RESUMO
BACKGROUND: The Adjuvant Chemotherapy Trial of TS-1 for Colon Cancer (ACTS-CC) is a phase III trial designed to validate the non-inferiority of S-1 to UFT/leucovorin (LV) as postoperative adjuvant chemotherapy for stage III colon cancer. We report the results of a planned safety analysis. METHODS: Patients aged 20-80 years with curatively resected stage III colon cancer were randomly assigned to receive UFT/LV (UFT, 300 mg m(-2) per day as tegafur; LV, 75 mg per day on days 1-28, every 35 days, 5 courses) or S-1 (80, 100, or 120 mg per day on days 1-28, every 42 days, 4 courses). Treatment status and safety were evaluated. RESULTS: Of 1535 enrolled patients, a total of 1504 (756 allocated to S-1 and 748 to UFT/LV) were analysed. The completion rate of protocol treatment was 77% in the S-1 group and 73% in the UFT/LV group. The overall incidence of adverse events (AEs) were 80% in S-1 and 74% in UFT/LV. Stomatitis, anorexia, hyperpigmentation, and haematological toxicities were common in S-1, whereas increased alanine aminotransferase and aspartate aminotransferase were common in UFT/LV. The incidences of î¶grade 3 AEs were 16% and 14%, respectively. CONCLUSION: Although AE profiles differed between the groups, feasibility of the protocol treatment was good. Both S-1 and UFT/LV could be safely used as adjuvant chemotherapy.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias do Colo/tratamento farmacológico , Leucovorina/administração & dosagem , Ácido Oxônico/administração & dosagem , Tegafur/administração & dosagem , Uracila/administração & dosagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Quimioterapia Adjuvante , Neoplasias do Colo/cirurgia , Intervalo Livre de Doença , Combinação de Medicamentos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Ácido Oxônico/efeitos adversos , Tegafur/efeitos adversos , Uracila/efeitos adversosRESUMO
BACKGROUND: This phase I first-in-human study was conducted in Japanese patients to investigate the safety, pharmacokinetics (PKs), and determine the maximum tolerated dose (MTD) of oral TAK-285, a novel dual erbB protein kinase inhibitor that specifically targets human epidermal growth factor receptor (EGFR) and HER2. METHODS: The TAK-285 dose was escalated until MTD was determined. A second patient cohort received TAK-285 at the MTD for at least 4 weeks. RESULTS: In all, 26 patients received TAK-285 at doses ranging from 50 to 400 mg once daily (q.d.) or twice daily (b.i.d.); 20 patients made up the dose escalation cohort and the remaining 6 patients were the repeated administration cohort. TAK-285 was well tolerated. Dose-limiting toxicities noted in two patients who received 400 mg b.i.d. were grade 3 increases in aminotransferases and grade 3 decreased appetite. Consequently, the MTD was determined to be 300 mg b.i.d. Absorption of TAK-285 was rapid after oral dosing, and plasma exposure at steady-state increased in a dose-proportional fashion for doses ranging from 50 to 300 mg b.i.d. A partial response was observed for one patient with parotid cancer who received 300 mg b.i.d. CONCLUSION: The toxicity profile and PK properties of oral TAK-285 warrant further evaluation.
