Top

International Journal of Clinical Oncology

Published in:

01-08-2013 | Original Article

Concomitant polypharmacy is associated with irinotecan-related adverse drug reactions in patients with cancer

Authors: Tetsuya Sasaki, Ken-ichi Fujita, Yu Sunakawa, Hiroo Ishida, Keishi Yamashita, Keisuke Miwa, Shigehira Saji, Yasuhisa Kato, Yasutsuna Sasaki

Published in: International Journal of Clinical Oncology | Issue 4/2013

Abstract

Background

Patients with cancer often receive chemotherapeutic agents concurrently with other medications to treat comorbidity. The practical effects of concomitant medications, especially polypharmacy, on adverse drug reactions related to irinotecan-based chemotherapy are not well documented.

Methods

Associations of adverse drug reactions related to irinotecan monotherapy or a combination of irinotecan, 5-fluorouracil, and l-leucovorin (FOLFIRI) with concomitant medicines used to treat comorbidity were retrospectively investigated in Japanese patients with cancer.

Results

Of the 172 patients, 118 received concomitant medications. Twenty-one patients had grade 4 neutropenia and/or grade 3 or 4 diarrhea. Univariate and multivariate analyses revealed that concomitant medications were significantly associated with irinotecan-related severe neutropenia and/or diarrhea (P = 0.023 and 0.044). Multiple concomitant medications were significantly related to severe irinotecan-related toxicity in patients given monotherapy or FOLFIRI (P = 0.01). The incidence of severe irinotecan-related toxicities increased in parallel with the number of concomitant medications.

Conclusion

We found that multiple concomitant medicines were significantly associated with severe irinotecan-related toxicity, indicating that polypharmacy must be effectively managed to decrease the risk of adverse drug reactions in patients with cancer who received irinotecan-based chemotherapy.

Beijnen JH, Schellens JH (2004) Drug interactions in oncology. Lancet Oncol 5:489–496PubMedCrossRef

Blower P, de Wit R, Goodin S et al (2005) Drug–drug interactions in oncology: why are they important and can they be minimized? Crit Rev Oncol Hematol 55:117–142PubMedCrossRef

Chan A, Yap KY, Koh D et al (2011) Electronic database to detect drug–drug interactions between antidepressants and oral anticancer drugs from a cancer center in Singapore: implications to clinicians. Pharmacoepidemiol Drug Saf 20:939–947PubMed

Jansman FG, Idzinga FS, Smit WM et al (2005) Classification and occurrence of clinically significant drug interactions with irinotecan and oxaliplatin in patients with metastatic colorectal cancer. Clin Ther 27:327–335PubMedCrossRef

Jansman FG, Reyners AK, van Roon EN et al (2011) Consensus-based evaluation of clinical significance and management of anticancer drug interactions. Clin Ther 33:305–314PubMedCrossRef

Riechelmann RP, Tannock IF, Wang L et al (2007) Potential drug interactions and duplicate prescriptions among cancer patients. J Natl Cancer Inst 99:592–600PubMedCrossRef

Kudoh S, Fujiwara Y, Takada Y et al (1998) Phase II study of irinotecan combined with cisplatin in patients with previously untreated small-cell lung cancer. West Japan Lung Cancer Group. J Clin Oncol 16:1068–1074PubMed

Negoro S, Fukuoka M, Masuda N et al (1991) Phase I study of weekly intravenous infusions of CPT-11, a new derivative of camptothecin, in the treatment of advanced non-small-cell lung cancer. J Natl Cancer Inst 83:1164–1168PubMedCrossRef

Rougier P, Van Cutsem E, Bajetta E et al (1998) Randomised trial of irinotecan versus fluorouracil by continuous infusion after fluorouracil failure in patients with metastatic colorectal cancer. Lancet 352:1407–1412PubMedCrossRef

10.

Fujita K, Sasaki Y (2007) Pharmacogenomics in drug-metabolizing enzymes catalyzing anticancer drugs for personalized cancer chemotherapy. Curr Drug Metab 8:554–562PubMedCrossRef

11.

Ando Y, Saka H, Ando M et al (2000) Polymorphisms of UDP-glucuronosyltransferase gene and irinotecan toxicity: a pharmacogenetic analysis. Cancer Res 60:6921–6926PubMed

12.

