gimeracil and Kidney-Failure--Chronic

An 80-year-old Japanese woman with chronic renal failure was diagnosed with gastric cancer and 2 primary colon cancers. The colon cancers were treated with laparoscopic colectomy, but the gastric cancer metastasized to the liver with inoperable dissemination. After operative treatment of the colon cancers, 1 year of combination chemotherapy consisting of tegafur/gimeracil/oteracil (TS-1®) and nab-PTX was administered to treat the advanced gastric cancer. Tegafur is a well-known prodrug of 5-FU. Serum densitometry of 5-FU was performed to determine the correct dose of TS-1®. After completion of chemotherapy, no tumor was detected on gastroscopy or dynamic computed tomography. The patient was well with no recurrence 6 months after completion of chemotherapy. CDDP, CPT-11, 5-FU, PTX, and DTX are known chemotherapy agents for treating gastric cancer. Renal excretion is not involved in the metabolism of CPT-11, 5-FU, PTX, or DTX. These agents are metabolized in the liver. CPT-11 metabolism depends on individual hepatic enzymes. Therefore, we believe that nab-PTX and TS-1® are safe and effective agents for patients with chronic renal failure and advanced gastric cancer. Additionally, we also conclude that using serum densitometry of 5-FU to guide the administration of TS-1® can improve both safety and efficacy.

Topics: Aged, 80 and over; Albumins; Antineoplastic Combined Chemotherapy Protocols; Female; Humans; Kidney Failure, Chronic; Oxonic Acid; Paclitaxel; Pyridines; Stomach Neoplasms; Tegafur

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.

Topics: Adenocarcinoma; Adult; Antimetabolites, Antineoplastic; Area Under Curve; Drug Administration Schedule; Drug Combinations; Drug Monitoring; Fluorouracil; Gastrectomy; Humans; Kidney Failure, Chronic; Male; Oxonic Acid; Peritoneal Neoplasms; Pyridines; Renal Dialysis; Stomach Neoplasms; Tegafur