Introduction
Patients and methods
Enrollment and assignment
Randomization and masking
Protocol treatment
Data collection
Statistical analysis
Results
Patient characteristics
6M group (n = 642) | 12M group (n = 636) | |||
---|---|---|---|---|
n
| (%) |
n
| (%) | |
Age | ||||
Median [range] | 65 [23–79] | 65 [34–79] | ||
Gender | ||||
Male | 347 | (54.0%) | 339 | (53.3%) |
Female | 295 | (46.0%) | 297 | (46.7%) |
ECOG performance status | ||||
0 | 611 | (95.2%) | 617 | (97.0%) |
1 | 31 | (4.8%) | 19 | (3.0%) |
Creatinine clearance (mL/min) | ||||
Median [range] | 76.6 [35.1–350.4] | 78.1 [39.2–176.3] | ||
Body surface area (m2) | ||||
Median [range] | 1.59 [1.06–2.42] | 1.56 [1.10–2.14] | ||
<1.33 (dose 3000 mg/body/day) | 41 | (6.4%) | 48 | (7.5%) |
≥1.33 to <1.57 (dose 3600 mg/body/day) | 262 | (40.8%) | 272 | (42.8%) |
≥1.57 to <1.81 (dose 4200 mg/body/day) | 274 | (42.7%) | 261 | (41.0%) |
≥1.81 (dose 4800 mg/body/day) | 65 | (10.1%) | 55 | (8.6%) |
Tumor location | ||||
Right-sided colon (C, A, T) | 261 | (40.6%) | 258 | (40.6%) |
Left-sided colon (D, S) | 247 | (38.5%) | 247 | (38.8%) |
Rectosigmoid colon | 134 | (20.9%) | 131 | (20.6%) |
Depth of tumor invasion (TNM 7th) | ||||
T1 | 44 | (6.9%) | 45 | (7.1%) |
T2 | 54 | (8.4%) | 52 | (8.2%) |
T3 | 360 | (56.1%) | 355 | (55.8%) |
T4 | 184 | (28.7%) | 184 | (28.9%) |
LN metastasis (JSCCR classificationa) | ||||
N1 | 491 | (76.5%) | 486 | (76.4%) |
N2 | 120 | (18.7%) | 121 | (19.0%) |
N3 | 31 | (4.8%) | 29 | (4.6%) |
Stage (TNM 7th) | ||||
IIIA | 91 | (14.2%) | 93 | (14.6%) |
IIIB | 455 | (70.9%) | 450 | (70.8%) |
IIIC | 96 | (15.0%) | 93 | (14.6%) |
Scope of LN dissection (JSCCR classificationa) | ||||
D2 | 129 | (20.1%) | 133 | (20.9%) |
D3 | 513 | (79.9%) | 503 | (79.1%) |
Surgical approach | ||||
Open (conventional) | 371 | (57.8%) | 388 | (61.0%) |
Laparoscopic | 271 | (42.2%) | 248 | (39.0%) |
Treatment duration
6M group (n = 642) | 12M group (n = 636) | |||
---|---|---|---|---|
n
| (%) |
n
| (%) | |
No. of patients discontinued | ||||
During cycle 1 | 23 | (3.6%) | 25 | (3.9%) |
During cycle 2 | 21 | (3.3%) | 32 | (5.0%) |
During cycle 3 | 37 | (5.8%) | 33 | (5.2%) |
During cycle 4 | 21 | (3.3%) | 26 | (4.1%) |
During cycle 5 | 23 | (3.6%) | 20 | (3.1%) |
During cycle 6 | 21 | (3.3%) | 13 | (2.0%) |
During cycle 7 | 23 | (3.6%) | 28 | (4.4%) |
During cycle 8 | 14 | (2.2%) | 42 | (6.6%) |
During cycle 9 | – | – | 19 | (3.0%) |
During cycle 10 | – | – | 15 | (2.4%) |
During cycle 11 | – | – | 16 | (2.5%) |
During cycle 12 | – | – | 10 | (1.6%) |
During cycle 13 | – | – | 14 | (2.2%) |
During cycle 14 | – | – | 14 | (2.2%) |
During cycle 15 | – | – | 25 | (3.9%) |
During cycle 16 | – | – | 11 | (1.7%) |
No. of patients completed 8 cycles of capecitabine | 459 | (71.5%) | 456 | (71.7%) |
No. of patients completed 16 cycles of capecitabine | – | – | 293 | (46.1%) |
Reasons for treatment discontinuation
6M group (n = 642) | 12M group (n = 636) | |||||
---|---|---|---|---|---|---|
n
| (%) | During cycles 1–8 | During cycles 9–16 | |||
n
| (%) |
n
| (%) | |||
No. of patients with discontinuation | 183 | (100%) | 219 | (100%) | 124 | (100%) |
Reasons for discontinuation
| ||||||
Oncologic events | ||||||
Recurrences | 17 | (9.3%) | 12 | (5.5%) | 12 | (9.7%) |
Second cancers | 3 | (1.6%) | 2 | (0.9%) | 1 | (0.8%) |
Adverse events (AEs) | ||||||
AEs (listed on the discontinuation criteria) or physician’s judgement | 92 | (50.3%) | 116 | (53.0%) | 43 | (34.7%) |
