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1.
Oncologist ; 24(6): e232-e240, 2019 06.
Artículo en Inglés | MEDLINE | ID: mdl-30413667

RESUMEN

BACKGROUND: Metastatic breast cancer (MBC) is highly prevalent in middle-aged or elderly patients. Eribulin is a nontaxane microtubule inhibitor, approved for the treatment of pretreated MBC. This multicentric study (sponsored by GIOGer, Italian Group for Geriatric Oncology) was designed to assess the efficacy and tolerability of eribulin, according to parameters usually used in geriatric oncology. SUBJECTS, MATERIALS, AND METHODS: An observational study was conducted on 50 consecutive elderly patients with MBC. The primary endpoint was to evaluate the change in items score of comprehensive geriatric assessment (CGA) and health-related quality of life (HRQL). Italian versions of the CGA and HRQL questionnaires were administered at baseline, before the third and fifth cycles, and then every three cycles until treatment discontinuation. Secondary endpoints were efficacy and safety. RESULTS: Overall, both EQ-5D scores and EQ-5D-3 L visual analogic scale did not significantly change from baseline; the percentage of subjects without problems doing usual activities tended to decrease during treatment (p for linear trend .018), and the percentage of patients with minor problems performing usual activities tended to increase (p for linear trend.012). Among CGA items, Instrumental Activities of Daily Living tended to decrease during treatment and Geriatric Depression Scale tended to increase. After 12 months follow-up, 24 patients (out of 47) showed clinical benefits; median progression-free survival was 4.49 months (2.10-10.33) and median OS was 7.31 months (3.70-14.03). The treatment was associated with mild toxicity. CONCLUSION: Eribulin treatment preserved quality of life and geriatric parameters included in the CGA, except for instrumental functioning and geriatric depression, in elderly patients with MBC. IMPLICATIONS FOR PRACTICE: A collaboration between oncologist and geriatric specialists is essential in the management of patients with metastatic breast cancer, who are frequently elderly or frail. The assessment of geriatric parameters in the decision-making process can contribute to direct toward the most appropriate therapeutic plan and preserve the quality of life of patients. Eribulin does not seem to affect quality of life or worsen the overall geriatric status; therefore, it can be considered a suitable option for elderly patients with metastatic breast cancer.


Asunto(s)
Antineoplásicos/administración & dosificación , Neoplasias de la Mama/tratamiento farmacológico , Furanos/administración & dosificación , Cetonas/administración & dosificación , Recurrencia Local de Neoplasia/tratamiento farmacológico , Moduladores de Tubulina/administración & dosificación , Actividades Cotidianas , Anciano , Anciano de 80 o más Años , Antineoplásicos/efectos adversos , Neoplasias de la Mama/complicaciones , Neoplasias de la Mama/patología , Femenino , Estudios de Seguimiento , Furanos/efectos adversos , Evaluación Geriátrica/estadística & datos numéricos , Humanos , Italia , Cetonas/efectos adversos , Recurrencia Local de Neoplasia/complicaciones , Estudios Prospectivos , Calidad de Vida , Resultado del Tratamiento , Moduladores de Tubulina/efectos adversos
2.
J Transl Med ; 17(1): 137, 2019 04 29.
Artículo en Inglés | MEDLINE | ID: mdl-31036005

RESUMEN

BACKGROUND: Over the past few years, next-generation sequencing (NGS) has become reliable and cost-effective, and its use in clinical practice has become a reality. A relevant role for NGS is the prediction of response to anti-EGFR agents in metastatic colorectal cancer (mCRC), where multiple exons from KRAS, NRAS, and BRAF must be sequenced simultaneously. METHODS: We optimized a 14-amplicon NGS panel to assess, in a consecutive cohort of 219 patients affected by mCRC, the presence and clinico-pathological associations of mutations in the KRAS, NRAS, BRAF, and PIK3CA genes from formalin-fixed, paraffin-embedded specimens collected for diagnostics and research at the time of diagnosis. RESULTS: We observed a statistically significant association of RAS mutations with sex, young age, and tumor site. We demonstrated that concomitant mutations in the RAS/RAF pathway are not infrequent in mCRC, and as anticipated by whole-genome studies, RAS and PIK3CA tend to be concurrently mutated. We corroborated the association of BRAF mutations in right mCRC tumors with microsatellite instability. We established tumor side as prognostic parameter independently of mutational status. CONCLUSIONS: To our knowledge, this is the first monocentric, consecutively accrued clinical mCRC cancer cohort tested by NGS in a real-world context for KRAS, NRAS, BRAF, and PIK3CA. Our study has highlighted in clinical practice findings such as the concomitance of mutations in the RAS/RAF pathway, the presence of multiple mutations in single gene, the co-occurrence of RAS and PIK3CA mutations, the prognostic value of tumor side and possible associations of sex with specific mutations.


