RESUMEN
Hospitalization for breast surgery is a distressing experience for women. This study investigated the impact of music therapy (MT), an integrative approach that is characterized by the establishment of a therapeutic relationship between patients and a certified music therapist, through different musical interventions targeted to the specific needs of the patients. The impact of two different MT experiences was compared on anxiety and distressing emotions. METHODS: One hundred fifty-one patients during hospitalization for breast surgery were randomly assigned to two music therapy treatment arms: individual/receptive (MTri) vs. group/active-receptive integrated (MTiGrp). Stress, depression, anger, and need for help were measured with the emotion thermometers (ET) and State Trait Anxiety Inventory Y-1 form (STAY-Y1). Data were collected before and after the MT intervention. RESULTS: Both types of MT interventions were effective in reducing all the variables: stress, depression, anger, and anxiety (T Student p<0.01). Patients' perception of help received was correlated with a significant reduction in anxiety and distressing emotions during hospitalization for breast surgery. CONCLUSION: Considerations regarding the implementation of MT interventions in clinical practice are discussed. In individual receptive MT, there was a significant decrease in anxiety levels, whereas in the integrated MT group, there was a higher perception of help received and use of inter-individual resources.
Asunto(s)
Neoplasias de la Mama , Musicoterapia , Música , Humanos , Femenino , Música/psicología , Neoplasias de la Mama/cirugía , Neoplasias de la Mama/psicología , Estrés Psicológico/etiología , Estrés Psicológico/terapia , Estrés Psicológico/psicología , Emociones , Ansiedad/etiología , Ansiedad/terapia , Ansiedad/psicologíaRESUMEN
INTRODUCTION: Sorafenib is currently the only approved therapy in hepatocellular carcinoma (HCC). Alternative first- and second-line treatments are a significant unmet medical need, and several biologic agents have been tested in recent years, with poor results. Therefore, angiogenic pathways and the cytokine cascade remain possible targets in HCC. Recent studies suggest a role of epigenetic processes, associated with the initiation and development of HCC. In this field, DNA methylation, micro-RNAs (miRNAs) and tumor microenvironment cells became a possible new target for HCC treatment. AREAS COVERED: This review explains the possible role of DNA methylation and histone deacetylase inhibitors as predictive biomarkers and target therapy, the extensive world of the promising miRNA blockade strategy, and the recent strong evidence of correlation between HCC tumors and peritumoral stroma cells. The literature and preclinic/clinic data were obtained through an electronic search. EXPERT OPINION: Future research should aim to understand how best to identify patient groups that would benefit most from the prescribed therapy. To overcome the 'therapeutic stranding' of HCC, a possible way out from the current therapeutic tunnel might be to evaluate the major epigenetic and genetic processes involved in HCC carcinogenesis, not underestimating the tumor microenvironment and its 'actors' (angiogenesis, immune system, platelets). We are only at the start of a long journey towards the elucidation of HCC molecular pathways as therapeutic targets. Yet, currently this path appears to be the only one to cast some light at the end of the tunnel.
