World J Oncol

World Journal of Oncology, ISSN 1920-4531 print, 1920-454X online, Open Access

Article copyright, the authors; Journal compilation copyright, World J Oncol and Elmer Press Inc

Journal website https://www.wjon.org

Original Article

Volume 14, Number 5, October 2023, pages 392-400

The Impact of Omitting 5-FU Bolus From mFOLFOX6 Chemotherapy Regimen on Hematological Adverse Events Among Patients With Metastatic Colorectal Cancer

Figure 3. Subgroup analysis for the percentage reduction of absolute neutrophil count between two cycles in patients who received mFOLFOX6 as a first-line treatment.

**Table 1.** Baseline Characteristics
Baseline characteristics	Non-bolus (N = 30)	Bolus (N = 80)	P-value
^aOther comorbidities: skin diseases, eye disorders, psychiatric disorders, chronic kidney disease, neurological disorders, pulmonary disease. ^bOther sites of metastasis: spleen, gastric, peritoneal, ovary, lymph node, Mx.^cTargeted therapy: bevacizumab, cetuximab, panitumumab. *Significantly different at P-value < 0.05. BSA: body surface area; BMI: body mass index; 5-FU: 5-fluorouracil; LV: leucovorin; SD: standard deviation.
Characteristics
Age (years), mean ± SD	72.4 ± 11.7	66.1 ± 10.7	0.0085*
Male, n (%)	15 (50.0)	43 (53.8)	0.8309
Weight (kg), mean ± SD	52.6 ± 8.6	59.3 ± 11.7	0.1890
BSA (m²), mean ± SD	1.5 ± 0.2	1.6 ± 0.2	0.0214*
BMI (kg/m²), mean ± SD	21.1 ± 3.2	22.6 ± 3.9	0.0627
Comorbidities, n (%)
Cardiovascular disease	16 (53.3)	58 (72.5)	0.0696
Endocrine disorders	7 (23.3)	24 (30.0)	0.6353
Gynecological disease	2 (6.7)	3 (3.8)	0.6123
Others^a	4 (13.3)	10 (12.5)	1.0000
Medications, n (%)
Cardiovascular medications	14 (46.7)	58 (72.5)	0.0005*
Endocrine medications	5 (16.7)	17 (21.3)	0.7899
Genitourinary medications	2 (6.7)	5 (6.3)	1.0000
Neuropsychiatric medications	4 (13.3)	6 (7.5)	0.4561
Respiratory medications	2 (6.7)	4 (5.0)	0.6633
Gastrointestinal medications	3 (10.0)	5 (6.3)	0.6809
Elemental nutrition	3 (10.0)	8 (10.0)	1.0000
Number of metastatic sites, n (%)
Single site	17 (56.7)	58 (72.5)	0.1669
Multiple sites	13 (43.3)	22 (27.5)
Site of metastasis, n (%)
Lung	12 (40.0)	26 (32.5)	0.5038
Liver	18 (60.0)	44 (55.0)	0.6719
Bone and soft tissue	2 (6.7)	5 (6.3)	1.0000
Other^b	10 (33.3)	40 (50.0)	0.1365
Lines of mFOLFOX6 regimen, n (%)
First line	27 (90.0)	61 (76.3)	0.1790
Second line	3 (10.0)	19 (23.8)
Previous exposure to chemotherapy, n (%)
5-FU/LV based regimen/capecitabine	2 (6.7)	12 (15.0)	0.3429
mFOLFIRI ± targeted therapy^c/IFL ± targeted therapy^c	0 (0.0)	4 (5)	0.5731
mFOLFOX/XELOX	1 (3.3)	6 (7.5)	0.6741

Table 1. Baseline Characteristics

Baseline characteristics

Non-bolus (N = 30)

Bolus (N = 80)

P-value

^aOther comorbidities: skin diseases, eye disorders, psychiatric disorders, chronic kidney disease, neurological disorders, pulmonary disease. ^bOther sites of metastasis: spleen, gastric, peritoneal, ovary, lymph node, Mx.^cTargeted therapy: bevacizumab, cetuximab, panitumumab. *Significantly different at P-value < 0.05. BSA: body surface area; BMI: body mass index; 5-FU: 5-fluorouracil; LV: leucovorin; SD: standard deviation.

