
Genes APC , Pólipos Intestinais/genética , Mutação , Proteínas Proto-Oncogênicas/genética , Fumar/efeitos adversos , Proteínas ras/genética , Adenocarcinoma/epidemiologia , Adenocarcinoma/genética , Pólipos Adenomatosos/epidemiologia , Pólipos Adenomatosos/genética , Idoso , Neoplasias Colorretais/epidemiologia , Neoplasias Colorretais/genética , Estudos Transversais , Análise Mutacional de DNA , Humanos , Pólipos Intestinais/epidemiologia , Masculino , Repetições de Microssatélites/genética , Pessoa de Meia-Idade , Prevalência , Proteínas Proto-Oncogênicas p21(ras) , Fumar/epidemiologia , Fumar/genética
13.
Clin Transl Oncol ; 12(7): 503-8, 2010 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-20615828

RESUMO

AIMS: Our aim was to evaluate first-line treatment of metastatic renal cell carcinoma (mRCC) with sorafenib in patients unwilling to receive immunotherapy or with early intolerance to immunotherapy. PATIENTS AND METHODS: Patients had clear-cell mRCC with good or intermediate risk status, were unsuited to cytokine therapy due to preference or intolerance (based on <4 weeks prior immunotherapy) and had not received antiangiogenic agents. Patients received sorafenib 400 mg twice daily until disease progression or unacceptable toxicity. The primary endpoint was progression-free survival (PFS). RESULTS: Twenty-six evaluable patients were enrolled at six centres between March and July 2006. The most common metastatic sites were lung and bone; nine patients had one or two metastatic lesions. Median PFS was 7.5 months (95% confidence interval [CI] 5.1-17.5) and overall survival (OS) 15.4 months (95% CI 12.9-17.4). Among 21 patients evaluable for response, 19 (90.5%) experienced disease control (including one complete response; four partial responses; 14 stable disease). The majority of adverse events were grade 1-2 (87.3%). The most common were asthenia (53.0%) and diarrhoea (50.0%). CONCLUSION: In patients with mRCC who were unwilling to receive or intolerant to immunotherapy, treatment with sorafenib led to a high rate of disease control with toxicities that were generally mild and manageable. The PFS achieved in this essentially treatment-naïve population compares favourably with that obtained in the randomised first-line phase II study.


Assuntos
Antineoplásicos/uso terapêutico , Benzenossulfonatos/uso terapêutico , Carcinoma de Células Renais/tratamento farmacológico , Carcinoma de Células Renais/secundário , Neoplasias Renais/tratamento farmacológico , Neoplasias Renais/patologia , Piridinas/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Neoplasias Ósseas/patologia , Neoplasias Ósseas/secundário , Feminino , Humanos , Imunoterapia , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/secundário , Masculino , Pessoa de Meia-Idade , Niacinamida/análogos & derivados , Compostos de Fenilureia , Indução de Remissão , Sorafenibe
14.
BMC Cancer ; 10: 36, 2010 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-20144226

RESUMO

BACKGROUND: Aromatase (CYP19A1) regulates estrogen biosynthesis. Polymorphisms in CYP19A1 have been related to the pathogenesis of breast cancer (BC). Inhibition of aromatase with letrozole constitutes the best option for treating estrogen-dependent BC in postmenopausal women. We evaluate a series of polymorphisms of CYP19A1 and their effect on response to neoadjuvant letrozole in early BC. METHODS: We analyzed 95 consecutive postmenopausal women with stage II-III ER/PgR [+] BC treated with neoadjuvant letrozole. Response to treatment was measured by radiology at 4th month by World Health Organization (WHO) criteria. Three polymorphisms of CYP19A1, one in exon 7 (rs700519) and two in the 3'-UTR region (rs10046 and rs4646) were evaluated on DNA obtained from peripheral blood. RESULTS: Thirty-five women (36.8%) achieved a radiological response to letrozole. The histopathological and immunohistochemical parameters, including hormonal receptor status, were not associated with the response to letrozole. Only the genetic variants (AC/AA) of the rs4646 polymorphism were associated with poor response to letrozole (p = 0.03). Eighteen patients (18.9%) reported a progression of the disease. Those patients carrying the genetic variants (AC/AA) of rs4646 presented a lower progression-free survival than the patients homozygous for the reference variant (p = 0.0686). This effect was especially significant in the group of elderly patients not operated after letrozole induction (p = 0.009). CONCLUSIONS: Our study reveals that the rs4646 polymorphism identifies a subgroup of stage II-III ER/PgR [+] BC patients with poor response to neoadjuvant letrozole and poor prognosis. Testing for the rs4646 polymorphism could be a useful tool in order to orientate the treatment in elderly BC patients.


