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1.
Int J Cardiovasc Imaging ; 33(2): 197-207, 2017 Feb.
Article in English | MEDLINE | ID: mdl-27696298

ABSTRACT

Trastuzumab (TZB) has been shown to be extremely effective in breast cancer patients over-expressing HER-2, but careful cardiac monitoring is required when TZB is administered with anthracyclines, since the combination can increase its toxicity. Myocardial deformation indexes associated with speckle tracking echocardiography (STE) have proven to be very sensitive in identifying early myocardial dysfunction. An observational, prospective study was designed to assess TZB-induced cardiac damage using STE in patients with HER-2 positive breast cancer who had been sequentially treated with TZB following epirubicin (EPI). Conventional echocardiographic parameters and STE deformation indexes (longitudinal, radial, and circumferential strain/strain rate and apical rotation) were analyzed at baseline, after each EPI treatment, and 1 week after every other dose of TZB administration until 1 year follow up, in order to focus on the timing and extent of myocardial impairment. In the forty-five enrolled patients, a reduction in subendocardial function after EPI treatment was observed by a significant impairment of the global longitudinal strain/strain rate (GLS/SR), while a significant increase in the activity of the subepicardial fibers was highlighted by an increase in apical rotation. After the second TZB dose, a sudden reduction of the apical rotation was seen, together with circumferential and radial strain/SR. Most importantly, the extent to which the apical rotation increased and decreased was found to strictly correlate with the GLS reduction at follow up. We found that after EPI therapy, subendocardial function was impaired, even while a compensatory increase in apical rotation occurred. Following TZB treatment, we observed impairment in apical rotation, which seems to be the first sign of global LV dysfunction predicting GLS reduction found at the end of treatment.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Breast Neoplasms/drug therapy , Epirubicin/administration & dosage , Myocardial Contraction/drug effects , Trastuzumab/administration & dosage , Ventricular Dysfunction, Left/prevention & control , Ventricular Function, Left/drug effects , Adult , Aged , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Cardiotoxicity , Drug Administration Schedule , Drug Synergism , Early Diagnosis , Echocardiography, Doppler, Pulsed , Epirubicin/adverse effects , Female , Humans , Middle Aged , Predictive Value of Tests , Prospective Studies , Risk Factors , Time Factors , Trastuzumab/adverse effects , Treatment Outcome , Ventricular Dysfunction, Left/chemically induced , Ventricular Dysfunction, Left/diagnostic imaging , Ventricular Dysfunction, Left/physiopathology
2.
Support Care Cancer ; 24(10): 4293-9, 2016 10.
Article in English | MEDLINE | ID: mdl-27169699

ABSTRACT

PURPOSE: The purpose of this study was to review the results of a single-center experience in the management of "closed abdomen" hyperthermic intraperitoneal chemotherapy (HIPEC) using a sophisticated technical device (EXIPER®) in the palliative setting of neoplastic ascites from peritoneal carcinomatosis in patients with advanced cancer of different primary sites. PATIENTS AND METHODS: The study was an open, prospective, single-center, non-randomized study conducted at the Department of Medical Oncology 1, University of Cagliari, Italy, from May 2006 to October 2012. Fifteen patients with peritoneal carcinomatosis were treated with HIPEC: 5 males and 10 females (age range 51-82, median 62 years), for a total of 30 procedures (5 patients were treated more than once). Malignant ascites were from ovarian, uterine cervical, colorectal, gastric, malignant pleural mesothelioma, and unknown primary cancer. Main endpoints were increase of free interval between two consecutive procedures, progressive reduction of ascites volumes and improvement of quality of life assessed with ECOG performance status and EORTC QLQ-C30 questionnaire, and improvement of immunologic function. RESULTS: Twelve patients were completely evaluable while three patients were "lost" to follow-up. The treatment was well tolerated. The mean free interval between two consecutive drainages increased from 11.2 to 39.5 days. The mean ascites volume drained decreased from 7.8 to 1.8 l. ECOG PS improved in the majority of patients and EORTC QLQ-C30 scores in all patients as well as immunologic function. In September 2015, only one patient was still alive. CONCLUSIONS: Our study shows that good results may be achieved in terms of symptom palliation and improvement of quality of life in very advanced cancer patients with MA from PC. The treatment was generally well tolerated considering the limited treatment options available for these patients.