Characteristics

Age (years), mean ± SD

72.4 ± 11.7

66.1 ± 10.7

0.0085*

Male, n (%)

15 (50.0)

43 (53.8)

0.8309

Weight (kg), mean ± SD

52.6 ± 8.6

59.3 ± 11.7

0.1890

BSA (m²), mean ± SD

1.5 ± 0.2

1.6 ± 0.2

0.0214*

BMI (kg/m²), mean ± SD

21.1 ± 3.2

22.6 ± 3.9

0.0627

Comorbidities, n (%)

Cardiovascular disease

16 (53.3)

58 (72.5)

0.0696

Endocrine disorders

7 (23.3)

24 (30.0)

0.6353

Gynecological disease

2 (6.7)

3 (3.8)

0.6123

Others^a

4 (13.3)

10 (12.5)

1.0000

Medications, n (%)

Cardiovascular medications

14 (46.7)

58 (72.5)

0.0005*

Endocrine medications

5 (16.7)

17 (21.3)

0.7899

Genitourinary medications

2 (6.7)

5 (6.3)

1.0000

Neuropsychiatric medications

4 (13.3)

6 (7.5)

0.4561

Respiratory medications

2 (6.7)

4 (5.0)

0.6633

Gastrointestinal medications

3 (10.0)

5 (6.3)

0.6809

Elemental nutrition

3 (10.0)

8 (10.0)

1.0000

Number of metastatic sites, n (%)

Single site

17 (56.7)

58 (72.5)

0.1669

Multiple sites

13 (43.3)

22 (27.5)

Site of metastasis, n (%)

Lung

12 (40.0)

26 (32.5)

0.5038

Liver

18 (60.0)

44 (55.0)

0.6719

Bone and soft tissue

2 (6.7)

5 (6.3)

1.0000

Other^b

10 (33.3)

40 (50.0)

0.1365

Lines of mFOLFOX6 regimen, n (%)

First line

27 (90.0)

61 (76.3)

0.1790

Second line

3 (10.0)

19 (23.8)

Previous exposure to chemotherapy, n (%)

5-FU/LV based regimen/capecitabine

2 (6.7)

12 (15.0)

0.3429

mFOLFIRI ± targeted therapy^c/IFL ± targeted therapy^c

0 (0.0)

4 (5)

0.5731

mFOLFOX/XELOX

1 (3.3)

6 (7.5)

0.6741

**Table 2.** Dosing and Regimen
Dosing and regimen	Non-bolus (N = 30)	Bolus (N = 80)	P-value
^aTargeted therapy: bevacizumab, cetuximab, panitumumab. *Significantly different at P-value < 0.05. N/A: not available; 5-FU: 5-fluorouracil; SD: standard deviation.
Duration between first and second cycles (days), mean ± SD	15.6 ± 3.9	16.9 ± 5.9	0.2664
Treatment regimen, n (%)
mFOLFOX6 + targeted therapy^a	4 (13.3)	11 (13.8)	1.0000
mFOLFOX6	26 (86.7)	69 (86.3)	1.0000
Treatment dose (mg/m²), mean ± SD
5-FU bolus	-	637.7 ± 75.2	N/A
5-FU infusion	1,769.7 ± 193.0	1,848.7 ± 352.8	0.2483
Leucovorin	295.5 ± 29.6	316.4 ± 43.8	0.0176*
Oxaliplatin	108.8 ± 17.4	134.7 ± 25.7	< 0.0001*
First-line treatment dose (mg/m²), mean ± SD	Non-bolus (N = 27)	Bolus (N = 61)
5-FU bolus	-	637.6 ± 71.4	N/A
5-FU infusion	1,778.9 ± 195.4	1,864.5 ± 283.5	0.1582
Leucovorin	295.5 ± 29.6	315.8 ± 43.9	0.0313*
Oxaliplatin	110.6 ± 17.2	135.0 ± 27.5	< 0.0001*

Table 2. Dosing and Regimen

Dosing and regimen

Non-bolus (N = 30)

Bolus (N = 80)

P-value

^aTargeted therapy: bevacizumab, cetuximab, panitumumab. *Significantly different at P-value < 0.05. N/A: not available; 5-FU: 5-fluorouracil; SD: standard deviation.