Asunto(s)
Neoplasias Colorrectales/genética , Neoplasias Colorrectales/secundario , Mutación/genética , Proteínas Proto-Oncogénicas B-raf/genética , Transducción de Señal , Proteínas ras/genética , Anciano , Neoplasias Colorrectales/patología , Femenino , Genes Relacionados con las Neoplasias , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Transducción de Señal/genética
3.
Future Oncol ; 14(14): 1339-1346, 2018 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-29846100

RESUMEN

The optimal duration and intensity of first-line therapy in metastatic colorectal cancer patients once they have achieved an objective response is controversial. In a molecularly selected RAS and BRAF wild-type (wt) population, this concern is amplified. Once disease control has been achieved with a combination therapy including an anti-EGFR antibody, further exposure both to cytotoxic drugs and targeted therapy might result only in increased toxicity. In unresectable metastatic RAS and BRAF wt colorectal cancer patients, a deintensified therapy could represent a valuable option that might preserve quality of life. We designed a study to compare FOLFIRI/cetuximab to FOLFIRI/cetuximab for eight cycles followed by cetuximab alone in first-line treatment of RAS and BRAF (wt) metastatic colorectal cancer patients.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Camptotecina/análogos & derivados , Cetuximab/uso terapéutico , Neoplasias Colorrectales/tratamiento farmacológico , Proteínas Proto-Oncogénicas B-raf/genética , Proteínas Proto-Oncogénicas p21(ras)/genética , Adulto , Anciano , Camptotecina/uso terapéutico , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/mortalidad , Neoplasias Colorrectales/patología , Análisis Mutacional de ADN , Supervivencia sin Enfermedad , Receptores ErbB/antagonistas & inhibidores , Femenino , Fluorouracilo/uso terapéutico , Humanos , Leucovorina/uso terapéutico , Masculino , Persona de Mediana Edad , Mutación , Calidad de Vida , Resultado del Tratamiento , Adulto Joven
4.
Recenti Prog Med ; 106(1): 23-7, 2015 Jan.
Artículo en Italiano | MEDLINE | ID: mdl-25621776

RESUMEN

In 2020 the percentage of patients with a diagnosis of cancer in people with more than 65 years will exceed 70% and 28% in ethnic minorities. The treatment of cancer in these populations is challenging for the oncologists due to socio-economic issues such as poverty, reduced access to the hospital care, level of education. The clinical pathway "diagnosis-treatment-cure", typical of the care of young patients has to be integrated in elderly patients with a more individualized treatment by means of comprehensive geriatric assessment (CGA). IADL (Instrumental Activities of Daily Living) have the best predictive role in oncological setting and their impairment significantly correlate with overall survival, chemotherapy toxicities and thirty days postoperative morbidities. The CGA is universally accepted as the most appropriate instrument to analitically evaluate the age related problems of elderly patients. The role of CGA is crucial to identify geriatric issues not easily diagnosed, to predict treatment toxicities, functional or cognitive decline, post operative complications and to estimate life expectancy. The CGA items are predictive of severe toxicity, however it is not clearly established which are the best performers and the best cut-offs points. Today CGA is integrated with physical performance tests (the most widely used is the "time up and go" test) and laboratory assay of Interleukin 6 and D-Dimer that correlate with mortality and physical decline. There are few prospective studies that evaluated the role of CGA in treatment choice. The first is a phase II study in solid tumors, the second is a haematological trial on non Hodgkin lymphoma. The largest trial is a 571 patients observational series that confirmed the role of CGA in decision making. The administration of CGA is time consuming and consequently some screening tools were developed. VES-13 is a 13 items tool that explores prevalently the functional status and the self reported health status. VES-13 showed a good sensibility (87.3%) but a low specificity (62%) with respect to CGA for the diagnosis of patients with disabilities. Overcash et al. proposed an abbreviated form of CGA using a reduced number of items of ADL, IADL, MMSE and GDS. There was a good correlation between complete and reduced scales (coefficient of correlation 0.8). G8 is a screening tool composed of 8 questions that explore functional, cognitive and nutritional status. The score with the best equilibrium between sensibility and specificity was 14 (sensibility 85% and specificity 65%). In the first observational trial age, hystotype, chemotherapy dose, haemoglobin (man: 11 g/dL; women: 10 g/dL), creatinine clearance less than 34 mL/min (Jelliffe formula), earing problems, at least a fall in the last six months, walking problems, low social activity, were related to a major risk of toxicity; in another trial IADL, diastolic blood pressure, LDH and MAX2 index were predictive of haematological toxicity, while performance status, Mini-Mental Status score, Mini-Nutritional Assessment (MNA) score and MAX2 index were predictive of non haematological toxicity. Based on these parameters a 0-2 score was developed. A recent "position article" of EORTC (European organization for Research and Treatment of Cancer) and SIOG analyzed the pro and the contra of the use of some indicators in elderly patients. The overall survival (OS) frequently used in classical clinical trial could give wrong messages as there are some competitive risks of death in elderly patients. Another important indicator is the disease specific survival (DSS). Concerning the design of clinical trials, a possible strategy is to enrol elderly patients without upper age limit and to plan stratification. An interesting trial design is the so called "extended trial" that allow to re-open the arm of a trial in which a too low number of older patients was enrolled.