Patient’s request due to AEs not mentioned in the discontinuation criteria | 27 | (14.8%) | 38 | (17.4%) | 19 | (15.3%) |
Others | ||||||
Aggravation of comorbidities | 5 | (2.7%) | 9 | (4.1%) | 8 | (6.5%) |
Patient’s request due to non-medical reasons | 16 | (8.7%) | 35 | (16.0%) | 20 | (16.1%) |
Others | 23 | (12.6%) | 7 | (3.2%) | 21 | (16.9%) |
6M group (n = 642) | 12M group (n = 636) | |||
---|---|---|---|---|
During cycles 1–8 | During cycles 9–16 | |||
Discontinuation due to AEs | 119 patients 123 AEs (100%) | 154 patients 160 AEs (100%) | 62 patients 65 AEs (100%) | |
AEs (listed on the discontinuation criteria) or physician’s judgement | Hematologic toxicities | 18 (14.6%) | 25 (15.6%) | 9 (13.8%) |
Abnormal liver function | 18 (14.6%) | 22 (15.8%) | 8 (12.3%) | |
Hand-foot syndrome | 38 (30.9%) | 60 (37.5%) | 19 (29.2%) | |
Non-hematologic toxicitiesa
| 18 (14.6%) | 11 (6.9%) | 7 (10.8%) | |
Patient’s request due to AEs not mentioned in the discontinuation criteria | Hematologic toxicities | 2 (1.6%) | 2 (1.3%) | 1 (1.5%) |
Abnormal liver function | 0 (0%) | 0 (0%) | 0 (0%) | |
Hand-foot syndrome | 11 (8.9%) | 21 (13.1%) | 10 (15.4%) | |
Non-hematologic toxicities* | 18 (14.6%) | 18 (11.3%) | 9 (13.8%) | |
Unknown | 0 (0%) | 1 (0.6%) | 2 (3.1%) |
Dose modification
Dose reduction | 6M group (n = 642) | 12M group (n = 636) | ||
---|---|---|---|---|
Overall (n = 636) | During cycles 1–8 (n = 636) | During cycles 9–16 (n = 417) | ||
n (%) |
n (%) |
n (%) |
n (%) | |
(−) | 401 (62.5%) | 330 (51.9%) | 379 (59.6%) | 308 (73.9%) |
(+) | 241 (37.5%) | 306 (48.1%) | 257 (40.4%) | 109 (26.1%) |
Safety profile (6M group vs 12M group)
6M group (n = 642) | 12M group (n = 636) | Any grade, p valuea
| |||
---|---|---|---|---|---|
Any grade (%) | Grade ≥3 (%) | Any grade (%) | Grade ≥3 (%) | ||
Hemoglobin | 36.0 | 0.3 | 40.6 | 0.3 | 0.103 |
Leukocytes | 19.2 | 0.6 | 25.6 | 0.3 | 0.007 |
Neutrophils | 15.4 | 2.6 | 20.6 | 3.6 | 0.020 |
Platelets | 13.7 | 0.5 | 13.7 | 0.5 | 0.839 |
Total bilirubin | 31.2 | 0.5 | 39.2 | 0.8 | 0.003 |
AST | 18.1 | 0.2 | 21.7 | 0.6 | 0.120 |
ALT | 17.0 | 0.3 | 20.6 | 0.5 | 0.113 |
Creatinine | 5.5 | 0 | 8.0 | 0 | 0.085 |
Anorexia | 20.9 | 1.2 | 21.4 | 0.9 | 0.877 |
Nausea | 15.6 | 0.5 | 13.7 | 0.6 | 0.379 |
Vomiting | 6.4 | 0.2 | 5.2 | 0.5 | 0.425 |
Stomatitis | 17.9 | 0.8 | 21.9 | 0.9 | 0.090 |
Diarrhea | 18.1 | 3.0 | 14.9 | 2.0 | 0.152 |
Fatigue | 15.3 | 1.7 | 16.0 | 1.3 | 0.762 |
Rash | 10.9 | 0.5 | 10.1 | 0.2 | 0.690 |
Hyperpigmentation | 27.9 | 0 | 25.2 | 0.5 | 0.299 |
Alopecia | 1.9 | 0.2 | 2.5 | 0.2 | 0.550 |
Hand-foot syndrome | 72.0 | 16.8 | 77.0 | 22.6 | 0.043 |
Safety profile (cycles 1–8 vs cycles 9–16)
During cycles 1–8 (n = 636) | During cycles 9–16 (n = 417) | |||
---|---|---|---|---|
Any grade (%) | Grade ≥3 (%) | Any grade (%) | Grade ≥3 (%) | |
Hemoglobin | 34.9 | 0 | 31.7 | 0.5 |
Leukocytes | 19.3 | 0.3 | 21.1 | 0 |
Neutrophils | 17.6 | 2.8 | 12.9 | 2.2 |
Platelets | 9.6 | 0.5 | 12.7 | 0 |
Total bilirubin | 32.5 | 0.6 | 36.0 | 0.5 |
AST | 16.2 | 0.3 | 17.5 | 0.5 |
ALT | 15.4 | 0.3 | 14.1 | 0.2 |
Creatinine | 5.2 | 0 | 7.7 | 0 |
Anorexia | 18.4 | 0.9 | 9.1 | 0 |
Nausea | 12.4 | 0.6 | 4.1 | 0 |
Vomiting | 4.2 | 0.5 | 1.7 | 0 |
Stomatitis | 18.9 | 0.9 | 10.6 | 0 |
Diarrhea | 11.6 | 1.7 | 6.7 | 0.5 |
Fatigue | 13.1 | 0.9 | 7.9 | 0.5 |
Rash | 7.5 | 0.2 | 6.7 | 0 |
Hyperpigmentation | 20.8 | 0.5 | 18.7 | 0 |
Alopecia | 1.9 | 0 | 1.4 | 0.2 |
Hand-foot syndrome | 71.1 | 19.0 | 66.7 | 8.6 |