Effect of Hangeshashin-To (Japanese Herbal Medicine Tj-14) on Tolerability of Irinotecan: Propensity Score and Instrumental Variable Analyses.

Hirokazu Urushiyama,Hideo Yasunaga,Kiyohide Fushimi,Yoshihisa Hiraishi,Wakae Hasegawa,Hayato Yamana,Hiroki Matsui,Nobuaki Michihata,Taisuke Jo,Takahide Nagase,Akihisa Mitani,Yasuhiro Yamauchi

doi:10.3390/jcm7090246

Abstract

Irinotecan hydrochloride (CPT-11) is used to treat a wide spectrum of malignant tumors. Hangeshashin-to (Japanese herbal medicine TJ-14) is reportedly effective in preventing and controlling diarrhea associated with CPT-11. However, the effect of TJ-14 on tolerability of chemotherapy with CPT-11 has not been fully investigated. We used the Japanese Diagnosis Procedure Combination inpatient database to retrospectively identify patients who had received CPT-11 on their first admission with and without TJ-14. Patients who did receive TJ-14 (N = 7092) received CPT-11 more often and in larger doses than those who did not receive TJ-14 (N = 82,019). The incidence rate ratio of CPT-11 administration was 1.34 for frequency (95% confidence interval [CI], 1.31–1.38; p < 0.001), and 1.16 for total dose (95% CI, 1.14–1.19; p < 0.001) according to stabilized inverse probability treatment weighting using propensity scores. Instrumental variable analysis showed similar trends. In-hospital mortality was significantly lower in patients who received TJ-14 than in those who did not. Odds ratios of in-hospital death in patients receiving TJ-14 was 0.81 (95% CI, 0.71–0.93; p = 0.002) according to stabilized inverse probability treatment weighting using propensity scores and 0.42 (95% CI, 0.22–0.81; p = 0.009) according to instrumental variable analysis. Our findings indicate that TJ-14 improve the tolerability of CPT-11.

Highlights

Irinotecan hydrochloride (CPT-11), a semisynthetic derivative of camptothecin, is an anticancer drug that inhibits nucleic acid synthesis by topoisomerase I inhibition [1]
The diarrhea in patients receiving CPT-11 is caused by enterocolitis associated with retained SN-38, which is an active metabolite of CPT-11, in the intestine [2]
We aimed to examine the influence of TJ-14 on tolerability of CPT-11 by comparing in-hospital mortality and dosage in early courses of chemotherapy with CPT-11 between patients who did and did not receive TJ-14, data being extracted from a national inpatient database in Japan

Summary

Introduction

Irinotecan hydrochloride (CPT-11), a semisynthetic derivative of camptothecin, is an anticancer drug that inhibits nucleic acid synthesis by topoisomerase I inhibition [1]. Diarrhea, a characteristic adverse effect of CPT-11, is often severe and a major reason for discontinuing it. The diarrhea in patients receiving CPT-11 is caused by enterocolitis associated with retained SN-38, which is an active metabolite of CPT-11, in the intestine [2]. Most SN-38 is inactivated by formation of SN-38-glucuronide conjugates and excreted in the bile. SN-38-glucuronide conjugate is deconjugated with β-glucuronidase from intestinal microflora [3] to SN-38, which cause diarrhea [2]

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