Assuntos
Antineoplásicos/uso terapêutico , Compostos Bicíclicos Heterocíclicos com Pontes/uso terapêutico , Receptores ErbB/antagonistas & inibidores , Hidroxibutiratos/uso terapêutico , Neoplasias/tratamento farmacológico , Receptor ErbB-2/antagonistas & inibidores , Administração Oral , Idoso , Antineoplásicos/efeitos adversos , Antineoplásicos/farmacocinética , Esquema de Medicação , Drogas em Investigação/uso terapêutico , Feminino , Humanos , Masculino , Dose Máxima Tolerável , Pessoa de Meia-IdadeRESUMO
BACKGROUND: The aim of this study was to evaluate the efficacy and feasibility of preoperative chemotherapy with S-1 plus cisplatin in patients with initially unresectable locally advanced gastric cancer. METHODS: We enrolled patients with initially unresectable locally advanced gastric cancer because of severe lymph node metastases or invasion of adjacent structures. Preoperative chemotherapy consisted of S-1 at 80 mg/m(2) divided in two daily doses for 21 days and cisplatin at 60 mg/m(2) intravenously on day 8, repeated every 35 days. If a tumor decreased in size, patients received 1 or 2 more courses. Surgery involved radical resection with D2 lymphadenectomy. RESULTS: Between December 2000 and December 2007, 27 patients were enrolled on the study. No CR was obtained, but PR was seen in 17 cases, and the response rate was 63.0%. Thirteen patients (48.1%) had R0 resections. There were no treatment related deaths. The median overall survival time (MST) and the 3-year overall survival (OS) of all patients were 31.4 months and 31.0%, respectively. Among the 13 patients who underwent curative resection, the median disease-free survival (DFS) and the 3-year DFS were 17.4 months and 23.1%, respectively. The MST and the 3-year OS were 50.1 months and 53.8%, respectively. The most common site of initial recurrence after the R0 resection was the para-aortic lymph nodes. CONCLUSIONS: Preoperative S-1 plus cisplatin can be safely delivered to patients undergoing radical gastrectomy. This regimen is promising as neoadjuvant chemotherapy for resectable gastric cancer. For initially unresectable locally advanced gastric cancer, new trials using more effective regimens along with extended lymph node dissection are necessary.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Cisplatino/administração & dosagem , Gastrectomia , Terapia Neoadjuvante/métodos , Ácido Oxônico/administração & dosagem , Pré-Medicação , Neoplasias Gástricas/terapia , Tegafur/administração & dosagem , Adulto , Idoso , Terapia Combinada , Intervalo Livre de Doença , Relação Dose-Resposta a Droga , Esquema de Medicação , Combinação de Medicamentos , Feminino , Seguimentos , Gastrectomia/métodos , Gastrectomia/mortalidade , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica/patologia , Estadiamento de Neoplasias , Medição de Risco , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/patologia , Análise de Sobrevida , Resultado do TratamentoRESUMO
BACKGROUND: The efficacy and safety of oxaliplatin combined with S-1 (SOX regimen) for unresectable advanced or recurrent gastric cancer were investigated. PATIENTS AND METHODS: Oxaliplatin was administered i.v. (100 mg/m(2)) on day 1, while S-1 was administered orally (80 mg/m(2)/day, b.i.d.) for 14 days followed by a 7-day rest. This schedule was repeated every 3 weeks. RESULTS: Among 55 patients enrolled, one patient received oxaliplatin for the other study, and three patients were considered unsuitable against the inclusion criteria. Accordingly, 51 patients were assessable for efficacy. The response rate was 59%, and the disease control rate was 84%. The median progression-free survival time was 6.5 months, the 1-year survival rate was 71%, and the median survival time was 16.5 months. In 54 patients assessed for safety, the major grade 3/4 toxic effects were neutropenia (22%), thrombocytopenia (13%), anemia (9%), anorexia (6%), fatigue (6%), and sensory neuropathy (4%). CONCLUSION: These findings indicate that SOX regimen with oxaliplatin at a dose of 100 mg/m(2) is feasible and shows promising efficacy against advanced gastric cancer.
Assuntos
Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Recidiva Local de Neoplasia/tratamento farmacológico , Neoplasias Peritoneais/tratamento farmacológico , Neoplasias Gástricas/tratamento farmacológico , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Combinação de Medicamentos , Feminino , Seguimentos , Humanos , Neoplasias Hepáticas/secundário , Neoplasias Pulmonares/secundário , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Compostos Organoplatínicos/administração & dosagem , Oxaliplatina , Ácido Oxônico/administração & dosagem , Neoplasias Peritoneais/secundário , Neoplasias Gástricas/patologia , Taxa de Sobrevida , Tegafur/administração & dosagem , Resultado do TratamentoRESUMO
A total of 12 patients with malignant localized renal or ureteral neoplasms underwent multi-slice computed tomography. Imaging data were sent to the dedicated workstation to create volume rendering and virtual laparoscopic images of the kidney which was displaced ventrally with retroperitoneal balloon. These findings were compared with video images obtained during retroperitoneal laparoscopic nephrectomy. The kidney displacement simulator depicted all renal arteries (100% sensitivity) and 13 of 14 renal veins (93% sensitivity). Hilar anatomy, including the tumor, major vessels and their relationships were visualized as in the actual laparoscopic views. The desired portions of major vessels as well as the left adrenal and gonadal veins visualized with this system completely corresponded with the actual laparoscopic images during surgery. The kidney displacement simulator is useful to foresee desired portions of major vessels and branched small vessels such as the adrenal or gonadal veins in advance of surgery. It is thus able to guide surgeons and reduce operative risks and possible complications.
