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1.
Anticancer Res ; 32(12): 5407-14, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23225444

RESUMO

BACKGROUND/AIM: The objective of this study was to investigate the influence of digestive gastrointestinal absorption function on the pharmacokinetics of the orally-administered anticancer drug, Tegafur-gimestat-otastat potassium (TS-1), by measuring the plasma 5-fluorouracil (5-FU) concentration using stable isotope breath tests. PATIENTS AND METHODS: Twenty-nine patients with progressive/recurrent digestive organ cancer were enrolled for this pharmacokinetic study, and blood samples were obtained from each patient. The area under-the-time-concentration curve between 0 and 480 min (AUC0-480 min), time-of-drug concentration peak (T(max)), maximum drug concentration (C(max)) and the half-life period (t(1/2)) of 5-FU were investigated. Simultaneously, a continuous (13)C-acetate breath test was performed for each patient. The parameters measured with the breath test were the area under the (13)CO(2) excretion rate curve between 0-4 h (AUC(0-4h)), peak (13)CO(2) value and elimination rate constant (K(el)) value. RESULTS: The AUC(0-8h) and C(max) of 5-FU were significantly correlated with K(el) (p=0.012 and p=0.024, respectively), and the 5-FU C(max) value was significantly correlated with the peak value of (13)CO(2) (p=0.037). Multivariate regression analysis also found the C(max) of 5-FU to be associated with K(el) (p=0.0118). The C(max) and AUC(0-8h) of 5-FU were also significantly correlated (p<0.0001). CONCLUSION: The results of this study suggest that gastrointestinal absorption is closely-related to plasma 5-FU concentration after oral administration of TS-1.


Assuntos
Antimetabólitos Antineoplásicos/farmacocinética , Neoplasias Esofágicas/metabolismo , Fluoruracila/sangue , Ácido Oxônico/farmacocinética , Neoplasias Gástricas/metabolismo , Tegafur/farmacocinética , Acetatos/análise , Acetatos/farmacocinética , Administração Oral , Idoso , Antimetabólitos Antineoplásicos/administração & dosagem , Testes Respiratórios , Isótopos de Carbono/análise , Combinação de Medicamentos , Neoplasias Esofágicas/tratamento farmacológico , Feminino , Fluoruracila/farmacocinética , Humanos , Absorção Intestinal , Masculino , Ácido Oxônico/administração & dosagem , Neoplasias Gástricas/tratamento farmacológico , Tegafur/administração & dosagem
2.
Gan To Kagaku Ryoho ; 35(11): 1945-9, 2008 Nov.
Artigo em Japonês | MEDLINE | ID: mdl-19011349

RESUMO

A 71-year-old man visited the hospital complaining of nausea in December 2002. Following a diagnosis of a gastrointestinal stromal tumor (GIST), partial resection of the stomach was performed in January 2003. The tumor was immunohistochemically positive for c-kit and CD34. The tumor size was 6.5 x 5.0 x 4.5 cm with a mitotic index of 25 out of 50 in the high-power field. The pathological diagnosis indicated a high-risk GIST. Treatment with imatinib at a dose of 400 mg/day was started because of liver metastasis of the GIST in January 2004. The liver metastasis was gradually reduced and exhibited cystic change. We considered that there was a complete response without accumulation by FDG-PET in June 2007. An hepatic segmentectomy was performed and imatinib was discontinued in July 2007. Most intratumorale in the specimen underwent hyaline degeneration after pathological examination, but there were viable cells in a portion of the tumor border. Imatinib treatment was resumed because of recurrence in the remnant stomach four months postoperatively owing to imatinib withdrawal. In making a diagnosis at the cell level by FDG-PET, it was difficult to determine the effectiveness of imatinib, and therefore, it is suggested that imatinib treatment must be continued after surgical resection.


Assuntos
Tumores do Estroma Gastrointestinal/tratamento farmacológico , Tumores do Estroma Gastrointestinal/patologia , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/secundário , Piperazinas/uso terapêutico , Pirimidinas/uso terapêutico , Idoso , Benzamidas , Tumores do Estroma Gastrointestinal/diagnóstico por imagem , Tumores do Estroma Gastrointestinal/cirurgia , Humanos , Mesilato de Imatinib , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/cirurgia , Masculino , Tomografia por Emissão de Pósitrons , Tomografia Computadorizada por Raios X
3.
Gan To Kagaku Ryoho ; 35(1): 71-6, 2008 Jan.
Artigo em Japonês | MEDLINE | ID: mdl-18195531

