Details

Autor(en) / Beteiligte

• Shirasu, Hiromichi
• Yamazaki, Kentaro
• Furuta, Mitsuhiro
• Kawahira, Masahiro
• Kawakami, Takeshi
• Yoshida, Yukio
• Kawai, Sadayuki
• Hamauchi, Satoshi
• Todaka, Akiko
• Tsushima, Takahiro
• Machida, Nozomu
• Yokota, Tomoya
• Fukutomi, Akira
• Onozawa, Yusuke
• Yasui, Hirofumi

Titel

Impact of UGT1A1 gene polymorphism on survival in metastatic colorectal cancer patients treated with irinotecan-containing therapy

Ist Teil von

• Journal of clinical oncology, 2018-02, Vol.36 (4_suppl), p.813-813

Erscheinungsjahr

2018

Quelle

EZB Free E-Journals

Beschreibungen/Notizen

• Abstract only 813 Background: UGT1A1 polymorphisms have been reported to be associated with increased irinotecan (IRI)-induced toxicity. However, influence of the polymorphisms on survival in metastatic colorectal cancer (mCRC) patients (pts) treated with IRI-containing therapy remains controversial. Methods: We retrospectively reviewed data of consecutive mCRC pts who received FOLFIRI/IRI with or without an anti-VEGF agent as 2nd line therapy at the Shizuoka Cancer Center between April 2008 and December 2015. The primary selection criteria were histologically confirmed adenocarcinoma, prior history of oxaliplatin-containing therapy, and adequate organ function. UGT1A1 polymorphisms were screened and pts with homozygous (*6/*6, *28/*28) or compound heterozygous (*6/*28) were excluded. Results: Among 103 pts found eligible for this analysis, 63 were wild type (W) (−/−) for UGT1A1, and 40 were heterozygous type (H) (-/*6, -/*28), with the following characteristics: median age (range), 60 (30–77) vs 67 (37–84); male/female, 41/22 vs 18/22; PS 0/1/2, 40/21/2 vs 21/18/1; tumor location right/left, 16/47 vs 9/31; peritoneal metastasis −/+, 49/14 vs 33/7; disease status metastasis/recurrence, 49/14 vs 23/17; RAS wild type/mutant, 25/37 vs 18/21; IRI regimen doublet/mono, 51/12 vs 33/7; anti-VEGF agent use −/+, 16/47 vs 12/28; and median IRI dose intensity, 63.7 vs 60 mg/m2/week. Incidences of grade 3/4 neutropenia, febrile neutropenia, and diarrhea in W/H pts were 36%/48%, 5%/9%, 5%/13% (initial IRI dose 180 mg/m2). Median PFS was 6.2 M in W, and 3.9 M in H (p = 0.36). Median OS was 12.1 M in W and 10.9 M in H (p = 0.86). RR was 13% in W, and 10% in H (p = 0.68). DCR was 81% in W, and 58% in H (p = 0.012). Multivariate analysis identified no liver-limited disease, disease status (metastatic), UGT1A1 H type, IRI monotherapy, and no anti-VEGF as independent predictors of poorer PFS (HR 1.76, 2.01, 1.67, 2.17, 2.58), and initial dose of CPT < 180mg/m2 and no anti-VEGF as independent predictors of poorer OS (HR 1.85 and 1.85). UGT1A1 polymorphism was not detected as an independent predictor of RR or DCR. Conclusions: UGT1A1 polymorphism may be useful in predicting PFS in mCRC pts treated with IRI-containing therapy.