Assuntos
Imageamento Tridimensional , Rim/anatomia & histologia , Laparoscopia , Nefrectomia , Tomografia Computadorizada Espiral , Cateterismo , Simulação por Computador , Humanos , Processamento de Imagem Assistida por Computador , Neoplasias Renais/diagnóstico por imagem , Neoplasias Renais/cirurgia , Espaço Retroperitoneal , Neoplasias Ureterais/diagnóstico por imagem , Neoplasias Ureterais/cirurgiaRESUMO
The aims of this phase I/II study of docetaxel and S-1 were to determine the dose-limiting toxicity (DLT), maximum-tolerated dose (MTD), and recommended dose (RD) in the phase I part and to explore the tumour response, survival and safety in the phase II part. Patients with histologically- or cytologically confirmed unresectable or recurrent gastric cancer were eligible. Treatment consisted of intravenous docetaxel on day 1 (starting dose 50 mg m(-2)) and oral S-1 at a fixed dose of 40 mg m(-2) twice daily on days 1-14, every 4 weeks up to six cycles. Nine patients took part in the phase I portion of the study. The MTD of docetaxel was determined to be 50 mg m(-2), with the DLTs of grade 3 infection associated with grade 3 neutropenia and grade 4 neutropenia during S-1 administration. The RD of docetaxel was 40 mg m(-2) in combination with S-1 40 mg m(-2) b.i.d. The efficacy and safety of this regimen was therefore assessed in 46 patients with at least one measurable lesion. The overall response rate and estimated median overall survival were 46% (95% CI, 31-61%) and 14.0 months (8.3-17.3 months), respectively. The most common grade 3/4 toxicity was neutropenia (67% of patients), which was predictable and manageable. This regimen showed promising activity with moderate toxicities in advanced gastric cancer.
Assuntos
Adenocarcinoma/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias Gástricas/tratamento farmacológico , Adenocarcinoma/mortalidade , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Docetaxel , Relação Dose-Resposta a Droga , Combinação de Medicamentos , Feminino , Humanos , Masculino , Dose Máxima Tolerável , Ácido Oxônico/efeitos adversos , Neoplasias Gástricas/mortalidade , Análise de Sobrevida , Taxa de Sobrevida , Taxoides/efeitos adversos , Tegafur/efeitos adversos , Resultado do TratamentoRESUMO
OBJECTIVES: To conduct a phase I/II study of irinotecan with cisplatin to establish a recommended dose, and assess the safety, efficacy and feasibility of this regimen in unresectable advanced or recurrent gastric cancer. PATIENTS AND METHODS: In the phase I portion of the study, patients received a fixed dose of cisplatin (30 mg/m2) with escalating doses of irinotecan, ranging from 30 mg/m2 to 70 mg/m2, on days 1 and 15. In the phase II portion of the study, 40 patients were evaluated for response and safety at the recommended dose. RESULTS: Eighteen patients were enrolled in the phase I study. Dose-limiting toxicity (diarrhea and neutropenia) appeared at the irinotecan dose of 70 mg/m2. Therefore, the recommended irinotecan dose was 60 mg/m2. In the phase II study, 40 patients received cisplatin (30 mg/m2) plus irinotecan (60 mg/m2). Twenty-five out of 40 patients had received prior chemotherapy. The median number of cycles was 3.5. The response rate was 32.5% (13/40) overall, and 53.3% (8/15) in patients without prior chemotherapy. The median time to tumor progression (TTP) was 162 days. The median survival time was 288 days. Four patients (10%) developed grade 4 neutropenia and 3 patients (7.5%) developed grade 4 anemia. The only observed non-hematological toxicity at grade 3 or higher was diarrhea, seen in 2.5% (1/40) of the patients. CONCLUSION: Bi-weekly administration of irinotecan and cisplatin is safe and active for the management of unresectable advanced or recurrent gastric cancer.