1. OATP1B1 and tumour OATP1B3 modulate exposure, toxicity, and survival after irinotecan-based chemotherapy
- Author
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Eric Winquist, Stephen Welch, Yun-Hee Choi, Richard B. Kim, Lenehan J, Parfitt J, and Wendy A. Teft
- Subjects
Adult ,Male ,Cancer Research ,Disease free survival ,medicine.medical_treatment ,Organic Anion Transporters ,colorectal cancer ,Pharmacology ,Organic Anion Transporters, Sodium-Independent ,Irinotecan ,Polymorphism, Single Nucleotide ,SN-38 ,Disease-Free Survival ,Solute Carrier Organic Anion Transporter Family Member 1B3 ,Medicine ,Humans ,heterocyclic compounds ,neoplasms ,Aged ,Aged, 80 and over ,Chemotherapy ,business.industry ,Liver-Specific Organic Anion Transporter 1 ,OATP1B3 ,OATP1B1 ,Middle Aged ,Antineoplastic Agents, Phytogenic ,digestive system diseases ,Multidrug Resistance-Associated Protein 2 ,stomatognathic diseases ,Oncology ,Toxicity ,Cancer research ,Camptothecin ,Female ,Multidrug Resistance-Associated Proteins ,business ,Colorectal Neoplasms ,Translational Therapeutics ,therapeutics ,medicine.drug - Abstract
Background: Treatment of advanced and metastatic colorectal cancer with irinotecan is hampered by severe toxicities. The active metabolite of irinotecan, SN-38, is a known substrate of drug-metabolising enzymes, including UGT1A1, as well as OATP and ABC drug transporters. Methods: Blood samples (n=127) and tumour tissue (n=30) were obtained from advanced cancer patients treated with irinotecan-based regimens for pharmacogenetic and drug level analysis and transporter expression. Clinical variables, toxicity, and outcomes data were collected. Results: SLCO1B1 521C was significantly associated with increased SN-38 exposure (P
- Published
- 2014