Incidence of opioid-induced constipation in Japanese patients with cancer pain: A prospective observational cohort study

Akihiro Tokoro, Hisao Imai, Soichi Fumita, Toshiyuki Harada, Toshio Noriyuki, Makio Gamoh, Yusaku Akashi, Hiroki Sato, Yoshiyuki Kizawa, Akihiro Tokoro, Hisao Imai, Soichi Fumita, Toshiyuki Harada, Toshio Noriyuki, Makio Gamoh, Yusaku Akashi, Hiroki Sato, Yoshiyuki Kizawa

Abstract

This multicenter, prospective, observational cohort study assessed opioid induced constipation (OIC) in Japanese patients with cancer. Eligible patients had stable cancer and an ECOG PS of 0-2. OIC incidence based on the Rome IV diagnostic criteria was determined by patient diary entries during the first 14 days of opioid therapy. The proportion of patients with OIC was calculated for each 1-week period and the overall 2-week study period. Secondary measurements of OIC included the Bowel Function Index (BFI) score (patient assessment administered by physician), spontaneous bowel movements (SBMs) per week (patient assessment), and physician assessments. Medication for constipation was allowed. Two hundred and twenty patients were enrolled. The mean morphine-equivalent dose was 22 mg/day. By Rome IV criteria, the cumulative incidence of OIC was 56% (95% CI: 49.2%-62.9%); week 1, 48% (95% CI: 40.8%-54.6%); week 2, 37% (95% CI: 30.1%-43.9%). The cumulative incidence of OIC was lower in patients who received prophylactic agents for constipation (48% [95% CI: 38.1%-57.5%]) than in patients who did not (65% [95% CI: 55.0%-74.2%]). The cumulative incidences of OIC were 59% (95% CI: 51.9%-66.0%), 61% (95% CI: 54.3%-68.1%), and 45% (95% CI: 38.0%-51.8%) based on BFI scores, physician assessments, and SBM frequency, respectively. Frequency of BMs/week before starting opioids was the most influential factor for the occurrence of OIC. Utilization of prophylactic agents for constipation was associated with a modest effect on reducing the incidence of OIC. The incidences of OIC reported were variable depending on the diagnostic tool involved.

Keywords: cancer pain; opioid; opioid-induced constipation; prophylactic; spontaneous bowel movements.

Conflict of interest statement

AT has received grants from Shionogi and Daiichi‐Sankyo and personal fees from Daiichi‐Sankyo, Mundipharma, Hisamitsu, Terumo, Sumitomo Dainippon, and Kracie. HI has received travel reimbursement from Shionogi. SF has received honoraria from Merck Serono, Ono Pharmaceutical Co., Bristol‐Myers Squibb, Takeda, and Bayer Yakuhin, and travel reimbursement from BeiGene. TH has received honoraria from Taiho Pharmaceutical, AstraZeneca KK, Boehringer Ingelheim, and Hisamitsu Pharmaceutical Co., Inc. TN has received personal fees from Shionogi, Taiho Pharmaceutical, and Chugai Pharmaceutical, and nonfinancial support from Shionogi. MG has received honoraria from Taiho Pharmaceutical, Chugai Pharmaceutical, Yakult Honsha, Ono Pharmaceutical, Takeda, Daiichi Sankyo, Nippon Kayaku, and Eli Lilly Japan. YA has received honoraria from AstraZeneca KK, Chugai Pharmaceutical Co., Ltd., MDS KK, Bristol‐Myers Squibb KK, Nippon Boehringer Ingelheim Co., Ltd., Pfizer Seiyaku KK, Taiho Pharmaceutical Co., Ltd., and Hisamitsu Pharmaceutical Co., Inc. HS is an employee of Shionogi & Co., Ltd. YK has received grants from Shionogi, Kyowa‐Kirin, and Terumo, and personal fees from Shionogi, Kyowa Kirin, Terumo, Johnson & Johnson, Daiichi‐Sankyo, Pfizer, Mundipharma, Chugai Pharmaceutical.

© 2019 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Figures

Figure 1
Figure 1
Patient disposition. FAS, full analysis set
Figure 2
Figure 2
Incidence of OIC by diagnostic criteria (FAS 1). aPatients were given a diagnosis of OIC in either week 1 or 2. bPatients were given a diagnosis based on criteria for the presence or absence of OIC set by individual attending physicians. cFor this analysis, patients with <3 SBMs per week were given a diagnosis of OIC. SBMs were defined as any BM, except for movements occurring within 24 hours after rescue use of laxative therapy. BFI, bowel function index; CI, confidence interval; OIC, opioid‐induced constipation; FAS; full analysis set; SBM, spontaneous bowel movement
Figure 3
Figure 3
Cumulative incidence of OIC in patients who did or did not receive prophylactic agents for constipation (FAS 1). aPatients were given a diagnosis of OIC in either week 1 or 2. CI, confidence interval; FAS, full analysis set; OIC, opioid‐induced constipation

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