RESUMEN
BACKGROUND: Soft tissue sarcomas (STSs) are a heterogeneous group of cancers with over 100 described subtypes. While these cancers are infrequent, the prognosis is quite poor, particularly for those with stage IV metastatic disease. Patients for whom curative resection is difficult or those with recurrent metastatic disease are treated with chemotherapy, although the options are very limited. Eribulin is an approved treatment of all STS subtypes in Japan. Efficacy and safety data for the treatment of rare STS subtypes other than liposarcoma and leiomyosarcoma (L-type sarcomas) are limited. This nationwide, multicenter, prospective, post-marketing observational study was conducted to assess the real-world effectiveness and safety of eribulin in Japanese patients with STS. METHODS: Patients with all types of STS and who consented to eribulin treatment were eligible to participate. The observation period was 1 year, starting at treatment initiation, and clinical outcomes were followed up for 2 years after initiating treatment. The primary endpoint was overall survival (OS). Additional outcomes included time-to-treatment failure (TTF), objective response rate (ORR), disease control rate (DCR), and safety. ORR and DCR were evaluated using imaging findings. Effectiveness results were analyzed both for all patients and by STS subtype. RESULTS: A total of 256 patients were enrolled; 252 and 254 were included in the effectiveness and safety analysis set, respectively. Most patients (83.1%) received an initial eribulin dose of 1.4 mg/m2 (standard dose). Respective median OS (95% confidence interval [CI]) was 10.8 (8.5-13.1), 13.8 (10.1-22.3) and 6.5 (5.7-11.1) months for all, L-type, and non-L-type subtypes. The respective median TTF (95% CI) was 2.5 (2.1-2.8), 2.8 (2.3-3.7), and 2.2 (1.6-2.6) months. The ORR and DCR were 8.1 and 42.6%, respectively. Adverse drug reactions (ADRs) and serious ADRs were reported for 83.5 and 18.9% of patients, respectively. The main ADRs were associated with myelosuppression. No significant difference was observed in the incidence of ADRs for patients ≥65 versus <65 years old. CONCLUSIONS: Eribulin demonstrated effectiveness and a manageable safety profile for patients with STS, although the effectiveness of eribulin was not demonstrated for some non-L-type subtypes. TRIAL REGISTRATION: NCT03058406 ( ClinicalTrials.gov ).
Asunto(s)
Sarcoma , Neoplasias de los Tejidos Blandos , Anciano , Furanos/efectos adversos , Humanos , Japón , Cetonas , Mercadotecnía , Estudios Prospectivos , Sarcoma/patología , Neoplasias de los Tejidos Blandos/tratamiento farmacológico , Resultado del TratamientoRESUMEN
BACKGROUND AND AIM: Endoscopic resection for early gastric cancer (EGC) is widely performed. However, there is still a paucity of strong evidence regarding long-term outcomes after endoscopic submucosal dissection (ESD) for the expanded indication criteria of the Japanese guidelines (ver. 2010). METHODS: Endoscopic submucosal dissection was performed in patients with EGC that met the expanded indication criteria: (i) cT1a, differentiated-type EGC of 2 to 5 cm, ulcer negative or (ii) cT1a, differentiated-type EGC of ≤3 cm, ulcer positive. Patients whose pathological examination fulfilled the curative resection criteria were then enrolled in this cohort study: negative vertical margin, negative lymphovascular invasion, and (i) pT1a, differentiated-type, and ulcer negative; (ii) pT1a, differentiated-type, ≤3 cm, and ulcer positive; or (iii) pT1b1 (<500-µm submucosal invasion), differentiated-type, and ≤3 cm. Patients with only a positive horizontal margin as a noncurative factor were included for follow-up. RESULTS: From September 2003 to February 2012, a total of 356 patients underwent ESD, and 214 were enrolled in the survival analysis. One hundred twenty patients (56%) had >2 cm in diameter and ulcer-negative lesions, and 94 (44%) had ≤3 cm and ulcer-positive lesions. The vital status at 5 years after ESD was confirmed in all (100%) patients. No local or metastatic recurrence was detected; however, 26 metachronous gastric cancers developed, and 1 patient died of metachronous gastric cancer. The 5-year disease-specific and overall survival rates were 99.5% (95% confidence interval [CI], 97.2%-100%) and 93.9% (95% CI, 89.8%-96.4%), respectively. CONCLUSION: ESD for EGC that fulfills the expanded criteria is feasible and shows favorable long-term outcomes.
