RESUMO
This multicentre phase II study was aimed at investigating the activity and safety of pegylated liposomal doxorubicin (PLD) and gemcitabine (GEM) as front-line therapy in a large series of chemotherapy-naïve recurrent/metastatic breast cancer patients. From June 2003 to December 2006, a total of 71 recurrent/metastatic breast cancer patients were enrolled. Median age was 63 years (range=37-79), and 31 patients (43.7%) were > or =65 years old. Patients received PLD, 25 mg m(-2), day 1, followed by GEM, 800 mg m(-2), days 1 and 8, q21. Response was evaluable in 64 cases. Eight complete (12.5%) and 17 partial responses (26.6%) were registered, with an overall response rate of 39.1%. Thirty patients (46.9%) experienced stable disease, with an overall clinical benefit of 85.9%. Median time to progression (TTP) was 11 months, whereas median overall survival (OS) was not reached. The rate of 1- and 2-year OS was 79 and 61%, respectively. A total of 443 courses were evaluable for toxicity: grade 3 and 4 neutropaenia affected 14 patients (20.3%) and 3 patients (4.3%), respectively. Grade 3 and 4 palmar-plantar erythrodysesthesia syndrome was documented in five cases (7.2%) and one case (1.4%), whereas grade 3 and 4 mucositis occurred in six cases (8.7%) and two cases (2.9%), respectively. Grade 2 cardiac toxicity was observed in only one case. Interestingly enough, there was no difference in the percentage and severity of either haematological or non-haematological toxicity according to the age of the patients (<65 vs > or =65 years). We confirmed in a large, very homogenous study sample of chemotherapy-naïve recurrent/metastatic breast cancer patients the efficacy and safety of PLD/GEM combination, providing response rates, median TTP and OS values comparable with those achieved with more toxic combinations.
Assuntos
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 , Desoxicitidina/administração & dosagem , Desoxicitidina/efeitos adversos , Desoxicitidina/análogos & derivados , Doxorrubicina/administração & dosagem , Doxorrubicina/efeitos adversos , Doxorrubicina/análogos & derivados , Feminino , Humanos , Pessoa de Meia-Idade , Metástase Neoplásica , Polietilenoglicóis/administração & dosagem , Polietilenoglicóis/efeitos adversos , Recidiva , Resultado do Tratamento , GencitabinaRESUMO
OBJECTIVES: We conducted a multicenter phase II study to evaluate the clinical efficacy, toxicity, and dose intensity of a new weekly schedule of docetaxel and gemcitabine as first-line treatment of metastatic breast cancer patients. METHODS: We enrolled 58 patients, 52% of whom had received a previous anthracycline-containing chemotherapy. The treatment schedule was: docetaxel 35 mg/m2 and gemcitabine 800 mg/m2 i.v. on days 1, 8, 15 every 28 days. RESULTS: All patients were assessable for toxicity and 56 for efficacy. Overall response rate was 64.3% with 16.1% of complete responses and 48.2% of partial responses. Median survival was 22.10 months (95% CI: 15.53-28.67) and median time to tumor progression was 13.6 months (95% CI: 10.71-16.49). The most common hematological toxicity was neutropenia (no febrile neutropenia), which occurred in 28 patients (48.3%) but grade 3-4 in only 8 patients (14%). Alopecia, the most common nonhematological toxicity, occurred in 20 (34.5%) patients, but only 5 patients (8.6%) experienced grade 3 alopecia. CONCLUSION: The activity of docetaxel and gemcitabine in metastatic breast cancer is confirmed. The promising results of the employed schedule, in agreement with other published studies, need to be further confirmed within a phase III study.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Carcinoma Ductal de Mama/tratamento farmacológico , Carcinoma Lobular/tratamento farmacológico , Carcinoma Medular/tratamento farmacológico , Adulto , Idoso , Neoplasias da Mama/patologia , Carcinoma Ductal de Mama/secundário , Carcinoma Lobular/secundário , Carcinoma Medular/secundário , Desoxicitidina/administração & dosagem , Desoxicitidina/análogos & derivados , Docetaxel , Feminino , Humanos , Dose Máxima Tolerável , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Taxa de Sobrevida , Taxoides/administração & dosagem , Resultado do Tratamento , GencitabinaRESUMO
Parathyroid carcinoma is a rare endocrine malignancy characterized by the exaggerated metabolic effects of the parathyroid glands. The preoperative differential diagnosis between parathyroid carcinoma and primary hyperparathyroidism is often difficult because many of the signs and symptoms are very similar. Intraoperative differentiation is obscured by the strict anatomic and histologic criteria required for diagnosis of parathyroid carcinoma. We have encountered three patients with parathyroid carcinoma during the last 10 years and managed them successfully. Two of them presented with recurrence of hypercalcemia, one 11 years after and the other 3 years after the primary operation for hyperparathyroidism; both patients were eventually diagnosed with parathyroid carcinoma. The third case was suspected as primary hyperparathyroidism preoperatively but confirmed as carcinoma subsequent to histologic examination.
