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BACKGROUND AND OBJECTIVE: Dupilumab, an anti-IL-4 receptor a monoclonal antibody, was recently approved for the treatment of chronic rhinosinusitis with nasal polyps (CRSwNP) and moderate-to-severe asthma. Onset of its clinical effects is rapid. CRSwNP is characterized by extended type 2 inflammatory involvement that can be assessed using extended nitric oxide analysis. We investigated whether dupilumab was associated with a rapid improvement in extended nitric oxide parameters, lung function, and clinical outcomes in patients with CRSwNP. METHODS: Consecutive patients with CRSwNP and an indication for dupilumab were evaluated for extended nitric oxide analysis (exhaled, FeNO; bronchial, JawNO; alveolar, CalvNO; nasal, nNO) and lung function 15 and 30 days after initiation of treatment and for clinical outcomes (nasal polyps score [NPS], quality of life questionnaires, visual analog scale [VAS] for the main symptoms, and the Asthma Control Test [ACT]) 30 days after initiation of treatment. RESULTS: We enrolled 33 patients. All extended nitric oxide and lung function parameters improved significantly after 15 days of treatment, remaining stable at 30 days. Scores on the NPS, VAS for the main RSwNP symptoms, quality of life questionnaires, and the ACT improved significantly 30 days after initiation of treatment. CONCLUSION: Dupilumab is associated with very rapid improvement in type 2 inflammation in all airway areas. This is associated with improved lung function and clinical parameters in patients with CRSwNP.
Assuntos
Asma , Pólipos Nasais , Rinite , Rinossinusite , Sinusite , Humanos , Rinite/tratamento farmacológico , Óxido Nítrico , Pólipos Nasais/tratamento farmacológico , Qualidade de Vida , Sinusite/tratamento farmacológico , Doença CrônicaRESUMO
BACKGROUND AND OBJECTIVE: Background: Dupilumab, an anti-IL-4 receptor alpha monoclonal antibody, has been recently approved for the treatment of chronic rhinosinusitis with nasal polyps (CRSwNP) and moderate to severe asthma, demonstrating a rapid onset of clinical effects. CRSwNP is characterized by an extended type-2 inflammatory involvement that can be assessed by extended nitric oxide analysis. Objective: In this study we investigated whether Dupilumab is associated with a rapid improvement in extended nitric oxide parameters, lung function and clinical outcomes in patients with CRSwNP. METHODS: : Consecutive patients with CRSwNP and indication to be treated with Dupilumab were evaluated for extended nitric oxide analysis (exhaled, FENO; bronchial, JawNO and alveolar, CalvNO components; nasal, nNO) and lung function 15 and 30 days after treatment initiation, and for clinical outcomes (nasal polyps score, NPS; quality of life questionnaires; visual analogue scales, VAS, for main symptoms, asthma control test, ACT) after 30 days of treatment initiation. RESULTS: 33 patients were enrolled. All extended nitric oxide and lung function parameters significantly improved after 15 days of treatment remaining stable at 30 days. NPS, VAS for main CRSwNP symptoms, quality of life questionnaires and ACT significantly improved after 30 days of treatment initiation. CONCLUSION: Dupilumab is associated with very rapid improvement in type 2 inflammation in all airway districts and this is associated with improved lung function and clinical parameters in patients with CRSwNP.
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INTRODUCTION: The numerous links between allergic rhinitis and asthma have been extensively explored in the last two decades, gaining great concern within the scientific community. These two conditions frequently coexist in the same patient and share numerous pathogenetic and pathophysiological mechanisms. AREAS COVERED: We reviewed major pathophysiological, epidemiological, and clinical links between allergic rhinitis and asthma. We also provided a comprehensive discussion of allergic rhinitis treatment according to current guidelines, with a particular focus on the relevance of allergic rhinitis therapies in patients with comorbid asthma. EXPERT OPINION: We believe that there are several unmet needs for our patients, however, there are promising advances forecasted for the future. Although allergic rhinitis is a recognized risk factor for asthma, a proper asthma detection and prevention plan in allergic rhinitis patients is not available. Allergen immunotherapy (AIT) represents a promising preventive strategy and may deserve an earlier positioning in allergic rhinitis management. A multidisciplinary approach should characterize the journey of patients with respiratory allergies, with an adequate referral to specialized Allergy/Asthma centers. Molecular Allergy Diagnosis may provide support for optimal AIT use. Finally, a possible evolution of biological treatment can be envisaged, mainly if biosimilars decrease such therapies' costs.