Asunto(s)
Antineoplásicos/farmacología , Carcinoma Hepatocelular/tratamiento farmacológico , Neoplasias Hepáticas/tratamiento farmacológico , Animales , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patología , Metilación de ADN/genética , Diseño de Fármacos , Epigénesis Genética , Inhibidores de Histona Desacetilasas/farmacología , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patología , MicroARNs/genética , Terapia Molecular Dirigida , Niacinamida/análogos & derivados , Niacinamida/farmacología , Compuestos de Fenilurea/farmacología , Sorafenib , Microambiente TumoralRESUMEN
INTRODUCTION: Sorafenib, an oral multikinase inhibitor, is the only targeted agent approved for the treatment of patients with hepatocellular carcinoma (HCC) after demonstration to increase overall survival compared to placebo in two randomized phase III study. GIDEON (Global Investigation of therapeutic DEcisions in HCC and Of its treatment with sorafeNib) is the largest, global, non-interventional, prospective study of patients with uHCC (n>3200) treated with sorafenib in real-life clinical practice conditions. Here we report the final analysis of safety and efficacy in the Italian cohort of patients. METHODS: Patients with unresectable HCC who are candidates for systemic therapy, and for whom a decision has been made to treat with sorafenib, are eligible for inclusion. Patients demographics disease characteristics and treatment history were recorded at baseline visit. Sorafenib dose, concomitant medications, performance status, liver function, adverse events and efficacy (survival and response rate) were collected throughout the study. RESULTS: In the Italian cohort of the GIDEON study 278 patients were included in 36 centers. The global rate of adverse events was 81%. Drug-related events accounted for 67%, mostly of grade 1 and 2, and only 8% were classified as serious. The most common were diarrhea (24%), fatigue (23%), dermatological (14%), rash/exfoliation (10%), hypertension (9%), hemorrage/bleeding of gastrointestinal tract (6%). Overall survival was 14.4 months and time to progression 6.2 months. Objective responses were observed in 14 patients (5%) with 3 complete responses (1%). Stable diseases of at least 6 weeks were observed in 113 patients (41%) with a 30% of disease control rate. DISCUSSION: The safety profile of sorafenib in terms of rate and type of adverse events is similar to that emerged in the global international GIDEON study as well as in the pivotal registration studies.
Asunto(s)
Antineoplásicos/uso terapéutico , Carcinoma Hepatocelular/tratamiento farmacológico , Neoplasias Hepáticas/tratamiento farmacológico , Niacinamida/análogos & derivados , Compuestos de Fenilurea/uso terapéutico , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Italia , Masculino , Persona de Mediana Edad , Niacinamida/uso terapéutico , Estudios Prospectivos , SorafenibRESUMEN
Metronomic chemotherapy (MC) refers to the close administration of a chemotherapeutic drug for a long time with no extended drug-free breaks. It was developed to overcome drug resistance, partly by shifting the therapeutic target from tumor cells to the tumor vasculature, with less toxicity. Because of this peculiar way of administration, MC can be viewed as a form of long-term 'maintenance' treatment, and can be integrated with standard and conventional chemotherapy in a "chemo-switching" strategy. Additional mechanisms are involved in its antitumor activity, such as activation of immunity, induction of tumor dormancy, chemotherapy-driven dependency of cancer cells, and the '4D effect'. In this paper we report the most important studies that have analyzed these processes. In fact, a number of preclinical and clinical studies in solid tumors as well as in multiple myeloma, have been reported regarding several chemotherapy drugs which have been proposed with a metronomic schedule: vinorelbine, cyclophosphamide, capecitabine, methotrexate, bevacizumab, etoposide, gemcitabine, sorafenib, everolimus and temozolomide. The results of these studies have been sometimes conflicting, highlighting the need to develop reliable tools for patient selection and stratification. However, a more precise evaluation of MC strategies with the ongoing randomized phase II/III clinical is fundamental, because of the strict correlation of this approach with translational research and target therapy. Moreover, because of the low toxicity of MC, these studies will also help to better evaluate the clinical benefit of this treatment, with a special focus on elderly and low performance status patients.