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Camptotecina/análogos & derivados , Camptotecina/administração & dosagem , Cisplatino/administração & dosagem , Neoplasias Gástricas/tratamento farmacológico , Adulto , Idoso , Anemia/induzido quimicamente , Camptotecina/efeitos adversos , Cisplatino/efeitos adversos , Diarreia/induzido quimicamente , Esquema de Medicação , Estudos de Viabilidade , Feminino , Humanos , Irinotecano , Masculino , Dose Máxima Tolerável , Pessoa de Meia-Idade , Neutropenia/induzido quimicamente , Neoplasias Gástricas/mortalidade , Taxa de SobrevidaRESUMO
Antibody-mediated acute rejection (AbAR) is one of the primary causes of graft impairment in kidney transplant recipients. Deoxyspergualin (DSG), which displays an antiproliferative action against antigen-stimulated B cells inhibiting antibody production, may be effective to rescue AbAR in combination with plasmapheresis by suppressing antibody production and elimination. In the present study, we report our experience with DSG/plasmapheresis therapy for the treatment of AbAR. Five kidney transplant patients experienced a steroid-resistant acute rejection requiring dialysis followed by an AbAR that was confirmed by biopsy and flow cytometry crossmatch (FCXM) results. DSG was administration at 3 mg/kg per day for 10 days with plasmapheresis reduce antidonor antibody. Treatment outcome, effectiveness, and adverse events were examined; in two cases sequential FCXM examinations were performed to evaluate antibody status. All five patients received DSG/plasmapheresis therapy. The number of plasmapheresis treatments ranged from 1 to 9 according to treatment outcomes. Four patients recovered graft function following treatment; whereas one showed no response to the treatment, and the graft was lost. No serious side effects or infections were observed during or after treatment. Monitoring of sequential FCXM correlated with the clinical course. AbAR shows a worse prognosis than cellular rejection. It is refractory to conventional antirejection therapy. In the present study, DSG/plasmapheresis therapy was effective in four of five patients (80%) with AbAR. It may be considered the first choice of treatment for cases of acute humoral rejection.
Assuntos
Rejeição de Enxerto/terapia , Guanidinas/uso terapêutico , Imunossupressores/uso terapêutico , Transplante de Rim/imunologia , Plasmaferese , Doença Aguda , Adulto , Terapia Combinada , Feminino , Rejeição de Enxerto/imunologia , Humanos , Isoanticorpos/sangue , Masculino , Estudos Retrospectivos , Resultado do TratamentoRESUMO
We present a case of low-flow priapism that was successfully treated. A 21-year-old man with a history of schizophrenia was admitted with a painful complete erection. He had taken propericiazine, phenothiazine derivatives, before hospitalization and was treated with a glandular-cavernosal shunt (El-Ghorab's procedure). Currently, he is able to have erections without any changes in his quality of life.