Assuntos
Asma , Medicamentos Biossimilares , Rinite Alérgica , Asma/epidemiologia , Asma/etiologia , Asma/terapia , Dessensibilização Imunológica/efeitos adversos , Humanos , Rinite Alérgica/epidemiologia , Rinite Alérgica/terapiaRESUMO
OBJECTIVE: To describe the oral health status and treatment needs of a sample of elderly people residing in nursing homes in Northern Italy. RESEARCH DESIGN: a sample of 595 elderly residents (mean age 83.2+/-9.2 yrs), with adequate cognitive skills were examined by six calibrated dentists. RESULTS: The sample (82% women) was divided into two groups: edentulous (43%) and dentate. In the edentulous group 58% wore dentures in both jaws, 8% in only one jaw and 34% had no dentures. The main problems were dirty or loose dentures and poor oral hygiene. In the dentate group the mean number of teeth was 8.4+/-7.4, 53% wore dentures (removable, fixed or a combination). Poor oral hygiene was found in 86%, root caries in 51% and coronal caries in 46%. Their main needs were professional cleaning (72%), oral hygiene instructions (62%) and tooth/root extractions (56%). While normative needs were noted for 82% of the whole sample, oral treatment needs were accurately perceived by only 20% of residents, poorly by 24%, while 46% indicated that they had no oral treatment needs.
Assuntos
Cárie Dentária/epidemiologia , Dentaduras/estatística & dados numéricos , Necessidades e Demandas de Serviços de Saúde/estatística & dados numéricos , Doenças da Boca/epidemiologia , Boca Edêntula/epidemiologia , Casas de Saúde , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Índice CPO , Reparação em Dentadura , Feminino , Humanos , Itália/epidemiologia , Masculino , Pessoa de Meia-Idade , Saúde Bucal , Higiene Bucal , Autoavaliação (Psicologia) , Extração DentáriaRESUMO
The treatment of refractory metastatic breast cancer is primarily palliative, without a significant impact on overall survival. Among the innovative combinations in this unfavourable setting, paclitaxel and gemcitabine showed a possible synergistic action and an encouraging activity in some clinical trials. This phase II study was carried out to evaluate paclitaxel-gemcitabine combination in very heavily pretreated advanced breast cancer on a bi-weekly schedule.Thirty-nine women with advanced breast cancer were treated with paclitaxel 150 mg/m2 as 3 hrs infusion, and gemcitabine 1,500 mg/m2 as 30 mins infusion, both drugs administered on days 1, 15, with cycles repeated every 28 days. All but two patients received granulocyte colony stimulating factor (G-CSF) on days 7 to 9 and 20 to 22 of every cycle. More than two third (71%) of the patients had previously received two or more chemotherapy regimens for advanced disease, including almost all active agents in this disease. Objective responses were observed in 18 out of 34 evaluable patients (53%; 95% CI, 36% to 70%). Disease remained stable in 7 patients (21%). Responses by sites were 67% in soft tissue and in bone, and 48% in visceral disease. Median time to progression and overall survival were 9 and 20 months, respectively. Treatment was well tolerated, with G3-4 neutropenia in 8%, and G 1-2 thrombocytopenia in 13% of the patients; non-hematological toxicities were mild, with G3 hepatotoxicity in 5% of the patients, and G3 peripheral neurotoxicity in 10% of the patients. Biweekly paclitaxel/gemcitabine combination with G-CSF support appears to be very active as salvage therapy in heavily pretreated breast cancer patients, with a very favourable safety profile.