Subject(s)
Ascites/drug therapy , Palliative Care/methods , Peritoneal Neoplasms/complications , Quality of Life/psychology , Adult , Aged , Aged, 80 and over , Combined Modality Therapy , Female , Humans , Male , Middle Aged , Peritoneal Neoplasms/surgery , Peritoneal Neoplasms/therapy , Prospective Studies
3.
Future Oncol ; 11(19): 2697-2710, 2015 Oct.
Article in English | MEDLINE | ID: mdl-26376740

ABSTRACT

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

4.
Expert Opin Pharmacother ; 16(14): 2163-77, 2015.
Article in English | MEDLINE | ID: mdl-26330024

ABSTRACT

INTRODUCTION: Cancer cachexia is a severe inflammatory metabolic syndrome accounting for fatigue, an impairment of normal activities and, eventually, death. The loss of muscle mass associated with body weight loss is the main feature of this syndrome. AREAS COVERED: The present review aims to describe the advances in the pharmacological approaches for cancer cachexia, highlighting the impact on weight loss, muscle wasting and related outcomes. EXPERT OPINION: Among the pharmacological agents, attention should yet be given to the currently most widely studied drugs, such as progestogens and NSAIDs. Emerging drugs, such as ghrelin and selective androgen receptor modulators, have obtained promising results in recent randomized clinical trials. Larger sample sizes and more robust data on the effectiveness of anti-cytokine agents are needed. Any pharmacological approach to counteract cancer cachexia should always be associated with an adequate caloric intake, obtained by diet or through enteral or parenteral supplementation, if indicated. Finally, we can currently state that a combined approach that simultaneously targets the fundamental pathways involved in the pathogenesis of cancer cachexia is likely to be the most effective in terms of improvements in body weight as well as muscle wasting, function, physical performance and quality of life.


Subject(s)
Cachexia/drug therapy , Neoplasms/complications , Amino Acids/therapeutic use , Body Weight/drug effects , Cachexia/etiology , Cachexia/physiopathology , Carnitine/therapeutic use , Clinical Trials as Topic , Cytokines/antagonists & inhibitors , Dietary Supplements , Drug Therapy, Combination , Eicosapentaenoic Acid/therapeutic use , Fatigue/etiology , Humans , Neoplasms/physiopathology , Progestins/therapeutic use , Quality of Life , Steroids/therapeutic use
5.
J Immunother ; 37(1): 26-35, 2014 Jan.
Article in English | MEDLINE | ID: mdl-24316553

ABSTRACT

The GOLFIG-2 phase III trial was designed to compare the immunobiological activity and antitumor efficacy of GOLFIG chemoimmunotherapy regimen with standard FOLFOX-4 chemotherapy in frontline treatment of metastatic colorectal cancer (mCRC) patients. This trial was conceived on the basis of previous evidence of antitumor and immunomodulating activity of the GOLFIG regimen in mCRC. GOLFIG-2 is a multicentric open/label phase III trial (EUDRACT: 2005-003458-81). Chemo-naive mCRC patients were randomized in a 1:1 ratio to receive biweekly standard FOLFOX-4 or GOLFIG [gemcitabine (1000 mg/m(2), day 1); oxaliplatin (85 mg/m(2), day 2); levofolinate (100 mg/m(2), days 1-2), 5-fluorouracil (5-FU) (400 mg/m(2) in bolus followed by 24 h infusion at 800 mg/m(2),days 1-2), sc. GM-CSF (100 µg, days 3-7); sc. aldesleukin (0·5 MIU bi-daily, days 8-14 and 17-30)] treatments. The study underwent early termination because of poor recruitment in the control arm. After a median follow-up of 43.83 months, GOLFIG regimen showed superiority over FOLFOX in terms of progression-free survival [median 9·23 (95% confidence interval (CI), 6·9-11.5) vs. median 5.70 (95% CI, 3.38-8.02) months; hazard ratio (HR): 0.52 (95% CI, 0.35-0.77), P=0·002] and response rate [66.1% (95% CI, 0.41-0.73) vs. 37·0% (95% CI, 0.28-0.59), P=0.002], with a trend to longer survival [median 21.63 (95% CI, 18.09-25.18) vs. 14.57 mo (95% CI, 9.07-20.07); HR: 0·79 (95% CI, 0.52-1.21); P=0.28]. Patients in the experimental arm showed higher incidence of non-neutropenic fever (18.5%), autoimmunity signs (18.5%), an increase in the number of monocytes, eosinophils, CD4(+) T lymphocytes, natural killer cells, and a decrease in immunoregulatory (CD3(+)CD4(+)CD25(+)FoxP3(+)) T cells. Taken together, these findings provide proof-of-principle that GOLFIG chemoimmunotherapy may represent a novel reliable option for first-line treatment of mCRC.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Colorectal Neoplasms/drug therapy , Colorectal Neoplasms/pathology , Adult , Aged , Aged, 80 and over , Colorectal Neoplasms/immunology , Colorectal Neoplasms/mortality , Deoxycytidine/administration & dosage , Deoxycytidine/analogs & derivatives , Female , Fluorouracil/administration & dosage , Fluorouracil/therapeutic use , Granulocyte-Macrophage Colony-Stimulating Factor/administration & dosage , Humans , Interleukin-2/administration & dosage , Leucovorin/administration & dosage , Leucovorin/therapeutic use , Lymphocytes, Tumor-Infiltrating/immunology , Lymphocytes, Tumor-Infiltrating/metabolism , Lymphocytes, Tumor-Infiltrating/pathology , Male , Middle Aged , Neoplasm Grading , Neoplasm Metastasis , Organoplatinum Compounds/administration & dosage , Organoplatinum Compounds/therapeutic use , Oxaliplatin , Treatment Outcome , Gemcitabine
6.
Drug Des Devel Ther ; 7: 645-56, 2013.
Article in English | MEDLINE | ID: mdl-23976842

