Elderly patients have become the leading drug consumers: it's high time to properly evaluate new drugs within the real targeted population.
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Biomedical subjects
Publications and source records attributed to Lazzaro Repetto.
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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.
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.
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.
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.
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OBJECTIVE: The study aimed at evaluating the activity and toxicity of gemcitabine monochemotherapy in a unselected series of elderly patients with advanced bladder cancer. The secondary objectives were to establish whether there is a correlation between treatment and Comprehensive Geriatric Assessment (CGA) and, in addition, to determine overall patient survival. METHODS: Treatment consisted of six courses of chemotherapy with gemcitabine at a dosage of 1,200 mg/m2 on days 1 and 8, every 21 days. CGA, as described by Gruppo Italiano di Oncologia Geriatrica, was assessed for evaluating the functional status of patients before, during, and after treatment. RESULTS: Twenty-five patients were enrolled (M/F 22/3), 22 of these were evaluable for response and 23 for toxicity. Characteristics of patients: median age 76 years (range 71-87); ECOG performance status (PS) 1 in 12 patients and 2 in 13 patients; clinical stage III in 6 patients and IV in 19 patients. At the end of the therapy the parameters of CGA improved in 4 cases (17%), remained unchanged in 17 cases (74%) and worsened only in 2 cases (9%). Two patients were not evaluable. Response evaluation showed 3 (13.5%) complete responses (CRs) and 7 (32%) partial responses (PRs), for an overall response rate of 45.5% [95% confidence interval (CI), 24.3-65.7%]. Three (13.5%) patients had stable disease (SD ) and 9 (41%) disease progression (DP). Median overall survival was 8 months and median time to progression was 5 months. Treatment was generally well tolerated, with 1 patient having grade 3 gastrointestinal toxicity and 3 having grade 4 neutropenia. CONCLUSIONS: We conclude that gemcitabine can be safely administered in monochemotherapy, is effective and does not worsen the functional status of elderly patients with advanced bladder cancer.
BACKGROUND: To evaluate the effectiveness and tolerability of the long-term treatment bone metastases with pamidronate in older patients. MATERIALS AND METHODS: Twenty-two ambulatory patients aged 70 or older were included in the study. The median age was 73 (range 70-77). Ten patients (46%) were affected by breast carcinoma, 7 (32%) by prostate carcinoma and 5 (22%) by multiple myeloma. Nine (40%) patients presented co-morbidity. All of the patients presented at least one metastatic lytic bone lesion measuring 1 cm or more in diameter; the median lesion number was 2 (range 1-4). Hormonal therapy or chemotherapy regimen, were allowed as clinically required. Patients were treated with a fixed dose of sodium pamidronate, 90 mg in 3 h infusion every 4 weeks. RESULTS: Partial response was shown in 6 (28%) patients, stable disease in 11 (50%), and progression (PD) in 5 (22%). 2 out of 5 patients with PD presented skeletal-related events (SREs) such as bone fracture. The median treatment duration was 19 months. The treatment was well tolerated; in 5 patients (23%) a GI fever was observed, in 3 patients (18%) G1 nausea, and in 3 patients (14) G1 diarrhea. Two cases (9%) of acute renal insufficiency (creatinine 1.7 and 1.6 mg/dl), and 3 cases (14%) of hypocalcemia (7.6, 7.5 and 7.8 mg/dl) were also registered. The renal dysfunction was reversible and without consequence. CONCLUSION: Our experience suggests that the bisphosphonates long-term administration is useful and did not cause significant side effects in elderly subjects. Low-grade pyrexia, nausea/vomiting, acute/reversible renal dysfunction and hypo-calcemia were the most frequent side effects reported. However, they were of low grade and in most cases, did not require dose modifications and/or hospitalization.
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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.
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.
The development of colony-stimulating factors (CSFs) has provided clinicians with a valuable tool for proactive management of chemotherapy-induced neutropenia. However, clinicians are also presented with the challenge of appropriately targeting this treatment to patients at serious risk of neutropenic complications, while maintaining an economic approach to prescribing. This article discusses the seriousness of chemotherapy-induced neutropenia and reviews current approaches to the management of this condition. Febrile neutropenia risk models, new therapy options and international guidelines for the use of CSFs are also discussed.
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.
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.
The increase in cancer incidence with increasing age is becoming more obvious and more important as the average age of the population increases. The close link between old age and cancer development is the result of three main factors: the substantial length of time required for carcinogenesis; the occurrence of age-related molecular changes that mimic carcinogenesis; and, changes in bodily environment that favour cancer progression, which is a consequence of increasing age. The clinical behaviour of common malignant diseases, eg, breast, ovarian, and lung cancers, lymphomas, and acute leukaemias, may change with age because of intrinsic variation of the neoplastic cells and the ability of the tumour host to support neoplastic growth. Therapeutic decisions should be based on an estimation of the patient's life expectancy, and risks and benefits should be weighted up accordingly. A comprehensive geriatric assessment of function, comorbidity, cognition, depression, social support, nutrition, and polypharmacy, would allow interventions to be tailored to individual needs. In developed countries, the numbers of older people who develop cancer are increasing and many questions remain unanswered. These issues include: the causes of the association of cancer and ageing; the age-related differences in cancer biology; the goals of cancer treatment in the aged; and the effectiveness of cancer prevention. We review the biological and clinical interactions of cancer and ageing and discuss the skills and knowledge necessary for caring for older patients.
The number of elderly women diagnosed with breast cancer by 2025, will increase by 72%. These elderly women do not yet participate in most screening programmes. One notes more favourable biological characteristics of the tumour, including more expression of steroid receptors (oestrogen receptor, progesterone receptor), low proliferative rate, good differentiation, normal p53 and low expression of epidermal growth factor. Elderly breast cancer patients are frequently treated with breast conservation, omitting axillary dissection, radiation therapy and chemotherapy. There is a paucity of data to substantiate that such an approach is better than a more radical one. The efficacy of chemotherapy and guidelines for its use vary by tumour stage and patient age. Drugs like modified anthracyclines, vinorelbine, the taxanes and capecitabine may be changing the paradigm of combination therapy superiority.
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