Innocenti F, Undevia SD, Iyer L et al (2004) Genetic variants in the UDP-glucuronosyltransferase 1A1 gene predict the risk of severe neutropenia of irinotecan. J Clin Oncol 22:1382–1388PubMedCrossRef

13.

Araki K, Fujita K, Ando Y et al (2006) Pharmacogenetic impact of polymorphisms in the coding region of the UGT1A1 gene on SN-38 glucuronidation in Japanese patients with cancer. Cancer Sci 97:1255–1259PubMedCrossRef

14.

Han JY, Lim HS, Shin ES et al (2006) Comprehensive analysis of UGT1A polymorphisms predictive for pharmacokinetics and treatment outcome in patients with non-small-cell lung cancer treated with irinotecan and cisplatin. J Clin Oncol 24:2237–2244PubMedCrossRef

15.

Minami H, Sai K, Saeki M et al (2007) Irinotecan pharmacokinetics/pharmacodynamics and UGT1A genetic polymorphisms in Japanese: roles of UGT1A1*6 and *28. Pharmacogenet Genomics 17:497–504PubMedCrossRef

16.

Brunton LL, Lazo JS, Parker KL (2006) Goodman & Gilman’s the pharmacological basis of therapeutics, 11th edn. McGraw-Hill, New York

17.

Corcoran ME (1997) Polypharmacy in the older patient with cancer. Cancer Control 4:419–428PubMed

18.

Yancik R (1997) Cancer burden in the aged: an epidemiologic and demographic overview. Cancer 80:1273–1283PubMedCrossRef

19.

Oda M, Kotegawa T, Tsutsumi K et al (2003) The effect of itraconazole on the pharmacokinetics and pharmacodynamics of bromazepam in healthy volunteers. Eur J Clin Pharmacol 59:615–619PubMedCrossRef

20.

Araki K, Yasui-Furukori N, Fukasawa T et al (2004) Inhibition of the metabolism of etizolam by itraconazole in humans: evidence for the involvement of CYP3A4 in etizolam metabolism. Eur J Clin Pharmacol 60:427–430PubMedCrossRef

21.

Sparreboom A, Fujita K, Zamboni WC (2010) Topoisomerase I-targeting drugs. In: Chabner BA, Longo DL (eds) Cancer chemotherapy and biotherapy: principles and practice, 5th edn. Lippincott Williams & Wilkins, Philadelphia, pp 342–355

22.

de Jong FA, van der Bol JM, Mathijssen RH et al (2008) Renal function as a predictor of irinotecan-induced neutropenia. Clin Pharmacol Ther 84:254–262PubMedCrossRef

Title: Concomitant polypharmacy is associated with irinotecan-related adverse drug reactions in patients with cancer
Authors: Tetsuya Sasaki
Ken-ichi Fujita
Yu Sunakawa
Hiroo Ishida
Keishi Yamashita
Keisuke Miwa
Shigehira Saji
Yasuhisa Kato
Yasutsuna Sasaki
Publication date: 01-08-2013
Publisher: Springer Japan
Published in: International Journal of Clinical Oncology / Issue 4/2013
Print ISSN: 1341-9625
Electronic ISSN: 1437-7772
DOI: https://doi.org/10.1007/s10147-012-0425-5

Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

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

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusion

Please log in to get access to this content

Other articles of this Issue 4/2013

Reduced-dose docetaxel for castration-resistant prostate cancer has no inferior impact on overall survival in Japanese patients

The contribution of neck dissection for residual neck disease after chemoradiotherapy in advanced oropharyngeal and hypopharyngeal squamous cell carcinoma patients

Weekly low-dose docetaxel combined with estramustine and dexamethasone for Japanese patients with metastatic castration-resistant prostate cancer

Prognostic scoring system for stage IV colorectal cancer: is the AJCC sub-classification of stage IV colorectal cancer appropriate?

A multicenter phase II study of TSU-68, a novel oral multiple tyrosine kinase inhibitor, in patients with metastatic breast cancer progressing despite prior treatment with an anthracycline-containing regimen and taxane

Pancreatic carcinoma-specific immunotherapy using synthesised alpha-galactosyl epitope-activated immune responders: findings from a pilot study

Keynote webinar | Spotlight on antibody–drug conjugates in cancer