RESUMO

PURPOSE: Hepaticarterial infusional(HAI)5-FU chemotherapy, which involves the use of interventional radiology technique, has matured technically in Japan in the 1990's. The antitumor effect of 5-FU is enhanced by combination with leucovorin. This study was performed to evaluate the efficacy and toxicity of HAI 5-FU and leucovorin chemotherapy for patients with unresectable liver metastases from colorectal cancer. METHODS: Treatment was given to 20 patients with unresectable liver metastases from colorectal cancer. The chemotherapy regimen consisted of weekly HAI of 5-FU(1,000 mg/body)and leucovorin(250 mg/body)over five hours. The survival and response rates to the therapy were assessed according to RECIST. Hematologic and non-hematologic toxicity was assessed according to CTCAE v3.0. RESULTS: Combined HAI 5-FU and leucovorin therapy was carried out an average of 27 times. The response rate for liver tumors was 75%, and the median survival time was 22 months. The applied regimen caused only mild adverse events. There was no evidence of myelosuppression except for platelet decrease(grade 3)in a patient with chronic renal failure. CONCLUSION: This HAI approach using 5-FU and leucovorin was effective and the therapy for unresectable liver metastases from colorectal cancer was tolerated well. Therefore the HAI approach should be reconsidered as an effective therapy against this disease in Japan.


Assuntos
Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/patologia , Fluoruracila/administração & dosagem , Fluoruracila/uso terapêutico , Artéria Hepática , Leucovorina/administração & dosagem , Leucovorina/uso terapêutico , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/secundário , Idoso , Idoso de 80 Anos ou mais , Feminino , Fluoruracila/efeitos adversos , Fluoruracila/sangue , Humanos , Infusões Intra-Arteriais , Leucovorina/efeitos adversos , Neoplasias Hepáticas/patologia , Masculino , Microcirculação , Pessoa de Meia-Idade , Taxa de Sobrevida , Tomografia Computadorizada por Raios X
4.
Gan To Kagaku Ryoho ; 34(6): 869-73, 2007 Jun.
Artigo em Japonês | MEDLINE | ID: mdl-17565248

RESUMO

We studied the pharmacokinetics of 5-FU after S-1 oral administration at the usual dose (80 mg/m2) for adjuvant chemotherapy in 13 advanced gastric cancer patients (Stage II, III), and at a decreased dose (60 mg/m2) for adjuvant or combined chemotherapy in 13 advanced gastric cancer patients. Pharmacokinetic parameters of 5-FU in the serum were as follows: Cmax, 159 .9 2+/-45.2 ng/mL, Tmax, 2.17+/-0.58 h;T1/2, 3.13+/-2.88 h; and AUC(0-8), 768.0+/-260.8 ng h/mL in the patients with the usual dose, and Cmax, 117.3+/-55.1 ng/mL; Tmax, 2.62+/-0.9 6 h; T1/2, 3.09+/-1.9 5 h and AUC(0-8), 565.9+/-216.8 ng h/mL in the patients with the decreased dose. No difference in AUC was observed between operative methods. Adverse events of more than grade 3 were recognized in 7 patients, and AUC of 6 patients were more than 800 ng h/mL. The plasma concentration of 5-FU was quite different between patients. The difference of Cmax and AUC was 3-4 times. It was concluded that we must pay attention to individual differences in the plasma concentration of 5-FU in postoperative gastric cancer patients when S-1 would be administered.


Assuntos
Antimetabólitos Antineoplásicos/administração & dosagem , Fluoruracila/farmacocinética , Gastrectomia , Ácido Oxônico/administração & dosagem , Neoplasias Gástricas/sangue , Neoplasias Gástricas/tratamento farmacológico , Tegafur/administração & dosagem , Administração Oral , Idoso , Antimetabólitos Antineoplásicos/sangue , Quimioterapia Adjuvante , Combinação de Medicamentos , Feminino , Gastrectomia/métodos , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias Gástricas/patologia , Neoplasias Gástricas/cirurgia
5.
Gan To Kagaku Ryoho ; 34(5): 725-8, 2007 May.
Artigo em Japonês | MEDLINE | ID: mdl-17496445

