Search

Abstract: Aim of the present phase II non-randomized study was to verify whether palonosetron might be able to prevent acute and especially delayed CINV for either HEC or MEC, starting from the second chemotherapy cycle, in patients who had failed to respond to a different antiemetic 5-HT3 antagonist during the first cycle. Stratification factor was age <65 years vs. ≥65 years of patients included. Forty-seven cancer patients (23 elderly and 24 non-elderly) scheduled to receive HEC or MEC regimens who had experienced CINV grade 3–4 during the first chemotherapy course and for whom the same course of chemotherapy regimen was further scheduled were enrolled. Complete response (CR) and complete control (CC) rates for the acute, delayed and overall phases of CINV were not significantly different between elderly and non-elderly patients. Palonosetron was safe: only grade 1–2 toxicities were observed with a peak of 12.9% for asthenia with no significant difference between elderly and non-elderly patients. In conclusion, single dose palonosetron (250μg) should be considered a safe and effective second generation 5-HT3 antagonist in the prevention of nausea and vomiting induced by HEC or MEC, irrespective of patients’ age. [Copyright &y& Elsevier]

A phase II, open, nonrandomized trial was carried out in a group of epirubicin-treated cancer patients with the aim of detecting early preclinical changes that are predictive of the risk for heart failure. Thirty-one patients (male/female ratio, 8/23; mean age ± standard deviation, 59 ± 14 years) with tumors at different sites and scheduled to be treated with an epirubicin-based chemotherapy regimen, were enrolled. We prospectively evaluated the acute (1 week after) and late (3, 6, 12, and 18 months of follow-up) effects of epirubicin administration. A significant impairment in systolic left ventricular (LV) function was observed at a cumulative epirubicin dose of 200 mg/m². This was shown by a reduction in the strain rate (SR) peak in comparison with baseline and persisted throughout the treatment and follow-up, up to 18 months; strain (∑) remained unchanged. The Sm wave showed a progressive reduction that became significant only at the 18-month follow-up. On TDI the Em/Am ratio declined at the 200-mg/m² cumulative epirubicin dose versus baseline and persisted throughout the treatment and up to the 18-month follow-up. On conventional echocardiography the E/A ratio declined significantly only at the 300-mg/m² cumulative epirubicin dose. Interleukin (IL)-6, soluble IL-6 receptor, and reactive oxygen species (ROS) increased significantly at the 200-mg/m² dose, and IL-6 was persistently high at the 300- and 400-mg/m² doses, returning to within baseline values during follow-up. ROS, after the peak reached at the 200-mg/m² dose, returned to within baseline values. A significant inverse correlation between ΔSR and the increase in both IL-6 and ROS was observed. A multiple regression analysis showed that both the IL-6 and ROS variables were independent and strongly predictive of ΔSR. The clinical meaningfulness of our findings warrants further investigations on a larger number of patients for a longer period of follow-up. [ABSTRACT FROM AUTHOR]

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

Abstract: The primary aim of the present study was to examine the relationship of changes in hemoglobin levels following recombinant human erythropoietin (rHuEPO) treatment to changes in cognitive functioning studied by Mini Mental State Examination (MMSE) in elderly cancer patients undergoing chemotherapy treatment. The secondary aim was that to assess the relationship of changes in hemoglobin levels following rHuEPO treatment to changes in functions studied by Comprehensive Geriatic Assessment (CGA), such as Activity of Daily Living (ADL), Instrumental Activities of Daily Living (IADL), Geriatric Depression Scale (GDS) and the Mini Nutritional Assessment (MNA). To this end, hemoglobin levels and cognitive functioning were evaluated in a sample of cancer patients prior to the start of chemotherapy treatment and again after 4, 8 and 12 weeks of treatment with chemotherapy plus rHuEPO. Ten elderly patients (mean age 71.4 years) were enrolled. At baseline, enrolled patients had a mean Hb value of 10.3g/dl. After 4 weeks of rHuEPO treatment, Hb values increased significantly (p <0.0001), with a mean increase of 1.2g/dl (range: 0.2–2.1). Remarkably, 8 out of 10 (80%) showed an increase of Hb levels ≥1g/dl in comparison to baseline and therefore were considered responders. At baseline, four patients (40%) showed a moderate cognitive impairment, whilst six patients (60%) showed a normal cognitive function. After 4 weeks of rHuEPO treatment nine patients (90%) showed a significant improvement of cognitive functions in comparison to baseline (p <0.005): eight of them were responders also to rHuEPO in terms of correction of anemia. The Spearman''s rank correlation test showed a statistical significant correlation between Hb increase and increase in cognitive functioning assessed by MMSE after 4 weeks (p =0.049), 8 weeks (p =0.044) and 12 weeks (p =0.031) of rHuEPO treatment. Therefore, the findings of this study provide support for the hypothesis that significant increases in hemoglobin over the course of chemotherapy supplemented with rHuEPO administration would be accompanied by significant improvement in cognitive performance over the same interval. [Copyright &y& Elsevier]