Assuntos
Antimetabólitos Antineoplásicos/administração & dosagem , Antineoplásicos Fitogênicos/administração & dosagem , Neoplasias da Mama/tratamento farmacológico , Desoxicitidina/análogos & derivados , Paclitaxel/administração & dosagem , Terapia de Salvação/métodos , Adulto , Idoso , Desoxicitidina/administração & dosagem , Progressão da Doença , Feminino , Fator Estimulador de Colônias de Granulócitos/uso terapêutico , Humanos , Pessoa de Meia-Idade , Metástase Neoplásica , Resultado do Tratamento , GencitabinaRESUMO
BACKGROUND: In patients locally progressing after two lines of chemotherapy, some locoregional approaches showed encouraging results in terms of local control of disease. The aim of our study was to evaluate toxicity, clinical response and quality of life in 48 patients with unresectable colorectal liver metastases submitted to selective internal radiotherapy (SIRT). MATERIALS AND METHODS: Up to now 35 patients with unresectable colorectal liver metastases, refractory to two lines of chemotherapy, underwent intra-arterial infusion of resin microspheres with yttrium-90 (SIR-spheres). Pre-treatment evaluation included a CT scan, blood tests, a PET scan and arteriography of celiac trunk, hepatic and superior mesenteric artery; extrahepatic uptakes and pulmonary shunts more than 10% were excluded by a Scinti-scan. The gastroduodenal artery was embolized before the SIR-spheres injection. Other exclusion criteria were liver dysfunction and anatomical vascular anomalies. The clinical response was evaluated by CT-scan following the RECIST criteria. Median follow-up was 4 months. RESULTS: Median number of metastases was 4 (range, 1-15), 38% of cases presenting hepatic involvement < 25%. The median SIRT dose delivered was 1.7 GBq. Median pulmonary shunt was 6%. No operative mortality occurred; early toxicity (within 48 hours) was 20.6%, shown as fever, acute pain and leucocytosis. The late toxicity was 24.1% with chronic pain, jaundice and nausea being the most frequent. All the toxic events were graded 2 or 3 according to the WHO scale. Preliminary results were available in terms of clinical response after 6 weeks: 12.5% had a partial response, 75% a stable disease, while progression of disease, was observed in 12.5% of the patients. CONCLUSION: SIRT is a safe treatment in terms of acute and late toxicity. Intra-arterial microspheres could represent a good therapeutic option for patients with progressing liver metastases only, after two lines of systemic chemotherapy.
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Neoplasias Colorretais/radioterapia , Neoplasias Hepáticas/radioterapia , Neoplasias Hepáticas/secundário , Radioisótopos de Ítrio/administração & dosagem , Antineoplásicos/uso terapêutico , Neoplasias Colorretais/patologia , Progressão da Doença , Humanos , Infusões Intra-Arteriais , Microesferas , Estudos Prospectivos , Qualidade de Vida , Dosagem Radioterapêutica , Fatores de Tempo , Resultado do Tratamento , Radioisótopos de Ítrio/efeitos adversosRESUMO
PURPOSE: We conducted a randomized trial to evaluate primarily the cardioprotective effect of dexrazoxane (DEX) in patients with advanced breast cancer and soft tissue sarcomas (STS) treated with high-dose epirubicin (EPI). We wished also to determine the value of radioimmunoscintigraphy (RIS) in the assessment of anthracycline cardiotoxicity. PATIENTS AND METHODS: Patients with breast cancer (n = 95) or STS (n = 34) received EPI 160 mg/m2 by intravenous (I.V.) bolus every 3 weeks with or without DEX 1,000 mg/m2 I.V. Cardiac monitoring included multigated radionuclide (MUGA) scans with determination of resting left ventricular ejection fraction (LVEF), and RIS with indium 111 antimyosin monoclonal antibodies. RESULTS: In either disease, antitumor response rates, time to progression, and survival did not significantly differ between the two arms. There was little difference in noncardiac toxicity for the two treatment groups. All methods of cardiac evaluation clearly documented the cardioprotective effect of DEX. Four patients developed congestive heart failure (CHF), all in the EPI arm. The decrease in LVEF from baseline was significantly greater in the control group. An abnormal antimyosin uptake was observed early in both arms and progressively increased during treatment. However, this increase was significantly higher in the EPI group (P = .004). CONCLUSION: DEX significantly protects against the development of cardiotoxicity when high single doses of EPI are used. Apparently, there was no evidence of an adverse impact of DEX on antitumor activity. Although RIS is a sensitive technique in detecting anthracycline cardiac damage, its specificity is low and it cannot be considered a primary test for guiding anthracycline treatment.
