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

Int J Clin Oncol. 2013 Aug;18(4):735-42. doi: 10.1007/s10147-012-0425-5. Epub 2012 May 26.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Agents, Phytogenic / adverse effects*
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Camptothecin / adverse effects
  • Camptothecin / analogs & derivatives*
  • Diarrhea / chemically induced
  • Female
  • Fluorouracil / adverse effects
  • Glucuronosyltransferase / genetics
  • Humans
  • Irinotecan
  • Leucovorin / adverse effects
  • Logistic Models
  • Male
  • Middle Aged
  • Neoplasms / drug therapy*
  • Neutropenia / chemically induced
  • Polypharmacy*
  • Retrospective Studies

Substances

  • Antineoplastic Agents, Phytogenic
  • Irinotecan
  • UGT1A1 enzyme
  • Glucuronosyltransferase
  • Leucovorin
  • Fluorouracil
  • Camptothecin

Supplementary concepts

  • IFL protocol