Life-threatening toxicities in a patient with UGT1A1*6/*28 and SLCO1B1*15/*15 genotypes after irinotecan-based chemotherapy

Cancer Chemother Pharmacol. 2009 May;63(6):1165-9. doi: 10.1007/s00280-008-0864-x. Epub 2008 Nov 8.


Introduction: To explore severe toxicities induced by irinotecan-based chemotherapy and UGT1A1*6/*28 and SLCO1B1*15/*15 genotypes.

Case report: A 66-year-old Japanese male diagnosed with left pharyngeal carcinoma (T2N2bM0, stage IVA) was treated with irinotecan (70 mg/m(2)) on days 1, 8 and 15 in combination with docetaxel (60 mg/m(2)) on day 1 of a 28-day cycle. After the first cycle, he suffered marked toxicities, including grade 4 diarrhea and febrile grade 4 neutropenia. Plasma concentrations of irinotecan, SN-38 and SN-38G were measured, and extensive accumulation of SN-38 was observed. Genotyping of UGT1A1 and OATP1B1 proteins showed UGT1A1*6/*28 and SLCO1B1*15/*15, respectively, which are known to lead to extremely low glucuronidation and transport activities of substrate drugs.

Conclusion: The severe toxicities in this patient are attributable to the extensive accumulation of SN-38, which may result from a synergistic or additive effect of low metabolic (UGT1A1*6/*28) and transport (SLCO1B1*15/*15) capabilities.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Antineoplastic Agents, Phytogenic / adverse effects*
  • Antineoplastic Agents, Phytogenic / blood
  • Antineoplastic Agents, Phytogenic / pharmacokinetics
  • Camptothecin / adverse effects
  • Camptothecin / analogs & derivatives*
  • Camptothecin / blood
  • Camptothecin / pharmacokinetics
  • Genotype
  • Glucuronosyltransferase / genetics*
  • Humans
  • Irinotecan
  • Liver-Specific Organic Anion Transporter 1
  • Male
  • Organic Anion Transporters / genetics*
  • Pharmacogenetics
  • Pharyngeal Neoplasms / drug therapy
  • Pharyngeal Neoplasms / genetics


  • Antineoplastic Agents, Phytogenic
  • Liver-Specific Organic Anion Transporter 1
  • Organic Anion Transporters
  • SLCO1B1 protein, human
  • Irinotecan
  • UGT1A1 enzyme
  • Glucuronosyltransferase
  • Camptothecin