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Antibióticos Antineoplásicos/efeitos adversos , Neoplasias da Mama/tratamento farmacológico , Fármacos Cardiovasculares/uso terapêutico , Monitoramento de Medicamentos/métodos , Epirubicina/efeitos adversos , Coração/efeitos dos fármacos , Razoxano/uso terapêutico , Sarcoma/tratamento farmacológico , Adulto , Idoso , Antibióticos Antineoplásicos/uso terapêutico , Neoplasias da Mama/patologia , Epirubicina/uso terapêutico , Feminino , Coração/diagnóstico por imagem , Frequência Cardíaca/efeitos dos fármacos , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Estudos Prospectivos , Cintilografia , Sarcoma/patologia , Função Ventricular Esquerda/efeitos dos fármacosRESUMO
PURPOSE: To verify the experience of the GOIM in the treatment of advanced colorectal cancer patients with the FOLFIRI combination therapy. PATIENTS AND METHODS: Patients entered in three consecutive trials of the GOIM (protocols no. 9706, 9901, and 2301) were reported in this analysis. A total of 287 chemotherapy-naive patients were treated with FOLFIRI regimen: Irinotecan 180 mg/m(2) on day 1 with LV5FU2 regimen (LV at 100 mg/m(2) administered as a 2-hour infusion before FU at 400 mg/m(2) as an intravenous bolus injection, and FU at 600 mg/m(2) as a 22-hour infusion immediately after 5FU bolus injection on day 1 and 2); the treatment was repeated every 2 weeks. RESULTS: 287 patients entered in these three trials, and 264 (92%) were evaluable for response. The overall response rate was 34.5% (95% confidence interval [CI]: 29% to 40%). When only assessable patients were analyzed, overall response rate was 37% (95% CI: 31% to 43%). Median time to progression, median duration of response and survival were 7 months, 10.5 months and 14 months, respectively. All but three patients were evaluable for toxicity which was globally mild; grade 3-4 toxicity was uncommon, and gastrointestinal disturbances were the most common. CONCLUSIONS: FOLFIRI regimen is effective and well-tolerated as first-line treatment in patients with advanced colorectal cancer. Further studies needed to evaluate the improvement in results with the addition of new drugs to this combination therapy.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma/tratamento farmacológico , Neoplasias Colorretais/tratamento farmacológico , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Camptotecina/efeitos adversos , Camptotecina/análogos & derivados , Camptotecina/uso terapêutico , Carcinoma/secundário , Celecoxib , Feminino , Fluoruracila/efeitos adversos , Fluoruracila/uso terapêutico , Humanos , Leucovorina/efeitos adversos , Leucovorina/uso terapêutico , Neoplasias Hepáticas/secundário , Masculino , Pessoa de Meia-Idade , Compostos Organoplatínicos/uso terapêutico , Pirazóis/administração & dosagem , Sulfonamidas/administração & dosagem , Resultado do TratamentoRESUMO
The aim of this study was to determine if lonidamine (LND) supplementation to single-agent epirubicin (EPI) could reverse anthracycline resistance in patients with metastatic breast cancer. 45 patients with metastatic breast cancer were treated with EPI 120 mg/m2 by intravenous (i.v.) bolus every 3 weeks. Patients who progressed were given the same chemotherapy regimen on day 4 in combination with oral LND, 150 mg on day 1, 300 mg on day 2 and 450 mg on days 3-5. Among the 40 evaluable patients, 6 complete responses (CR) and 14 partial responses (PR) were achieved with EPI treatment alone for an overall response rate of 50%. The median duration of response was 6.5 months. Among the 25 patients treated with EPI+LND, 5 PR (21% of 24 evaluable patients) were observed with a median duration of response of 7 months. The median survival in patients receiving both treatments was 20 months. The survival for all patients was 18 months. The survival of patients receiving LND was not significantly longer than for the other patients. Myelotoxicity was the most common side-effect followed by alopecia, nausea and vomiting, and stomatitis. LND-related toxic effects were mild-to-moderate epigastralgia and myalgia. Anthracycline-related toxicity was the same in the two treatment groups. This study indicates that LND may circumvent clinical resistance to EPI without altering the pattern or severity of the toxicity of this anthracycline. Continued investigation of the clinical modulation of EPI resistance by LND in breast cancer is warranted, hopefully in patients with known multidrug resistance status.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias da Mama/patologia , Progressão da Doença , Resistencia a Medicamentos Antineoplásicos , Epirubicina/administração & dosagem , Epirubicina/efeitos adversos , Feminino , Seguimentos , Humanos , Indazóis/administração & dosagem , Indazóis/efeitos adversos , Pessoa de Meia-Idade , Metástase Neoplásica , Taxa de SobrevidaRESUMO
