Skip to main content
Top
Published in: Cancer Chemotherapy and Pharmacology 3/2019

Open Access 01-03-2019 | Original Article

Prophylactic effect of scopolamine butylbromide, a competitive antagonist of muscarinic acetylcholine receptor, on irinotecan-related cholinergic syndrome

Authors: Hirotoshi Iihara, Hironori Fujii, Chiaki Yoshimi, Ryo Kobayashi, Nobuhisa Matsuhashi, Takao Takahashi, Kazuhiro Yoshida, Akio Suzuki

Published in: Cancer Chemotherapy and Pharmacology | Issue 3/2019

Login to get access

Abstract

Background/aim

Cholinergic syndrome frequently occurs within the first 24 h after irinotecan injection. We evaluated the prophylactic effect of scopolamine butylbromide on irinotecan-related cholinergic syndrome.

Patients and methods

Fifty-nine patients who received irinotecan-based regimens at our outpatient chemotherapy clinic between April 2013 and May 2014 were enrolled. Patients who developed irinotecan-related cholinergic syndrome were prophylactically administered scopolamine butylbromide at the next scheduled treatment. Risk factors for irinotecan-related cholinergic syndrome were determined using logistic regression analysis.

Results

Irinotecan-related cholinergic syndrome occurred in 50.8% of patients. Scopolamine butylbromide administration significantly reduced the incidence to 3.4% (P < 0.01). The irinotecan dose (≥ 150 mg/m2) was the only risk factor associated with irinotecan-related cholinergic syndrome. The incidence of cholinergic syndrome in patients with this risk factor was 75%.