Assuntos
Antipsicóticos/efeitos adversos , Pênis/cirurgia , Priapismo/cirurgia , Adulto , Antipsicóticos/uso terapêutico , Humanos , Masculino , Fenotiazinas , Priapismo/induzido quimicamente , Esquizofrenia/tratamento farmacológicoRESUMO
PURPOSE: We reviewed 54 pediatric patients with ectopic ureter treated at our institution from 1975 to 1999. MATERIALS AND METHODS: Our series comprised 40 female and 14 male children, with age from 1 month to 11 years. Clinical records of the patients were reviewed retrospectively. RESULTS: Chief complaint was urinary incontinence in 24, high fever in 18, abdominal mass in 6, scrotal swelling in 3 and growth retardation in 2 patients. Two patients were found to have ectopic ureters without symptom during urological work-ups for their anorectal anomaly. The ectopic ureters opened into vagina in 19, vestibulum in 8, bladder neck in 7, urethra in 17, seminal vesicle in 2 and ejaculatory duct in 1 patient (s). Treatment was ureterocystoneostomy in 30, nephroureterectomy in 19, hemi-nephroureterectomy in 2, and ureteral ligature in 1 patient (s). Postoperatively, most of the patients became symptom free except for 6 patients in whom urinary incontinence was not cured due to mal-development of the bladder neck and sphincter, and due to Gartner's duct cyst. CONCLUSION: Urinary incontinence and urinary tract infection are most frequent presentations of ectopic ureter in children. Although most of the patients are cured with ureterocystoneostomy or nephroureterectomy, some incontinent girls continue to have urinary incontinence due to mal-development of the bladder neck and sphincter or Gartner's duct cyst.
Assuntos
Ureter/anormalidades , Ureter/cirurgia , Incontinência Urinária/etiologia , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Rim/anormalidades , Masculino , Estudos Retrospectivos , Uretra/anormalidades , Vagina/anormalidadesRESUMO
The combination of 5-fluorouracil (5-FU) and cisplatin is used most commonly for gastric carcinoma. Recent studies have indicated that vascular endothelial growth factor (VEGF) is related to drug delivery through angiogenesis and vascular permeability. In this study, we evaluated the efficacy and toxicity of continuous infusion of 5-FU and low dose cisplatin infusion as first-line treatment in patients with unresectable gastric adenocarcinoma. We also examined the relationship between chemotherapy response and immunohistochemical expression of VEGF in the biopsy samples of gastric primary. All 30 patients enrolled in this study were assessable for response, adverse reactions, and VEGF expression. The regimen consisted of 5-FU (350 mg/m2/day every day by continuous venous infusion) and low dose cisplatin (7 mg/m2/day by drip infusion over 1 h on days 1-5 every week). This treatment was repeated weekly for 3 consecutive weeks. Four weeks after the second cycle, mesurable lesions were estimated for response. An overall response rate was 46.7% (14/30). Patients with intestinal histologic type (10/12) and good performance status ([PS], 13/18) showed good response rate (83.3%, and 72.2%, respectively) compared to patients with diffuse histologic type (4/18) and poor PS [(1/12) 22.2%, and 8. 3%, respectively]. The response rate of VEGF-positive cases and VEGF-negative cases was 75% (12/16), and 16.7% (2/14), respectively. Multivarite analysis revealed that VEGF-positive and good PS had a significant impact on chemotherapy response in this treatment. The most common garde 3 or higher toxicities were myelosuppression (30%) and diarrhea (13.3%). Continuous infusion of 5-FU and low dose cisplatin infusion is an effective treatment for patients with unresectable gastric carcinoma, and VEGF expression may be a useful predictor of chemotherapy response in this regimen.
Assuntos
Adenocarcinoma/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Fatores de Crescimento Endotelial/análise , Linfocinas/análise , Neoplasias Gástricas/tratamento farmacológico , Adenocarcinoma/mortalidade , Adenocarcinoma/patologia , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Biópsia , Cisplatino/administração & dosagem , Feminino , Fluoruracila/administração & dosagem , Humanos , Imuno-Histoquímica , Infusões Intravenosas , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Valor Preditivo dos Testes , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/patologia , Taxa de Sobrevida , Fatores de Tempo , Fator A de Crescimento do Endotélio Vascular , Fatores de Crescimento do Endotélio VascularRESUMO
PURPOSE: Patients undergoing urinary diversion by ureterosigmoidostomy after complete cystectomy for malignant bladder tumors show a high incidence of neoplasia at and near the site of anastomosis. We examined a risk factor for tumor occurrence in the area of anastomosis, alterations of mucus glycoproteins in the surrounding colonic mucosa. METHODS: Colonoscopy was performed in 37 patients who had undergone ureterosigmoidostomy. Biopsy specimens were obtained near the ureteral anastomosis and were stained with hematoxylin and eosin, high iron-diamine alcian blue (pH 2.5), and a fluorescent lectin conjugate (peanut agglutinin). RESULTS: At the anastomotic site colonoscopy showed protruding lesions in 26 of 37 patients (71 percent), all histologically representing inflammatory granulomas. The mucosa around the anastomosis was normal in endoscopic appearance; however, histologically, slight inflammatory cell infiltration, edema, and increased numbers of Paneth cells were observed. Alcian blue staining revealed an increase in mucosal sialomucin postoperatively compared with preoperatively. The proportion of peanut agglutinin-binding mucin, not observed in normal mucosa but seen in malignant or premalignant tissue, was increased. CONCLUSION: As postoperative interval increases, changes in properties of the "background" mucosa become greater, which suggests an association with colonic carcinogenesis.