Asunto(s)
Endoscopía Gastrointestinal/métodos , Mucosa Gástrica/cirugía , Neoplasias Gástricas/cirugía , Anciano , Estudios de Factibilidad , Femenino , Humanos , Japón , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Guías de Práctica Clínica como Asunto , Estudios Prospectivos , Neoplasias Gástricas/mortalidad , Neoplasias Gástricas/patología , Tasa de Supervivencia , Factores de Tiempo , Resultado del TratamientoRESUMEN
BACKGROUND: Gastric cancer is one of the leading causes of malignant disease-related mortality, worldwide. With the use of recently developed anti-tumor agents, the prognoses of patients with unresectable gastric cancer are improving. However, the development of an aggressive treatment strategy for older patients (OPs) remains under debate due to concerns regarding treatment feasibility or patient frailty. We aimed to elucidate whether aggressive chemotherapy has survival benefits for OPs with advanced gastric cancer. METHODS: We analyzed consecutive patients diagnosed with inoperable advanced gastric cancer across seven hospitals from August 2007 to July 2015. We defined OPs as patients aged 75 years or older and compared their survival rates with those of non-older patients (NPs). RESULTS: A total of 256 OPs and 425 NPs were enrolled. Of the OPs, 152 patients received chemotherapy and 104 patients received best supportive care (BSC). In contrast, among the NPs, 375 patients received chemotherapy and 50 patients received BSC. There was no significant difference of the median survival time between OPs and NPs in the response to BSC (61 vs 43 days) or chemotherapy (312 vs 348 days). Combination chemotherapy significantly improved survival compared to monotherapy in both OPs and NPs groups (382 vs 253 days in OPs, 381 vs 209 days in NPs). Good performance status, combination therapy, and male, but not age, were significant independent prognostic factors. CONCLUSION: When the performance status of a gastric cancer patient is good, active chemotherapy may improve survival, regardless of age.
Asunto(s)
Neoplasias Gástricas/tratamiento farmacológico , Neoplasias Gástricas/mortalidad , Anciano , Anciano de 80 o más Años , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Estudios de Cohortes , Femenino , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos , Neoplasias Gástricas/patología , Resultado del TratamientoRESUMEN
For cancer patients undergoing chemotherapy, there is an onset of a variety of adverse events related to treatment. Among the adverse events at the moment is taste disorder, for which there is no established effective supportive care. We report the measurement and study their relationship across the changes in serum zinc and changes in the taste of patients undergoing chemotherapy. For cancer patients undergoing chemotherapy, taste threshold and serum zinc levels were measured on the day before administration of the therapeutic anti-cancer agent, and after administration of anticancer drugs on day 4 and day 7. Of taste thresholds in the test results, the threshold was salty on day 4 and day 7 after administration of anticancer agents, and a significant difference was found on day 7 after treatment with anticancer drugs on a day prior to administration of anticancer agents on day 1 (p<0. 001, p=0. 007), respectively. The serum zinc level was measured. There was no significant difference on day 7 after administration of anticancer agents and anti-cancer agent before administration on day 1 and day 7 after administration of anticancer drugs on day 4(p<0. 001, p<0. 05), respectively. A negative correlation was shown between the "salt of the fourth day threshold" and "serum zinc levels" (r=-0. 418, pAsunto(s)
Antineoplásicos/efectos adversos
, Trastornos del Gusto/sangre
, Umbral Gustativo
, Zinc/sangre
, Adulto
, Anciano
, Anciano de 80 o más Años
, Antineoplásicos/uso terapéutico
, Femenino
, Humanos
, Masculino
, Persona de Mediana Edad
, Neoplasias/tratamiento farmacológico
, Trastornos del Gusto/inducido químicamente
RESUMEN
BACKGROUND: Irinotecan hydrochloride and S-1, an oral fluoropyrimidine, have shown antitumor activity against advanced gastric cancer as single agents in phase I/II studies. The combination of irinotecan and S-1 (IRI-S) is also active against advanced gastric cancer. This study was conducted to compare the efficacy and safety of IRI-S versus S-1 monotherapy in patients with advanced or recurrent gastric cancer. METHODS: Patients were randomly assigned to oral S-1 (80 mg/m² daily for 28 days every 6 weeks) or oral S-1 (80 mg/m² daily for 21 days every 5 weeks) plus irinotecan (80 mg/m² by intravenous infusion on days 1 and 15 every 5 weeks) (IRI-S). The primary endpoint was overall survival. Secondary endpoints included the time to treatment failure, 1- and 2-year survival rates, response rate, and safety. RESULTS: The median survival time with IRI-S versus S-1 monotherapy was 12.8 versus 10.5 months (P = 0.233), time to treatment failure was 4.5 versus 3.6 months (P = 0.157), and the 1-year survival rate was 52.0 versus 44.9%, respectively. The response rate was significantly higher for IRI-S than for S-1 monotherapy (41.5 vs. 26.9%, P = 0.035). Neutropenia and diarrhea occurred more frequently with IRI-S, but were manageable. Patients treated with IRI-S received more courses of therapy at a relative dose intensity similar to that of S-1 monotherapy. CONCLUSIONS: Although IRI-S achieved longer median survival than S-1 monotherapy and was well tolerated, it did not show significant superiority in this study.