Assuntos
Regiões 3' não Traduzidas , Aromatase/genética , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Terapia Neoadjuvante/métodos , Nitrilas/farmacologia , Polimorfismo Genético , Triazóis/farmacologia , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/farmacologia , Progressão da Doença , Feminino , Humanos , Imuno-Histoquímica/métodos , Letrozol , Pessoa de Meia-Idade , Pós-Menopausa , Resultado do Tratamento
15.
Crit Rev Oncol Hematol ; 68 Suppl 1: S9-S22, 2008 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-18723368

RESUMO

A multidisciplinary panel of 20 international experts, including urologists, radiation oncologists, and medical oncologists, convened during the Advanced Prostate Cancer Multidisciplinary Team meeting in Rome, Italy, in January 2007, to discuss the multidisciplinary team approach and current patterns of care for patients with hormone-refractory prostate cancer (HRPC). During the meeting, the experts discussed several definitions currently used in prostate cancer management, including those for senior adult patients. In addition, the panel reviewed a series of patient case studies in order to provide feedback on current treatment practices and to identify possible strategies for best practice. It was stressed that treatment decisions for senior adult patients should not be based solely on patient age. Additionally, although historically treatment decisions for advanced prostate cancer have focused on palliative care, given the survival benefit associated with docetaxel-based chemotherapy across patient subgroups, more men are likely to be offered chemotherapy for advanced-stage disease in the future.


Assuntos
Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/patologia , Estudos de Casos e Controles , Progressão da Doença , Humanos , Masculino , Antígeno Prostático Específico/análise , Neoplasias da Próstata/diagnóstico
17.
Lancet Oncol ; 8(3): 219-25, 2007 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-17329192

RESUMO

BACKGROUND: We aimed to compare the additional benefit of gemcitabine when combined with vinorelbine above that of standard vinorelbine treatment in patients with metastatic breast cancer. METHODS: In this phase III, multicentre, open-label, randomised study, 252 women with locally recurrent and metastatic breast cancer who had been pretreated with anthracyclines and taxanes were randomly assigned single-agent vinorelbine (30 mg/m(2), days 1 and 8) or gemcitabine plus vinorelbine (1200/30 mg/m(2), days 1 and 8). Both study treatments were administered intravenously every 21 days until disease progression, unacceptable toxic effects, or stoppage at the request of investigator or patient. The primary endpoint was median progression-free survival. Secondary objectives included assessments of response rate, disease duration, overall survival, and characterisation of the toxicity profiles of both regimens. This study is registered with ClinicalTrials.gov, number NCT00128310. FINDINGS: Between 2001 and 2005, 252 women were recruited and randomised for treatment. One of these patients was ineligible. Prognostic factors were well balanced between treatment groups (median number of metastatic sites in combination group 2 (range 0-5) and in vinorelbine group 2 (range 1-6); visceral disease in 76% and 75% of patients, respectively). Median progression-free survival was 6.0 months (95% CI 4.8-7.1) for patients given gemcitabine plus vinorelbine and 4.0 months (2.9-5.1) for those assigned vinorelbine; there was 1.9 months of difference (hazard ratio 0.66 [0.50-0.88]; p=0.0028). Overall survival was 15.9 months (12.6-19.1) for the gemcitabine plus vinorelbine group and 16.4 months (11.6-21.0) for the vinorelbine group; there was 0.5 months of difference (hazard ratio 1.04 [0.78-1.39]; p=0.8046). Objective response rates were 36% for patients assigned gemcitabine plus vinorelbine (n=45) and 26% for those assigned vinorelbine (n=33) (p=0.093). Grade 3 or 4 neutropenia was reported in 75 (61% [52-70]) of the participants assigned gemcitabine plus vinorelbine, compared with 55 (44% [35-53]) of those assigned vinorelbine alone (p=0.0074). Febrile neutropenia occurred in 13 (11%) of those assigned gemcitabine plus vinorelbine, and in seven (6%) of those assigned vinorelbine alone (p=0.15). Incidences of grade 3 or 4 non-haematological toxic effects were similar between the two treatment groups. INTERPRETATION: Patients with metastatic breast cancer assigned gemcitabine and vinorelbine had better progression-free survival compared with those assigned vinorelbine alone. However, this finding did not translate into a difference in overall survival. Although toxicity was manageable, patients in the combined group had more haematological toxic effects. These factors should be taken into account when deciding which chemotherapy patients should receive.


