Table 1. Literature in support of an association of UGT1A1 variance and untoward effects with irinotecan- treated patients
Meta-analysis publish date Which Meta-analysis (or meta-analyses) included this study Individual study publish date Citation Study design Patient population Total (n) Observation arm description Comparator arm description Interventions Event(s)     Event count in observation arm  Total (n) in observation arm Percent incidence of Events in observation arm (in decimal form) Event count in comparator arm  Total (n) in comparator arm Percent incidence of Events in comparator arm (in decimal form) Total number of Events Measurement type Meaurement value Statistitical measurement type Statistitical measurement value Statistitical measurement value Statistitical measurement value  
Tuesday, March 26, 2013 Friday, June 22, 2018; Wednesday, June 13, 2012; Saturday, February 25, 2017; Monday, June 5, 2017 PMID: 23529007; 29932297;  22676194; 28367249; 28585035 Tuesday, July 13, 2010 PMID: 20628391 multicenter, prospective, randomized phase 3 study metastatic colorectal cancer patients  149 (UGT1A9*22/*1, *22/*22), UGT1A7*3/*3, *2/*3, *2/*2, *1/*3, *1/*2) UGT1A1*28/*28, UGT1A1*1/*28 FOLFIRI (biweekly irinotecan (180 mg m-2) + 5FU/LV OR FUIRI (weekly irinotecan 80 mg m-2) + 5FU/LV Neutropenia  - - 46 216 0.21 23 93 0.25 69              
      PMID: 20628391 multicenter, prospective, randomized phase 3 study metastatic colorectal cancer patients 149 (UGT1A9*22/*1, *22/*22), UGT1A7*3/*3, *2/*3, *2/*2, *1/*3, *1/*2) UGT1A1*28/*28, UGT1A1*1/*28 FOLFIRI (biweekly irinotecan (180 mg m-2) + 5FU/LV OR FUIRI (weekly irinotecan 80 mg m-2) + 5FU/LV - Diarrhea - 58 216 0.27 32 93 0.344 90              
Tuesday, March 26, 2013;
Tuesday, August 9, 2016; Friday, June 22, 2018; Sunday, August 1, 2010; Wednesday, January 22, 2014; Wednesday, March 24, 2010; Saturday, February 25, 2017; Tuesday, August 5, 2008		 PMID: 23529007; 27503581;  29932297; 20562211; 24448639; 20335017; 28367249; 18681783 Thursday, May 17, 2007 PMID: 17510208 randomized, phase 3 trial metastatic colorectal cancer patients 184 UGT1A1*1 UGT1A1 -3156G>A polymorphism LV5FU2 (leucovorin 200 mg/m2 as a 2-h infusion, 5FU 400 mg/m2 bolus and 600 mg/m2 22 h continuous infusion) to LV5FU2 + CPT-11 (LV5FU2  + irinotecan 180 mg/m2 90 min infusion) every 2 weeks for 12 cycles Neutropenia (grade 3+) - - 4 79 0.05 4 83 0.048 8              
Tuesday, March 26, 2013;
Tuesday, August 9, 2016; Friday, June 22, 2018; Monday, November 16, 2020; Wednesday, June 13, 2012; Wednesday, February 12, 2014		 PMID: 23529007; 27503581;  29932297; 24709690; 22676194; 24519753 Tuesday, February 23, 2010 PMID: 20177420 multicenter, randomized, controlled trial metastatic colorectal cancer patients  140 UGT1A1*1 UGT1A1*28/*28, UGT1A1*1/*28 no prior chemotherapy other than adjuvant 5FU based chemotherapy completed at least 6 months before the study. FLIRI (irinotecan 180 mg-2 as 60 min infusion day 1, 5FU 500 mg m-2 as bolus, FA 60 mg m-2 bolus) or LV5FU2-IRI (irinotecan 180 mg m-2 infusion, 5FU bolus 400 mg m-2 and FA 200 mg m-2 2 hr infusion, and 22 hr infusion of 5FU 600 mg m-2) Neutropenia (grade 3-4) Diarrhea (grade 3-4) - 15 72 0.21 20 64 0.3125 35 no separation between the data in diarrhea and neutropenia toxicities, study grouped those together            