Asunto(s)
Envejecimiento , Antifibrinolíticos/sangre , Biomarcadores de Tumor/sangre , Productos de Degradación de Fibrina-Fibrinógeno/metabolismo , Evaluación Geriátrica , Interleucina-6/sangre , Neoplasias/diagnóstico , Neoplasias/terapia , Actividades Cotidianas , Anciano , Anciano de 80 o más Años , Algoritmos , Medicina Basada en la Evidencia , Evaluación Geriátrica/métodos , Humanos , Esperanza de Vida , Neoplasias/sangre , Neoplasias/mortalidad , Valor Predictivo de las Pruebas , Medición de Riesgo , Factores de Riesgo , Sensibilidad y Especificidad
5.
Ann Pharmacother ; 43(3): 542-5, 2009 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-19261961

RESUMEN

OBJECTIVE: To report a case of erlotinib-induced hepatitis complicated by fatal lactic acidosis in an elderly patient with lung adenocarcinoma and diabetes mellitus. CASE SUMMARY: A 77-year-old man with stage IIIB lung adenocarcinoma was treated with erlotinib 100 mg/day, an epidermal growth factor receptor inhibitor, after failure of chemotherapy and radiotherapy. The patient also had type 2 diabetes mellitus; metformin therapy had been initiated 5 years before presentation. Twelve days after the start of erlotinib therapy, he developed drug-related acute hepatitis complicated by renal deterioration (aspartate aminotransferase 1400 U/L, alanine aminotransferase 1299 U/L, creatinine 4.4 mg/dL, urea nitrogen 55 mg/dL). Viral causes of hepatitis were excluded and a recent computed tomography scan had ruled out liver metastases. According to the Roussel-Uclaf causality assessment method, the erlotinib-related hepatitis was classified as probable. The patient's condition was soon complicated by the onset of lactic acidosis, which caused death 2 hours after admission. DISCUSSION: In this patient, lactic acidosis was promoted by erlotinib-related hepatitis with initial liver failure (decreased lactate clearance), concomitant metformin treatment (increased lactate production), and acute renal deterioration (metformin accumulation). This is the second case of fatal erlotinib-induced liver toxicity in a patient with lung cancer. In the previous case, death occurred after about 11 days and was entirely due to fulminant hepatitis, whereas in our patient, the liver injury only initiated a drug-disease interaction that caused fatal lactic acidosis within a few hours. CONCLUSIONS: Liver function should be carefully monitored during erlotinib treatment, particularly in elderly and frail patients on multiple medications. Further studies are therefore needed for better testing the safety of erlotinib in such people, commonly encountered in the real world, but often excluded from participation in randomized trials of cancer treatment.


Asunto(s)
Acidosis Láctica/complicaciones , Enfermedad Hepática Inducida por Sustancias y Drogas/etiología , Quinazolinas/efectos adversos , Adenocarcinoma/complicaciones , Adenocarcinoma/tratamiento farmacológico , Anciano , Antineoplásicos/efectos adversos , Diabetes Mellitus/tratamiento farmacológico , Clorhidrato de Erlotinib , Resultado Fatal , Humanos , Neoplasias Pulmonares/complicaciones , Neoplasias Pulmonares/tratamiento farmacológico , Masculino , Metformina/efectos adversos , Quinazolinas/uso terapéutico
8.
Crit Rev Oncol Hematol ; 65(2): 143-55, 2008 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-18068997

