[Show abstract][Hide abstract] ABSTRACT: Paclitaxel (PTX), which is used for ovarian cancer, lung cancer, breast cancer and gastric cancer, is administered at a dose of 210 mg/m(2) once every three weeks. However, WHO grade 3-4 hematological and non-hematological toxicity occurred frequently in this manner. In recent studies about ovarian cancer and lung cancer, a schedule in which PTX was given weekly could have the same or better efficacy, with fewer side effects. The response rate of PTX administered every three weeks for gastric cancer, was 23.3 to approximately 28.0%, while that of PTX administered weekly was 24.0 to approximately 25.8%. Because of fewer adverse events, weekly PTX is widely used for gastric cancer in Japan. To prove the validity of PTX weekly administration, we performed a study using six specimens removed surgically and one specimen collected from ascites. A chemosensitivity test was performed on the basis of two assumptions: a high concentration for a short time, and a low concentration for a long time. A similar PTX effect was obtained when the AUC was equal. In this study, we demonstrated that the effect of low-dose PTX was equal to the effect of high-dose PTX in gastric cancer.
No preview · Article · Mar 2008 · Gan to kagaku ryoho. Cancer & chemotherapy
[Show abstract][Hide abstract] ABSTRACT: Cytotoxic drug-induced emesis is the side effect most feared by cancer patients. The Acute emesis has become well controlled by the emergence appearance of 5-HT3 receptor antagonist, but control of delayed emesis (DE) is insufficient. The mechanism of DE is different from acute emesis,and the existence of a mediator different from serotonin is contemplated. There were some reports suggesting the role of substance P (SP) and its receptor, neurokinin receptor 1 (NK 1), in the development of emesis.
We investigated the relationship between DE and SP in patients treated with anticancer agents.
Digestive cancer and breast cancer patients, who were administered cytotoxic agents, were the objects of this study. We measured plasma levels of SP for 20 cases on the day before administration of anticancer agents and for five days after administration.
Plasma levels of SP increased significantly on the first and third days after administration. In the patient who experienced DE, the difference in plasma levels on the day before and the first day after chemotherapy was higher than that of who never experienced.
The plasma levels of SP were transiently increased by chemotherapy. The difference in plasma levels between the day before and the first day after chemotherapy is important.
No preview · Article · Jul 2007 · Gan to kagaku ryoho. Cancer & chemotherapy
[Show abstract][Hide abstract] ABSTRACT: We report 3 gastric cancer patients with peritoneal dissemination who were successfully treated with weekly paclitaxel and cisplatin. The patients were 2 men and 1 woman from 57 to 70 years in age. The histological types were 2 poorly-differentiated adenocarcinomas and 1 moderately-differentiated adenocarcinoma. Intravenous infusion of PTX (80 mg/m(2)) and CDDP (25 mg/m(2)) after short premedication was continued for 3 weeks followed by 1 week rest. Ascites improved only after administration of 1 course in all patients.PTX/CDDP is thought to be an effective chemotherapy showing acceptable toxicity against advanced gastric cancer with ascites.
No preview · Article · Jun 2007 · Gan to kagaku ryoho. Cancer & chemotherapy
[Show abstract][Hide abstract] ABSTRACT: 5-Fluorouracil (5-FU) and its derivatives are widely known as some of the most commonly prescribed anticancer drugs, especially for gastrointestinal cancer. Orotate phosphoribosyl transferase (OPRT), dihydropyrimidine dehydrogenase (DPD) and thymidylate synthase (TS) are initial key enzymes in the 5-FU metabolic pathway. The activities of these enzymes may have the potential to affect the chemosensitivity of 5-FU.
This study was designed to investigate the effect of OPRT, DPD and TS in sensitivity to 5-FU.
We measured OPRT, DPD and TS activities in 11 colonic cancer tissues. The Collagen Gel Droplet Embedded Culture Drug Sensitivity Test (CD-DST) was used in an in vitro chemosensitivity assay. In these samples, the correlation between sensitivity to 5-FU and enzyme activities was investigated.
There were no correlations among OPRT, TS activities and sensitivity to 5-FU. In contrast, there was a significant inverse correlation (r=-0.738) between DPD activity and 5-FU sensitivity. With regression analysis, the coefficient of determination of the activity of the three enzymes versus the sensitivity to 5-FU was 0.61.
Though measuring OPRT, DPD, TS activities is valuable for prediction of sensitivity to 5-FU, DPD is considered to be the most important predictive factor of 5-FU sensitivity. To improve its accuracy, the finding of a fourth factor such as P-glycoprotein and multidrug resistance-associated proteins (MRP), to be added to OPRT, DPD and TS, is desired.
No preview · Article · Dec 2006 · Gan to kagaku ryoho. Cancer & chemotherapy
[Show abstract][Hide abstract] ABSTRACT: A 65-year-old female with unresectable advanced gastric cancer accompanied by multiple lung metastases underwent jejunostomy and was treated with TS-1 and CDDP. One course consisted of TS-1 (80 mg/day) via an intestinal fistula tube from days 1 to 14 followed by 14 days rest and CDDP (80 mg/day) was administered by 24-hour continuous intravenous infusion on day 8. After 3 courses, the primary tumor and lymph node metastases decreased in size (PR), and CT scan showed the multiple lung metastases had disappeared. Total gastrectomy (D 2) and splenectomy were performed after chemotherapy. The final diagnosis was Stage IIIA and the pathological response to chemotherapy was Grade 2. The patient has survived for over 14 months after surgery and has presented no signs of recurrence.
No preview · Article · Jul 2006 · Gan to kagaku ryoho. Cancer & chemotherapy