A randomized controlled, open-label early phase II trial comparing incidence of FOLFIRI.3-induced diarrhoea between Hangeshashinto and oral alkalization in Japanese patients with colorectal cancer

J Clin Pharm Ther. 2019 Dec;44(6):946-951. doi: 10.1111/jcpt.13020. Epub 2019 Aug 13.

Abstract

What is known and objective: We conducted a pilot clinical trial to investigate whether Hangeshashinto (TJ-14) could be substituted for oral alkalization in patients scheduled to undergo chemotherapy by FOLFIRI.3 regimen for colorectal cancer (CRC).

Methods: Patients with CRC were randomized 1:1 to a TJ-14 (7.5 g/day) group or an oral alkalization (sodium bicarbonate, 1.8 g/day; ursodeoxycholic acid, 300 mg/day) group. The primary endpoint was incident of late-onset diarrhoea. A total of 30 patients were randomized to either the TJ-14 group or the alkalization group.

Results and discussion: There was no statistical difference in age, concomitantly used drugs or UGT1A1 genotypes between the groups. In the alkalization group (n = 15), the frequency of grade 0/1/2 and grade 3 diarrhoea was 73% and 27%, respectively. In the TJ-14 group (n = 14), the frequency of grade 0/1/2 and grade 3 diarrhoea was 79% and 21%, respectively. Grade 4 diarrhoea was not observed in either group. There was no statistically significant difference in other adverse events or in response to FOLFIRI.3 between the groups.

What is new and conclusion: This pilot trial suggests that TJ-14 is a promising alternative treatment option to reduce FOLFIRI.3-induced late-onset diarrhoea, although additional clinical study with a larger number of patients is necessary to confirm these results.

Keywords: FOLFIRI.3; Hangeshashinto; RCT; alkalization; diarrhoea.

Publication types

  • Clinical Trial, Phase II
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects*
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Asian People
  • Camptothecin / adverse effects
  • Camptothecin / analogs & derivatives*
  • Camptothecin / therapeutic use
  • Colorectal Neoplasms / drug therapy*
  • Colorectal Neoplasms / genetics
  • Diarrhea / chemically induced*
  • Drug-Related Side Effects and Adverse Reactions / etiology
  • Drug-Related Side Effects and Adverse Reactions / genetics
  • Female
  • Fluorouracil / adverse effects
  • Fluorouracil / therapeutic use
  • Glucuronosyltransferase / genetics
  • Humans
  • Incidence
  • Leucovorin / adverse effects
  • Leucovorin / therapeutic use
  • Male
  • Middle Aged
  • Young Adult

Substances

  • UGT1A1 enzyme
  • Glucuronosyltransferase
  • Leucovorin
  • Fluorouracil
  • Camptothecin

Supplementary concepts

  • IFL protocol