RESUMEN

Despite the high prevalence of depressive disorders in cancer patients and elderly people, the topic of depression in elderly cancer patients still remains unexplored. This emerges from a systematic review of the literature conducted to investigate issues of depression, diagnosis, pathogenesis, treatment and their complex neuroimmunobiological interactions. Indeed, it becomes apparent that depression in elderly patients with cancer may have a peculiar phenomenology. In addition, the moderate rate of major depressive disorder and the high rate of minor depressive disorder are accompanied by subthreshold forms of depression that are at risk to be underrecognized and untreated. Immune dysfunction may represent a common pathogenic ground of depression, cancer and aging. This may have important implications for treatment. In the near future, we need to develop validated mood disorder diagnoses and verify antidepressant treatment efficacy for elderly cancer patients with depression in order to improve their clinical outcome and quality of life.


Asunto(s)
Depresión , Trastorno Depresivo , Neoplasias , Factores de Edad , Anciano , Anciano de 80 o más Años , Comorbilidad , Depresión/diagnóstico , Depresión/epidemiología , Depresión/terapia , Trastorno Depresivo/diagnóstico , Trastorno Depresivo/epidemiología , Trastorno Depresivo/terapia , Humanos , Persona de Mediana Edad , Neoplasias/diagnóstico , Neoplasias/epidemiología , Neoplasias/terapia , Factores de Riesgo , Suicidio
9.
J Clin Oncol ; 23(28): 6865-72, 2005 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-16192578

RESUMEN

PURPOSE: To study the prognostic value for overall survival of baseline assessment of functional status, comorbidity, and quality of life (QoL) in elderly patients with advanced non-small-cell lung cancer treated with chemotherapy. PATIENTS AND METHODS: Data from 566 patients enrolled onto the phase III randomized Multicenter Italian Lung Cancer in the Elderly Study (MILES) study were analyzed. Functional status was measured as activities of daily living (ADL) and instrumental ADL (IADL). The presence of comorbidity was assessed with a checklist of 33 items; items 29 and 30 of the European Organisation for Research and Treatment of Cancer (EORTC) core questionnaire QLQ-C30 (EORTC QLQ-C30) were used to estimate QoL. ADL was dichotomized as none versus one or more dependency. For IADL and QoL, three categories were defined using first and third quartiles as cut points. Comorbidity was summarized using the Charlson scale. Analysis was performed by Cox model, and stratified by treatment arm. RESULTS: Better values of baseline QoL (P = .0003) and IADL (P = .04) were significantly associated with better prognosis, whereas ADL (P = .44) and Charlson score (P = .66) had no prognostic value. Performance status 2 (P = .006) and a higher number of metastatic sites (P = .02) also predicted shorter overall survival. CONCLUSIONS: Pretreatment global QoL and IADL scores, but not ADL and comorbidity, have significant prognostic value for survival of elderly patients with advanced non-small-cell lung cancer who were treated with chemotherapy. Using these scores in clinical practice might improve prognostic prediction for treatment planning.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Estado de Salud , Neoplasias Pulmonares/tratamiento farmacológico , Calidad de Vida , Actividades Cotidianas , Factores de Edad , Anciano , Anciano de 80 o más Años , Carcinoma de Pulmón de Células no Pequeñas/complicaciones , Carcinoma de Pulmón de Células no Pequeñas/patología , Comorbilidad , Desoxicitidina/administración & dosificación , Desoxicitidina/análogos & derivados , Femenino , Humanos , Neoplasias Pulmonares/complicaciones , Neoplasias Pulmonares/patología , Masculino , Pronóstico , Vinblastina/administración & dosificación , Vinblastina/análogos & derivados , Vinorelbina , Gemcitabina
10.
Cancer Treat Rev ; 32 Suppl 2: S5-9, 2006.
Artículo en Inglés | MEDLINE | ID: mdl-16725267

RESUMEN

Patients with cancer receiving myelosuppressive chemotherapy frequently develop anaemia; platinum-based chemotherapy, in particular, leads to reduced production of the bone marrow-stimulating hormone erythropoietin. The European Cancer Anaemia Survey showed that many patients do not receive erythropoiesis-stimulating agent (ESA) therapy and highlighted the need for clear guidelines for the diagnosis and treatment of anaemia in cancer patients. In response to a fast-moving therapeutic environment and guidelines produced in the USA, the European Organisation for Research and Treatment of Cancer established an independent task force to develop evidence-based guidelines for the use of ESAs in European anaemic cancer patients that were first published in 2004. The guidelines recommend that, in patients receiving chemotherapy/radiotherapy, ESA therapy should be initiated at haemoglobin levels of 9-11 g/dL based on the severity of symptoms (target haemoglobin concentration: 12-13 g/dL) to improve quality of life and prevent the need for red blood cell transfusions. Treatment should be maintained as long as Hb levels remain <12-13 g/dL and patients continue to show symptomatic improvement, and should be discontinued, due to marginally elevated risks of thromboembolic events, when haemoglobin levels exceed 14 g/dL. Treatment of anaemia with ESAs is cost-effective and is associated with long-term gains in quality-adjusted life years.