ABSTRACT

Cancer-related anorexia and cachexia syndrome (CACS) is a complex multifactorial condition, with loss of lean body mass, chronic inflammation, severe metabolic derangements, reduced food intake, reduced physical activity, and poor quality of life as key symptoms. Cachexia recognizes different phases or stages, moving from precachexia through overt cachexia to advanced or refractory cachexia. The purpose of this review is to describe currently effective approaches for the treatment of cachexia, moving forward to drugs and treatments already shown to be effective but needing further clinical trials to confirm their efficacy. We then introduce novel promising investigational drugs and approaches which, based on a strong rationale from the most recent data on the molecular targets/pathways driving the pathophysiology of cachexia, need to be tested either in currently ongoing or appropriate future clinical trials to confirm their clinical potential. Although different drugs and treatments have been tested, we can speculate that a single therapy may not be completely successful. Indeed, considering the complex clinical picture and the multifactorial pathogenesis of CACS, we believe that its clinical management requires a multidisciplinary and multitargeted approach. In our opinion, appropriate treatment for cachexia should target the following conditions: inflammatory status, oxidative stress, nutritional disorders, muscle catabolism, immunosuppression, quality of life, and above all, fatigue. A comprehensive list of the most interesting and effective multitargeted treatments is reported and discussed, with the aim of suggesting the most promising with regard to clinical outcome. A critical issue is that of testing therapies at the earliest stages of cachexia, possibly at the precachexia stage, with the aim of preventing or delaying the development of overt cachexia and thereby obtaining the best possible clinical outcome for patients.

7.
Springerplus ; 2(1): 198, 2013 Dec.
Article in English | MEDLINE | ID: mdl-23741643

ABSTRACT

PURPOSE: The primary objective of the present study was to show the long lasting cardioprotective activity, at different time-points, up to 18 month-follow-up, of telmisartan in preserving the systolic function (assessed as Strain Rate-SR) in cancer patients treated with EPI both in the adjuvant and metastatic setting; the secondary objective was to confirm the correlation of the cardioprotective activity of telmisartan with a reduction of inflammation and oxidative stress induced by EPI. METHODS: Phase II single blind placebo-controlled randomized trial. Sample size 50 patients per arm: based on a pre-planned interim analysis for early stopping rules, the study was discontinued for ethical reasons at 49 patients. Cardiovascular disease-free patients with cancer at different sites eligible for EPI-based treatment randomized to: telmisartan n = 25 or placebo n = 24. Echocardiography Tissue Doppler imaging (TDI) strain and strain rate was performed, serum levels of proinflammatory cytokines (IL-6, TNF-α) and oxidative stress (reactive oxygen species, ROS) were assessed at baseline, every 100 mg/m(2) EPI dose and at 6-, 12- and 18-month follow-up (FU). RESULTS: Significant SR peak reduction in both arms was observed at t2 (cumulative dose EPI 200 mg/m(2)) vs t0. Conversely, at t3, t4, 6-, 12- and 18-month FU SR increased towards normal range in the telmisartan arm, while in the placebo arm SR remained significantly lower. Differences between SR changes in the placebo and telmisartan arm were significant from t3 up to 18 month-FU. IL-6 and ROS increased significantly in the placebo arm at t2 but did not change in the telmisartan arm. A significant (p < 0.05) correlation between changes of SR vs IL-6 and ROS was observed. CONCLUSIONS: Our results suggest that the protective effect of telmisartan is long lasting, probably by ensuring a permanent (at least up to 18-month FU) defense against chronic or late-onset types of anthracycline-induced cardiotoxicity.