Experimental models have demonstrated the Adriamycin (doxorubicin; Adria Laboratories, Columbus, OH)-potentiating activity of lonidamine. Phase II clinical trials on advanced breast cancer have shown that this drug induced a 16% objective response rate. Present multicentric randomized trial was conducted to verify whether lonidamine can potentiate the antineoplastic effects of conventional fluorouacil, Adriamycin, cyclophosphamide (FAC) chemotherapy in advanced breast cancer. From January 1987 to December 1989, 265 patients were enrolled in this study, and 231 are evaluable for response. After stratification according to institution and ECOG performance status (PS), the patients were randomly allocated to receive either standard FAC therapy (group A) or FAC plus lonidamine (600 mg orally daily three times a day) (group B). After three FAC courses, the patients with no progressive disease were further randomized to either receive continuous treatment up to the time of tumor progression (maximum: 10 courses) or to discontinue therapy when a response "plateau" was reached. In this latter group, the same therapy was restarted at relapse or disease progression. Objective response (complete response plus partial response) was significantly higher in group B (66.3%) compared to group A (42.3%). The actuarial median times to disease progression was also significantly longer (P less than 0.0001) in group B (median 9 months) than in group A (median 6 months). Other than myalgia and gastric pain, no increased toxicity was observed in the lonidamine. The analysis of second randomization are yet available because of the longer follow-up time required. Present findings suggest an interesting additive effect of lonidamine when combined with FAC chemotherapy and warrant further investigation in other therapeutic regimens and in other neoplastic diseases.
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Antineoplásicos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Ciclofosfamida/administração & dosagem , Doxorrubicina/administração & dosagem , Fluoruracila/administração & dosagem , Indazóis/administração & dosagem , Adulto , Idoso , Antineoplásicos/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias da Mama/patologia , Ciclofosfamida/efeitos adversos , Doxorrubicina/efeitos adversos , Esquema de Medicação , Feminino , Fluoruracila/efeitos adversos , Seguimentos , Humanos , Indazóis/efeitos adversos , Pessoa de Meia-Idade , Estudos Prospectivos , Indução de Remissão , Fatores de TempoRESUMO
In this study, we investigated the effects of a 3-min insulin incubation both at physiological and at supraphysiological concentrations on platelet aggregation and intraplatelet cyclic guanosine monophosphate (cGMP) levels both in the absence and in the presence of phosphodiesterase inhibition. We observed that insulin at concentration in the range 0.25-2 nmol/L decreases platelet response to adenosine 5-diphosphate (ADP), being Effective Dose 50 (ED50) for ADP with 2 nmol/L insulin 164 +/- 15% of the basal value, p = 0.005; furthermore, insulin increases intraplatelet content of cGMP (from basal 7.3 +/-0.6 pmol/10(9) plts to 14.6 +/- 1.2 pmol/10(9) plts with 2 nmol/L insulin, p=0.0001) and does not affect the platelet cGMP increase induced by nitrates. On the contrary, at very elevated concentrations (25-200 nmol/L) insulin increases platelet aggregation to ADP (ADP ED50 with 200 nmol/L insulin being 81 +/- 4% of the basal value, p = 0.01), decreases intraplatelet content of cGMP (from basal 7.2 +/- 0.1 pmol/10(9) plts to 5.7 +/- 0.2 pmol/10(9) plts with 200 nmol/L insulin, p = 0.01) and attenuates the platelet cGMP increase induced by nitrates. When cGMP catabolism is inhibited by theophylline or the selective cGMP phosphodiesterase inhibitor zaprinast, insulin shows anti-aggregating effects also at highly supraphysiological concentration (25-200 nmol/L). These results indicate that insulin, depending on the concentrations employed, shows opposite effects on platelet function, and they provide information about the mechanisms involved: actually, insulin is able to increase both cGMP synthesis, through guanylate cyclase activation, and cGMP catabolism, through phosphodiesterase activation. At physiological or slightly supraphysiological concentrations the first phenomenon is prevailing, so that cGMP intraplatelet values increase and insulin shows antiaggregating properties, whereas, at supraphysiological concentrations, insulin reduces cGMP levels through a prevailing phosphodiesterase activation, as supported by the fact that, when cGMP catabolism is prevented, insulin shows anti-aggregating properties also at the highest concentrations used.