Assuntos
Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Recidiva Local de Neoplasia/tratamento farmacológico , Vimblastina/análogos & derivados , Adulto , Idoso , Idoso de 80 Anos ou mais , Antraciclinas/uso terapêutico , Neoplasias da Mama/patologia , Desoxicitidina/administração & dosagem , Desoxicitidina/análogos & derivados , Feminino , Humanos , Pessoa de Meia-Idade , Metástase Neoplásica , Taxoides/uso terapêutico , Vimblastina/administração & dosagem , Vimblastina/uso terapêutico , Vinorelbina , Gencitabina
18.
Expert Rev Anticancer Ther ; 5(6): 963-72, 2005 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-16336087

RESUMO

The tolerability of chemotherapy has been significantly improved by the advent of effective drugs and protocols for the amelioration of chemotherapy-induced nausea and vomiting. Variables such as the timing of nausea and vomiting (acute, delayed or anticipatory) and the emetogenicity of the chemotherapy must be taken into account in developing guidelines for antiemetic prophylaxis and treatment. Although there are a number of 5-hydroxytryptamine antagonists available, the clinical differences between them are small. The use of drugs with a different mechanism of action, such as the recently introduced neurokinin-1 receptor antagonist aprepitant, may be a useful adjunct to 5-hydroxytryptamine-3 receptor antagonists or steroid prophylaxis. The addition of aprepitant to standard antiemetic regimens increases the proportion of complete responses to antiemetic therapy. For the use of highly emetogenic chemotherapy in oncology a combination of 5-hydroxytryptamine-3 receptor antagonist, dexamethasone and aprepitant is recommended in the acute phase, and dexamethasone plus aprepitant during the subsequent days (many patients do not have their symptoms controlled by 5-hydroxytryptamine-3 receptor antagonist and steroid alone). In either case, lorazepam can be added as required. For moderately emetogenic chemotherapy, a regimen of 5-hydroxytryptamine, dexamethasone and aprepitant is recommended in the acute phase, followed by aprepitant alone in the delayed phase. Alternatively, a 5-hydroxytryptamine-3 receptor antagonist and dexamethasone can be used in the acute phase, followed by dexamethasone for prophylaxis in the delayed phase. For chemotherapy with a low emetogenicity, either dexamethasone, metoclopramide, prochlorperazine or triethyperazine alone is recommended. No prophylaxis is generally required during the delayed phase and indeed may not be necessary during the acute phase either.


Assuntos
Antieméticos/uso terapêutico , Antineoplásicos/efeitos adversos , Náusea/tratamento farmacológico , Guias de Prática Clínica como Assunto , Vômito/tratamento farmacológico , Quimioterapia Combinada , Humanos , Náusea/induzido quimicamente , Neoplasias/tratamento farmacológico , Receptores 5-HT3 de Serotonina , Antagonistas da Serotonina/uso terapêutico , Vômito/induzido quimicamente
19.
J Clin Oncol ; 23(23): 5323-33, 2005 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-15939921

RESUMO

PURPOSE: To evaluate the antitumor activity and pharmacodynamic/biologic effect of gefitinib 500 mg/day monotherapy in patients with previously treated, advanced breast cancer. METHODS: In this phase II multicenter trial, the primary objective was assessment of the tumor response rate with gefitinib; secondary objectives included analysis of the pharmacodynamic and biologic profiles in healthy and tumor tissue. RESULTS: while phosphorylation of mitogen-activated protein kinase was inhibited in both tissues, gefitinib treatment induced p27 and a decrease in Ki67 in skin but not in tumors. Furthermore, gefitinib did not inhibit the activated form of Akt in the tumors. CONCLUSION: This study demonstrates a good correlation between the degree of inhibition of EGFR in skin and in breast tumors. The lack of significant clinical activity of gefitinib in our study population is not due to lack of receptor inhibition in these tumors but rather to lack of EGFR dependence in the tested population.