Asunto(s)
Anemia/tratamiento farmacológico , Antineoplásicos/efectos adversos , Hematínicos/uso terapéutico , Guías de Práctica Clínica como Asunto , Comités Consultivos , Anemia/inducido químicamente , Anemia/economía , Análisis Costo-Beneficio , Europa (Continente) , Medicina Basada en la Evidencia , Hematínicos/administración & dosificación , Hematínicos/economía , Hemoglobinas/análisis , Humanos , Neoplasias/tratamiento farmacológico , Neoplasias/radioterapia , Años de Vida Ajustados por Calidad de Vida , Estados Unidos
11.
J Clin Oncol ; 20(2): 494-502, 2002 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-11786579

RESUMEN

PURPOSE: To appraise the performance of Comprehensive Geriatric Assessment (CGA) in elderly cancer patients (> or = 65 years) and to evaluate whether it could add further information with respect to the Eastern Cooperative Oncology Group performance status (PS). PATIENTS AND METHODS: We studied 363 elderly cancer patients (195 males, 168 females; median age, 72 years) with solid (n = 271) or hematologic (n = 92) tumors. In addition to PS, their physical function was assessed by means of the activity of daily living (ADL) and instrumental activities of daily living (IADL) scales. Comorbidities were categorized according to Satariano's index. The association between PS, comorbidity, and the items of the CGA was assessed by means of logistic regression analysis. RESULTS: These 363 elderly cancer patients had a good functional and mental status: 74% had a good PS (ie, lower than 2), 86% were ADL-independent, and 52% were IADL-independent. Forty-one percent of patients had one or more comorbid conditions. Of the patients with a good PS, 13.0% had two or more comorbidities; 9.3% and 37.7% had ADL or IADL limitations, respectively. By multivariate analysis, elderly cancer patients who were ADL-dependent or IADL-dependent had a nearly two-fold higher probability of having an elevated Satariano's index than independent patients. A strong association emerged between PS and CGA, with a nearly five-fold increased probability of having a poor PS (ie, > or = 2) recorded in patients dependent for ADL or IADL. CONCLUSION: The CGA adds substantial information on the functional assessment of elderly cancer patients, including patients with a good PS. The role of PS as unique marker of functional status needs to be reappraised among elderly cancer patients.


Asunto(s)
Actividades Cotidianas , Envejecimiento , Evaluación Geriátrica , Indicadores de Salud , Neoplasias/complicaciones , Anciano , Anciano de 80 o más Años , Comorbilidad , Estudios Transversales , Recolección de Datos , Femenino , Humanos , Masculino , Salud Mental , Sensibilidad y Especificidad
12.
Crit Rev Oncol Hematol ; 55(3): 207-12, 2005 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-15979886

RESUMEN

Cancer increases the risk for venous thromboembolism (VTE) and patients presenting with a seemingly idiopathic VTE often have an occult cancer. Aging also is a risk factor for VTE. Therefore, old patients with cancer are supposed to be at very high risk for VTE, but inherent data are sporadic and contrasting. We reviewed the literature about the relation between cancer and VTE, with particular attention to findings concerning elderly patients. While aging and postmenopausal status enhance the risk of chemotherapy-induced VTE in women with breast cancer, the rate of a cancer diagnosis in the first year after VTE seems to be even lower in elderly compared to young subjects. Thus, further studies are needed to understand whether or not aging and cancer have additive thrombogenic effects. Finally, we discuss prophylactic and therapeutic strategies.