8.
Expert Opin Pharmacother ; 13(17): 2453-72, 2012 Dec.
Article in English | MEDLINE | ID: mdl-23072481

ABSTRACT

INTRODUCTION: Anorexia and cachexia syndrome represents a complex clinical picture that occurs in the late stage of several chronic inflammatory diseases, including cancer. Unless counteracted cancer-related anorexia and cachexia syndrome affects quality of life (QL) and survival. However, to date a standard effective treatment is lacking. AREAS COVERED: The aim of this review is to describe the current pharmacological approaches for anorexia and cachexia syndrome, focusing on cancer-related syndrome. The several pharmacological agents tested so far are discussed, distinguishing them in unproven drugs, effective drugs, and drugs under investigation. Moreover, a section is devoted to the promising use of nutritional supplements and nutraceuticals. The emerging role of a multitargeted combined treatment approach is exhaustively reviewed. EXPERT OPINION: Considering the complex clinical picture and the multifactorial pathogenesis of anorexia and cachexia syndrome, we believe that its clinical management requires a multidisciplinary and multipharmacological approach. In our opinion the anorexia and cachexia syndrome treatment should include drugs that target the following conditions: inflammatory status, oxidative stress, nutritional disorders, muscle catabolism, anemia, immunosuppression, and fatigue. The multidimensional therapies for anorexia and cachexia syndrome should ideally be introduced within a context of the "best supportive care," which includes optimal symptom management and careful psychosocial counseling.


Subject(s)
Anorexia/drug therapy , Cachexia/drug therapy , Neoplasms/complications , Animals , Anorexia/etiology , Cachexia/etiology , Humans , Neoplasms/drug therapy , Quality of Life , Syndrome
9.
Crit Rev Oncog ; 17(3): 305-14, 2012.
Article in English | MEDLINE | ID: mdl-22831161

ABSTRACT

Cancer cachexia is defined as a multifactorial syndrome characterized by an ongoing loss of skeletal muscle mass (with or without loss of fat mass) that cannot be fully reversed by conventional nutritional support and leads to progressive functional impairment. The prominent clinical feature of cachexia is weight loss in adults. Anorexia, inflammation, insulin resistance, and increased muscle protein breakdown frequently are associated with cachexia. One single therapy may not be completely successful in the treatment of cachexia because of the complexity of the pathogenesis and symptoms of the cachexia syndrome. Among effective treatments, progestogens currently are considered the best available treatment option and are the only approved drugs in Europe for the treatment of cancer- and AIDS-related cachexia. However, they have limited efficacy in treating cancer cachexia. However, thalidomide, selective COX-2 inhibitors, ghrelin mimetics, and selective androgen receptor modulators showed promising results but should be defined further and confirmed in clinical trials. Therefore, to date, despite several years of coordinated efforts in basic and clinical research, the practice guidelines for the prevention and treatment of cancer-related anorexia cachexia syndrome (CACS) are lacking. The management of CACS is a complex challenge that should address the different causes underlying this clinical event. Recent studies showed that integrated, multitargeted approaches are more effective than single-agent approaches for the treatment of CACS. Further clinical trials to improve and refine current strategies to counteract cancer cachexia using multimodal interventions, including nutritional supplementation, anabolic agents, and antiinflammatory drugs along with an appropriate physical exercise program, are warranted.


Subject(s)
Cachexia/drug therapy , Neoplasms/complications , Cachexia/etiology , Drug Therapy, Combination , Humans , Inflammation/complications , Progestins/therapeutic use
11.
Curr Pharm Des ; 18(31): 4813-8, 2012.
Article in English | MEDLINE | ID: mdl-22632861

ABSTRACT

Cachexia influences morbidity, mortality and quality of life of cancer patients at advanced stage of disease. Therefore, the knowledge of its pathophysiology is critical to develop effective therapies to be integrated in the comprehensive approach of cancer patients. Oxidative stress, unless counteracted by effective antioxidant therapies, contributes to the development of anorexia and cachexia in cancer patients. In the present review the potential role of targeting oxidative stress in the treatment of cachexia is reported. Efficacy data on the use of antioxidants in advanced cancer patients are promising. However, the optimal dosage and route of administration as well as the timing and the most effective combination are not well established. Moreover, since cachexia is a multifactorial syndrome, targeting only oxidative stress as a contributing factor would be inadequate and likely to achieve a limited clinical therapeutic benefit. According to this rationale, antioxidants should be included as essential components of a multitargeted combined treatment of cancer cachexia, which has been shown to be the most successful approach for this syndrome.


