RESUMEN
BACKGROUND: A multicenter phase II study was conducted to evaluate the efficacy and safety of a combination regimen of weekly paclitaxel plus S-1 in patients with advanced gastric cancer. METHODS: Patients with previously untreated metastatic or recurrent gastric cancer received intravenous paclitaxel 50 mg/m(2) on days 1, 8, and 15, plus oral S-1 40 mg/m(2) b.i.d. on days 1 to 14 followed by 2 weeks off, in a 28-day cycle. RESULTS: A total of 54 patients were registered. All of them had measurable disease and were determined to be eligible for the present study. Two complete responses and 23 partial responses were confirmed, giving an overall response rate of 46.3%. At a final follow up of 3 years, the median progression-free survival and median overall survival were 6.0 and 14.3 months, respectively. Grade 3 neutropenia occurred in 14 patients, and grade 4 in 1 patient (total, 27.8%). The most serious nonhematological toxicity was diarrhea, where grade 3 occurred in 5 patients (9.3%). There were no treatment-related deaths. CONCLUSION: A combination of weekly paclitaxel plus S-1 was found to be well tolerated and effective in patients with advanced gastric cancer. Further investigation with comparative trials is needed for confirmation.
Asunto(s)
Antimetabolitos Antineoplásicos/uso terapéutico , Antineoplásicos Fitogénicos/uso terapéutico , Ácido Oxónico/uso terapéutico , Paclitaxel/uso terapéutico , Neoplasias Gástricas/tratamiento farmacológico , Tegafur/uso terapéutico , Adulto , Anciano , Antimetabolitos Antineoplásicos/administración & dosificación , Antimetabolitos Antineoplásicos/efectos adversos , Antineoplásicos Fitogénicos/administración & dosificación , Antineoplásicos Fitogénicos/efectos adversos , Intervalos de Confianza , Progresión de la Enfermedad , Combinación de Medicamentos , Femenino , Humanos , Japón , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia , Recurrencia Local de Neoplasia , Ácido Oxónico/administración & dosificación , Ácido Oxónico/efectos adversos , Paclitaxel/administración & dosificación , Paclitaxel/efectos adversos , Neoplasias Gástricas/mortalidad , Neoplasias Gástricas/patología , Tegafur/administración & dosificación , Tegafur/efectos adversosRESUMEN
BACKGROUND: Laparoscopic surgery is widely used for the treatment of colorectal cancer, but little is known about perioperative risk factors for complications. METHODS: Clinical data were reviewed for 401 consecutive unselected colorectal cancer patients who underwent laparoscopic surgery at Kyoto Medical Center between 1998 and 2005. The outcome variable was incidence of postoperative complications. Using logistic regression analysis, 58 background, clinical, preoperative, and intraoperative factors were assessed as potential predictors of complications. RESULTS: The set of independent protective factors that had the greatest influence on the incidence of local complications after colon surgery was as follows: cefmetazole use for prophylaxis (versus oral only; adjusted odds ratio (OR) 0.18, 95% confidence interval (CI) 0.06-0.54), high operative infusion rate (per ml/min; OR 0.82, 95% CI 0.70-0.95), regular laxative use (OR 0.33, 95% CI 0.12-0.79), and double-stapled anastomosis (versus hand-sewn; OR 0.15, 95% CI 0.03-0.83). Independent risk factors for local complications after rectal surgery were abdominoperineal resection (versus low anterior resection, OR 4.84, 95% CI 1.64-14.9), long operative time (per hour, OR 1.55, 95% CI 1.11-2.23), and history of heart disease (OR 5.18, 95% CI 1.34-21.5). The occurrence of complications was not found to be associated with overall survival in this study. CONCLUSIONS: We identified intraoperative management such as low operative infusion rate is one of the independent significant risk factors for complications after laparoscopic surgery for colorectal cancer in addition to patient characteristics and surgical procedure.