Asunto(s)
Envejecimiento , Neoplasias de la Mama , Tromboembolia/prevención & control , Trombosis de la Vena/prevención & control , Factores de Edad , Anciano , Neoplasias de la Mama/complicaciones , Neoplasias de la Mama/terapia , Femenino , Humanos , Masculino , Persona de Mediana Edad , Factores de Riesgo , Tromboembolia/etiología , Trombosis de la Vena/etiología
13.
Crit Rev Oncol Hematol ; 55(3): 241-52, 2005 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-16084735

RESUMEN

BACKGROUND: As more and more cancers occur in elderly people, oncologists are increasingly confronted with the necessity of integrating geriatric parameters in the treatment of their patients. METHODS: The International Society of Geriatric Oncology (SIOG) created a task force to review the evidence on the use of a comprehensive geriatric assessment (CGA) in cancer patients. A systematic review of the evidence was conducted. RESULTS: Several biological and clinical correlates of aging have been identified. Their relative weight and clinical usefulness is still poorly defined. There is strong evidence that a CGA detects many problems missed by a regular assessment in general geriatric and in cancer patients. There is also strong evidence that a CGA improves function and reduces hospitalization in the elderly. There is heterogeneous evidence that it improves survival and that it is cost-effective. There is corroborative evidence from a few studies conducted in cancer patients. Screening tools exist and were successfully used in settings such as the emergency room, but globally were poorly tested. The article contains recommendations for the use of CGA in research and clinical care for older cancer patients. CONCLUSIONS: A CGA, with or without screening, and with follow-up, should be used in older cancer patients, in order to detect unaddressed problems, improve their functional status, and possibly their survival. The task force cannot recommend any specific tool or approach above others at this point and general geriatric experience should be used.


Asunto(s)
Comités Consultivos , Evaluación Geriátrica , Geriatría , Directrices para la Planificación en Salud , Oncología Médica , Sociedades Médicas , Anciano , Femenino , Evaluación Geriátrica/métodos , Geriatría/tendencias , Humanos , Masculino , Oncología Médica/tendencias , Sociedades Médicas/tendencias
14.
Clin Cancer Res ; 9(7): 2678-82, 2003 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-12855647

RESUMEN

PURPOSE: Despite the great number of studies performed to detect circulating markers of disease progression in colorectal cancer, few have shown a clinical use; among those, epidermal growth factor receptor (EGFR) and, more recently, interleukin (IL)-10. In this article, we sought to investigate how primary surgery could affect expression levels of EGFR, IL-6, and IL-10 in blood from colorectal cancer patients. EXPERIMENTAL DESIGN: We investigated by reverse transcriptase-PCR assay the expression at mRNA level of EGFR, IL-6, and IL-10 in blood samples taken from 56 colorectal cancer patients. Each gene expression was evaluated 1 day before and 20 days after primary surgery. Persistence of each gene in blood after surgery was then correlated to the relapse free time in a follow-up of 3 years. RESULTS: In blood samples taken before surgery, EGFR, IL-6, and IL-10 were found expressed in 62, 100, and 100% of patients, respectively. EGFR expression, but not IL-6 and IL-10, correlates with stage of disease. In the group of 41 patients who underwent follow-up studies, EGFR was found persistently high in 67%; 94% of them had relapse. Persistence of IL-10 after surgery also identifies relapses in 89% of cases. IL-6 persistence was not found to significantly correlate to progression of disease. CONCLUSIONS: Persistence of both EGFR and IL-10 in blood of colorectal cancer patients after surgery identifies patients with high propensity to relapse. These findings may suggest a clinical use of preoperative EGFR/IL-10 reverse transcriptase-PCR assay in the prediction of tumor recurrence.


Asunto(s)
Neoplasias Colorrectales/sangre , Receptores ErbB/sangre , Interleucina-10/sangre , Actinas/metabolismo , Neoplasias Colorrectales/patología , Supervivencia sin Enfermedad , Femenino , Células HeLa , Humanos , Interleucina-10/metabolismo , Interleucina-6/sangre , Masculino , Recurrencia , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Riesgo , Factores de Tiempo
15.
Crit Rev Oncol Hematol ; 45(2): 123-8, 2003 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-12604125

RESUMEN

Over 70% of the total incidence of cancer recorded in Europe in 1996 was in the elderly population (> or =60 years). Despite such high statistics, elderly cancer patients have often been denied the treatment that younger patients routinely receive. The response of elderly cancer patients to full-dose chemotherapy treatment in several neoplasms is similar to that of younger patients, demonstrating that age should not be a barrier to the administration of potentially curative or palliative chemotherapy. In order to provide optimal treatment to elderly cancer patients, management guidelines are recommended which take into account various factors, such as the physical well-being of the patient, the type of malignancy and any conditions that may hamper compliance with chemotherapy. The evidence-based guidelines of the National Comprehensive Cancer Network (NCCN) in the US recommend that the safest and most effective treatment of cancer in older individuals may be achieved by proper patient selection based on comprehensive geriatric assessment, dose adjustment of renally excreted drugs, prophylactic use of haematopoietic growth factors in patients treated with chemotherapy of dose-intensity comparable to cyclophosphamide/doxorubicin/vincristine/prednisone (CHOP) and maintenance of haemoglobin levels > or =12 g/l. The objective of this article is to report the conclusions of the meeting of the International Society of Geriatric Oncology (SIOG) in September 2001, including the need for geriatric assessment to tailor the management of patients to their personal circumstances and general health and the importance of evidence-based guidelines for the management of elderly cancer patients cannot be over-estimated.