Friday, June 22, 2018; Wednesday, January 22, 2014; Friday, December 6, 2013; Wednesday, February 12, 2014; Saturday, Febraury 25, 2017; Monday, June 5, 2017 PMID: 29932297; 24448639; 24308720; 24519753; 28367249; 28585035 Friday, April 24, 2009 PMID: 19390945 prospective, randomized, controlled trial Japanese cancer patients  135 SLCO1B1*1b, *5, and haplotype *15 UGT1A1*6, *28, *60 Irinotecan alone, irinotecan + platinum, irinotecan + other anticancer agents, FOLFIRI Neutropenia (grade 3-4) - - 0 41 0 1 62 0.02 1              
Tuesday, March 26, 2013; Friday, June 22, 2018; Monday, November 16, 2020; Wednesday, February 12, 2014 PMID: 23529007; 29932297; 24709690; 24519753   Wednesday, October 28, 2009 PMID: 19859999 multicenter, randomized, controlled trial metastatic colorectal cancer patients  105 UGT1A1*6/*6 (wildtype) UGT1A1*6/*7, UGT1A1 *7/*7 FOLFIRI (irinotecan 80 mg/m2 iv over 30 mins, folinic acid 500 mg/m2 iv over 120 mins followed by 5FU 2000 mg/m2 iv over 24 hr weekly x6weeks) or modified IROX (oxaliplatin 85 mg/m2 iv over 120 min every 2 weeks and irinotecan 80 mg/m2 iv over 30 min weekly) Neutropenic fever (grade 3-4) - - 12 41 0.29 22 62 0.35 34              
      PMID: 19859999 multicenter, randomized, controlled trial metastatic colorectal cancer 105 UGT1A1*6/*6 (wildtype) UGT1A1*6/*7, UGT1A1 *7/*7 FOLFIRI (irinotecan 80 mg/m2 iv over 30 mins, folinic acid 500 mg/m2 iv over 120 mins followed by 5FU 2000 mg/m2 iv over 24 hr weekly x6weeks) or modified IROX (oxaliplatin 85 mg/m2 iv over 120 min every 2 weeks and irinotecan 80 mg/m2 iv over 30 min weekly) - Diarrhea (grade 3-4) - 9 41 0.22 27 62 0.44 36              
Tuesday, March 26, 2013;
Tuesday, August 9, 2016; Friday, June 22, 2018; Sunday, August 1, 2010; Monday, November 16, 2020; Wednesday, September, 5, 2007; Wednesday, January 22, 2014; Wednesday, March 24, 2010; Saturday, February 25, 2017; Tuesday, August 5, 2008		 PMID: 23529007; 27503581; 20562211; 24709690; 17728214; 24448639; 20335017; 28367249; 18681783 Monday, August 16, 2004 PMID: 15280927 Cohort metastatic colorectal cancer patients 95 UGT1A1*28 - *6/*6 UGT1A1*28 - *6/*7 and *7/*7 regimen A: irinotecan alone (350 mg m2 infused in 45 min iv q3weeks), regimen B: irinotecan + tomudex (3 mg m2 infused in 15 min iv), regimen C: irinotecan (80 mg m2 infused in 45 min iv every week) with a dose of 2250 mg m2 of 5FU in every cycle, and regimen D: irinotecan (180 mg m2 every 2 weeks iv) and 5FU + leucovorin iv. Neutropenia (grade 3-4) - - 6 40 0.15 16 55 0.3 22 This study grouped heamatological toxicities together as (g3-4 neutropenia, anaemia, and thrombocytopenia)           28 patients experienced more than 2 severe adverse effects at the same time.