Subject(s)
Antioxidants/therapeutic use , Cachexia/diet therapy , Cachexia/etiology , Dietary Supplements , Neoplasms/physiopathology , Oxidative Stress , Animals , Anorexia/drug therapy , Anorexia/etiology , Anorexia/metabolism , Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Antineoplastic Agents/adverse effects , Antineoplastic Agents/therapeutic use , Appetite Stimulants/therapeutic use , Cachexia/immunology , Cachexia/metabolism , Humans , Neoplasms/drug therapy , Neoplasms/immunology , Oxidative Stress/drug effects
12.
Clin Nutr ; 31(6): 889-95, 2012 Dec.
Article in English | MEDLINE | ID: mdl-22608917

ABSTRACT

BACKGROUND & AIMS: Tumour growth is associated with weight loss resulting from both adipose and muscle wasting. METHODS: Administration of L-carnitine (1 g/kg body weight) to rats bearing the AH-130 Yoshida ascites hepatoma, a highly cachectic rat tumour. RESULTS: The treatment results in a significant improvement of food intake and in muscle weight (gastrocnemius, EDL and soleus). These beneficial effects are directly related to improved physical performance (total physical activity, mean movement velocity and total travelled distance). Administration of L-carnitine decreases proteasome activity and the expression of genes related with this activity, such as ubiquitin, C8 proteasome subunit and MuRF-1. Interestingly, L-carnitine treatment also decreases caspase-3 mRNA content therefore suggesting a modulation of apoptosis. Moreover, addition of 50 µM of L-carnitine to isolated EDL muscles results in a significant decrease in the proteolytic rate suggesting a direct effect. CONCLUSIONS: It can be concluded that L-carnitine supplementation may be a good approach for a multi-targeted therapy for the treatment of cancer-related cachexia.


Subject(s)
Carnitine/pharmacology , Dietary Supplements , Muscular Atrophy/drug therapy , Neoplasms/drug therapy , Animals , Cachexia/complications , Cachexia/drug therapy , Cachexia/pathology , Carcinoma, Hepatocellular/drug therapy , Carcinoma, Hepatocellular/pathology , Caspase 3/metabolism , Liver Neoplasms/drug therapy , Liver Neoplasms/pathology , Male , Muscle, Skeletal/drug effects , Muscle, Skeletal/pathology , Muscular Atrophy/complications , Muscular Atrophy/pathology , Neoplasms/complications , Neoplasms/pathology , Organ Size/drug effects , Proteasome Endopeptidase Complex/metabolism , Rats , Rats, Wistar , Ubiquitin/metabolism
13.
Support Care Cancer ; 20(8): 1919-28, 2012 Aug.
Article in English | MEDLINE | ID: mdl-22314972

ABSTRACT

PURPOSE: There is little information about the nutritional status of cancer outpatients because the practice of nutritional screening is rarely performed. This study aims to define the pattern of scores of nutritional risk in 1,453 outpatients and factors associated with a high nutrition risk score, to facilitate the identification of such patients by the oncologists. METHODS: We prospectively screened the nutritional status of cancer outpatients according to the NRS-2002 score which combines indicators of malnutrition and of severity of the disease (1-3 points, respectively). A score ≥ 3 indicates "nutritional risk". The association of the nutritional scores with some patient/tumour/therapy-related variables was investigated through univariable and multivariable linear regression models. RESULTS: Thirty-two percent of outpatients were at nutritional risk. Primary tumour site, Eastern Cooperative Oncology Group score and presence of anorexia or fatigue were significantly associated with the nutrition risk score. Depending on the combination of these variables, it was possible to estimate different probabilities of nutritional risk. CONCLUSIONS: The frequency of a relevant nutritional risk was higher than expected considering the favourably selected population. The nutritional risk was associated with common clinical variables which are usually recorded in the charts and could easily alert the oncologist on the need of a further nutritional assessment or a nutritional support.