Assuntos
Carcinoma , Neoplasias das Paratireoides , Adulto , Carcinoma/diagnóstico , Carcinoma/terapia , Diagnóstico Diferencial , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias das Paratireoides/diagnóstico , Neoplasias das Paratireoides/terapiaRESUMO
The baroreflex was observed in neonatal swine as young as 4 h of age. Bolus injections of Na nitroprusside (NP) and phenylephrine (PE), induced changes in blood pressure and elicited changes in both heart rate and in cervical sympathetic and splanchnic discharge; changes in sympathetic discharge were reflected in altered power spectral magnitude. Measures of heart rate showed that the magnitude of the PE-induced decreases was positively correlated with increasing postnatal age. The results indicate that the baroreflex, as indicated by changes in sympathetic discharge and heart rate, is present in early neonatal swine.
Assuntos
Pressorreceptores/fisiologia , Reflexo/fisiologia , Envelhecimento/fisiologia , Animais , Animais Recém-Nascidos , Pressão Sanguínea/efeitos dos fármacos , Frequência Cardíaca/efeitos dos fármacos , Pescoço/inervação , Nitroprussiato/farmacologia , Fenilefrina/farmacologia , Nervos Esplâncnicos/fisiologia , Suínos , Sistema Nervoso Simpático/fisiologiaRESUMO
Cervical sympathetic nerve discharges in kittens were examined using power spectral techniques to describe the frequency components of nerve activities and to obtain evidence of modulation by central rhythm generators. Peaks in sympathetic spectra appeared in the 4-11 Hz band; however, coherences between sympathetic nerves occurred at 4-5 Hz, while that between sympathetic and phrenic nerves occurred at 8-9 Hz. These findings indicate modulation by sympathetic and inspiratory rhythm generators.
Assuntos
Sistema Nervoso Simpático/fisiologia , Animais , Pressão Sanguínea/fisiologia , Gatos , Estimulação Elétrica , Eletrocardiografia , Feminino , Masculino , Nervo Frênico/fisiologiaRESUMO
The effects of two levels of Saffan anesthesia (standard recording level: 2-4 mg/kg/min, and 10X recording level) and a single level of pentobarbital (5 mg/kg) on the power spectral density of efferent phrenic discharge were investigated in piglets aged from less than 1 day to 50 days. The phrenic high frequency oscillation (HFO) was present in decerebrate, unanesthetized piglets and in piglets anesthetized with Saffan, albeit reduced at 10 times recording level, but was absent under pentobarbital. The results indicate that Saffan does not have a significantly depressant effect on the phrenic HFO in developing swine.
Assuntos
Anestesia , Animais Recém-Nascidos/fisiologia , Neurônios Eferentes/efeitos dos fármacos , Nervo Frênico/fisiologia , Mistura de Alfaxalona Alfadolona , Animais , Pressão Sanguínea/efeitos dos fármacos , Estado de Descerebração , Eletrocardiografia , Halotano , Ketamina , Neurônios Eferentes/fisiologia , Óxido Nitroso , Pentobarbital/farmacologia , Nervo Frênico/efeitos dos fármacos , SuínosRESUMO
Mg is being used as a therapeutic agent in different clinical conditions, i.e. preeclampsia or eclampsia, and as a tocolytic agent to prevent premature delivery. For these reasons we decided to systematically investigate the cardiovascular and respiratory effects of excess Mg in 25 piglets less than 1 day to 3 months of age, lightly anesthetized with Saffan, tracheotomized, paralyzed with C-10 and artificially ventilated on 100% O2. A 1.0 M infusion of MgCl2 was given for 15-60 min, and arterial plasma samples were drawn before and at the end of the infusion for the determination of plasma Mg and Ca levels. Phrenic nerve activity was recorded monophasically simultaneously with arterial blood pressure, electrocardiogram, end-tidal CO2 and intratracheal pressure on a dynograph and on analog tape. In a subset of experiments (n = 6), spontaneous ventilation was monitored in piglets of different ages to determine the Mg concentration at which spontaneous ventilation ceased. Blood gases were measured at 45-min intervals, as well as both immediately before and after the MgCl2 infusion, and pCO2 and pH were maintained within normal limits. As a consequence of the high plasma concentration of Mg, mean arterial pressure and heart rate declined, and the inspiratory duration significantly decreased. Our results indicate that young piglets can survive high levels of plasma Mg (greater than 14 mM).
Assuntos
Animais Recém-Nascidos/fisiologia , Sistema Cardiovascular/efeitos dos fármacos , Cloreto de Magnésio/farmacologia , Magnésio/sangue , Respiração/efeitos dos fármacos , Animais , Pressão Sanguínea/efeitos dos fármacos , Fenômenos Fisiológicos Cardiovasculares , Frequência Cardíaca/efeitos dos fármacos , Nervo Frênico/efeitos dos fármacos , Nervo Frênico/fisiologia , SuínosRESUMO
We report the results obtained in the treatment of 52 advanced non-small-cell lung cancer patients with the combination chemotherapy VP16 (120 mg/m2 i.v., days 1-2-3), epirubicin (50 mg/m2 i.v., day 1) and procarbazine (100 mg/m2 p.o., days 1 through 8). The courses were repeated every 21 days. No patient had been pretreated. A median of 5 courses was administered. Partial response was obtained in 33% and no change in 21% of patients. Median remission time was 6.5 months, and median survival of responders was 10 months. The best response rate and median survival were obtained in the lowest grade performance status patients and in locally advanced disease patients. Major chemotherapy related toxicities were grade 1-2 leukopenia and grade 2-3 alopecia.