細谷 好則

We report a patient with unresectable advanced gastric cancer who has been being treated by TS-1 administration on alternate days for 2 years. The patient was a 50-year-old female with type 4 gastric cancer accompanied by Schnitzler metastasis and pleural effusion. TS-1 administration was initiated at a daily dose of 100 mg with a schedule of 4-week administration and 2-week suspension. However, grade 2 hepatic dysfunction and leukocytopenia developed. When the daily TS-1 administration was changed to alternate-day administration at the same dose, no side effects were observed, allowing the continuation of treatment. She has maintained a minor response (MR)-no change (NC) for 1 year and 5 months, and is still symptom-free and being treated on an outpatient basis at present, 2 years after treatment. TS-1 is an anti-cancer drug that plays a central role in chemotherapy for gastric cancer. However, in some patients, side effects sometimes develop using the routine administration method, making continuation of administration difficult. Alternate-day TS-1 administration has great potential as a protocol that produces long-term anti-tumor effects while reducing side effects.

Cardiac toxicity of 5-fluorouracil (5-FU) has been rarely reported. We encountered a case of angina attack caused by 5-FU. A 58-year-old Japanese woman underwent sigmoidectomy for a sigmoid colon carcinoma with multiple liver metastases. Two months after surgery, she received chemotherapy comprising hepatic arterial infusion of 5-FU. During the 2nd chemotherapy session 7 days after the first, she complained of anterior chest pain. Her electrocardiograms showed elevations of the ST segment in almost all leads, confirming the diagnosis of angina pectoris. Soon after the third chemotherapy session the same type of attack occurred again. The close association of the attacks with 5-FU administration suggested that the angina might have been induced by 5-FU. Further attacks were avoided by discontinuing the 5-FU thereafter. The incidence of cardiac toxicity 5-FU has been reported to be 1.6-7.6%. Labianca et al. found 17 cases of 5-FU-associated cardiopathy, 15 of which were angina pectoris, out of 1,083 patients treated with the drug for various kinds of neoplasm. Analysis of 6 domestic cases including ours revealed that all patient lacked a previous history of cardiac disease except one who had an arrhythmia. There seemed to be no dose-dependent correlation with 5-FU-induced angina. Cardiac events were found even in the earlier phase of chemotherapy. Since 5-FU is widely used in the treatment of a number of gastrointestinal malignancies, one should bear in mind its cardiac toxicity, manifested as angina pectoris.

We report 3 cases in which palliation was achieved with every-other-day administration of TS-1 for recurrent or non-curative advanced gastric carcinoma that had resulted in obstructive jaundice. Two patients had received MTX-5-FU chemotherapy as first-line therapy and showed progressive disease, presenting with obstructive jaundice 6-24 months later. One of them experienced obstructive jaundice 2 months after surgery. After lowering serum bilirubin via per-cutaneous transhepatic biliary drainage (PTBD), TS-1 was given not in full dose but every other day based upon Shirasaka's theory, as well as for fear of further liver damage. Palliation in terms of long NC and/or decreased serum CEA level persisted for 4-14 months without severe liver dysfunction. Other side effects of the drug were negligible. Shirasaka's theory stresses the difference in proliferation cycles between cancer cells and normal tissue cells (GI tract, bone marrow, etc.); therefore, with every-other-day administration of chemotherapeutic agents, the cytotoxic effects against tumors would be augmented while the adverse reactions in normal cells could be reduced. The present experience seems to support the theoretical and clinical feasibility of every-other-day TS-1 administration for unresectable gastric cancer.