Erratum: Associations of ABCB1, ABCC2, and ABCG2 polymorphisms with irinotecan‐pharmacokinetics and clinical outcome in patients with advanced non‐small cell lung cancer

Abstract

The data listed in two parts of this article were inaccurate. The following are the results sections of the abstract and the main article, respectively.Results: Among 8 polymorphisms, 3435TT and 2677TT were associated with AUC SN-38G and CL . When haplotypes are assigned, 2677TT/3435TT carriers showed significantly lower AUC SN-38G (P ¼ .006), whereas, 2677GG/3435CC carriers showed significantly higher AUC (P ¼.039). These findings suggest that 2677TT and 3435TT variants are associated with higher efflux activity. In toxicity, the 2677G/T or A was associated with grade 4 neutropenia. The 2677GG carriers showed significantly lower absolute neutrophil count during the 1st cycle (P ¼ .012) as well as entire course of chemotherapy (P ¼ .042). The 3435TT was associated with higher frequency of grade 3 diarrhea (P ¼ .047). In tumor response, ABCC2 À24TT and 3972TT genotypes were associated with higher response rates (P ¼ .031 and P ¼ .048, respectively) and longer progression-free survival (P ¼ .010 and P ¼ .019, respectively), which was sustained in haplotype analysis.Of the 107 patients enrolled, 103 were assessable for response and 48 [36 (44%) in 80 mg/m 2 group v 12 (46%) in 65 mg/m 2 group, P ¼ 1.0\patients achieved partial responses (PR). 27 By genotypes, patients with ABCC2 À24T and 3972T genotypes showed a significantly higher tumor response rate (P ¼ .031 and P ¼ .048, respectively, Table 6). We also examined the effect of haplotypes on the tumor response to IP chemotherapy. Only patients with À24C/3972C or À24T/3972T were associated with tumor response rates. Patients with À24T/3972T were associated with higher tumor response rates than absence of this haplotype [24/38 (63%) v 24/65 (36%), P ¼ .014], whereas, those with homozygous À24C/3972C were associated with lower tumor response rates than heterozygous or absence of this haplotype [12/38 (31%) v 36/65 (55%), P ¼ .025].Likewise the association of genotypes with tumor response rates, the ABCC2 À24C>T and 3972C>T were associated with progression-free survival (PFS). Patients with À24TT or 3972TT showed significantly longer progression-free survival (P ¼ .010 and P¼.019, respectively, Fig. 2). When haplotypes were analyzed, patients with homozygous À24T/3972T showed significantly longer PFS than heterozygous or absence of this haplotype (P ¼ .036). Whereas, patients with at least one À24C/3972C showed significantly shorter PFS than those without this haplotype (P ¼ .03).The authors regret this error.

Breast Cancer Resistance Protein (ABCG2) in Clinical Pharmacokinetics and Drug Interactions: Practical Recommendations for Clinical Victim and Perpetrator Drug-Drug Interaction Study Design

“…For example, intravenous diflomotecan exhibited 3-fold higher intravenous exposure in c.421C/A (n = 5) versus c.421C/C carriers (n = 15) but no change in area under the concentration-time curve (AUC) following oral drug administration , while rosuvastatin exposure was 1.8-fold higher in a combined cohort of c.421C/A and A/A (n = 5 C/A and n = 2 A/A) versus c.421C/C carriers (n = 7) (Zhang et al, 2006) (Table 1). In contrast, no effect of the c.421C/A SNP was observed on the oral PK of the following BCRP substrates: nitrofurantoin, lamivudine, pravastatin, pitavastatin, and intravenous irinotecan (Ferrante et al, 1991;de Jong et al, 2004;Han et al, 2007;Ieiri et al, 2007;Jada et al, 2007;Adkison et al, 2008;Keskitalo et al, 2009a;Zhou et al, 2013). Lack of effect of BCRP c.421C.A on pravastatin exposure (Keskitalo et al, 2009a) stands in contrast to rosuvastatin (which has comparable low passive permeability to pravastatin) and supports the hypothesis that P-glycoprotein (P-gp) and MRP2 play more prominent roles than BCRP in pravastatin absorption.…”

Comprehensive Pharmacogenetic Analysis of Irinotecan Neutropenia and Pharmacokinetics

“…For example, it has been suggested that variation in genes encoding for SLCO1B1, ABC transporters, and other UGT1A enzymes is associated with the pharmacokinetics and pharmacodynamics of CPT-11. [12][13][14][15][16][17] In the present study, we provide the first assessment of the association between genetic variants in the vast majority of the known genes in the CPT-11 pathway and the pharmacokinetic parameters of CPT-11, SN-38, SN-38 glucuronide (SN-38G), and APC in patients previously treated with single-agent CPT-11. 6,18 We also investigated the polygenic basis of neutropenia, a common adverse effect of CPT-11.…”

Impact of ABCC2 haplotypes on transcriptional and posttranscriptional gene regulation and function

“…5 Non-small lung cancer patients exhibiting the variant allele showed a higher response to irinotecan therapy suggesting a higher bioavailability for this anti-neoplastic drug. 6 Moreover, hepatotoxicity of diclofenac and herbal remedies was associated with À24T. 7,8 In vitro assays in HepG2 cells revealed a reduced reporter gene activity for the variant construct.…”