Duration between first and second cycles (days), mean ± SD

15.6 ± 3.9

16.9 ± 5.9

0.2664

Treatment regimen, n (%)

mFOLFOX6 + targeted therapy^a

4 (13.3)

11 (13.8)

1.0000

mFOLFOX6

26 (86.7)

69 (86.3)

1.0000

Treatment dose (mg/m²), mean ± SD

5-FU bolus

637.7 ± 75.2

N/A

5-FU infusion

1,769.7 ± 193.0

1,848.7 ± 352.8

0.2483

Leucovorin

295.5 ± 29.6

316.4 ± 43.8

0.0176*

Oxaliplatin

108.8 ± 17.4

134.7 ± 25.7

< 0.0001*

First-line treatment dose (mg/m²), mean ± SD

Non-bolus (N = 27)

Bolus (N = 61)

5-FU bolus

637.6 ± 71.4

N/A

5-FU infusion

1,778.9 ± 195.4

1,864.5 ± 283.5

0.1582

Leucovorin

295.5 ± 29.6

315.8 ± 43.9

0.0313*

Oxaliplatin

110.6 ± 17.2

135.0 ± 27.5

< 0.0001*

**Table 3.** Adverse Events Outcome
Adverse events outcome	Non-bolus (N = 30)	Bolus (N = 80)	OR (95% CI), P-value
*Significantly different at P-value < 0.05. ANC: absolute neutrophil count; CI: confidence interval; Hb: hemoglobin; N/A: not available; OR: odds ratio; Plt: platelet.
Hematological adverse events, n (%)
Any grade
Neutropenia	0 (0.0)	5 (6.3)	4.44 (0.24, 82.90), 0.3023
Anemia	6 (20.0)	22 (27.5)	1.52 (0.55, 4.21), 0.4722
Thrombocytopenia	0 (0.0)	1 (1.3)	1.15 (0.04, 29.05), 1.0000
Grade 3/4
Neutropenia	0 (0.0)	1 (1.3)	1.15 (0.04, 29.05), 1.0000
Anemia	1 (3.3)	3 (3.8)	1.13 (0.11, 11.31), 1.0000
% Reduction, mean	Mean difference, P-value
ANC	+25.64%, ± 79.99	-17.49%, ± 38.05	43.13 (20.74, 65.51), 0.0002*
Hb	+0.31%, ± 12.77	-0.74%, ± 15.40	1.05 (-7.31, 5.21), 0.7402
Plt	-9.98%, ± 18.96	-14.48%, ± 25.61	4.763 (-14.97, 5.44), 0.3567
Cycle two growth factor added	0 (0.0)	1 (1.3)	1.15 (0.04, 29.05), 1.000
Other adverse event, n (%)			OR (95% CI), P-value
Any grade
Mucositis	0 (0.0)	7 (8.8)	6.22 (0.34, 112.50), 0.1863
Nausea and vomiting	0 (0.0)	3 (3.8)	2.75 (0.14, 54.97), 0.5607
Diarrhea	0 (0.0)	0 (0.0)	N/A

Table 3. Adverse Events Outcome

Adverse events outcome

Non-bolus (N = 30)

Bolus (N = 80)

OR (95% CI), P-value

*Significantly different at P-value < 0.05. ANC: absolute neutrophil count; CI: confidence interval; Hb: hemoglobin; N/A: not available; OR: odds ratio; Plt: platelet.