Subject(s)
Nutrition Disorders/etiology , Outpatients/statistics & numerical data , Aged , Female , Humans , Italy/epidemiology , Linear Models , Male , Middle Aged , Nutrition Assessment , Nutrition Disorders/epidemiology , Nutritional Status , Prospective Studies , Risk Assessment , Severity of Illness Index
14.
Gynecol Oncol ; 124(3): 417-25, 2012 Mar.
Article in English | MEDLINE | ID: mdl-22198049

ABSTRACT

OBJECTIVES: Gynecological neoplastic disease progression is characterized by specific energy metabolism alterations and by symptoms including fatigue, anorexia, nausea, anemia, and immunodepression, which result in a cachexia syndrome and a marked decrease in patient quality of life (QoL). Therapeutic protocols associated with appropriate and effective psychological and social support systems are essential to counteract the symptoms of neoplastic disease in incurable patients. METHODS: A phase III randomized study was performed to establish the most effective and safest treatment to improve the key symptoms in advanced gynecological cancer patients, i.e., lean body mass (LBM), resting energy expenditure (REE), fatigue, and QoL. In addition, the impact of the treatment arms on the main metabolic and inflammatory parameters, including C-reactive protein (CRP), interleukin (IL)-6, tumor necrosis factor (TNF)-α, leptin, reactive oxygen species (ROS), and glutathione peroxidase, was evaluated. The change in the Glasgow Prognostic Score (GPS) during treatment was also assessed. A total of 104 advanced-stage gynecological cancer patients were enrolled and randomly assigned to receive either megestrol acetate (MA) plus l-carnitine, celecoxib, and antioxidants (arm 1) or MA alone (arm 2). The treatment duration was 4 months. RESULTS: The combination arm was more effective than arm 2 with respect to LBM, REE, fatigue, and global QoL. As for the secondary efficacy endpoints, patient appetite increased, and ECOG PS decreased significantly in both arms. The inflammation and oxidative stress parameters IL-6, TNF-α, CRP, and ROS decreased significantly in arm 1, while no significant change was observed in arm 2. CONCLUSIONS: The combined treatment improved both immunometabolic alterations and patient QoL. Multimodality therapies for cachexia ideally should be introduced within a context of "best supportive care" that includes optimal symptom management and careful psychosocial counseling.


Subject(s)
Antioxidants/therapeutic use , Cachexia/drug therapy , Carnitine/therapeutic use , Genital Neoplasms, Female/drug therapy , Genital Neoplasms, Female/metabolism , Megestrol Acetate/therapeutic use , Pyrazoles/therapeutic use , Sulfonamides/therapeutic use , Adult , Aged , Antioxidants/adverse effects , Cachexia/metabolism , Cachexia/pathology , Carnitine/adverse effects , Celecoxib , Female , Genital Neoplasms, Female/pathology , Humans , Inflammation/metabolism , Inflammation/pathology , Megestrol Acetate/adverse effects , Middle Aged , Prospective Studies , Pyrazoles/adverse effects , Quality of Life , Sulfonamides/adverse effects , Treatment Outcome
15.
Clin Nutr ; 31(2): 176-82, 2012 Apr.
Article in English | MEDLINE | ID: mdl-22047681

ABSTRACT

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


Subject(s)
Anorexia/drug therapy , Cachexia/drug therapy , Carnitine/therapeutic use , Megestrol Acetate/therapeutic use , Neoplasms/complications , Pyrazoles/therapeutic use , Sulfonamides/therapeutic use , Absorptiometry, Photon , Aged , Aged, 80 and over , Anorexia/complications , Appetite , Cachexia/complications , Celecoxib , Combined Modality Therapy , Drug Combinations , Endpoint Determination , Female , Humans , Male , Middle Aged , Neoplasms/drug therapy , Patient Compliance , Quality of Life , Treatment Outcome
16.
J Am Med Dir Assoc ; 12(6): 403-9, 2011 Jul.
Article in English | MEDLINE | ID: mdl-21640657

ABSTRACT

A consensus conference convened by the Society of Sarcopenia, Cachexia and Wasting Disorders has concluded that "Sarcopenia, ie, reduced muscle mass, with limited mobility" should be considered an important clinical entity and that most older persons should be screened for this condition. "Sarcopenia with limited mobility" is defined as a person with muscle loss whose walking speed is equal to or less than 1 m/s or who walks less than 400 m during a 6-minute walk, and who has a lean appendicular mass corrected for height squared of 2 standard deviations or more below the mean of healthy persons between 20 and 30 years of age of the same ethnic group. The limitation in mobility should not clearly be a result of otherwise defined specific diseases of muscle, peripheral vascular disease with intermittent claudication, central and peripheral nervous system disorders, or cachexia. Clinically significant interventions are defined as an increase in the 6-minute walk of at least 50 meters or an increase of walking speed of at least 0.1 m/s.


Subject(s)
Consensus , Internationality , Mobility Limitation , Sarcopenia/prevention & control , Aged , Female , Humans , Male , Middle Aged , Muscle, Skeletal/physiology
17.
Lancet Oncol ; 12(5): 489-95, 2011 May.
Article in English | MEDLINE | ID: mdl-21296615

ABSTRACT

To develop a framework for the definition and classification of cancer cachexia a panel of experts participated in a formal consensus process, including focus groups and two Delphi rounds. Cancer cachexia was defined as a multifactorial syndrome defined by an ongoing loss of skeletal muscle mass (with or without loss of fat mass) that cannot be fully reversed by conventional nutritional support and leads to progressive functional impairment. Its pathophysiology is characterised by a negative protein and energy balance driven by a variable combination of reduced food intake and abnormal metabolism. The agreed diagnostic criterion for cachexia was weight loss greater than 5%, or weight loss greater than 2% in individuals already showing depletion according to current bodyweight and height (body-mass index [BMI] <20 kg/m(2)) or skeletal muscle mass (sarcopenia). An agreement was made that the cachexia syndrome can develop progressively through various stages--precachexia to cachexia to refractory cachexia. Severity can be classified according to degree of depletion of energy stores and body protein (BMI) in combination with degree of ongoing weight loss. Assessment for classification and clinical management should include the following domains: anorexia or reduced food intake, catabolic drive, muscle mass and strength, functional and psychosocial impairment. Consensus exists on a framework for the definition and classification of cancer cachexia. After validation, this should aid clinical trial design, development of practice guidelines, and, eventually, routine clinical management.


Subject(s)
Cachexia/classification , Cachexia/diagnosis , Muscle, Skeletal/physiopathology , Neoplasms/complications , Anorexia , Cachexia/etiology , Cachexia/metabolism , Cachexia/physiopathology , Consensus , Delphi Technique , Energy Intake , Energy Metabolism , Expert Testimony , Focus Groups , Humans , International Cooperation , Muscle Strength , Muscle, Skeletal/metabolism , Neoplasms/physiopathology , Sarcopenia/etiology , Severity of Illness Index , Syndrome , Weight Loss
18.
Exp Ther Med ; 2(5): 1003-1009, 2011 Sep.
Article in English | MEDLINE | ID: mdl-22977612

ABSTRACT

Chronic inflammation, oxidative stress and the renin-angiotensin system (RAS) play a significant role in chemotherapy-induced cardiotoxicity (CTX). Telmisartan (TEL), an antagonist of the angiotensin II type-1 receptor, was found to reduce anthracycline (ANT)-induced CTX. We carried out a phase II placebo (PLA)-controlled randomized trial to assess the possible role of TEL in the prevention of cardiac subclinical damage induced by epirubicin (EPI). Forty-nine patients (mean age ± SD, 53.0±8 years), cardiovascular disease-free with cancer at different sites and eligible for EPI-based treatment, were randomized to one of two arms: TEL n=25; PLA n=24. A conventional echocardiography equipped with Tissue Doppler imaging, strain and strain rate (SR) was performed, and serum levels of proinflammatory cytokines, IL-6 and TNF-α, and oxidative stress parameters, reactive oxygen species (ROS) and glutathione peroxidase were determined. All assessments were carried out at baseline, after every 100 mg/m(2) of EPI dose and at the 12-month follow-up (FU). A significant reduction in the SR peak both in the TEL and PLA arms was observed at t(2) (cumulative dose of 200 mg/m(2) of EPI) in comparison to t(0). Conversely, at t(3) (300 mg/m(2) EPI), t(4) (400 mg/m(2) EPI) and the 12-month FU, the SR increased reaching the normal range only in the TEL arm, while in the PLA arm the SR remained significantly lower as compared to t(0) (baseline). The differences between SR changes in the PLA and TEL arms were significant from 300 mg/m(2) EPI (t(3)) up to the 12-month FU. Serum levels of IL-6 increased significantly in the PLA arm at 200 mg/m(2) EPI (t(2)) in comparison to baseline, but remained unchanged in the TEL arm. The same trend was demonstrated for ROS levels which significantly increased at t(2) vs. baseline in the PLA arm, while remained unchanged in the TEL arm. The mean change in ROS and IL-6 at t(2) was significantly different between the two arms. In the present study, we confirmed at the 3-month FU a trend toward a decrease in ROS and IL-6 from t(2) in the PLA arm. Our results suggest that TEL is able to reverse acute (early) EPI-induced myocardial dysfunction and to maintain later a normal systolic function up to the 12-month FU. These effects are likely to be due to different mechanisms, RAS blockade and prevention of chronic inflammation/oxidative stress.