Asunto(s)
Administración Metronómica , Antineoplásicos/administración & dosificación , Neoplasias/tratamiento farmacológico , Animales , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Ensayos Clínicos como Asunto , Evaluación Preclínica de Medicamentos , Humanos , Inmunidad/efectos de los fármacos , Neoplasias/irrigación sanguínea , Neoplasias/inmunología , Neoplasias/patología , Neovascularización Patológica/tratamiento farmacológico , Neovascularización Patológica/inmunología , Neovascularización Patológica/patologíaRESUMEN
BACKGROUND: Rhabdomyolysis is an uncommon side effect of trabectedin which is used for the second line therapy of metastatic sarcoma after anthracycline and ifosfamide failure. This side effect may be due to pharmacokinetic interactions caused by shared mechanisms of metabolism involving the cytochrome P450 (CYP) system in the liver. Here, for the first time in literature, we describe the unexpected onset of heavy toxicity, including rhabdomyolysis, after the fourth course of trabectedin in a patient with retroperitoneal liposarcoma who at the same time was taking an alternative herbal medicine suspected of triggering this adverse event. CASE PRESENTATION: This is the case of a 56 year old Caucasian man affected by a relapsed de-differentiated liposarcoma who, after the fourth cycle of second-line chemotherapy with trabectedin, complained of sudden weakness, difficulty walking and diffuse muscle pain necessitating complete bed rest. Upon admission to our ward the patient showed grade (G) 4 pancytopenia and a marked increase in liver lytic enzymes, serum levels of myoglobin, creatine phosphokinase (CPK) and lactate dehydrogenase. No cardiac or kidney function injuries were present. Based on these clinical and laboratory features, our conclusive diagnosis was of rhabdomyolysis induced by trabectedin.The patient did not report any trauma or muscular overexertion and no co-morbidities were present. He had not received any drugs during treatment with trabectedin, but upon further questioning the patient informed us he had been taking a folk medicine preparation of chokeberry (Aronia melanocarpa) daily during the last course of trabectedin and in the 2 subsequent weeks.One week after hospitalization and cessation of intake of chokeberry extract, CPK and other markers of myolysis slowly returned to standard range, and the patient noted a progressive recovery of muscle strength.The patient was discharged on day 14 when a blood transfusion and parenteral hydration gradually lowered general toxicity. Progressive mobilization of the patient was obtained as well as a complete normalization of the laboratory findings. CONCLUSIONS: The level of evidence of drug interaction leading to the adverse event observed in our patient was 2 (probable). Thus our case underlines the importance of understanding rare treatment-related toxicities such as trabectedin-induced rhabdomyolysis and the possible role of the drug-drug interactions in the pathogenesis of this rare side effect. Furthermore, this report draws attention to a potential problem of particular concern, that of nutritional supplements and complementary and alternative drug interactions. These are not widely recognized and can cause treatment failure.
Asunto(s)
Dioxoles/administración & dosificación , Interacciones de Hierba-Droga , Liposarcoma/tratamiento farmacológico , Extractos Vegetales/administración & dosificación , Rabdomiólisis/etiología , Tetrahidroisoquinolinas/administración & dosificación , Humanos , Masculino , Persona de Mediana Edad , Photinia/química , TrabectedinaRESUMEN
We present the case of a 58-year-old woman with breast cancer metastasizing to the liver after adjuvant chemotherapy. A liver biopsy confirmed metastatic lesions from breast cancer that were immunohistochemically positive for estrogen/progesterone receptors and HER2. After first-line treatment with trastuzumab and vinorelbine, the patient commenced therapy with capecitabine (1000 mg/m2 twice daily, days 1-14) and lapatinib (1250 mg/day). Three months after the administration of this combination therapy, the liver metastases had shrunk substantially. Lapatinib may have the potential to convert trastuzumab-refractory tumors to trastuzumab-sensitive tumors in HER2-positive breast cancer by upregulation of the cell surface expression of HER2. Further study will be needed to evaluate in the clinic the combination of lapatinib and an m-TOR inhibitor as a treatment approach in HER2 overexpressing breast cancer that shows a poor response to trastuzumab.