Hematological adverse events, n (%)

Any grade

Neutropenia

0 (0.0)

5 (6.3)

4.44 (0.24, 82.90), 0.3023

Anemia

6 (20.0)

22 (27.5)

1.52 (0.55, 4.21), 0.4722

Thrombocytopenia

0 (0.0)

1 (1.3)

1.15 (0.04, 29.05), 1.0000

Grade 3/4

Neutropenia

0 (0.0)

1 (1.3)

1.15 (0.04, 29.05), 1.0000

Anemia

1 (3.3)

3 (3.8)

1.13 (0.11, 11.31), 1.0000

% Reduction, mean

Mean difference, P-value

ANC

+25.64%, ± 79.99

-17.49%, ± 38.05

43.13 (20.74, 65.51), 0.0002*

+0.31%, ± 12.77

-0.74%, ± 15.40

1.05 (-7.31, 5.21), 0.7402

Plt

-9.98%, ± 18.96

-14.48%, ± 25.61

4.763 (-14.97, 5.44), 0.3567

Cycle two growth factor added

0 (0.0)

1 (1.3)

1.15 (0.04, 29.05), 1.000

Other adverse event, n (%)

OR (95% CI), P-value

Any grade

Mucositis

0 (0.0)

7 (8.8)

6.22 (0.34, 112.50), 0.1863

Nausea and vomiting

0 (0.0)

3 (3.8)

2.75 (0.14, 54.97), 0.5607

Diarrhea

0 (0.0)

N/A

**Table 4.** Subgroup Analysis for First-Line Treatment With mFOLFOX6
Adverse events	Non-bolus (N=27)	Bolus (N = 61)	OR (95% CI), P-value
*Significantly different at P-value < 0.05. ANC: absolute neutrophil count; CI: confidence interval; Hb: hemoglobin; N/A: not available; OR: odds ratio; Plt: platelet.
First-line hematological adverse events, n (%)
Any grade
Neutropenia	0 (0.0)	5 (8.2)	5.35 (0.28, 100.40), 0.3179
Anemia	6 (22.2)	20 (32.8)	1.71 (0.59, 4.89), 0.4480
Grade 3/4
Neutropenia	0 (0.0)	1 (1.6)	1.36 (0.05, 34.58), 1.0000
Anemia	1 (3.7)	3 (4.9)	1.34 (0.13, 13.56), 1.0000
% Reduction, mean	Mean difference, P-value
ANC	+27.23%, ± 84.29	-18.78%, ± 38.77	46.01 (19.99, 72.03), 0.0007*
Hb	-0.36%, ± 13.27	-0.55%, ± 17.12	0.19 (-7.58, 7.20), 0.9593
Plt	-10.38%, ± 19.77	-14.71%, ± 23.88	4.33 (-14.79, 6.126), 0.4119
First-line other adverse events, n (%)
Any grade
Mucositis	0 (0.0)	3 (4.9)	3.29 (0.16, 65.99), 0.5497
Nausea and vomiting	0 (0.0)	2 (3.3)	2.31 (0.11, 49.81), 1.0000
Diarrhea	0 (0.0)	0 (0.0)	N/A

Table 4. Subgroup Analysis for First-Line Treatment With mFOLFOX6

Adverse events

Non-bolus (N=27)

Bolus (N = 61)

OR (95% CI), P-value

*Significantly different at P-value < 0.05. ANC: absolute neutrophil count; CI: confidence interval; Hb: hemoglobin; N/A: not available; OR: odds ratio; Plt: platelet.

First-line hematological adverse events, n (%)

Any grade

Neutropenia

0 (0.0)

5 (8.2)

5.35 (0.28, 100.40), 0.3179

Anemia

6 (22.2)

20 (32.8)

1.71 (0.59, 4.89), 0.4480

Grade 3/4

Neutropenia

0 (0.0)

1 (1.6)

1.36 (0.05, 34.58), 1.0000

Anemia

1 (3.7)

3 (4.9)

1.34 (0.13, 13.56), 1.0000

% Reduction, mean

Mean difference, P-value

ANC

+27.23%, ± 84.29

-18.78%, ± 38.77

46.01 (19.99, 72.03), 0.0007*

-0.36%, ± 13.27

-0.55%, ± 17.12

0.19 (-7.58, 7.20), 0.9593

Plt

-10.38%, ± 19.77

-14.71%, ± 23.88

4.33 (-14.79, 6.126), 0.4119

First-line other adverse events, n (%)

Any grade

Mucositis

0 (0.0)

3 (4.9)

3.29 (0.16, 65.99), 0.5497

Nausea and vomiting

0 (0.0)

2 (3.3)

2.31 (0.11, 49.81), 1.0000

Diarrhea

0 (0.0)

N/A