19.
Lung Cancer ; 73(1): 78-88, 2011 Jul.
Article in English | MEDLINE | ID: mdl-21144614

ABSTRACT

BACKGROUND: A recent pooled analysis of randomized trials indicated significant improvement in overall survival from cisplatin-based adjuvant chemotherapy for non-small cell lung cancer (NSCLC), depending on disease stage (only in stages II and III) and PS (≤ 1). Post-operative radiotherapy (RT) is optional for pN2 tumours. PATIENTS AND METHODS: To evaluate opinions and daily clinical practice of Italian Oncologists about adjuvant treatment of NSCLC, a 46-item questionnaire was delivered via e-mail. RESULTS: Seventy-eight physicians from 68 Centers (out of 98 contacted) returned their questionnaire. Seventy-four, 86, 94, and 78% of them give the indication for adjuvant chemotherapy for stage IIA, IIB, IIIA, and IIIB disease, respectively and 14% in stage IB disease. Stage, PS, and age are taken into consideration evaluating adjuvant approach by 97, 95 and 73%, respectively. Cisplatin-vinorelbine (64%) and cisplatin-gemcitabine (33%), for 4 cycles (81%), are the preferred regimens, while 32% use different regimens. Ninety-two percent indicate RT in pN2 disease and/or positive resection margins. Real Number of patients Needed to Treat (NNT) is probably not completely known/understood and/or used by physicians. CONCLUSIONS: A substantial adherence between clinical daily practice in Italy and scientific progresses is described in this paper, even with some discordances regarding the most appropriate adjuvant chemotherapy regimen.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma, Non-Small-Cell Lung/therapy , Chemotherapy, Adjuvant/statistics & numerical data , Health Care Surveys , Lung Neoplasms/therapy , Carboplatin/administration & dosage , Cisplatin/administration & dosage , Deoxycytidine/administration & dosage , Deoxycytidine/analogs & derivatives , Humans , Neoplasm Staging , Paclitaxel/administration & dosage , Radiotherapy, Adjuvant/statistics & numerical data , Vinblastine/administration & dosage , Vinblastine/analogs & derivatives , Vinorelbine , Gemcitabine
20.
Oral Oncol ; 46(11): 818-21, 2010 Nov.
Article in English | MEDLINE | ID: mdl-20920877

ABSTRACT

The aim of the present study was to identify a potentially effective new treatment regimen for patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck in disease progression after at least two previous chemotherapy regimens. The "novel" regimen was Cetuximab administered weekly plus Vinorelbine on days 1, 8, 15 every 28days. The regimen was administered to patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck previously treated with surgery, radiotherapy or both and progressing after at least two chemotherapy regimens. Twenty-four patients with histologically confirmed tumors of oral cavity, oropharynx, hypopharynx and larynx were enrolled. All patients were stage IV and 91.6% had an ECOG PS 0-1. After 3 cycles of treatment 23 patients (95.8%) were evaluable for response: 4 patients had partial response; 12 stable disease and 7 progressive disease. Disease control rate was 69.5%. At a median follow-up of 21.3months, the median progression-free survival was 5.8months. Median duration of response was 5.2months. At May 2010, 11/24 (45.8%) patients were alive. The safety profile was quite good. The present study shows that the combination of Vinorelbine and Cetuximab in recurrent and/or metastatic squamous cell carcinoma of the head and neck patients is effective, feasible and has a good safety profile. Our findings warrant further investigation in a wider patient population.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Carcinoma, Squamous Cell/drug therapy , Head and Neck Neoplasms/drug therapy , Neoplasm Recurrence, Local/drug therapy , Adult , Aged , Antibodies, Monoclonal/administration & dosage , Antibodies, Monoclonal, Humanized , Carcinoma, Squamous Cell/pathology , Carcinoma, Squamous Cell/secondary , Cetuximab , Cisplatin/administration & dosage , Female , Head and Neck Neoplasms/pathology , Head and Neck Neoplasms/secondary , Humans , Male , Middle Aged , Neoplasm Recurrence, Local/pathology , Vinblastine/administration & dosage , Vinblastine/analogs & derivatives , Vinorelbine
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