Asunto(s)
Antimetabolitos Antineoplásicos/uso terapéutico , Antineoplásicos Fitogénicos/uso terapéutico , Camptotecina/análogos & derivados , Ácido Oxónico/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 , Protocolos de Quimioterapia Combinada Antineoplásica , Camptotecina/administración & dosificación , Camptotecina/efectos adversos , Camptotecina/uso terapéutico , Progresión de la Enfermedad , Combinación de Medicamentos , Femenino , Estudios de Seguimiento , Humanos , Irinotecán , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia , Ácido Oxónico/administración & dosificación , Ácido Oxónico/efectos adversos , Tegafur/administración & dosificación , Tegafur/efectos adversos , Resultado del Tratamiento , Adulto JovenRESUMEN
BACKGROUND: Paclitaxel has shown promise against advanced gastric cancer and associated malignant ascites with non-measurable lesions. In order to evaluate the therapeutic effect of paclitaxel against malignant gastric ascites, a prospective phase II clinical trial was designed according to our previously proposed criteria represented by the clinical benefit response in gastric cancer (CBR-GC) criteria and the five-point method (5PM). METHODS: Patients with advanced gastric cancer with malignant ascites were treated with 1-h intravenous (i.v.) infusions of 80 mg/m² of paclitaxel weekly over a 3-week cycle on days 1, 8, and 15, followed by 1 week of rest. Therapeutic responses were measured according to the CBR-GC criteria and the 5PM. RESULTS: The CBR-GC criteria showed improved ascites volume and functional status in 39.1% of patients. A positive CBR-GC response in abdominal girth was seen in 31.3% of patients, and this was significantly correlated with the 5PM-estimated change in ascites volume (p < 0.001). The median number of treatment cycles was 3 (range 1-12). The most common non-hematological toxicity was anorexia, in 22.2% of patients. CONCLUSION: Weekly i.v. paclitaxel is a safe and effective chemotherapeutic regimen based on validated CBR-CG criteria.
Asunto(s)
Antineoplásicos Fitogénicos/efectos adversos , Antineoplásicos Fitogénicos/uso terapéutico , Ascitis/tratamiento farmacológico , Paclitaxel/efectos adversos , Paclitaxel/uso terapéutico , Neoplasias Gástricas/tratamiento farmacológico , Adulto , Anciano , Anciano de 80 o más Años , Ascitis/etiología , Ascitis/patología , Líquido Ascítico/patología , Progresión de la Enfermedad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia , Neoplasias Gástricas/mortalidad , Neoplasias Gástricas/patología , Tasa de Supervivencia , Insuficiencia del Tratamiento , Resultado del Tratamiento , Circunferencia de la CinturaRESUMEN
AIM: The Hiroshima Oncology Group of Gastric Cancer(HOG-GC)distributed a multiple-answer questionnaire to investigate the realities of chemotherapy for gastric cancer. SUBJECTS AND METHOD: Seventy-six hospitals in Hiroshima were surveyed. The Japanese classification was used for the staging criteria. RESULTS: Forty-one hospitals, including 10 centers for cancer treatment, completed and returned the questionnaires. For stage II & III cases requiring adjuvant chemotherapy, S-1 was the most commonly used(84%)regimen. A standard starting dose was used in 79% of these cases, and S-1 was administered for one year continuously in 84% of the cases. For stage I B & II (T1), S-1 and UFT were used in 45%and 20%of the cases, respectively. In cases with non-resectable gastric cancer, S-1 plus CDDP and S-1 alone were used as a first-line therapy in 62% and 26% of the patients under 75 years age, respectively, and in 33% and 46% of the patients older than 75 years of age, respectively. In patients with ascites and peritoneal dissemination, S-1 plus CDDP, S-1, S-1 plus DTX, S-1 plus PTX, and PTX were used in 26%, 15%, 21%, 17%, and 17% of cases, respectively. Some of the patients with peritoneal dissemination underwent gastrectomy. CONCLUSION: S-1 was widely used for gastric cancer chemotherapy in Hiroshima Prefecture. Taxane-containing regimens or palliative gastrectomy were commonly used in cases with peritoneal dissemination.