      PMID: 15280927 Cohort metastatic colorectal cancer 95 UGT1A1*28 - *6/*6 UGT1A1*28 - *6/*7 and *7/*7 regimen A: irinotecan alone (350 mg m2 infused in 45 min iv q3weeks), regimen B: irinotecan + tomudex (3 mg m2 infused in 15 min iv), regimen C: irinotecan (80 mg m2 infused in 45 min iv every week) with a dose of 2250 mg m2 of 5FU in every cycle, and regimen D: irinotecan (180 mg m2 every 2 weeks iv) and 5FU + leucovorin iv. - Diarrhea (grade 3-4) - 7 40 0.175 22 55 0.4 29              
Tuesday, March 26, 2013; Friday, June 22, 2018; Wednesday, September 5, 2007; Wednesday, March 24, 2010; Saturday, February 25, 2017; Tuesday, August 5, 2008 PMID: 23529007; 29932297;  17728214; 20335017; 28367249; 18681783 Sunday, August 1, 2004 PMID: 15297419 Retrospective Cohort metastatic colorectal cancer patients 75 UGT1A1*6/*6  UGT1A1*6/*7, UGT1A1 *7/*7 IRIFUFOL regimen: irinotecan (85 mg/m2), 90 min weekly infusion + 5FU (1200 mg/m2) 7 hr weekly infusions and 100 mg/m2 bolus of L-folinic acid (28 patients). FOLFIRI regimen: 180 mg/m2 irinotecan biweekly infusion over 90 min + 2500 mg/m2 5FU, 46 hr continuous infusion and 400 mg/m2 bolus L-folinic acid (47 patients) Neutropenia (grade 3-4) - - 3 31 0.097 19 42 0.45 22              
                    - Diarrhea - 1 31 0.032 4 42 0.095 5              
Tuesday, August 9, 2016; Wednesday, January 22, 2014; Wednesday, March 24, 2010; Saturday, February 25, 2017 PMID: 27503581; 24448639; 20335017; 28367249 Tuesday, September 16, 2008 PMID: 18797458 clinical trial metastatic colorectal cancer patients 49 UGT1A1*28 wildtype UGT1A1*28 heterozygous and homozygous FOLFIRI regimen: folinic acid 400 mg m-2 as a 2 hr IV infusion; 5FU 400 mg m-2 IV bolus, then 2400 mg m-2 as IV infusion over 46 hrs and irinotecan 180 mg m-2 as a 1.5 hr infusion q 2 weeks Neutropenia - - 3 23 0.13 9 21 0.43 12              
                    - Diarrhea - 4 23 0.17 4 21 0.19 8              
Tuesday, March 26, 2013; Friday, June 22, 2018; Monday, November 16, 2020; Wednesday, June 13, 2012; Saturday, February 25, 2017 PMID: 2359007; 29932297; 24709690; 22676194; 28367249 Saturday, July 10, 2010 PMID: 20530282 clinical trial metastatic colorectal cancer patients 520 UGT1A1*28 (6/6) UGT1A1*28 (6/7, 7/7) IFL (Fluorouracil + Irinotecan), FOLFOX (FU + oxaliplatin) and IROX (IRN + oxaliplatin) Neutropenia (grade >=4) - - 34 230 0.15 57 267 0.21 91              
                    - Diarrhea (grade >=3) - 43 230 0.19 50 267 0.19 93              
  not included in any Thursday, October 29, 2020 PMID: 33119477 Multicenter, randomized, open-label prospective, phase III Clinical Trial advanced rectal cancer 356 UGT1A1*1/*1 UGT1A1*1/*28 pelvic radiation of 50 Gy/25 fractions with concurrent capecitabine, followed by oxaliplatin and capecitabine; or radiation with capecitabine combined with weekly irinotecan 80 mg/m2 for patients with UGT1A1*1/*1 or 65 mg/m2 for patients with UGT1A1*1/*28 followed by irinotecan and capecitabine.  Neutropenia (grade 3-4)     - 266 - - 90 - 38              
                    - Diarrhea (grade 3-4) - - 266 - - 90 - 27              