Conclusion

Scopolamine butylbromide was effective in preventing irinotecan-related cholinergic syndrome. It is recommended for patients receiving ≥ 150 mg/m2 irinotecan who may develop cholinergic syndrome at high frequency.
Literature
2.
go back to reference Kono A, Hara Y (1991) Conversion of CPT-11 into SN-38 in human tissues. Gan To Kagaku Ryoho 18:2175–2178PubMed Kono A, Hara Y (1991) Conversion of CPT-11 into SN-38 in human tissues. Gan To Kagaku Ryoho 18:2175–2178PubMed
3.
go back to reference Kawato Y, Aonuma M, Matsumoto K (1991) Production of SN-38, a main metabolite of the camptothecin derivative CPT-11, and its species and tissue specificities. Gan To Kagaku Ryoho 6:899–907 Kawato Y, Aonuma M, Matsumoto K (1991) Production of SN-38, a main metabolite of the camptothecin derivative CPT-11, and its species and tissue specificities. Gan To Kagaku Ryoho 6:899–907
4.
go back to reference Iyer L, Hall D, Das S, Mortell MA, Ramírez J, Kim S, Di Rienzo A, Ratain MJ (1999) Phenotype-genotype correlation of in vitro SN-38 (active metabolite of irinotecan) and bilirubin glucuronidation in human liver tissue with UGT1A1 promoter polymorphism. Clin Pharmacol Ther 65:576–582CrossRefPubMed Iyer L, Hall D, Das S, Mortell MA, Ramírez J, Kim S, Di Rienzo A, Ratain MJ (1999) Phenotype-genotype correlation of in vitro SN-38 (active metabolite of irinotecan) and bilirubin glucuronidation in human liver tissue with UGT1A1 promoter polymorphism. Clin Pharmacol Ther 65:576–582CrossRefPubMed
5.
go back to reference Sai K, Sawada J, Minami H (2008) Irinotecan pharmacogenetics in Japanese cancer patients: roles of UGT1A1*6 and *28. Yakugaku Zasshi 128:575–584CrossRefPubMed Sai K, Sawada J, Minami H (2008) Irinotecan pharmacogenetics in Japanese cancer patients: roles of UGT1A1*6 and *28. Yakugaku Zasshi 128:575–584CrossRefPubMed
6.
go back to reference Satoh T, Ura T, Yamada Y, Yamazaki K, Tsujinaka T, Munakata M, Nishina T, Okamura S, Esaki T, Sasaki Y, Koizumi W, Kakeji Y, Ishizuka N, Hyodo I, Sakata Y (2011) Genotype-directed, dose-finding study of irinotecan in cancer patients with UGT1A1*28 and/or UGT1A1*6 polymorphisms. Cancer Sci 102:1868–1873CrossRefPubMed Satoh T, Ura T, Yamada Y, Yamazaki K, Tsujinaka T, Munakata M, Nishina T, Okamura S, Esaki T, Sasaki Y, Koizumi W, Kakeji Y, Ishizuka N, Hyodo I, Sakata Y (2011) Genotype-directed, dose-finding study of irinotecan in cancer patients with UGT1A1*28 and/or UGT1A1*6 polymorphisms. Cancer Sci 102:1868–1873CrossRefPubMed
7.
go back to reference Ando Y, Saka H, Ando M, Sawa T, Muro K, Ueoka H, Yokoyama A, Saitoh S, Shimokata K, Hasegawa Y (2000) Polymorphisms of UDP-glucuronosyltransferase gene and irinotecan toxicity: a pharmacogenetic analysis. Cancer Res 60:6921–6926PubMed Ando Y, Saka H, Ando M, Sawa T, Muro K, Ueoka H, Yokoyama A, Saitoh S, Shimokata K, Hasegawa Y (2000) Polymorphisms of UDP-glucuronosyltransferase gene and irinotecan toxicity: a pharmacogenetic analysis. Cancer Res 60:6921–6926PubMed
8.
go back to reference Minami H, Sai K, Saeki M, Saito Y, Ozawa S, Suzuki K, Kaniwa N, Sawada J, Hamaguchi T, Yamamoto N, Shirao K, Yamada Y, Ohmatsu H, Kubota K, Yoshida T, Ohtsu A, Saijo N (2007) Irinotecan pharmacokinetics/pharmacodynamics and UGT1A genetic polymorphisms in Japanese: roles of UGT1A1*6 and *28. Pharmacogenet Genom 17:497–504CrossRef Minami H, Sai K, Saeki M, Saito Y, Ozawa S, Suzuki K, Kaniwa N, Sawada J, Hamaguchi T, Yamamoto N, Shirao K, Yamada Y, Ohmatsu H, Kubota K, Yoshida T, Ohtsu A, Saijo N (2007) Irinotecan pharmacokinetics/pharmacodynamics and UGT1A genetic polymorphisms in Japanese: roles of UGT1A1*6 and *28. Pharmacogenet Genom 17:497–504CrossRef
9.
go back to reference Abigerges D, Chabot GG, Armand JP, Hérait P, Gouyette A, Gandia D (1995) Phase I and pharmacologic studies of the camptothecin analog irinotecan administered every 3 weeks in cancer patients. J Clin Oncol 13:210–221CrossRefPubMed Abigerges D, Chabot GG, Armand JP, Hérait P, Gouyette A, Gandia D (1995) Phase I and pharmacologic studies of the camptothecin analog irinotecan administered every 3 weeks in cancer patients. J Clin Oncol 13:210–221CrossRefPubMed
10.
go back to reference Rougier P, Bugat R (1996) CPT-11 in the treatment of colorectal cancer: clinical efficacy and safety profile. Semin Oncol 23:34–41PubMed Rougier P, Bugat R (1996) CPT-11 in the treatment of colorectal cancer: clinical efficacy and safety profile. Semin Oncol 23:34–41PubMed
11.
go back to reference Blandizzi C, Danesi R, De Paolis B, Di Paolo A, Colucci R, Falcone A, Del Tacca M (2002) Cholinergic toxic syndrome by the anticancer drug irinotecan: acetylcholinesterase does not play a major role. Clin Pharmacol Ther 71:263–271CrossRefPubMed Blandizzi C, Danesi R, De Paolis B, Di Paolo A, Colucci R, Falcone A, Del Tacca M (2002) Cholinergic toxic syndrome by the anticancer drug irinotecan: acetylcholinesterase does not play a major role. Clin Pharmacol Ther 71:263–271CrossRefPubMed
12.
go back to reference Dodds HM, Rivory LP (1999) The mechanism for the inhibition of acetylcholinesterases by irinotecan (CPT-11). Mol Pharmacol 56:1346–1353CrossRefPubMed Dodds HM, Rivory LP (1999) The mechanism for the inhibition of acetylcholinesterases by irinotecan (CPT-11). Mol Pharmacol 56:1346–1353CrossRefPubMed
