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A dose-escalation study was conducted for postoperative patients with stage IV gastric cancer to determine the recommended dose of daily intravenous cisplatin combined with a fixed dose of TS-1. TS-1 was administered orally twice daily for 2 weeks followed by a 1-week rest. The dose of TS-1 was based on the body surface area (BSA) as follows: 80 mg/day for BSA less than 1.25, 100 mg/day for BSA 1.25 to less than 1.50, and 120 mg/day for BSA 1.5 or more. Three dose levels of cisplatin (2, 4, 6 mg/m(2)) were studied, and two courses were performed. Cisplatin was infused on day 1-5 and 8-12 for 30 minutes. The National Cancer Institute common toxicity criteria (NCI-CTC Version 3) were used to evaluate the grade of toxicity. Three patients enrolled in each level. Dose escalation was performed when dose-limiting toxicities (DLT) were seen in 0/3, and 3 more cases of the same level were added when DLTs were seen 1-2/3. Maximum-tolerated dose (MTD) were determined when DLTs were seen in 3 cases. DLTs were not recorded during the administration of CDDP up to 4 mg/m(2). However, DLTs were seen 3/3 at level 3. From these results, cisplatin of 4 mg/m(2)was determined to be the recommended dose (RD) in this protocol for postoperative stage IV gastric carcinoma.

The optimum dose of TS-1 for the treatment of peritoneally disseminated gastric cancer in a patient with chronic renal failure undergoing chronic dialysis was estimated by monitoring the blood concentrations of 5-FU and gimeracil (CDHP) [therapeutic drug monitoring (TDM)] during administration of TS-1. Immediately after dialysis, 50 mg or 40 mg of TS-1, corresponding to 50% and 40% of the standard dose (100mg for this patient), respectively, was administered orally once a day every other day, and TDM was conducted. Compared with the pharmacokinetic parameters of 5-FU at the time of the initial administration of 50 mg or 40 mg of TS-1 and that of cancer patients with normal renal function, the AUC shown in the administration of 40 mg was equivalent to that observed with a single safe dose of 100 mg in patients with normal renal function. Based on this observation, the daily TS-1 dose was set at 40 mg in this patient, and TS-1 treatment was started after confirming the absence of the accumulation of 5-FU or CDHP during repeated administrations. In this treatment protocol, TS-1 was administered 11 times at a daily dose of 40 mg every other day immediately after dialysis, followed by a rest. This .administration schedule was defined as one course. Under these conditions, the patient was treated on an outpatient basis, and the treatment could be safely continued without the development of any severe adverse events, such as myelosuppression.

An enzyme immunoassay for the determination of potassium oxonate in the plasma has been developed. The procedure is based on a competitive enzyme-linked immunosorbent assay using the second antibody solid phase method. The antiserum for potassium oxonate was prepared using oxonic acid 6-carboxypentylamide-BSA conjugate as immunogen. The specific antibody for oxonic acid was isolated from the antiserum using oxonic acid 6-carboxypentylamide immobilized immunosorbent gel. The purified antibody resulted in high sensitivity and low cross-reactivity as compared with the unpurified antiserum. Potassium oxonate in the plasma could be assayed in the range from 20 to 1000 ng/ml by the proposed EIA. The recovery was ranged from 82 to 117% and the coefficient of variation was from 6.6 to 14.7% (n = 6).