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Insulina/administração & dosagem , Agregação Plaquetária/efeitos dos fármacos , Difosfato de Adenosina/farmacologia , Adulto , GMP Cíclico/sangue , Relação Dose-Resposta a Droga , Feminino , Humanos , Masculino , Nitroglicerina/farmacologia , Inibidores de Fosfodiesterase/farmacologia , Diester Fosfórico Hidrolases/sangue , Inibidores da Agregação Plaquetária/farmacologia , Purinonas/farmacologia , Teofilina/farmacologia , Vasodilatadores/farmacologiaRESUMO
The nuclear family is the consequence and reflection of rapid industrialization of the country. It requires a wider safeguarding of infancy in the framework of more extensive social and care service structures. Kindergartens and nursery schools are the basic answers to child care, coupled with the network of independent institutions, and hospitals, out-patients centres and school medical services, and the local health unit, which supervises services in its district. Mention is also made of the measures still needed to ensure that kindergartens and nursery schools are available and efficient, and what must still be done with regard to school medicine (prophylaxis, retrieval of the handicapped, rehabilitation) to achieve a more advanced system of social protection in childhood.
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Creches/normas , Família , Serviços de Saúde Escolar/normas , Criança , Serviços de Saúde da Criança/organização & administração , Serviços de Saúde da Criança/normas , Pré-Escolar , Educação em Saúde , História do Século XIX , História do Século XX , Humanos , Itália , Berçários para Lactentes/históriaRESUMO
We observed, during Holter recording, a case of inferior acute myocardial infarction complicated by paroxystic hyperkinetic atrial fibrillation, which occurred 12 min after the onset of acute irreversible myocardial ischemia. The atrial fibrillation was preceded by a complex pattern of hyperkinetic supraventricular arrhythmias characterized by single premature supraventricular beats, paired premature supraventricular beats and many runs of paroxystic supraventricular tachycardia. The most plausible hypothesis is that atrial fibrillation and the preceding arrhythmic pattern have been due to an extension of ischemia from ventricular to atrial myocardium.
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Fibrilação Atrial/etiologia , Infarto do Miocárdio/complicações , Fibrilação Atrial/fisiopatologia , Eletrocardiografia Ambulatorial , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/fisiopatologiaRESUMO
We report two case histories of long surviving patients after resection of liver methastases from colorectal cancer. In the first case the patient underwent a right hepatectomy to resect a 3 cm-lesion revealed by a CT scan three years after surgery for a rectal adenocarcinoma. Subsequently, she received two cycles of 5-day continuous infusion of fluorouracil. Four years and 11 months after hepatectomy, the patient is alive and free of disease. The second patient underwent resection of a large hepatic methastasis 3 months after left emicolectomy. The lesion substituted almost completely the right lobe and extended to the IV segment of the left lobe of the liver. After hepatectomy, the patient had a disease-free survival longer than 10 years, until a chest X-ray and a CT scan revealed a primary right lung cancer (citologically, adenocarcinoma) with a methastasis in the left lung. Surgical resection represents the only potentially curative therapy for hepatic methastases from colorectal cancer. Recent data about patient selection for hepatic methastasectomy are presented, and the opportunity of postoperative chemotherapy is discussed.
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Adenocarcinoma/cirurgia , Neoplasias Colorretais/patologia , Neoplasias Hepáticas/secundário , Neoplasias Retais/patologia , Adenocarcinoma/patologia , Adenocarcinoma/secundário , Colectomia , Neoplasias Colorretais/cirurgia , Feminino , Hepatectomia , Humanos , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/cirurgia , Pessoa de Meia-Idade , Radiografia Torácica , Neoplasias Retais/cirurgia , Tomografia Computadorizada por Raios XRESUMO
Malignant peritoneal mesothelioma is a rare tumor whose prognosis is poor. We report a case history of a 57-year old woman with large peritoneal masses and ascites refractory to several chemotherapeutic regimens. The patient benefited of a dramatic regression of disease with symptomatic improvement during chemotherapy with gemcitabine. Serum CA-125 values declined consensually to tumor regression. The duration of response was 12 months. The activity of gemcitabine in malignant mesothelioma has been already confirmed in phase II studies. Data are also available suggesting that better results can be obtained combining this agent with cisplatin, and a multicenter phase II study is now exploring the activity of this combination.
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Antimetabólitos Antineoplásicos/uso terapêutico , Desoxicitidina/análogos & derivados , Mesotelioma/tratamento farmacológico , Neoplasias Peritoneais/tratamento farmacológico , Antimetabólitos Antineoplásicos/administração & dosagem , Antígeno Ca-125/sangue , Desoxicitidina/administração & dosagem , Desoxicitidina/uso terapêutico , Feminino , Humanos , Imageamento por Ressonância Magnética , Mesotelioma/diagnóstico , Pessoa de Meia-Idade , Neoplasias Peritoneais/diagnóstico , Fatores de Tempo , GencitabinaRESUMO
PURPOSE: To evaluate the activity and toxicity of docetaxel (TXT) as second line therapy in advanced soft-tissue sarcoma. PATIENTS AND METHODS: Adult patients (pts) with histologically proven locally advanced or metastatic soft tissue sarcoma, were treated with TXT at a dose of 100 mg/m2 in a 1-hour i.v. infusion every 21 days and steroid premedication with oral prednisone 50 mg twice a day for five days starting 24 hours prior to TXT. RESULTS: From November 1995 to May 1997, 19 pretreated pts entered the trial. Characteristics of the pts: males/females 11/8, median age 58 years (30-74), median WHO performance status 1 (0-2); histotypes: leiomyosarcoma 6 pts, malignant fibrous histiocytoma 6 pts, fibrosarcoma 2 pts, others 5 pts. No objective responses were seen. The disease remained stable in 8 pts (42%). Median time to progression was 3.5 months (range, 2-8), median survival 6 months (range, 2-20). The treatment was well-tolerated: the main side effect was hematological toxicity with G3/4 leukopenia and neutropenia in 58% of the pts; G3 anemia and thrombocytopenia occurred only in 1 case. Other toxicities were alopecia that was universal, G3 emesis in 1 pt, G3 diarrhea in 2 pts, G3 stomatitis in 1 pt. Mild fluid retention was recorded only in 2 pts. CONCLUSIONS: The results of this study do not suggest the use of TXT at this dosage and schedule in advanced soft tissue sarcoma.
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Antineoplásicos Fitogênicos/uso terapêutico , Fibrossarcoma/tratamento farmacológico , Histiocitoma Fibroso Benigno/tratamento farmacológico , Leiomiossarcoma/tratamento farmacológico , Paclitaxel/análogos & derivados , Sarcoma/tratamento farmacológico , Taxoides , Adulto , Idoso , Antineoplásicos Fitogênicos/efeitos adversos , Docetaxel , Feminino , Fibrossarcoma/patologia , Histiocitoma Fibroso Benigno/patologia , Humanos , Leiomiossarcoma/patologia , Leucopenia/induzido quimicamente , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Estadiamento de Neoplasias , Neutropenia/induzido quimicamente , Paclitaxel/efeitos adversos , Paclitaxel/uso terapêutico , Prednisona/administração & dosagem , Pré-Medicação , Sarcoma/patologia , Trombocitopenia/induzido quimicamenteRESUMO
PURPOSE: To evaluate the efficacy and toxicity of a sequential low-dose methotrexate (MTX) and 5-fluorouracil (5FU) regimen in the palliative treatment of patients with advanced colorectal cancer. PATIENTS AND METHODS: Enrolled in the study were patients with advanced colorectal cancer, refractory to 5FU + FA. Patients were treated with MTX 40 mg/m2 i.v. bolus d 1 and 8, 5FU 700 mg/m2 i.v. bolus d 2 and 9 (24 hours after MTX bolus). The cycle was repeated every 4 weeks. RESULTS: 48 patients entered the study, and 45 are evaluable. The overall response rate was 15% with 1 complete response and 6 partial responses. Eight patients obtained disease stabilization. Median time to progression was 9 months. Toxicity was mild. Grade 3 stomatitis was observed in 7 (15%) patients. CONCLUSIONS: Sequential MTX/5FU is a well tolerated regimen with mild antitumor activity in refractory advanced colorectal patients.