13.
go back to reference Blandizzi C, De Paolis B, Colucci R, Lazzeri G, Baschiera F, Del Tacca M (2001) Characterization of a novel mechanism accounting for the adverse cholinergic effects of the anticancer drug irinotecan. Br J Pharmacol 132:73–84CrossRefPubMedPubMedCentral Blandizzi C, De Paolis B, Colucci R, Lazzeri G, Baschiera F, Del Tacca M (2001) Characterization of a novel mechanism accounting for the adverse cholinergic effects of the anticancer drug irinotecan. Br J Pharmacol 132:73–84CrossRefPubMedPubMedCentral
14.
go back to reference Takasuna K, Hagiwara T, Hirohashi M, Kato M, Nomura M, Nagai E, Yokoi T, Kamataki T (1996) Involvement of beta-glucuronidase in intestinal microflora in the intestinal toxicity of the antitumor camptothecin derivative irinotecan hydrochloride (CPT-11) in rats. Cancer Res 56:3752–3757PubMed Takasuna K, Hagiwara T, Hirohashi M, Kato M, Nomura M, Nagai E, Yokoi T, Kamataki T (1996) Involvement of beta-glucuronidase in intestinal microflora in the intestinal toxicity of the antitumor camptothecin derivative irinotecan hydrochloride (CPT-11) in rats. Cancer Res 56:3752–3757PubMed
15.
go back to reference Cheng C, Lau JE, Earl MA (2015) Use of atropine-diphenoxylate compared with hyoscyamine to decrease rates of irinotecan-related cholinergic syndrome. J Community Support Oncol 13:3–7CrossRefPubMed Cheng C, Lau JE, Earl MA (2015) Use of atropine-diphenoxylate compared with hyoscyamine to decrease rates of irinotecan-related cholinergic syndrome. J Community Support Oncol 13:3–7CrossRefPubMed
16.
go back to reference Yumuk PF, Aydin SZ, Dane F, Gumus M, Ekenel M, Aliustaoglu M, Karamanoglu A, Sengoz M, Turhal SN (2004) The absence of early diarrhea with atropine premedication during irinotecan therapy in metastatic colorectal patients. Int J Colorectal Dis 19:609–610CrossRefPubMed Yumuk PF, Aydin SZ, Dane F, Gumus M, Ekenel M, Aliustaoglu M, Karamanoglu A, Sengoz M, Turhal SN (2004) The absence of early diarrhea with atropine premedication during irinotecan therapy in metastatic colorectal patients. Int J Colorectal Dis 19:609–610CrossRefPubMed
17.
18.
go back to reference Tytgat GN (2007) Hyoscine butylbromide: a review of its use in the treatment of abdominal cramping and pain. Drugs 67:1343–1357CrossRefPubMed Tytgat GN (2007) Hyoscine butylbromide: a review of its use in the treatment of abdominal cramping and pain. Drugs 67:1343–1357CrossRefPubMed
19.
go back to reference Robenshtok E, Luria S, Tashma Z, Hourvitz A (2002) Adverse reaction to atropine and the treatment of organophosphate intoxication. Isr Med Assoc J 4:535–539PubMed Robenshtok E, Luria S, Tashma Z, Hourvitz A (2002) Adverse reaction to atropine and the treatment of organophosphate intoxication. Isr Med Assoc J 4:535–539PubMed
20.
go back to reference Van Deuren H, Missotten L (1979) Atropine intoxication and the acute delirium of the elderly blind patient. Bull Soc Belge Ophtalmol 186:27–29PubMed Van Deuren H, Missotten L (1979) Atropine intoxication and the acute delirium of the elderly blind patient. Bull Soc Belge Ophtalmol 186:27–29PubMed
21.
go back to reference Pitot HC, Goldberg RM, Reid JM, Sloan JA, Skaff PA, Erlichman C, Rubin J, Burch PA, Adjei AA, Alberts SA, Schaaf LJ, Elfring G, Miller LL (2000) Phase I dose-finding and pharmacokinetic trial of irinotecan hydrochloride (CPT-11) using a once-every-three-week dosing schedule for patients with advanced solid tumor malignancy. Clin Cancer Res 6:2236–2244PubMed Pitot HC, Goldberg RM, Reid JM, Sloan JA, Skaff PA, Erlichman C, Rubin J, Burch PA, Adjei AA, Alberts SA, Schaaf LJ, Elfring G, Miller LL (2000) Phase I dose-finding and pharmacokinetic trial of irinotecan hydrochloride (CPT-11) using a once-every-three-week dosing schedule for patients with advanced solid tumor malignancy. Clin Cancer Res 6:2236–2244PubMed
22.
go back to reference Kanbayashi Y, Ishikawa T, Kanazawa M, Nakajima Y, Tabuchi Y, Kawano R, Yoshioka T, Yoshida N, Hosokawa T, Takayama K, Taguchi T (2018) Predictive factors for the development of irinotecan-related cholinergic syndrome using ordered logistic regression analysis. Med Oncol 35:82CrossRefPubMed Kanbayashi Y, Ishikawa T, Kanazawa M, Nakajima Y, Tabuchi Y, Kawano R, Yoshioka T, Yoshida N, Hosokawa T, Takayama K, Taguchi T (2018) Predictive factors for the development of irinotecan-related cholinergic syndrome using ordered logistic regression analysis. Med Oncol 35:82CrossRefPubMed
Metadata
Title
Prophylactic effect of scopolamine butylbromide, a competitive antagonist of muscarinic acetylcholine receptor, on irinotecan-related cholinergic syndrome
Authors
Hirotoshi Iihara
Hironori Fujii
Chiaki Yoshimi
Ryo Kobayashi
Nobuhisa Matsuhashi
Takao Takahashi
Kazuhiro Yoshida
Akio Suzuki
Publication date
01-03-2019
Publisher
Springer Berlin Heidelberg
Published in
Cancer Chemotherapy and Pharmacology / Issue 3/2019
Print ISSN: 0344-5704
Electronic ISSN: 1432-0843
DOI
https://doi.org/10.1007/s00280-018-3736-z

Other articles of this Issue 3/2019

Cancer Chemotherapy and Pharmacology 3/2019 Go to the issue
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine