Abstract
JCOG1113 is a randomized phase III trial in patients with advanced biliary tract cancers (BTCs) (UMIN000001685), and gemcitabine plus S-1 (GS) was not inferior to gemcitabine plus cisplatin (GC). However, poor renal function often results in high toxicity of S-1. Therefore, we examined whether GS can be recommended for patients with low creatinine clearance (CCr). Renal function was classified by CCr as calculated by the Cockcroft-Gault formula: high CCr (CCr ≥ 80 ml/min) and low CCr (80 > CCr ≥ 50 ml/min). Of 354 patients, 87 patients on GC and 91 on GS were included in the low CCr group, while there were 88 patients on GC and 88 patients on GS in the high CCr group. The HR of overall survival for GS compared with GC was 0.687 (95% CI 0.504–0.937) in the low CCr group. Although the total number of incidences of all Grade 3–4 non-haematological adverse reactions was higher (36.0% vs. 11.8%, p = 0.0002), the number of patients who discontinued treatment was not different (14.1% vs. 16.9%, p = 0.679) for GS compared with GC in the low CCr group. This study suggests that GS should be selected for the treatment of advanced BTC patients with reduced renal function.
Highlights
Biliary tract cancers (BTCs) include those in the intrahepatic bile duct (IHBD), extrahepatic bile duct (EHBD), gallbladder (GB), and ampulla of Vater (AV)
Previous studies examined the influence of renal function on the toxicity of S-1 monotherapy (80 mg/day for a body surface area [BSA] on days 1–28 followed by a 14-day rest); patients with low creatinine clearance (CCr) showed a high incidence of severe adverse events (AEs) that resulted in treatment discontinuation[15,16,17]
There are no reports that have evaluated the influence of renal function on survival outcomes for patients with advanced BTCs, high incidence of AEs may result in a poor prognosis due to a low dose intensity
Summary
Biliary tract cancers (BTCs) include those in the intrahepatic bile duct (IHBD), extrahepatic bile duct (EHBD), gallbladder (GB), and ampulla of Vater (AV). The serum concentration of gimeracil increases in patients with renal dysfunction, which theoretically results in a higher serum concentration of fluorouracil. Based on this mechanism, previous studies examined the influence of renal function on the toxicity of S-1 monotherapy (80 mg/day for a body surface area [BSA] on days 1–28 followed by a 14-day rest); patients with low creatinine clearance (CCr) showed a high incidence of severe adverse events (AEs) that resulted in treatment discontinuation[15,16,17]. There are no reports that have evaluated the influence of renal function on survival outcomes for patients with advanced BTCs, high incidence of AEs may result in a poor prognosis due to a low dose intensity. We examined whether GS can be recommended for patients with low CCr in JCOG1113 as an exploratory analysis
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