  not included in any Wednesday, January 5, 2022 PMID: 34998046 prospective, multicenter, non-randomized study pathological malignancy  350 UGT1A1 poor metabolizers (homozygous for UGT1A1*28/*28 and *93/*93) UGT1A1 non-poor metabolizers (heterozygous for UGT1A1*28 and/or UGT1A1*93 and UGT1A1 wild type) irinotecan >=180 mg/m2 or 450-600 mg dose. PMs were given 30% dose reduction. Neutropenia (grade 3-4) - - 16 31 0.52 81 319 0.25 97              
                    - Diarrhea (grade >=3) - 3 31 0.097 51 319 0.16 54              
  not included in any Thursday, September 26, 2019 PMID: 31558477 Multicenter prospective advanced gastrointestinal cancers 50 UGT1A1*1/*1 UGT1A1*1/*28, UGT1A1*28/*28 FOLFIRABRAX + prophylactic pegfilgrastim q14d. UGT1A1 *1/*1, *1/*28, *28/*28 Irinotecan doses of 180, 135, and 90 mg/m2 respectively. Febrile neutropenia (grade 3) - - 1 23 0.04 0 26 0 1              
                    - Diarrhea (grade 3) - 3 23 0.13 0 26 0 3              
  not included in any Monday, April 12, 2021 PMID: 33728696 prospective , observational cohort small lung cancer 213 UGT1A1*28 homozygous wild, UGT1A1*6 homozygous wild UGT1A1*28 homo/heterozygous mutant, UGT1A1*6 homo/heterozygous mutant  irinotecan 100 mg/m2 + cisplatin 60 mg/m2 each on day 1 of a 3 week cycle. An alternate regimen was irinotecan 65 mg.m2 + cisplatin 30 mg/m2 each on days 1 and 8 of a 3 week cycle. Neutropenia (grade >= 3) - - 19 141 0.135 13 72 0.18 32              
                    - Diarrhea (grade >=3) - 23 141 0.16 22 72 0.31 45              
  not included in any Wednesday, January 2, 2019 PMID: 30603911 retrospective analysis advanced gastric cancer 74 UGT1A1*28/UGT1A1*6 (WT) UGT1A1*6 G/G and *28 6/7, or *6 G/A and *28 6/6 SH (single heterozygous), homozygous/double heterozygosity with *6 A/A and *28 6/6 (homo for *6), *6 G/G and *28 7/7 (homo for *28) or UGT1A1*6 G/A and *28 6/7 (DH) third line chemotherapy with irinotecan 150 mg/m2 q2weeks Neutropenia (grade 3) - - 5 37 0.14 9 37 0.24 14              
                    - Diarrhea (grade 3) - 3 37 0.08 2 37 0.05 5              
  not included in any Friday, July 24, 2020 PMID: 32666389 restrospectively reviewed clinical data advanced gastric cancer 100 UGT1A1 WT UGT1A1 SH (*6 for sure, possibly *28) irinotecan 150 mg/m2 within 120 mins q2weeks Neutropenia (grade >=3) - - 9 62 0.15 12 38 0.32 21              
                    - Diarrhea (grade >=3) - 2 62 0.03 1 38 0.03 3              
  not included in any Thursday, August 20, 2020 PMID: 32829105 randomized, controlled trial metastatic colorectal cancer patients 107 UGT1A1*6/*6 UGT1A1*6/*7, UGT1A1*7/*7 Biweekly FOLFIRI + bevacizumab Neutropenia (grade 3-4) - - - 82 - - 25 - 8              
                    - Diarrhea (grade 3-4) - - 82 - - 25 - 4              
  not included in any Wednesday, August 5, 2020 PMID: 32758288 Retrospective study cervical cancer 51 UGT1A1 WT (*1/*1) UGT1A1 HT/HZ (*1/*6, *1/*28, *6/*6, *28/*28) Irinotecan as neoadjuvant and/or adjuvant treatment Neutropenia (grade 3-4) - - 7 24 0.29 15 27 0.55 22              
                    - Diarrhea (grade > 3) - 4 24 0.166 3 27 0.11 7              