Assuntos
Transformação Celular Neoplásica , Neoplasias do Colo/etiologia , Mucinas/química , Neoplasias da Bexiga Urinária/cirurgia , Derivação Urinária/efeitos adversos , Adulto , Idoso , Anastomose Cirúrgica , Colo Sigmoide/cirurgia , Neoplasias do Colo/patologia , Colonoscopia , Cistectomia , Feminino , Seguimentos , Humanos , Mucosa Intestinal/patologia , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Ureterostomia , Neoplasias da Bexiga Urinária/patologiaRESUMO
A 79-year-old male was admitted to our hospital for further examination on gastric carcinoma (1' type) in the cardia. The histology of biopsied tissue was moderately differentiated adenocarcinoma (tub2). The patient refused a gastrectomy and received three cycles of local injection therapy with OK-432 + Beriplast into the tumor. However, the tumor showed no decrease in size. Considering the quality of life, the patient was given out patient treatment with 5'-DFUR (Furtulon, 800 mg/day). Three months later, the patient showed a partial response (PR) on the basis of gastric X-ray and endoscopic findings. No adverse reactions to the drug were seen. The patient has been receiving the same drug since then, and has continued to show PR for 15 months. Biopsied tissues were checked immunohistochemically for expression of thymidine phosphorylase (TdRPase), and changes in tissue TdRPase level were examined by ELISA. The TdRPase level decreased with shrinking of the tumor. These results suggest that the shrinking of tumor following 5'-DFUR therapy is closely related to TdRPase.
Assuntos
Adenocarcinoma/tratamento farmacológico , Antineoplásicos/uso terapêutico , Floxuridina/uso terapêutico , Neoplasias Gástricas/tratamento farmacológico , Adenocarcinoma/enzimologia , Adenocarcinoma/patologia , Administração Oral , Idoso , Cárdia , Esquema de Medicação , Humanos , Masculino , Neoplasias Gástricas/enzimologia , Neoplasias Gástricas/patologia , Timidina Fosforilase/metabolismoRESUMO
The incidence of carcinoma of the stomach is low in the United States, Canada, and Australia but is a significant health problem in Asia, South America, Eastern Europe, and countries of the previous Soviet Union. For patients with advanced disease, chemotherapy remains palliative. With the increasing emphasis on patients' quality of life, convenience, and cost containment, oral chemotherapy has come into increasing focus. We review oral chemotherapy agents for use in patients with advanced gastric carcinoma. Etoposide, given intravenously, has modest activity in gastric carcinoma. We studied oral etoposide, which was administered to 28 patients at the starting dose of 50 mg/m2/day for 21 days followed by a 7-day rest period. Five patients achieved a partial response and 4 patients achieved a minor response. The drug was well tolerated. Common toxicities included myelosuppression, alopecia, and nausea. Oral etoposide thus shows evidence of modest activity against gastric carcinoma. In Japan, considerable advances have been made in the oral chemotherapy of gastric carcinoma. The second generation fluorouracil prodrug tegafur/uracil (UFT) has been extensively evaluated in Japan, Korea, and Spain. Data predominantly from Japan indicate that tegafur/uracil has a response rate of approximately 20% in treatment naive patients with advanced gastric carcinoma. When combined with other active agents, tegafur/uracil has a response rate of more than 30% in these patients. The available data also suggest that tegafur/uracil is well tolerated and that patient acceptance is high. In conclusion, future clinical research is likely to focus on the development of convenient outpatient regimens with efficacy equal to that of intravenous regimens.
