Association of renal function with the safety and efficacy of cisplatin plus S-1 therapy and docetaxel plus cisplatin plus S-1 therapy in patients with advanced gastric cancer: an exploratory analysis of JCOG1013. (20th October 2021)

• Record Type: Journal Article
• Authors: Hironaka, Shuichi; Sadachi, Ryo; Machida, Nozomu; Iwasa, Satoru; Yamada, Yasuhide; Sasako, Mitsuru; Yoshikawa, Takaki; Boku, Narikazu; Terashima, Masanori
• Is Part Of: Japanese journal of clinical oncology. Volume 52:Number 1(2022)
• Page Start: 14
• Page End: 23
• Publication Date: 2021-10-20
• Subjects: gastric cancer -- renal function -- creatinine clearance -- S-1 -- cisplatin; Oncology -- Periodicals; Cancer -- Periodicals; 616.994005
• DOI: 10.1093/jjco/hyab160
• Languages: English
• ISSNs: 0368-2811

Abstract

Abstract: Background: Although cisplatin and 5-chloro-2, 4-dihydropyrimidine (dihydropyrimidine dehydrogenase inhibitor contained in S-1) are excreted into the urine, it remains unknown how creatinine clearance (CrCl) affects the safety and efficacy of cisplatin plus S-1 and docetaxel plus cisplatin plus S-1 in patients with advanced gastric cancer. Methods: Among the 741 participants in JCOG1013 comparing cisplatin plus S-1 with docetaxel plus cisplatin plus S-1, 723 with serum creatinine levels ≤1.2 mg/dL were categorized into A1 (CrCl ≥ 80 mL/min), A2 (60 ≤ CrCl <80) and A3 (CrCl < 60) in the cisplatin plus S-1 arm and similarly B1, B2 and B3 in the docetaxel plus cisplatin plus S-1 arm. The initial dose modification by CrCl was pre-specified in the docetaxel plus cisplatin plus S-1 arm but not in the cisplatin plus S-1 arm. Results: The numbers of patients categorized as A1/A2/A3 and B1/B2/B3 were 169/136/57 and 170/138/53, respectively. In the cisplatin plus S-1 arm, a lower CrCl was associated with higher incidences of grade 4 leukopenia ( P = 0.006), neutropenia ( P = 0.002), and grade 3/4 anorexia ( P = 0.004) and febrile neutropenia ( P = 0.049), whereas there was no association in the docetaxel plus cisplatin plus S-1 arm. No significant differences were observed according to CrCl in the overall survival [median: 15.4/15.5/15.4 months in A1/A2/A3 ( P = 0.886) and 15.3/13.7/13.7 months in B1/B2/B3 (P = 0.719)], progression-free survival [median: 7.1/6.8/6.2 months in A1/A2/A3 ( P = 0.884) and 7.5/7.2/7.8 months in B1/B2/B3 ( P = 0.851)] and response rates [58.9/57.8/46.9% in A1/A2/A3 ( P = 0.311) and 62.0/61.5/51.5% in B1/B2/B3 ( P = 0.362)]. Conclusions: Renal impairment was associated with severe adverse events in cisplatin plus S-1 therapy but not with the efficacy in cisplatin plus S-1 and docetaxel plus cisplatin plus S-1 therapy. Abstract : Renal impairment was associated with severe adverse events in CS therapy but not with the efficacy in CS and DCS therapy.