Pre-treatment serum total bilirubin level as an indicator of optimal CPT-11 dosage.

BACKGROUND: Irinotecan (CPT-11), a highly effective chemotherapeutic agent, can cause severe neutropenia and diarrhea. The area under the curve of plasma levels over time of SN-38, an active metabolite of CPT-11, was previously reported to correlate with the pre-treatment serum total bilirubin level (PTB). However, there are no established criteria for selecting CPT-11 dose on the basis of PTB. Therefore, we evaluated PTB as an indicator for the optimal CPT-11 dose. METHODS: Retrospective analyses were conducted in patients administered CPT-11 as a single agent at the Osaka National Hospital from June 2006 to July 2013. Data obtained during the first 28 days following CPT-11 administration were analyzed to compare PTB between patients with and without grade 3-4 neutropenia and grade 3-4 diarrhea. Receiver operating characteristics (ROC) curve analysis was performed to determine the optimal PTB cutoff value for PTB-associated toxicity. Subgroup analysis was performed comparing the incidence of toxicity in patients with PTB values below or above the cutoff value. RESULTS: Although PTB incidence was significantly higher in patients who developed grade 3-4 neutropenia than in those who did not, PTB was not associated with grade 3-4 diarrhea. The PTB cutoff value for association with grade 3-4 neutropenia occurrence was set at 0.8 mg/dL. The incidence of febrile neutropenia (FN) significantly elevated to 21% in patients with PTB ≥0.8 mg/dL, whereas that of patients with PTB <0.8 mg/dL was 4%. In the subgroup analysis, no difference was found in the neutropenia incidence between patients treated with a dose below 80 mg/m(2) and those treated on a weekly schedule. CONCLUSIONS: PTB can be used as a predictive marker of CPT-11-induced severe neutropenia and FN. In patients with PTB ≥0.8 mg/dL, the CPT-11 dose should be reduced to less than 80 mg/m(2) with weekly dosing.

[Construction of a system for proper TS-1 application].

TS-1 is an oral anti-tumor drug, which contains 5-chloro-2, 4-dihydroxypyridine (CDHP), a compound mainly excreted in urine. Since the CDHP concentration is increased among patients with impaired renal function, the frequency of side effects of TS-1 increases in such patients. Therefore, we constructed a computer-aided system that enables prompt monitoring of creatinine clearance (Ccr) calculated from the serum creatinine levels of patients prescribed TS-1 at the time pharmacists prepare the medicine. With this system, we found two cases who were prescribed TS-1, despite their decreased Ccr. One was a patient whose estimated Ccr was less than 30 mL/min/m2. With such renal malfunction, pharmacokinetics of the drug was considerably changed compared with normal control, and the dosage should be reduced. The other case presented with severe jaundice and had only a mild decrease of renal function (Ccr: 50 mL/min/m2). So we measured the concentration of uracil in the urine and performed a drug lymphocyte stimulation test for further investigation of concomitant affecting factors. Our system is useful because it can show pharmacists both the dosage TS-1 patients take and their renal function at a glance in real time. This system can be adapted for every medicine which might accumulate in patients with renal dysfunction.