Assuntos
Antineoplásicos/uso terapêutico , Neoplasias Ósseas/tratamento farmacológico , Neoplasias da Mama/tratamento farmacológico , Receptores ErbB/antagonistas & inibidores , Quinazolinas/uso terapêutico , Terapia de Salvação , Neoplasias de Tecidos Moles/tratamento farmacológico , Adulto , Idoso , Antineoplásicos/farmacocinética , Área Sob a Curva , Neoplasias Ósseas/sangue , Neoplasias Ósseas/secundário , Neoplasias da Mama/sangue , Neoplasias da Mama/patologia , Proteínas de Ciclo Celular/metabolismo , Inibidor de Quinase Dependente de Ciclina p27 , Resistencia a Medicamentos Antineoplásicos , Receptores ErbB/metabolismo , Feminino , Gefitinibe , Humanos , Antígeno Ki-67/metabolismo , Masculino , Dose Máxima Tolerável , Pessoa de Meia-Idade , Proteínas Quinases Ativadas por Mitógeno/antagonistas & inibidores , Fosforilação/efeitos dos fármacos , Quinazolinas/farmacocinética , Neoplasias de Tecidos Moles/sangue , Neoplasias de Tecidos Moles/secundário , Resultado do Tratamento , Proteínas Supressoras de Tumor/metabolismo
20.
Clin Colorectal Cancer ; 3(2): 108-12, 2003 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-12952567

RESUMO

This study was designed to evaluate the safety and tolerability of oxaliplatin combined with weekly boluses of 5-fluorouracil (5-FU) and low doses of leucovorin (LV) and to determine objective response, progression-free survival, and overall survival of patients with previously untreated advanced colorectal cancer. Seventy-nine patients enrolled in an observational, multicenter, prospective, open-label phase II study received intravenous (I.V.) infusions of oxaliplatin 85 mg/m2 over the course of 2 hours on days 1 and 14 and LV 20 mg/m2 over the course of 2 hours and 5-FU 500 mg/m2 as a bolus on days 1, 7, and 14 every 4 weeks until disease progression or unacceptable toxicity occurred. Seventy-nine patients were evaluable for safety, and data from 70 patients were used for efficacy analysis. The objective response rate was 51.4%. Complete responses occurred in 7 patients (10%), and partial responses occurred in 29 patients (41.4%). Disease control, defined as response or stable disease, was obtained in 56 of 70 patients (80%). The median duration of response was 8.34 weeks (range, 7.3-11.5 weeks). The median time to progression was 7.13 months (range, 6.28-7.72 months), and median overall survival time was 15 months (range, 12.32-18.37 months). Acute dose-limiting toxicities were grade 3/4 diarrhea and neutropenia, which occurred in 10.5% and 3.9% of patients, respectively. Among the 70 patients who experienced neurosensory toxicity, it was estimated that only 1.3% had grade 3 symptoms. Preliminary data showed that the regimen is at least as active as other regimens combining oxaliplatin and infusional schedules of 5-FU and might be more convenient for patients because it avoids the need for I.V. catheter implantation.


Assuntos
Adenocarcinoma/tratamento farmacológico , Antineoplásicos/farmacologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Compostos Organoplatínicos/farmacologia , Adenocarcinoma/patologia , Adulto , Idoso , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Neoplasias Colorretais/patologia , Diarreia/induzido quimicamente , Progressão da Doença , Esquema de Medicação , Feminino , Fluoruracila/administração & dosagem , Humanos , Infusões Intravenosas , Injeções Intravenosas , Leucovorina/administração & dosagem , Masculino , Pessoa de Meia-Idade , Neutropenia/induzido quimicamente , Compostos Organoplatínicos/administração & dosagem , Compostos Organoplatínicos/efeitos adversos , Oxaliplatina , Resultado do Tratamento
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