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Biomarcadores de Tumor/análisis , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/patología , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/secundario , Receptor ErbB-2/análisis , Anticuerpos Monoclonales Humanizados/administración & dosificación , Neoplasias de la Mama/cirugía , Capecitabina , Quimioterapia Adyuvante , Desoxicitidina/administración & dosificación , Desoxicitidina/análogos & derivados , Esquema de Medicación , Femenino , Fluorouracilo/administración & dosificación , Fluorouracilo/análogos & derivados , Humanos , Inmunohistoquímica , Lapatinib , Neoplasias Hepáticas/diagnóstico por imagen , Persona de Mediana Edad , Quinazolinas/administración & dosificación , Receptores de Estrógenos/análisis , Receptores de Progesterona/análisis , Tomografía Computarizada por Rayos X , Trastuzumab , Resultado del Tratamiento , Regulación hacia Arriba , Vinblastina/administración & dosificación , Vinblastina/análogos & derivados , VinorelbinaRESUMEN
OBJECTIVES: This study sought to evaluate in vivo the minimal dose of apolipoprotein (apo) A-I(Milano) phospholipid complex (recombinant apoA-I(Milano) and 1-palmitoyl-2-oleoyl phosphatidylcholine complexes [ETC-216]) able to induce atherosclerosis regression in a rabbit model of lipid-rich plaques. BACKGROUND: A single high dose of recombinant apoA-I(Milano) has promoted atherosclerosis regression in animal models. More recently, regression of atherosclerosis was achieved in coronary patients by repeated infusions of ETC-216. METHODS: Thirty-six rabbits underwent perivascular injury at both carotid arteries, followed by a 1.5% cholesterol diet. After 90 days, rabbits were randomly divided into 6 groups and treated 5 times with vehicle or ETC-216 at 5, 10, 20, 40, or 150 mg/kg dose every 4 days. Carotid plaque changes were evaluated in vivo by intravascular ultrasound (IVUS) and magnetic resonance imaging (MRI), performed before and at the end of treatments. Magnetic resonance imaging scans were also recorded after administration of the second dose for rabbits infused with vehicle 40 or 150 mg/kg. RESULTS: Atheroma volume in vehicle-treated rabbits increased dramatically between the first and the second IVUS analyses (+26.53%), whereas in ETC-216-treated animals, a reduced progression at the lower doses and a significant regression at the higher doses, up to -6.83%, was detected. Results obtained by MRI analysis correlated significantly with those at IVUS (r = 0.706; p < 0.0001). The MRI evaluations after the second infusion established that a significant regression was achieved with only 2 administrations of the highest dose. CONCLUSIONS: These results confirm the efficacy of ETC-216 for atherosclerosis treatment and provide guidance for dose selection and frequency to obtain a significant reduction of plaque volume.
Asunto(s)
Anticolesterolemiantes/administración & dosificación , Apolipoproteína A-I/administración & dosificación , Aterosclerosis/diagnóstico , Aterosclerosis/tratamiento farmacológico , Arteria Carótida Común/efectos de los fármacos , Estenosis Carotídea/tratamiento farmacológico , Fosfatidilcolinas/administración & dosificación , Animales , Estenosis Carotídea/diagnóstico , HDL-Colesterol/sangre , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Imagen por Resonancia Magnética , Masculino , Conejos , Distribución Aleatoria , UltrasonografíaRESUMEN
BACKGROUND: A biweekly regimen of irinotecan 200 mg/m2 on day 1 and levo-leucovorin (LV) 250 mg/m2 plus 5-fluorouracil (5-FU) 850 mg/m2 via intravenous bolus on day 2 was assessed in 2 consecutive randomized trials in metastatic colorectal cancer (CRC). PATIENTS AND METHODS: Individual data of 254 patients were merged, and baseline features potentially affecting overall response rate (ORR), progression-free survival (PFS), overall survival (OS), and occurrence of severe toxicity were analyzed by univariate and multivariate analyses. RESULTS: In the pooled series, ORR was 33% (95% confidence interval [CI], 27%-39%). Liver-only disease (47% vs. 25%; P=0.0012) and absence of previous weight loss (38% vs. 20%; P=0.0189) were significantly associated with a higher ORR on the multivariate analysis. Absence of weight loss (hazard ratio, 1.40; 95% CI, 1.02-1.93; P=0.0377) was significantly associated with a longer PFS (7.5 months vs. 6 months). Median OS was 15.1 months (95% CI, 13.5-16.6 months). Primary surgery, good performance status (PS), only one metastatic site, and oxaliplatin-based second-line treatment independently predicted a longer OS. Grade 4 neutropenia was significantly associated with a PS>or=1, whereas risk of grade>or=3 diarrhea was directly related to age and previous weight loss. CONCLUSION: Patients with no weight loss and/or preserved PS and with a limited disease extent appeared to obtain the greatest benefit from our irinotecan/5-FU/LV regimen, with acceptable toxicity. Notably, the regimen was effective and well tolerated by elderly patients. This regimen may represent the rationale for assessing the addition of novel antiangiogenic drugs to the treatment of metastatic CRC.