Asunto(s)
Neoplasias Colorrectales/cirugía , Laparoscopía , Complicaciones Posoperatorias/epidemiología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Femenino , Humanos , Incidencia , Japón/epidemiología , Modelos Logísticos , Masculino , Persona de Mediana Edad , Factores de Riesgo , Resultado del TratamientoRESUMEN
Patients with thyrotoxic crisis presenting with another emergency are at a considerable risk. We report the successful treatment of a 55-year-old woman having gastric perforation with thyrotoxic crisis; the principle of treatment was delayed surgery after rapid preoperative restoration of thyroid function and cardiovascular status. The patient was admitted for severe abdominal pain and nausea with delirium, exophthalmos, diffuse goiter, tremulousness, diaphoresis, tabescence, pretibial edema, and atrial fibrillation. Computed tomography revealed free air over the liver surface. She had been diagnosed with uncontrolled hyperthyroidism 3 days before admission, with a free liothyronine (T(3)) of 23.2 pg/mL, a free levothyroxine sodium (T(4)) of greater than 7.78 ng/dL, and thyrotropin of less than 0.01 ng/mL. She was diagnosed with gastroduodenal perforation and thyrotoxic crisis, and we planned nonoperative management comprising nasogastric aspiration, cefmetazole sodium, omeprazole, thiamazole, and Lugol's solution. We also used landiolol, an ultrashort-acting beta(1)-adrenoceptor antagonist, and hydrocortisone. On the third day of admission, her thyroid function had improved with a free T(3) of 4.7 pg/mL and a free T(4) of 2.9 ng/dL; however, perforative peritonitis had worsened, and hence, omental patch repair was performed. She recovered uneventfully and was discharged after radioiodine administration. We discuss the management of a thyrotoxic patient with gastric perforation and focus on the importance of changing the management according to the patient's clinical course considering his thyroid function status and comparing the stress of surgery with that of perforative peritonitis in nonoperative management.
Asunto(s)
Perforación Intestinal/complicaciones , Gastropatías/complicaciones , Gastropatías/terapia , Crisis Tiroidea/complicaciones , Femenino , Humanos , Perforación Intestinal/fisiopatología , Perforación Intestinal/cirugía , Persona de Mediana Edad , Índice de Severidad de la Enfermedad , Gastropatías/fisiopatología , Crisis Tiroidea/tratamiento farmacológico , Crisis Tiroidea/fisiopatologíaRESUMEN
OBJECTIVE: A phase I study of weekly intravenous paclitaxel combined with a fixed dose of S-1, a dihydropyrimidine-dehydrogenase-inhibitory oral fluoropyrimidine, was conducted for patients with advanced or recurrent gastric cancer (ARGC). Endpoints of this study were to examine the toxicity profile OF this regimen and to determine the recommended dose (rd) of paclitaxel. METHODS: S-1 was fixed at a dose of 80 mg/m(2) per day and was administered for 2 weeks (days 1--14) followed by a 2-week rest. Two dose levels of paclitaxel (level 1: 60 mg/m(2), level 0: 50 mg/m(2)) were studied. Paclitaxel was infused over 1 h on days 1, 8, and 15. Plasma sampling was performed to characterize the pharmacokinetics and pharmacodynamics of paclitaxel in some patients. Fifteen patients were enrolled (6 patients in level 1, and 9 patients in level 0). Dose-limiting toxicities were defined as grade 4 hematological (including grade 3 febrile neutropenia) and grade 3 non-hematological (except anorexia, nausea, vomiting and depilation) toxicities. RESULTS: Three of 6 patients in level 1 developed grade 4 neutropenia or grade 3 febrile neutropenia, and 1 of them also showed grade 3 diarrhea, which settled the maximum-tolerated dose at this level. At level 0, 2 of 9 patients developed grade 4 neutropenia or grade 3 febrile neutropenia, and the RD of paclitaxel for this protocol was set at this level. Pharmacologic studies demonstrated the persistence of significant serum paclitaxel levels over 24 h after drug administration at both levels. Objective responses according to Response Evaluation Criteria in Solid Tumors were observed in 3 of 6 patients who had measurable disease. CONCLUSION: A combination of S-1 and weekly paclitaxel was feasible and well tolerated, and is suggested to produce a worthwhile response in ARGC. These results warrant further investigation, and a phase II study has already been started.