Asunto(s)
Antineoplásicos/uso terapéutico , Neoplasias Gástricas/tratamiento farmacológico , Terapia Combinada , Humanos , Japón , Estadificación de Neoplasias , Neoplasias Gástricas/patología , Neoplasias Gástricas/cirugía , Encuestas y CuestionariosRESUMEN
BACKGROUND: We conducted this study to evaluate the efficacy of S-1 combination chemotherapy as second-line treatment for advanced/recurrent gastric cancer that was resistant to S-1 based chemotherapy as first-line treatment. PATIENTS AND METHODS: We evaluated patients included in phase II.III clinical trials, that is SPIRITS trial(S-1 vs CDDP +S-1), GC0301/TOP-002(S-1 vs CPT-11+S-1), OGSG0002(S-1+CPT-11)and OGSG0105(S-1+paclitaxel). Eligibility criteria at first-line included; pathologically proven gastric cancer, adequate bone marrow, hepatic, and renal functions, PS 0-2, no prior therapy, life expectancy estimated > or =12 weeks, age 20-75 years and written informed consent. Endpoints were as follows; )PFS in first-line and second-line, )Time to Second Progression(TSP), 3) OS. RESULTS: Sixty-six patients were evaluable in this study. We classified these patients into 4 groups according to the protocol. A)S-1 alone in first-line and S-1 combination in second-line(n=7), B)S-1 alone in first-line and other drugs in second-line(n=13), C)S-1 combination in first-line and another S-1 combination in second-line(n=33), D) S-1 combination in first-line and other drugs in second-line(n=13). We compared S-1 combination group(A+C)to other drugs group(B+D)in second-line. In first-line, PFS was 157.5 days in group(A+C)and 130 days in group(B +D)(p=0.2749). In second-line, PFS, TSP and OS were as follows; 72.5, 256.5, 473 days in group(A+C)and 56, 201.5, 398.5 days(PFS; p=0.0806, TSP: p=0.0718, OS: p=0.0204)in group(B+D), respectively. With regards to adverse events, group(A+C)in first-line showed higher frequency in grade 3/4 leukopenia(10%), febrile neutropenia(5%)and grade 3 diarrhea(10%)than group(B+D). In second-line, group(B+D)showed grade 3/4 leukopenia (12%)and neutropenia(8%)than group(A+C). There were no treatment-related deaths. CONCLUSION: These results indicate that S-1 combination chemotherapy is efficient as second-line for advanced/recurrent gastric cancer that got resistant to S-1 based chemotherapy as first-line.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Ácido Oxónico/uso terapéutico , Terapia Recuperativa , Neoplasias Gástricas/tratamiento farmacológico , Neoplasias Gástricas/patología , Tegafur/uso terapéutico , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Combinación de Medicamentos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Ácido Oxónico/efectos adversos , Recurrencia , Neoplasias Gástricas/cirugía , Tasa de Supervivencia , Tegafur/efectos adversosRESUMEN
BACKGROUND: Phase I/II clinical trials of S-1 plus cisplatin for advanced gastric cancer have yielded good responses and the treatment was well tolerated. In this S-1 Plus cisplatin versus S-1 In RCT In the Treatment for Stomach cancer (SPIRITS) trial, we aimed to verify that overall survival was better in patients with advanced gastric cancer treated with S-1 plus cisplatin than with S-1 alone. METHODS: In this phase III trial, chemotherapy-naive patients with advanced gastric cancer were enrolled between March 26, 2002, and Nov 30, 2004, at 38 centres in Japan, and randomly assigned to S-1 plus cisplatin or S-1 alone. In patients assigned to S-1 plus cisplatin, S-1 (40-60 mg depending on patient's body surface area) was given orally, twice daily for 3 consecutive weeks, and 60 mg/m(2) cisplatin was given intravenously on day 8, followed by a 2-week rest period, within a 5-week cycle. Those assigned to S-1 alone received the same dose of S-1 twice daily for 4 consecutive weeks, followed by a 2-week rest period, within a 6-week cycle. The primary endpoint was overall survival. Secondary endpoints were progression-free survival, proportions of responders, and safety. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00150670. FINDINGS: 305 patients were enrolled; seven patients were ineligible or withdrew consent, therefore, 148 patients were assigned to S-1 plus cisplatin and 150 patients were assigned to S-1 alone. Median overall survival was significantly longer in patients assigned to S-1 plus cisplatin (13.0 months [IQR 7.6-21.9]) than in those assigned to S-1 alone (11.0 months [5.6-19.8]; hazard ratio for death, 0.77; 95% CI 0.61-0.98; p=0.04). Progression-free survival was significantly longer in patients assigned to S-1 plus cisplatin than in those assigned to S-1 alone (median progression-free survival 6.0 months [3.3-12.9] vs 4.0 months [2.1-6.8]; p<0.0001). Additionally, of 87 patients assigned S-1 plus cisplatin who had target tumours, one patient had a complete response and 46 patients had partial responses, ie, a total of 54% (range 43-65). Of 106 patients assigned S-1 alone who had target tumours, one patient had a complete response and 32 had partial responses, ie, a total of 31% (23-41). We recorded more grade 3 or 4 adverse events including leucopenia, neutropenia, anaemia, nausea, and anorexia, in the group assigned to S-1 plus cisplatin than in the group assigned to S-1 alone. There were no treatment-related deaths in either group. INTERPRETATION: S-1 plus cisplatin holds promise of becoming a standard first-line treatment for patients with advanced gastric cancer.