Assuntos
Antineoplásicos Fitogênicos/administração & dosagem , Antineoplásicos/administração & dosagem , Neoplasias Gástricas/tratamento farmacológico , Administração Oral , Animais , Ensaios Clínicos como Assunto , Combinação de Medicamentos , Etoposídeo/administração & dosagem , Humanos , Neoplasias Gástricas/epidemiologia , Tegafur/administração & dosagem , Uracila/administração & dosagemRESUMO
PURPOSE: The second-generation oral anticancer agent UFT, a combination of uracil and tegafur (TGF), results in a higher fluorouracil (5-FU) concentration in the tumor tissues than is achieved by TGF or comparable doses of intravenous 5-fluorouracil. UFT has been extensively studied in Japan and has been in use in the Orient for many years, particularly for patients with gastric carcinoma. UFT has recently entered extensive investigations in North America and Europe. METHODS: Relevant studies that have chronicled the establishment of UFT, its mechanism of action, preclinical toxicology, human pharmacokinetics, phase I studies, and activity against gastric carcinoma are described in detail. RESULTS: The uracil in UFT slows degradation of 5-FU by dihydropyrimidine dehydrogenase (DPD), which results in sustained concentrations of 5-FU in blood and tumor tissues. UFT is well tolerated, but such toxic effects as nausea, vomiting, and diarrhea are dose- and schedule-dependent. In phase I pharmacokinetic studies, UFT given orally on a 28-day schedule resulted in blood concentrations comparable to those following low-dose continuous intravenous infusion of 5-FU. In patients with gastric carcinoma, UFT alone has a response rate of approximately 20%. In the adjuvant setting, UFT plus mitomycin appears superior to TGF plus mitomycin. In Japan, UFT is part of the standard adjuvant chemotherapy for gastric carcinoma. CONCLUSION: UFT is one of the first second-generation oral 5-FU prodrugs under investigation in North America and Europe. The literature suggests UFT is well tolerated and has cellular pharmacokinetic superiority over the first-generation 5-FU prodrug TGF. UFT has a more favorable toxicity profile than intravenous 5-FU. The issues of efficacy, patient convenience, and quality of life need to be studied in controlled randomized trials.
Assuntos
Antineoplásicos/uso terapêutico , Neoplasias Gástricas/tratamento farmacológico , Tegafur/uso terapêutico , Uracila/uso terapêutico , Antineoplásicos/efeitos adversos , Combinação de Medicamentos , Humanos , Tegafur/administração & dosagem , Tegafur/efeitos adversos , Uracila/administração & dosagem , Uracila/efeitos adversosRESUMO
A 59-year old male patient had been operated on for sigmoid colon cancer in July, 1990. Operative findings were, P0, H0, S1, N (-), Stage I, and histological findings were ss, ly 2, v0, n (-). In July 1994, the CEA level elevated, and be was diagnoted as having para-aortic LN swelling and stenosis of anastomosis of colon. He was admitted for treatment of recurrent colon cancer. Initially, he was treated with continuous injection of 5-FU, low-dose CDDP and Leucovorin. His CEA level decreased and para-aortic LN diminished in size. But, in December 1995, the CEA level and para-aortic LN relapsed. 5-FU, CDDP and Leucovorin were administered, but the CEA level became more and more elevated. This regimen was not considered responsible for drug resistance. CPT-11 was administered at 60 mg/week 6 times, and 80 mg/week 3 times. The side effects disappeared, LN sightly diminished in size, and the CEA level decreased. Judging by the anticancer effect without severe side effect, we found CPT-11 a useful drug for second-line chemotherapy.