Asunto(s)
Antineoplásicos/uso terapéutico , Factores de Crecimiento de Célula Hematopoyética/uso terapéutico , Neoplasias/tratamiento farmacológico , Anciano , Antineoplásicos/efectos adversos , Costo de Enfermedad , Medicina Basada en la Evidencia , Humanos , Neoplasias/economía , Guías de Práctica Clínica como Asunto
16.
Crit Rev Oncol Hematol ; 46(2): 127-37, 2003 May.
Artículo en Inglés | MEDLINE | ID: mdl-12711358

RESUMEN

Evidence exists that the geriatric intervention guided by Comprehensive Geriatric Assessment (CGA) has positive effects on a number of important health outcomes in frail older patients. Although a number of observational studies, editorials, special articles and clinical reports, suggest that CGA should be used to guide the assessment and clinical decision-making in older cancer patients, there is limited support to this view in the literature. Older patients that are diagnosed with cancer are usually healthier and less problematic than persons of the same age who are randomly sampled from the general population. In these persons, the cancer dominates the clinical picture and, therefore, instruments especially tuned for the frail elderly may provide little information. The concept of the frailty syndrome, characterized by high susceptibility, low functional reserve and unstable homeostasis, has recently received a lot of attention by the geriatric community. A CGA approach, which also evaluates elements of the frailty syndrome, may be of great interest for those oncologists who want to identify older patients likely to develop severe toxicity and severe side effects in response to aggressive treatment. Improvements in the definition of the frailty syndrome may profit from the clinical experience of oncologists.


Asunto(s)
Anciano Frágil , Evaluación Geriátrica , Neoplasias/terapia , Planificación de Atención al Paciente , Adaptación Fisiológica , Anciano , Susceptibilidad a Enfermedades , Geriatría/métodos , Servicios de Salud para Ancianos , Homeostasis , Humanos , Oncología Médica/métodos , Neoplasias/epidemiología , Síndrome
17.
J Support Oncol ; 1(4 Suppl 2): 18-24, 2003.
Artículo en Inglés | MEDLINE | ID: mdl-15346996

RESUMEN

Complications of cytotoxic chemotherapy are more common in older patients (65 years of age and older) with cancer than in younger patients, and the occurrence of myelosuppression, mucositis, cardiodepression, peripheral neuropathy, and central neurotoxicity can complicate treatment. Age-related physiologic changes that can increase the toxicity of chemotherapy are decreased stem-cell reserves, decreased ability to repair cell damage, progressive loss of body protein, and accumulation of body fat. A decline in organ function can alter the pharmacokinetics of many of the commonly used chemotherapeutic agents in some elderly patients, making toxicity less predictable. Comorbidities increase the risk of toxicity through their effects on the body. Furthermore, the drugs used to treat comorbidities may interact with chemotherapeutic drugs, potentially increasing toxicity in elderly patients. Prospective trials in older patients with lymphoma or solid tumors have found that age is a risk factor for chemotherapy-induced neutropenia and its complications. Anemia may be present because of the disease or its treatment, and, if left uncorrected, it can alter drug activity and increase toxicity. Being able to predict which elderly patients are at greater risk of toxicity on the basis of pretreatment factors would be valuable, and there is a need for prospective trials to determine regimen- and patient-specific prognostic factors. Effective management of the toxicity associated with chemotherapy with appropriate supportive care is crucial, especially in the elderly population, to give them the best chance of cure and survival, or to provide palliation. For example, management of neutropenic complications with colony-stimulating factors makes treatment with standard-dose chemotherapy possible, which can lead to better outcomes. A better understanding of drug activity and toxicity in older patients is necessary for developing guidelines for safe and effective treatment. Few randomized controlled trials of antitumor drugs in older patients with cancer have been conducted, but a number of agents with favorable efficacy and toxicity profiles in elderly patients have been identified.


