[TS-1 treatment for progressive gastric cancer in a patient on chronic dialysis--assessment of dosage regimen by monitoring blood concentrations of therapeutic drugs (TDM)].

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.

Association of CYP17 genetic polymorphism with intra-tumoral estradiol concentrations but not with CYP17 messenger RNA levels in breast cancer tissue.

The variant allele(1931C) of CYP17 (1931C/T), which is one of the key enzymes involved in estrogens synthesis, has been shown to be associated with breast cancer risk. Since this variant allele creates an additional putative Sp-1 binding site (CCACC) in the promoter region, it is speculated that it enhances the transcription of CYP17, leading to the enhanced estrogens synthesis in breast tumors. CYP17 messenger RNA (mRNA) expression could be detected in all the normal breast (n=51) and tumor tissues (n=67) by a real-time polymerase chain reaction but CYP17 mRNA expression was not significantly different between the variant allele carriers and non-carriers. In addition, no significant correlation was observed between CYP17 mRNA and E2 levels in tumors, indicating an unimportant role of CYP17 in in situ synthesis of E2. On the other hand, intra-tumoral E2 levels were significantly (P=0.025) higher in the variant allele carriers (127.2+/-11.0 pg/g) than non-carriers (88.2+/-8.5 pg/g). Since it has been previously reported that serum E2 levels are higher in variant allele carriers than non-carriers, it is speculated that the higher intra-tumoral E2 levels in the variant allele carriers might be ascribed to the higher serum E2 levels.

[A case of metastatic pheochromocytoma with remarkable response to combination of cyclophosphamide, vincristine and dacarbazine].

We report the case of a 58-year-old man with metastatic tumors 13 months after the initial surgery for paraganglioma at the left adrenal gland. A CT scan revealed a large tumor at the right scapula and abdominal paraaortic lymph nodes, and the patient received combination therapy of cyclophosphamide, vincristine and dacarbazine (CVD) every 3 to 4 weeks. After 11 courses, the serum catecholamine level was reduced to the normal range. The metastatic tumors showed optimal reduction in size, and the patient remains alive with no symptoms of the disease one year after the primary chemotherapy. The combination therapy of cyclophosphamide, vincristine and dacarbazine is considered a feasible and effective chemotherapy for metastatic malignant pheochromocytoma.