  not included in any Monday, October 22, 2018 PMID: 30246377 clinical trial locally advanced lower rectal cancer 46 UGT1A1*1/*1 (WT) UGT1A1 Heterozygous (*28/*1, *6/*1) and homozygous (*28/*28, *6/*6, *28/*28), double heterozygous (*28/*6) 80 mg/m2 per day tegafur/gimeracil/oteracil (S‐1; days 1‐5, 8‐12, 22‐26, and 29‐33), 60 mg/m2 per day irinotecan (days 1, 8, 22, and 29), and 45 Gy radiation (1.8 Gy/day, 5 days per week for 5 weeks). Neutropenia (grade 3-4) - - 0 26 0 8 20 0.4 8              
                    - Diarrhea (grade 3-4) - 9 26 0.35 6 20 0.3 15              
Wednesday, February 12, 2014; Saturday, February 25, 2017; Wednesday, September 5, 2007; Wednesday, March 24, 2010; Wednesday, July 28, 2010; Tuesday, April 04, 2014; Friday, June 22, 2018 PMID: 24519753; 28367249; 17728214; 20335017; 20562211; 24709690; 29932297 Wednesday, April 14, 2004 PMID: 15007088 clinical trial histologically confirmed solid tumor or lymphoma 66 UGT1A1 6/6 UGT1A1 6/7, 7/7 Irinotecan 350 mg/m2 q3weeks  Neutropenia (grade 3-4) - - 0 29 0 6 31 0.19 6              
Saturday, February 25, 2017; Tuesday, August 5, 2008; Wednesday, September 5, 2007; Wednesday, March 24, 2010; Wednesday, July 28, 2010; Thursday, June 7, 2012; Tuesday, March 26, 2013; Wednesday, January 22, 2014; Tuesday, April 4, 2014; Tuesday, August 9, 2016; Friday, June 22, 2018 PMID: 28367249; 18681783; 17728214; 20335017; 20562211; 22676194; 23529007; 24448639; 24709690; 27503581; 29932297 Saturday, July 1, 2006 PMID: 16809730 prospective interinstitutional study metastatic colorectal cancer 250 UGT1A1 WT (TA6/TA6) UGT1A1*28 (TA7/TA7, TA6/TA7) modified FOLFIRI regimen (irinotecan 180 mg/m2, + FU 400 mg/m2 bolus dollowed by FU 600 mg/m2 continuous infusion + LV 200 mg/m2) Neutropenia (grade 3-4) - - 11 114 0.096 24 136 0.18 35              
                    - Diarrhea (grade 3) - 6 114 0.05 15 136 0.11 21              
Saturday, February 25, 2017; Tuesday, March 26, 2013; Tuesday, August 9, 2016; Friday, June 22, 2018 PMID: 28367249; 23529007; 27503581; 29932297 Thursday, April 26, 2012 PMID: 22535333 retrospective chart review metastatic colorectal cancer 101 UGT1A1*1/*1,  *1/*28, *28/*28 UGT1A1 (*60, *93) 5FU/Irinotecan based chemotherapy (Irinotecan 180 mg/m2) q2weeks, (Irinotecan (180 mg/m2) IV 2h infusion concurrent with leucovorin (200 mg/m2) followed by 5-FU (400 mg/m2) IV bolus followed by 5FU (2400 mg/m2) as a continuous 46 h infusion q 2weeks.) Neutropenia (grade 3-4) - - 18 59 0.31 38 42 0.9 56              
                    - Diarrhea (grade 3-4) - 12 59 0.2 24 42 0.57 36              
Wednesday, February 12, 2014; Saturday, February 25, 2017; Tuesday, March 26, 2013; Tuesday, April 4, 2014; Friday, June 22, 2018 PMID: 24519753; 28367249; 23529007; 24709690; 29932297 Tuesday, February 1, 2011 PMID: 21287524 population based case-control study metastatic colorectal cancer 214 UGT1A1*28 (*6/*6) UGT1A1*28 (*6/*7, *7/*7) FOLFIRI, IFL, TEGAFIRI, XELIRI Neutropenia (grade 3-4) - - 5 91 0.05 14 123 0.11 19              
                    - Diarrhea (grade 3-4) - 25 91 0.27 23 123 0.19 48              