Asunto(s)
Anciano/fisiología , Antineoplásicos/efectos adversos , Neoplasias/tratamiento farmacológico , Factores de Edad , Enfermedad Crónica/epidemiología , Comorbilidad , Humanos , Mucosa Bucal , Neoplasias/epidemiología , Neutropenia/inducido químicamente , Riesgo , Estomatitis/inducido químicamente
19.
J Geriatr Oncol ; 5(2): 204-18, 2014 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-24495695

RESUMEN

Aging of an individual entails a progressive decline of functional reserves and loss of homeostasis that eventually lead to mortality. This process is highly individualized and is influenced by multiple genetic, epigenetic and environmental factors. This individualization and the diversity of factors influencing aging result in a significant heterogeneity among people with the same chronological age, representing a major challenge in daily oncology practice. Thus, many factors other than mere chronological age will contribute to treatment tolerance and outcome in the older patients with cancer. Clinical/comprehensive geriatric assessment can provide information on the general health status of individuals, but is far from perfect as a prognostic/predictive tool for individual patients. On the other hand, aging can also be assessed in terms of biological changes in certain tissues like the blood compartment which result from adaptive alterations due to past history of exposures, as well as intrinsic aging processes. There are major signs of 'aging' in lymphocytes (e.g. lymphocyte subset distribution, telomere length, p16INK4A expression), and also in (inflammatory) cytokine expression and gene expression patterns. These result from a combination of the above two processes, overlaying genetic predispositions which contribute significantly to the aging phenotype. These potential "aging biomarkers" might provide additional prognostic/predictive information supplementing clinical evaluation. The purpose of the current paper is to describe the most relevant potential "aging biomarkers" (markers that indicate the biological functional age of patients) which focus on the biological background, the (limited) available clinical data, and technical challenges. Despite their great potential interest, there is a need for much more (validated) clinical data before these biomarkers could be used in a routine clinical setting. This manuscript tries to provide a guideline on how these markers can be integrated in future research aimed at providing such data.


Asunto(s)
Envejecimiento/genética , Biomarcadores de Tumor/genética , Marcadores Genéticos/genética , Evaluación Geriátrica , Neoplasias/genética , Anciano , Envejecimiento/metabolismo , Medicina Basada en la Evidencia , Regulación de la Expresión Génica , Genes p16 , Guías como Asunto , Humanos , Proteínas de Unión a Factor de Crecimiento Similar a la Insulina/genética , Interleucina-6/genética , Interleucina-8/genética , Subgrupos Linfocitarios/metabolismo , Neoplasias/sangre , Neoplasias/diagnóstico , Neoplasias/metabolismo , Neoplasias/mortalidad , Inhibidor 1 de Activador Plasminogénico/genética , Valor Predictivo de las Pruebas , Sensibilidad y Especificidad , Inhibidores de Serina Proteinasa/genética , Telómero/genética
20.
J Clin Oncol ; 32(24): 2595-603, 2014 Aug 20.
Artículo en Inglés | MEDLINE | ID: mdl-25071125

RESUMEN

PURPOSE: To update the International Society of Geriatric Oncology (SIOG) 2005 recommendations on geriatric assessment (GA) in older patients with cancer. METHODS: SIOG composed a panel with expertise in geriatric oncology to develop consensus statements after literature review of key evidence on the following topics: rationale for performing GA; findings from a GA performed in geriatric oncology patients; ability of GA to predict oncology treatment­related complications; association between GA findings and overall survival (OS); impact of GA findings on oncology treatment decisions; composition of a GA, including domains and tools; and methods for implementing GA in clinical care. RESULTS: GA can be valuable in oncology practice for following reasons: detection of impairment not identified in routine history or physical examination, ability to predict severe treatment-related toxicity, ability to predict OS in a variety of tumors and treatment settings, and ability to influence treatment choice and intensity. The panel recommended that the following domains be evaluated in a GA: functional status, comorbidity, cognition, mental health status, fatigue, social status and support, nutrition, and presence of geriatric syndromes. Although several combinations of tools and various models are available for implementation of GA in oncology practice, the expert panel could not endorse one over another. CONCLUSION: There is mounting data regarding the utility of GA in oncology practice; however, additional research is needed to continue to strengthen the evidence base.


Asunto(s)
Evaluación Geriátrica/métodos , Geriatría/normas , Neoplasias/diagnóstico , Neoplasias/terapia , Factores de Edad , Anciano , Anciano de 80 o más Años , Consenso , Geriatría/métodos , Humanos
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