Copyright
©2009 The WJG Press and Baishideng.
World J Gastroenterol. Oct 28, 2009; 15(40): 5058-5066
Published online Oct 28, 2009. doi: 10.3748/wjg.15.5058
Published online Oct 28, 2009. doi: 10.3748/wjg.15.5058
Table 1 Patient characteristics and UGT1A1 status (%)
| Total (n = 103) | WT (6/6) (n = 41) | (6/7) (n = 52) | (7/7) (n = 10) | |
| Age (yr) median (range) | 64 (41-79) | 63 (41-76) | 65 (42-79) | 65 (52-74) |
| Gender (M/F) | 70.5/29.5 | 70.7/29.3 | 67.3/32.7 | 80.0-20.0 |
| Colon cancer | 59.0 | 51.2 | 63.5 | 80.0 |
| Rectal cancer | 41.0 | 48.8 | 36.5 | 20.0 |
| Adjuvant pre-treatment | 35.2 | 43.9 | 30.8 | 20.0 |
| KPS 70%-90% | 43.8 | 29.3 | 51.9 | 70.0 |
| KPS 100% | 56.2 | 70.7 | 48.1 | 30.0 |
| LDH ≤ 240 U/L | 55.2 | 61.0 | 48.1 | 70.0 |
| LDH > 240 U/L | 44.8 | 39.0 | 51.9 | 30.0 |
Table 2 Genotype distribution with regard to treatment n (%)
| UGT1A1 status | FOLFIRI | IROX | All |
| WT (6/6) | 19 (34.5) | 22 (44.0) | 41 (39.0) |
| (6/7) | 28 (50.9) | 24 (48.0) | 52 (49.5) |
| (7/7) | 7 (12.7) | 3 (6.0) | 10 (9.5) |
| (5/7) | 1 (1.8) | 1 (2.0) | 2 (1.9) |
Table 3 Response to treatment with regard to UGT1A1 status n (%)
| WT (6/6) | (6/7, 7/7) | All | χ² test [WT vs (6/7, 7/7)] | |
| CR | 3 (8.1) | 7 (11.5) | 10 (10.2) | |
| PR | 13 (35.1) | 20 (32.8) | 33 (33.7) | |
| SD | 11 (29.7) | 29 (47.5) | 40 (40.8) | |
| PD | 7 (18.9) | 5 (8.2) | 12 (12.2) | |
| NA | 3 (8.1) | - | 3 (3.1) | |
| OR | 16 (43.2) | 27 (44.3) | 43 (43.9) | P > 0.05 |
| DCR | 27 (73.0) | 56 (91.8) | 83 (84.7) | P < 0.05 |
Table 4 Toxicity and UGT1A1 status according to treatment arm n (%)
| Toxicity WHO | mFOLFIRI | mIROX | χ² test | ||||||
| Grade 1 | Grade 2 | Grade 3 | Grade 4 | Grade 1 | Grade 2 | Grade 3 | Grade 4 | ||
| WT (6/6) | 2 (33.3) | 10 (33.3) | 6 (37.5) | 1 (33.3) | - | 17 (53.1) | 3 (23.1) | 2 (50.0) | P > 0.05 |
| (6/7) | 3 (50.0) | 16 (53.3) | 7 (43.8) | 2 (66.7) | 1 (100) | 14 (43.8) | 7 (53.8) | 2 (50) | P > 0.05 |
| (7/7) | 1 (16.7) | 4 (13.3) | 2 (12.5) | - | - | 1 (3.1) | 2 (15.4) | - | P > 0.05 |
| (5/7) | - | - | 1 (6.3) | - | - | - | 1 (7.7) | - | P > 0.05 |
Table 5 Haematological toxicity and UGT1A1 status (per cycle analysis) cycles (%)
| WT (6/6) | (6/7, 7/7) | χ² test | |||||
| Grade 0 | Grade 1-2 | Grade 3-4 | Grade 0 | Grade 1-2 | Grade 3-4 | ||
| Leucocytes | 69 (61.1) | 43 (38.1) | 1 (0.9) | 102 (52.8) | 85 (44.0) | 6 (3.1) | P > 0.05 |
| Neutropenic fever | 113 (100.0) | - | - | 191 (98.9) | 1 (0.5) | 1 (0.5) | P > 0.05 |
| Anaemia | 30 (26.5) | 80 (70.8) | 3 (2.7) | 47 (24.3) | 142 (73.6) | 4 (2.1) | P > 0.05 |
| Thrombocytes | 89 (78.8) | 23 (20.4) | 1 (0.9) | 157 (81.3) | 36 (18.7) | - | P > 0.05 |
Table 6 Non-haematological toxicity and UGT1A1 status (per cycle analysis) cycles (%)
| WT (6/6) | (6/7, 7/7) | χ² test | |||||
| Grade 0 | Grade 1-2 | Grade 3-4 | Grade 0 | Grade 1-2 | Grade 3-4 | ||
| Nausea | 35 (30.9) | 77 (68.1) | 1 (0.9) | 69 (35.8) | 122 (63.2) | 2 (1.0) | P > 0.05 |
| Vomiting | 77 (68.1) | 35 (31.0) | 1 (0.9) | 123 (63.7) | 69 (35.8) | 1 (0.5) | P > 0.05 |
| Diarrhoea early | 81 (71.7) | 30 (26.5) | 2 (1.8) | 149 (77.2) | 42 (21.8) | 2 (1.0) | P > 0.05 |
| Diarrhoea delayed | 51 (45.1) | 55 (48.7) | 7 (6.2) | 78 (40.4) | 90 (46.6) | 25 (13.0) | P > 0.05 |
| Mucositis | 97 (85.8) | 16 (14.2) | - | 160 (82.9) | 31 (16.1) | 2 (1.0) | P > 0.05 |
Table 7 Dose reductions, treatment delays and UGT1A1 status (per cycle analysis) n (%)
| WT (6/6) | (6/7, 7/7) | χ² test | |
| Dose reduction | 22 (19.3) | 48 (25.1) | P > 0.05 |
| Dose delayed | 31 (27.2) | 41 (21.5) | P > 0.05 |
-
Citation: Schulz C, Heinemann V, Schalhorn A, Moosmann N, Zwingers T, Boeck S, Giessen C, Stemmler HJ.
UGT1A1 gene polymorphism: Impact on toxicity and efficacy of irinotecan-based regimens in metastatic colorectal cancer. World J Gastroenterol 2009; 15(40): 5058-5066 - URL: https://www.wjgnet.com/1007-9327/full/v15/i40/5058.htm
- DOI: https://dx.doi.org/10.3748/wjg.15.5058