In the present study we tested the ability of different antioxidant agents, used alone or in combination, to reduce the reactive oxygen species (ROS) levels and to increase the glutathione peroxidase (GPx) activity. Moreover, we tested the ability of such antioxidant agents to reduce the serum levels of proinflammatory cytokines IL-6 and TNFα. Fifty-six advanced stage cancer patients with tumors at different sites were included in the study: they were mainly stage III (12.5%) and stage IV (82.1%). The study was divided into two phases. In the 1[supst] phase 28 patients were divided into five groups and a single different antioxidant agent was administered to each group. The selected antioxidant agents were: alpha lipoic acid or carboxycysteine-lysine salt, amifostine, reduced glutathione, vitamin A plus vitamin E plus Vitamin C. In the 2[supnd] phase of the study 28 patients were divided into five groups and a combination of two different antioxidant agents was administered to each group. The antioxidant treatment was administered for 10 consecutive days. The patients were studied at baseline and after antioxidant treatment. Our results show that all single antioxidants tested were effective in reducing the ROS levels and three of them in increasing GPx activity, too. Among the combinations of antioxidant agents, three were effective in reducing ROS, while three were effective in increasing GPx activity (arm 4 was effective in both instances). Comprehensively, the "antioxidant treatment" was found to be effective both on ROS levels and GPx activity. Moreover, the antioxidant treatment was able to reduce serum levels of IL-6 and TNFα. Furthermore, a correlation was shown between the Eastern Cooperative Oncology Group Performance Status of patients and blood levels of ROS, GPx activity, serum levels of proinflammatory cytokines. [ABSTRACT FROM AUTHOR]

Leptin is a recently identified hormone produced by the adipocyte ob gene which acts as a negative feedback signal critical to the normal control of food intake and body weight. A number of proinflammatory cytokines, such as interleukin 6, tumor necrosis factor α, and interferon γ, have been proposed as mediators of cancer cachexia; these data suggest that abnormalities in leptin production/release or in its feedback mechanism play a role in cancer patients. We therefore studied the relationship between serum leptin and serum cytokines interleukin 6 and tumor necrosis factor α levels in advanced-stage cancer patients. Twenty-nine advanced stage cancer patients (all but one stage IV) with tumors at various sites were included in the study. A direct correlation between body mass index and serum leptin levels was found both in cancer patients and in healthy individuals. The serum levels of interleukin 6 were significantly higher in cancer patients than in healthy individuals. In cancer patients an inverse correlation was found between serum levels of leptin and proinflammatory cytokines. There was an inverse correlation between the Eastern Cooperative Oncology Group performance status scale and serum levels of leptin. Regarding survival, patients with very high serum levels of proinflammatory cytokines and very low levels of leptin had very short survival. Although obtained in a cancer patient population not overtly cachectic, our results provide further evidence that a simple dysregulation of leptin production and/or release cannot be involved in cancer-associated pathophysiological changes leading to cachexia. [ABSTRACT FROM AUTHOR]

Leptin is a recently identified hormone produced by the adipocyte ob gene which acts as a negative feedback signal critical to the normal control of food intake and body weight. A number of proinflammatory cytokines, such as interleukin (IL) 1α, IL-6, tumor necrosis factor (TNF) α and interferon (IFN) γ, have been proposed as mediators of cancer cachexia. These data suggest that abnormalities in leptin production/release or in its feedback mechanism play a role in cancer patients. To elucidate this we studied the relationship between total serum leptin and serum cytokines IL-1α, IL-6, TNFα as well as the production of leptin and cytokines by peripheral blood mononuclear cells (PBMC) isolated from cancer patients. Sixteen advanced cancer patients (mainly stage IV) with tumors at different sites were included in the study. The serum levels of leptin in cancer patients were significantly lower than those of healthy individuals at all times (7 a.m., noon, 3 p.m.). No significant differences were found in circadian rhythm between patients and controls. Serum levels of IL-1α, IL-6, and TNFα were significantly higher in cancer patients than in healthy individuals. An inverse correlation between serum levels of leptin and IL-6 was found in cancer patients. The production in culture of leptin by unstimulated PBMCs and those stimulated by phytohemagglutinin M or by phorbol myristate acetate isolated from cancer patients was very low; no differences were observed in comparison with leptin production by PBMCs from healthy individuals. [ABSTRACT FROM AUTHOR]

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