Tuesday, March 26, 2013 PMID: 23529007 Wednesday, February 9, 2011 PMID: 21310730 controlled trial advanced colorectal cancer 87 UGT1A1*1/*1, *1/*28 or *1/*6 UGT1A1*28/*28, *6/*6, *28/*6, or *28/*27 : FOLFOX ( 2-h intravenous infusion of oxaliplatin (85 mg/m2) and LV (200 mg/m2), followed by an intravenous bolus injection of 5-FU (400 mg/m2) and a 46-h intravenous infusion of 5-FU (2400 mg/m2), repeated every 2 weeks.) OR FOLFIRI (2-h intravenous infusion of irinotecan (150 or 180 mg/m2) and LV (200 mg/m2) on Day 1, followed by an intravenous bolus injection of 5-FU (400 mg/m2) and a 46-h intravenous infusion of 5-FU (2400 mg/m2), repeated every 2 weeks.) Neutropenia (grade 3-4) - - 29 81 0.36 0 6 0 29              
                    - Diarrhea (grade 3-4) - 2 81 0.025 0 6 0 2              
Saturday, February 25, 2017; Wednesday, March 24, 2010; Tuesday, March 26, 2013 PMID: 28367249; 20335017; 23529007 Friday, September 8, 2006 PMID: 16951398 multicenter, double-blind, randomized, placebo-controlled trial metastatic colorectal cancer 62 UGT1A1 TA 6/TA6 UGT1A1 TA7/TA6, TA7/TA7 (*28/*28) Irinotecan (350 mg/m2 once every 3 weeks) combined with neomycin (660 mg three times daily for 3 consecutive days, starting 2 days before chemotherapy) or combined with placebo Neutropenia (grade 3-4) - - 6 26 0.23 6 26 0.23 12              
                    - Diarrhea (grade 2-3) - 9 26 0.35 9 26 0.35 18              
Wednesday, February 12, 2014; Saturday, February 25, 2017; Wednesday, March 24, 2010; Thursday, June 7, 2012; Tuesday, March 26, 2013; Tuesday, April 4, 2014 PMID: 24519753; 28367249; 20335017; 22676194; 23529007; 24709690 Monday, April 21, 2008 PMID: 18300238 retrospective metastatic colorectal cancer 128 UGT1A1 TA6/TA6 (WT) UGT1A1 polymorphism (TA6/TA7 or TA7/TA7) Irinotecan + 5-FU/Leucovorin Neutropenia (grade 3-4) - - 5 102 0.05 14 26 0.54 19              
                    - Diarrhea (grade 3-4) - 6 102 0.06 7 26 0.27 13              
Friday, June 22, 2018 PMID: 29932297 Sunday, December 6, 2015 PMID: 26494856 open-label, non-randomized, phase II trial metastatic colorectal cancer 86 UGT1A1*1/*1 UGT1A1*1/*28 bevacizumab 5 mg/kg D1, irinotecan 260 mg/m2 D1, LV 400 mg/m2 D1, 5FU 400 mg/m2 IV bolus D1, and 5FU 2,400 mg/m2 46-hour infusion D1-2 every 2 weeks. Neutropenia (grade 3-4) - - 10 40 0.25 14 46 0.3 24              
                    - Diarrhea (grade 3-4) - 7 40 0.175 4 46 0.09 11              
Wednesday, October 21, 2020; Saturday, February 25, 2017; Monday, June 5, 2017; Friday, June 22, 2018 PMID: 32936306; 28367249; 28585035; 29932297 Tuesday, May 24, 2016 PMID: 27220761 retrospective analysis advanced colorectal cancer 183 UGT1A1*6 UGT1A1*28 (*1/*1, *1/*28, *28/*28) FOLFIRI: first day, intravenous (iv) injection with irinotecan 150 mg/m2; first and second day, iv injection with tetrahydrofolic acid (THFC) 200 mg/m2 and 5-FU 400 mg/m2, and afterward with a continuous infusion pump with 5-FU 1200 mg/m2 for 44 h; repeated every 2 weeks, four cycles of treatment. Combination of irinotecan and capecitabine: first day, iv drip with irinotecan 150 mg/m2 for 90 min; second to the fifteenth day, iv drip with capecitabine 1000 mg/m2 (twice a day); repeated every 3 weeks. Neutropenia (grade 3-4) - - 14 114 0.12 14 114 0.12 28              