Asunto(s)
Antimetabolitos Antineoplásicos/uso terapéutico , Antineoplásicos/uso terapéutico , Cisplatino/uso terapéutico , Ácido Oxónico/uso terapéutico , Neoplasias Gástricas/tratamiento farmacológico , Tegafur/uso terapéutico , Adulto , Anciano , Antimetabolitos Antineoplásicos/administración & dosificación , Antimetabolitos Antineoplásicos/efectos adversos , Antineoplásicos/administración & dosificación , Antineoplásicos/efectos adversos , Cisplatino/administración & dosificación , Cisplatino/efectos adversos , Esquema de Medicación , Combinación de Medicamentos , Femenino , Humanos , Japón , Masculino , Persona de Mediana Edad , Ácido Oxónico/administración & dosificación , Ácido Oxónico/efectos adversos , Neoplasias Gástricas/mortalidad , Tasa de Supervivencia , Tegafur/administración & dosificación , Tegafur/efectos adversos , Resultado del TratamientoRESUMEN
OBJECTIVES: A phase II study of weekly paclitaxel combined with S-1, a novel oral fluoropyrimidine, was performed to evaluate the efficacy and tolerability in unresectable or metastatic gastric cancer. PATIENTS AND METHODS: Twenty-nine patients with unresectable and/or metastatic gastric cancer were enrolled in the study. Paclitaxel 50 mg/m(2) was administered on days 1 and 8. S-1 was administered orally at 40 mg/m(2) b.i.d. for 14 consecutive days, followed by a 1-week rest. The primary endpoint was the response rate. Secondary endpoints were safety and overall survival. RESULTS: The overall response rate in 29 patients was 48.3%, differentiated 36.4% and undifferentiated 55.6%. The median survival time was 13.9 months. Grade 3 or higher toxicity was observed in neutropenia (3.4%), diarrhea (3.4%), bilirubin (3.4%) and neuropathy (3.4%). CONCLUSIONS: Combination chemotherapy of weekly paclitaxel and S-1 demonstrated tolerable toxicity and efficacy. This regimen will be one of the initial treatment options for unresectable or metastatic gastric cancer.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Gástricas/tratamiento farmacológico , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Combinación de Medicamentos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Ácido Oxónico/administración & dosificación , Paclitaxel/administración & dosificación , Tegafur/administración & dosificación , Resultado del TratamientoRESUMEN
BACKGROUND: EMR and endoscopic submucosal dissection (ESD) are now being increasingly used for the treatment of esophageal cancers. However, their efficacies in smaller lesions have not been compared. OBJECTIVE: For effective use of these methods, we compared the results of ESD and 2 major EMR methods for treating esophageal cancers of Asunto(s)
Adenocarcinoma/patología
, Adenocarcinoma/cirugía
, Carcinoma de Células Escamosas/patología
, Carcinoma de Células Escamosas/cirugía
, Neoplasias Esofágicas/patología
, Neoplasias Esofágicas/cirugía
, Esofagoscopía
, Adulto
, Anciano
, Anciano de 80 o más Años
, Femenino
, Humanos
, Japón
, Masculino
, Persona de Mediana Edad
, Membrana Mucosa/cirugía
, Estadificación de Neoplasias
, Estudios Retrospectivos
RESUMEN
BACKGROUND: A pre-clinical study demonstrated that paclitaxel induced thymidine phosphorylase in the tumor tissues. The combination of paclitaxel and doxifluridine is expected to exert extra anti-tumor effects. We evaluated the efficacy of this combination in patients with unresectable or recurrent gastric cancer who had been previously treated with S-1. METHODS: Registration was started to enroll 35 patients with advanced/recurrent gastric cancer, who were selected among those with measurable lesions fitting to response evaluation criteria in solid tumors, and with resistant to S-1 treatment. This regimen is consisted of paclitaxel, 80 mg/m(2), iv on days 1 and 8; and doxifluridine, 600 mg/m(2), po on days 1-14. The treatment was repeated every three weeks. Primary endpoint was response rate (RR); and secondary endpoints were overall survival (OS), progression free survival (PFS) and onset rate of adverse events. RESULTS: From September 2003 to March 2005, 35 patients were registered: including 28 men; 7 women; median age of 66 years (range, 49-75 years); and performance status (PS) levels were, zero with 21 and one with 14 patients. In 33 eligible patients, except two, clinical usefulness was evaluated resulting in RR of 18.2% (partial response, 6; stable disease, 15; progressive disease, 10; and not evaluable, 2 patients). Median survival time was 321 days and median PFS was 119 days. Severe adverse events were found in three patients to discontinue the present treatment. CONCLUSIONS: The combination of paclitaxel and doxifluridine might be a treatment of choice as a second line chemotherapy for patient undergone S-1 treatment.