Assuntos
Neoplasias Colorretais/patologia , Fluoruracila/uso terapêutico , Leucovorina/uso terapêutico , Metotrexato/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/toxicidade , Neoplasias Colorretais/tratamento farmacológico , Fluoruracila/toxicidade , Humanos , Leucovorina/toxicidade , Neoplasias Hepáticas/secundário , Metotrexato/toxicidade , Estadiamento de Neoplasias , Estomatite/induzido quimicamenteRESUMO
PURPOSE: To assess the activity and toxicity of gemcitabine in locally advanced or metastatic soft tissue sarcoma patients (pts). PATIENTS AND METHODS: Gemcitabine was administered on days 1, 8, 15 every 4 weeks at a dose of 1.000/1.250 mg/m2, respectively, in pretreated or not pretreated pts. RESULTS: Eighteen pts entered this phase II trial; sixteen had been previously treated with anthracyclines and ifosfamide. A partial response was observed in a woman with fibrous malignant istocytoma, whereas in 7 pts the disease remained stable. Median time to progression was 4 months. The treatment was well tolerated. Grade 4 toxicity was not observed. CONCLUSIONS: These results do not suggest that gemcitabine, in the dose and schedule used in this trial, may be of value in the treatment of soft tissue sarcomas.
Assuntos
Antimetabólitos Antineoplásicos/uso terapêutico , Desoxicitidina/análogos & derivados , Sarcoma/cirurgia , Desoxicitidina/uso terapêutico , Feminino , Humanos , Estadiamento de Neoplasias , Sarcoma/tratamento farmacológico , Sarcoma/patologia , GencitabinaRESUMO
PURPOSE: We performed a randomized trial to evaluate the cardioprotective effect of dexrazoxane (DEX) in advanced breast cancer patients (ABC) treated with high single-dose epirubicin (EPI). A secondary objective was to determine the role of radioimmunoscintigraphy (RIS) in the assessment of epirubicin cardiotoxicity. PATIENTS AND METHODS: Ninety-five patients with ABC were treated with EPI 160 mg/m2 by i.v. bolus every 3 weeks with or without DEX, 1,000 mg/m2 i.v. Cardiac monitoring included multigated radionuclide (MUGA) scan with determination of resting left ventricular ejection fraction (LVEF), and RIS with 111-Indium antimyosin monoclonal antibodies. RESULTS: The overall response rate was 69% in the EPI arm and 67% in the EPI + DEX arm; median time to response and median time to progression were identical in both arms, being 2 and 8 months, respectively. Median survival was 19 months versus 29 months (p 0.21), respectively. DEX did not appear to contribute to extracardiac EPI toxicity. Congestive heart failure occurred only in the EPI arm (2 instances). LVEF significantly decreased from baseline only in the EPI group. An abnormal tracer uptake at RIS was observed early in both arms, but the increase in heart to lung ratio was much more evident in the control group. CONCLUSIONS: DEX significantly protects against the development of high dose epirubicin cardiotoxicity apparently without evidence of an adverse impact on antitumor activity and non cardiac toxicity. RIS is a very sensitive technique in detecting anthracycline cardiac damage, but its specificity is low and cannot be considered alone a primary test for guiding anthracycline treatment.