                    - Diarrhea (grade 3-4) - 27 114 0.24 27 114 0.24 54              
Friday, December 6, 2013; Wednesday, February 12, 2014; Saturday, February 25, 2017; Monday, June 5, 2017; Wednesday, March 24, 2010; Thursday, June 7, 2012; Wednesday, January 22, 2014; Tuesday, April 4, 2014; Friday, June 22, 2018 PMID: 24308720; 24519753; 28367249; 28585035; 20335017; 22676194; 24448639; 24709690; 29932297 Monday, April 24, 2006 PMID: 16636344 phase II study NSCLC 81 UGT1A1*6/*6, UGT1A7*3/*3 UGT1A9-118 irinotecan 80 mg/m2 + cisplatin 60 mg/m2 Neutropenia (grade 4) - - 10 12 0.83 5 21 0.24 15              
                    - Diarrhea (grade 3) - 4 12 0.33 5 21 0.24 9              
Friday, December 6, 2013; Wednesday, February 12, 2014; Saturday, February 25, 2017; Monday, June 5, 2017; Wednesday, January 22, 2014; Tuesday, August 9, 2016; Friday, June 22, 2018 PMID: 24308720; 24519753; 28367249; 28585035; 24448639; 27503581; 29932297 Friday, December 7, 2012 PMID: 23236239 clinical trial  metastatic colorectal cancer 138 UGT1A1*6 (G/G, G/A, A/A) UGT1A1*28 (TA 6/6, TA 6/7, TA 7/7) FOLFIRI AND IFL, FOLFIRI: irinotecan 180 mg/m2 90-min i.v. infusion on day 1; leucovorin 200 mg/m2 i.v. infusion on days 1 and 2; followed on days 1 and 2 by 5-FU 400 mg/m2 i.v. bolus, then 600 mg/m2 i.v. over 22 h continuous infusion; repeated every 2 wk; (2) IFL: irinotecan 125 mg/m2 as a 90-min i.v. infusion on days 1, 8, 15 and 22; leucovorin 20 mg/m2 i.v. infusion on days 1, 8, 15 and 22; 5-FU 500 mg/m2 i.v. bolus on days 1, 8, 15 and 22; every 6 wk. Neutropenia (grade 3-4) - - 38 130 0.29 38 130 0.29 76              
                    - Diarrhea (grade 3-4) - 23 130 0.178 23 130 0.178 46              
Saturday, February 25, 2017; Wednesday, September 5, 2007; Wednesday, March 24, 2010; Wednesday, July 28, 2010 PMID: 28367249; 17728214; 20335017; 20562211 Thursday, March 14, 2002 PMID: 11990381 phase I clinical trial solid tumors  20 *6/*6 *6/*7, *7/*7 Irinotecan 300 mg/m2 q3weeks Neutropenia (grade 3-4) - - 0 9 0 3 11 0.27 3              
                    - Diarrhea (grade 3-4) - 0 9 0 2 11 0.2 2              
Friday, December 6, 2013; Wednesday, February 12, 2014; Monday, June 5, 2017; Wednesday, January 22, 2014; Tuesday, August 9, 2016; Friday, June 22, 2018 PMID: 24308720; 24519753; 28585035; 24448639; 27503581; 29932297 Saturday, July 9, 2011 PMID: 21740478 clinical trial  metastatic gastronitestinal cancer 82 UGT1A1*1/*1 UGT1A1*28/*1, *6/*1, *28/*28, *6/*6, *28/*6 Irinotecan 150 mg/m2 Neutropenia (grade 3-4) - - 9 41 0.22 17 41 0.4 26              
                    - Diarrhea (grade 3-4) - 0 41 0 1 41 0.02 1              
Wednesday, February 12 2014; Wednesday, September 5, 2007; Wednesday, July 28, 2010; Wednesday, January 22, 2014 PMID: 24519753; 17728214; 20562211; 24448639 Friday, December 15, 2000 PMID: 11156391 case control study cancer patients 118 UGT1A1*6  UGT1A1*28   irinotecan containing chemotherapy Neutropenia (grade 3-4) - - - - - - - - -              
                    - Diarrhea (grade 3-4) - 26 118 0.22 26 118 0.22 52              