RESUMO

As a 2nd-line treatment for relapsed or refractory esophageal cancer patients after chemoradiotherapy, we performed a combination chemotherapy of DOC/CDGP for 11 patients. Intravenous drip infusion of DOC 30 mg/m(2)and CDGP 30 mg/m(2)on days 1, 8 and 15, and 4 weeks treatment was assumed as 1 cycle. We treated 8 of 11 patients with more than 2 cycles, and 4 of 8 patients were treated with radiation therapy (RT). The effects by RECIST revealed partial response (PR) in 2 patients (50%), stable disease (SD) in 1 patient and progress disease (PD) in 1 patient without RT, and PR in 3 patients and not effective in 1 patient with RT, respectively. There was no treatment-related death nor adverse event of grade 4. The Hematological toxicities of leukopenia of grade 3 were observed in 3 patients. Non-hematological toxicites more than grade 3 were not observed. The combination chemotherapy of DOC/CDGP was concluded to be safe and effective for relapsed or refractory esophageal cancer patients as a 2nd line treatment.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma de Células Escamosas/tratamento farmacológico , Neoplasias Esofágicas/tratamento farmacológico , Recidiva Local de Neoplasia/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/radioterapia , Carcinoma de Células Escamosas/secundário , Terapia Combinada , Docetaxel , Esquema de Medicação , Neoplasias Esofágicas/patologia , Neoplasias Esofágicas/radioterapia , Estudos de Viabilidade , Humanos , Infusões Intravenosas , Linfonodos/patologia , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/radioterapia , Compostos Organoplatínicos/administração & dosagem , Taxoides/administração & dosagem
6.
Surg Today ; 36(10): 874-8, 2006.
Artigo em Inglês | MEDLINE | ID: mdl-16998680

RESUMO

PURPOSE: Proximal gastrectomy and lymph node dissection are often performed for T1 cancer of the gastric cardia; however, direct esophagogastrostomy is frequently complicated by reflux esophagitis. We describe a simple technique for preventing esophageal reflux and discuss its results. METHODS: This technique is indicated for T1 cancer of the gastric cardia without lymphadenopathy. Partial resection, including the lesion, is performed, preserving the vagus nerve and lower esophageal sphincter (LES). Lymph node dissection is done around the left gastric, celiac, and splenic arteries. The esophagus is then anastomosed to the anterior wall in the center of the remnant stomach. RESULTS: We evaluated the results of this procedure in eight patients. X-ray films showed no esophageal reflux in either the supine or the right decubitus position. None of the patients complained of reflux or other dyscrasic symptoms, and none had any feeling of microgastria. One patient had some localized erosion near the anastomosis. CONCLUSIONS: This simple and safe technique does not result in post-gastrectomy syndrome or microgastria, and the risk of leaving cancer cells is minimal.


Assuntos
Cárdia/patologia , Esfíncter Esofágico Superior/cirurgia , Gastrectomia/métodos , Neoplasias Gástricas/cirurgia , Nervo Vago/cirurgia , Idoso , Idoso de 80 Anos ou mais , Cárdia/inervação , Esfíncter Esofágico Superior/inervação , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias Gástricas/patologia , Resultado do Tratamento
7.
Gan To Kagaku Ryoho ; 33(13): 2021-6, 2006 Dec.
Artigo em Japonês | MEDLINE | ID: mdl-17197746

RESUMO

The therapy 5-FU and CDDP with radiation is thought to be the standard therapy for esophageal cancer patients by now. However, the therapy is associated with a comparatively high incidence of gastrointestinal disorders and requires hospitalization. We have proposed a new regimen of Docetaxel and TS-1 with radiation for maintaining of QOL and improving outcome. Step 1 of the clinical phase I/ II study was conducted for 10 cases from May 2004 to March 2006. Treatment could be accomplished in all cases, and no treatment-related deaths or adverse events of grade 4 were observed in any case. As for hematotoxicity, one case had leucopenia of grade 3 and neutropenia of grade 2. As for non-hematotoxic adverse events, anorexia of grade 3 was recognized in one case of level 3. The response rate evaluated by RECIST was 66% (CR in 2 cases, PR in 4 cases), and the rate based on the Guide Lines for the Clinical and Pathologic Studies on Carcinoma of Esophagus by the Japanese Society for Esophageal Cancer was 70% (CR in 3 cases, PR in 4 cases). We assumed that the recommended dosage of TXT was 30 mg/m(2) and that of TS-1 was 60 mg/m(2) with radiotherapy of 60 Gy. This combination therapy may be recommended because of fewer adverse events and a higher responsive rate than the standard therapies. We intend to continue this study to step 2 and 3, and to reveal the response rate and adverse events for more esophageal cancer patients.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Esofágicas/tratamento farmacológico , Neoplasias Esofágicas/radioterapia , Idoso , Anorexia/induzido quimicamente , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Terapia Combinada , Docetaxel , Esquema de Medicação , Combinação de Medicamentos , Humanos , Leucopenia/induzido quimicamente , Masculino , Dose Máxima Tolerável , Pessoa de Meia-Idade , Ácido Oxônico/administração & dosagem , Dosagem Radioterapêutica , Radioterapia Adjuvante , Taxoides/administração & dosagem , Tegafur/administração & dosagem
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