Asunto(s)
Adenocarcinoma/tratamiento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Floxuridina/administración & dosificación , Recurrencia Local de Neoplasia/tratamiento farmacológico , Paclitaxel/administración & dosificación , Neoplasias Gástricas/tratamiento farmacológico , Adenocarcinoma/mortalidad , Adenocarcinoma/secundario , Anciano , Anemia/inducido químicamente , Anorexia/inducido químicamente , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Supervivencia sin Enfermedad , Combinación de Medicamentos , Resistencia a Antineoplásicos , Femenino , Humanos , Neoplasias Hepáticas/secundario , Neoplasias Pulmonares/secundario , Metástasis Linfática , Masculino , Persona de Mediana Edad , Neutropenia/inducido químicamente , Ácido Oxónico/farmacología , Neoplasias Peritoneales/secundario , Neoplasias Gástricas/mortalidad , Tasa de Supervivencia , Tegafur/farmacología , Trombocitopenia/inducido químicamenteRESUMEN
Acquired coagulation factor inhibitor is a rare coagulation disorder. We herein report a patient with acquired factor V inhibitor showing a decrease in multiple coagulation factor activities. A high titer of factor V inhibitor presumably led to a marked inhibition of factor V activity in the specific factor-deficient plasma used in coagulation factor activity assays based on either an activated partial thromboplastin time (APTT) or prothrombin time (PT) clotting assay, resulting in false low values of the coagulation activity. We re-examined the coagulation factor activity using several dilutions of the patient's plasma and confirmed that the high factor V inhibitor titer had caused an apparent decrease in multiple coagulation factor activities.
Asunto(s)
Antiinflamatorios/uso terapéutico , Trastornos de la Coagulación Sanguínea/tratamiento farmacológico , Trastornos de la Coagulación Sanguínea/inmunología , Inhibidores de Factor de Coagulación Sanguínea/sangre , Factor V/antagonistas & inhibidores , Prednisolona/uso terapéutico , Anciano , Pueblo Asiatico , Trastornos de la Coagulación Sanguínea/fisiopatología , Pruebas de Coagulación Sanguínea , Femenino , Humanos , Tiempo de Tromboplastina Parcial , Tiempo de Protrombina , Resultado del TratamientoRESUMEN
BACKGROUND/AIMS: To investigate the efficacy and safety of the combination therapy of irinotecan (CPT-11) plus S-1 in patients with advanced gastric cancer at the dose recommended by a previous phase I study. METHODS: A total of 23 patients received 80 mg/m(2) of CPT-11 on days 1 and 15, and S-1 at a dose level set on the basis of the body surface area (BSA): 40 (BSA <1.25 m(2)), 50 (BSA > or =1.25 to <1.5 m(2)) or 60 mg (BSA > or =1.5 m(2)) b.i.d. was given from days 1-21. RESULTS: The overall response rate was 47.8% (11 of 23, 95% confidence interval, CI: 27.4-68.2%). The median time to progression (TTP) was 210 days (95% CI: 145-322 days) and the median survival time was 394 days (95% CI: 241-484 days). The incidence of grade 3 or 4 hematological and non-hematological toxicity was 17.4 and 8.7%. The most common hematological toxicity was anemia and the most common non-hematological toxicity was diarrhea. CONCLUSION: The combination therapy of CPT-11 and S-1 provided prolonged TTP with low toxicity, and the results warrant a further phase III study to define the efficacy in improvement of survival in patients with advanced gastric cancer.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Gástricas/tratamiento farmacológico , Adulto , Anciano , Anemia/inducido químicamente , Antimetabolitos Antineoplásicos/administración & dosificación , Antineoplásicos Fitogénicos/administración & dosificación , Camptotecina/administración & dosificación , Camptotecina/análogos & derivados , Diarrea/inducido químicamente , Supervivencia sin Enfermedad , Esquema de Medicación , Combinación de Medicamentos , Femenino , Humanos , Irinotecán , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Ácido Oxónico/administración & dosificación , Neoplasias Gástricas/patología , Análisis de Supervivencia , Tegafur/administración & dosificación , Resultado del TratamientoRESUMEN
UNLABELLED: Treatment of metastatic colorectal cancer remains inadequate. PATIENTS AND METHODS: In a multicentre Phase II study, irinotecan (100 mg/m2), 5-fluorouracil (5-FU) (500 mg/m2), and l-leucovorin (l-LV) (250 mg/m2) were administered on days 1, 8, and 15 of a five-week cycle. Forty-five patients were enrolled. RESULTS: The objective response rate was 26.7%. The median survival time was 21.8 months and the one-year survival rate was 73.3%. The median number of cycles was 4.0, with a median relative dose intensity of 83.3% for both irinotecan and 5-FU. Grade 3 or 4 haematological toxicities were anaemia in four patients, leukopaenia in six patients, and neutropaenia in 15 patients, while non-haematological toxicities were diarrhoea in three patients, and nausea, vomiting, anorexia and increased transaminases in two patients each. No treatment-related deaths occurred. CONCLUSION: Irinotecan plus 5-FU/l-LV can be used to treat metastatic colorectal cancer on an outpatient basis.