Saturday, February 25, 2017; Wednesday, March 24, 2010; Wednesday, July 28, 2010; Thursday, June 7, 2012; Tuesday, March 26, 2013; Tuesday, April 4, 2014; Friday, June 22, 2018 PMID: 28367249; 20335017; 20562211; 22676194; 23529007; 24709690; 29932297 Tuesday, July 1, 2008 PMID: 18594531 multicenter, phase III trial  metastatic colorectal cancer 218 UGT1A1*28 TA6/TA6 UGT1A1*28 TA6/TA7, TA7/TA7 genotype IRI OR CAPIRI regimen A: first-line capecitabine (1250 mg m−2 day−1 b.i.d. on days 1–14, every 3 weeks), second-line IRI (350 mg m−2 day−1 on day 1, every 3 weeks) and third-line capecitabine plus oxaliplatin. Regimen B: first-line capecitabine (1000 mg m−2 day−1 b.i.d. on days 1–14, every 3 weeks) plus IRI (250 mg −2 day−1 on day 1, every 3 weeks: capecitabine plus IRI (CAPIRI), followed by second-line capecitabine plus oxaliplatin. Neutropenia (grade 3-4) - - 2 105 0.02 12 99 0.12 14              
                    - Diarrhea (grade 3-4) - 21 105 0.2 27 99 0.27 48              
Friday, December 6, 2013; Wednesday, October 21, 2020; Wednesday, February 12, 2014; Saturday, February 25, 2017; Tuesday, March 26, 2013; Wednesday, January 22, 2014; Friday, June 22, 2018 PMID: 24308720; 32936306; 24519753; 28367249; 28585035; 23529007; 24448639; 29932297 Monday, February 7, 2011 PMID: 21303789 prospective phase II study metastatic colorectal cancer 52 UGT1A1*6 UGT1A1*28 FOLFIRI (irinotecan 150 mg/m2) Neutropenia (grade 3-4) - - 17 39 0.44 17 39 0.44 34              
Saturday, February 25, 2017; Wednesday, March 24, 2010; Wednesday, January 22, 2014; Friday, June 22, 2018 PMID: 28367249; 20335017; 24448639; 29932297 Wednesday, July 11, 2007 PMID: 17627617 clinical trial  asian cancer patients  45 UGT1A1*6 UGT1A1*28 irinotecan 375 mg/m2 q3weeks  Neutropenia (grade 3-4) - - 16 45 0.36 - - - 16              
                    - Diarrhea (grade 3-4) - 6 45 0.13 - - - 6                
Friday, December 6, 2013; Wednesday, February 12, 2014; Monday, June 5, 2017; Tuesday, March 26, 2013; Wednesday, January 22, 2014 PMID: 24308720; 24519753; 28585035; 23529007; 24448639 Tuesday, October 19, 2010 PMID: 20957480 retrospective study advanced colorectal cancer 42 UGT1A1*1/*1 UGT1A1*1/*6, *1/*28 Irinotecan 180 mg/m2 + 5-FU 400 mg/m2 bolus, 46 hr infusion of 2400 mg/m2 + Leucovorin 200 mg/m2 q2weeks (FOLFIRI) Neutropenia (grade 3-4) - - 8 24 0.33 6 18 0.33 14              
                    - Diarrhea (grade 3-4) - 0 24 0 1 18 0.05 1              
  not included in any Monday, February 28, 2022 PMID: 35267552 Retrospective pancreatic cancer 154 UGT1A1*1/*28, UGT1A1*1/*6 UGT1A1*28/*28, UGT1A1*6/*6, UGT1A1*6/*28 FOLFIRINOX, oxaliplatin (85 mg/m2) as a 2-h intravenous infusion (IVF), followed by leucovorin (400 mg/m2) administered as a 2-h IVF, and after 30 min, the addition of irinotecan (180 mg/m2) given as 90-min IVF, immediately followed by a 5-FU 400 mg/m2 bolus and 2400 mg/m2 IVF for 46 h, every 2 weeks. Neutropenia (grade 3-4) - - 42 66 0.64 14 17 0.82 59              
                    - Diarrhea (grade 3-4) - 5 66 0.076 1 17 0.06 6              

 

MetaCensus: a blockchain meta-analysis network to improve scientific consensus and clinical decision support in pharmacogenomics