Assuntos
Antineoplásicos Fitogênicos/uso terapêutico , Camptotecina/análogos & derivados , Neoplasias do Colo/tratamento farmacológico , Recidiva Local de Neoplasia/tratamento farmacológico , Camptotecina/uso terapêutico , Antígeno Carcinoembrionário/análise , Cisplatino , Neoplasias do Colo/cirurgia , Resistencia a Medicamentos Antineoplásicos , Humanos , Irinotecano , Leucovorina , Masculino , Pessoa de Meia-Idade , Indução de RemissãoRESUMO
There have been a few reports on the spontaneous rupture of renal cell carcinoma. A 67-year-old female patient complaining of vomiting and severe abdominal pain was referred to our hospital. Plain computerized tomography demonstrated large heterogenous mass in the right retroperitoneum. We suspected the hemorrhagic shock because of the rupture of the right kidney and therefore emergent laparotomy was performed. Simple nephrectomy for the right kidney was performed. A pathological report revealed renal cell carcinoma, granular cell subtype, grade 1, pT3a. The patient has been followed for one year and five months after the operation, there has been no evidence of local recurrence or distant metastasis of cancer. Thirteen cases of spontaneous rupture of renal cell carcinoma in the Japanese literature are reviewed.
Assuntos
Carcinoma de Células Renais/patologia , Neoplasias Renais/patologia , Idoso , Carcinoma de Células Renais/complicações , Feminino , Hemorragia/etiologia , Humanos , Nefropatias/etiologia , Neoplasias Renais/complicações , Ruptura EspontâneaRESUMO
We studied the gastric acidity, gastric emptying, and proton pump inhibitor (PPI) plasma levels in 10 patients with PPI-resistant ulcers. The pH3 holding-time ratio was low in nine of these patients, with an average ratio of only 39%. PPI plasma levels in those patients were also much lower than in those with nonresistant ulcers. Gastric emptying, determined by the acetaminophen method, was reduced in all 10 patients. Therefore, PPI-resistant ulcers appear to result from insufficient inhibition of gastric acidity, with reduced gastric emptying interfering with the absorption of PPIs. In patients with mild reductions in gastric emptying, PPI plasma levels increased after a change from single-unit enteric-coated tablets (omeprazole) to multiunit enteric-coated granules in capsules (lansoprazole). This change in formulation markedly inhibited gastric acidity and led to rapid healing. In patients with moderate reductions in gastric emptying, doubling the dose of lansoprazole was effective. In patients with severely reduced gastric emptying, there appeared to be a limit to the effectiveness of oral administration of PPIs. Changing the formulation and doubling the dose to compensate for reduced gastric emptying are effective approaches in the treatment of patients with PPI-resistant ulcers.
Assuntos
Antiulcerosos/uso terapêutico , Úlcera Péptica/tratamento farmacológico , Úlcera Péptica/fisiopatologia , Inibidores da Bomba de Prótons , 2-Piridinilmetilsulfinilbenzimidazóis , Resistência a Medicamentos , Úlcera Duodenal/tratamento farmacológico , Úlcera Duodenal/fisiopatologia , Ácido Gástrico/metabolismo , Esvaziamento Gástrico , Humanos , Concentração de Íons de Hidrogênio , Lansoprazol , Omeprazol/administração & dosagem , Omeprazol/análogos & derivados , Omeprazol/farmacocinética , Omeprazol/uso terapêutico , Úlcera Gástrica/tratamento farmacológico , Úlcera Gástrica/fisiopatologiaRESUMO
In November 1991, a third generation extracorporeal shock wave lithotriptor (Piezolith 2500) was installed in our clinic. We examined the effective and safe aspect of this machine for urolithiasis. From November 1991 to October 1993, we experienced 530 sessions of ESWL treatment on 235 patients (270 cases). All patients except two underwent ESWL treatment without anesthesia, and in situ ESWL treatment was possible on 247 cases. The mean number of shock waves and sessions per patient of renal stone were 3369 and 2.1, respectively. Those of ureteral stone were 3970 and 1.9, respectively. The complete removal rate of renal and ureteral stone 3 months after the last session were 86% and 92%, respectively. This outcome was very satisfactory. On the other hand, endoscopic procedure was needed on 13 patients. In almost all cases hematuria was noted after ESWL, but major complications such as subcapsular hematoma or gastrointestinal hemorrhage were not experienced at all. It was concluded that Piezolith 2500 was very effective and safe in the treatment of urolithiasis.