Asunto(s)
Adenocarcinoma/tratamiento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Colorrectales/tratamiento farmacológico , Adenocarcinoma/patología , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Camptotecina/administración & dosificación , Camptotecina/efectos adversos , Camptotecina/análogos & derivados , Neoplasias Colorrectales/patología , Esquema de Medicación , Femenino , Fluorouracilo/administración & dosificación , Fluorouracilo/efectos adversos , Humanos , Irinotecán , Leucovorina/administración & dosificación , Leucovorina/efectos adversos , Masculino , Persona de Mediana Edad , Metástasis de la NeoplasiaRESUMEN
OBJECTIVE: The primary objective of this study was to explore the efficacy and safety of combined chemotherapy with CPT-11 and UFT in patients with advanced/metastatic colorectal cancer. METHODS: Twenty-two patients with metastatic colorectal cancer were enrolled in the phase I trial and 35 patients (including eight patients treated at level 4 during phase I) were evaluated in the phase II trial. Treatment consisted of two 35-day cycles of combination chemotherapy with CPT-11 and UFT. During phase I, CPT-11 was administered on days 1 and 15 as an intravenous infusion over 90 min at four different dose levels, starting from a dose of 80 mg/m2 (level 1). During phase II, the dose of CPT-11 was fixed at 150 mg/m2 based on the results of the phase I study. UFT was administered orally at a fixed dose of 300 mg/m2 on days 1-28, followed by a 1-week drug holiday, during each course (35 days). RESULTS: The maximum tolerated dose (MTD) of CPT-11 was determined to be 150 mg/m2 during the phase I trial. The major toxicities detected during phase II in 35 patients receiving CPT-11 at this recommended dose were grade 3/4 neutropenia in nine patients (25.7%) and grade 3/4 anorexia in six patients (11.4%). No severe adverse events occurred. The overall response rate and the median overall survival time was 22.9% (8/35) and 23.9 months for all patients, respectively. For pre-treated patients they were 26.3% (5/19) and 25.1 months, respectively. CONCLUSION: This combination of CPT-11 and UFT is considered to be both feasible and relatively safe. The response rate of the patients receiving CPT-11 at a dose of 150 mg/m2 was comparable to that reported previously for 5-FU-based regimens coupled with CPT-11, and this regimen can probably be beneficial for patients with pre-treated advanced colorectal cancer on an outpatient basis.
Asunto(s)
Adenocarcinoma/tratamiento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Colorrectales/tratamiento farmacológico , Adenocarcinoma/mortalidad , Administración Oral , Adolescente , Adulto , Anciano , Antineoplásicos Fitogénicos/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/toxicidad , Camptotecina/administración & dosificación , Camptotecina/análogos & derivados , Neoplasias Colorrectales/mortalidad , Humanos , Infusiones Intravenosas , Irinotecán , Persona de Mediana Edad , Recurrencia Local de Neoplasia , Tegafur/administración & dosificación , Uracilo/administración & dosificaciónRESUMEN
PURPOSE: S-1 has shown a response rate of 35% in chemonaïve patients with metastatic colorectal cancer (mCRC). Leucovorin enhances the antitumor activity of 5-fluorouracil, and concurrent oral administration of S-1 and leucovorin may represent a more active treatment option for mCRC. METHODS: S-1 (35 mg/m2) and leucovorin (25 mg/body) were orally administered twice daily to chemonaïve patients with mCRC. Predefined dose (schedule)-limiting toxicities (DLTs) during the first course and treatment continuity during the first two courses were evaluated during three periods of treatment with S-1 plus leucovorin (level 0, 2 weeks; level 1, 3 weeks; and level 2, 4 weeks), each followed by a 2-week rest. The pharmacokinetics (PK) of S-1 and leucovorin were studied on days 1 and 14 of the first course. RESULTS: Fifteen patients were enrolled. All three patients had DLTs at level 2, and this level was considered the maximum tolerated schedule. Level 0 was designated as the recommended schedule based on the incidences of DLTs and treatment continuity. The main toxic effects were gastrointestinal, such as diarrhea and stomatitis. There was no grade 4 adverse event or treatment-related death. The overall response rate was 67% (95% confidence interval, 38-88%). The PK profiles of S-1 plus leucovorin were similar to those in previous studies. CONCLUSIONS: The recommended schedule was 2 weeks of S-1 plus leucovorin followed by a 2-week rest. The increased response and gastrointestinal toxicities of S-1 plus leucovorin as compared with S-1 monotherapy suggest that co-administration of leucovorin enhanced the activity of S-1.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Colorrectales/tratamiento farmacológico , Administración Oral , Adulto , Anciano , Combinación de Medicamentos , Femenino , Humanos , Leucovorina/administración & dosificación , Leucovorina/efectos adversos , Leucovorina/farmacocinética , Masculino , Persona de Mediana Edad , Ácido Oxónico/administración & dosificación , Ácido Oxónico/efectos adversos , Ácido Oxónico/farmacocinética , Tegafur/administración & dosificación , Tegafur/efectos adversos , Tegafur/farmacocinéticaRESUMEN
Epithelioid hemangioendothelioma (EHAE) is a vascular tumor which, due to its rarity, is often misdiagnosed as other hepatic tumors based on radiological characteristics. We herein report a case of EHAE in the liver and the mesentery of the small intestine. A 64-year-old asymptomatic woman was admitted to the hospital due to a hepatic tumor identified using computed tomography (CT). An enhanced CT scan revealed multiple tumors in the liver and a tumor in the mesentery. One of the hepatic tumors and the mesenteric tumor were resected and histologically examined. The two tumors exhibited similar histological characteristics and were diagnosed as EHAE. When multiple tumors are found in the liver, EHAE should be included in the differential diagnosis, as the prognosis of EHAE differs from that of carcinoma or benign tumors.
RESUMEN
AIM: To test protracted irinotecan infusion plus a low-dose cisplatin in this Phase II trial to decrease its toxicity. METHODS: The eligibility criteria were: (1) histologically proven measurable gastric cancer; (2) performance status of 0 or 1; (3) no prior chemotherapy or completion of prior therapy at least 4 wk before enrollment; (4) adequate function of major organs; (5) no other active malignancy; and (6) written informed consent. The regimen consisted of irinotecan (60 mg/m(2)) on d 1 and 15 by 24-h infusion and cisplatin (10 mg/m(2)) on d 1, 2, 3, 15, 16, and 17. Treatment was repeated every 4 wk. RESULTS: Thirty-one patients were registered between April 2000 and January 2001. The response rate for all 31 patients, 20 patients without prior chemotherapy, and 11 patients with prior chemotherapy was 52% (16/31), 60% (12/20), and 36% (4/11), respectively. The median survival time was 378 d. The median number of courses given to all patients was 2. Grade 4 neutropenia occurred in 11 (35%) patients, while grade 3 to 4 diarrhea or nausea occurred in 1 (3%) and 3 (10%) patients, respectively. Fatigue was minimal as grade 1 fatigue was found only in 3 (10%) patients. Other adverse events were mild and no treatment-related deaths occurred. CONCLUSION: This regimen showed a high level of activity and acceptable toxicity in patients with metastatic gastric cancer.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Metástasis de la Neoplasia/tratamiento farmacológico , Neoplasias Gástricas/tratamiento farmacológico , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Camptotecina/administración & dosificación , Camptotecina/análogos & derivados , Cisplatino/administración & dosificación , Relación Dosis-Respuesta a Droga , Quimioterapia Combinada , Femenino , Humanos , Infusiones Intravenosas , Irinotecán , Masculino , Persona de Mediana Edad , Tasa de Supervivencia , Resultado del TratamientoRESUMEN
The effectiveness of systemic chemotherapy for metastatic gastric cancer has already been established. However, a standard chemotherapy still remains uncertain. New agents such as S-1, CPT-11 and taxanes are markedly improving the response rates for gastric cancer. Including these new drugs, several randomized phase III trials are ongoing in Japan. In the near future, the candidate for standard regimen to treat gastric cancer will be reported. In this article, we described the current state of S-1 +CPT-11 combination chemotherapy for gastric cancer. Among various CPT-11 based chemotherapy, S-1 +CPT-11 appears to be the most effective and less toxic treatment.