Impact of oxaliplatin and trastuzumab combination therapy on tumor markers and T lymphocyte subsets for advanced gastric cancer

Table 1 Baseline characteristics of the patients (n = 60), n (%)

Characteristics	Value
Median age, years (range)	58 (35-75)
Sex
Male	36 (60)
Female	24 (40)
ECOG performance status
0	42 (70)
1	18 (30)
Metastatic sites
Liver	28 (47)
Peritoneum	24 (40)
Lymph nodes	20 (33)
Lung	12 (20)
Bone	8 (13)
HER2 status
IHC 3+	48 (80)
IHC 2+/FISH+	12 (20)

ECOG: Eastern Cooperative Oncology Group; HER2: Human epidermal growth factor receptor 2; IHC: Immunohistochemistry; FISH: Fluorescence in situ hybridization.

Table 2 Changes in serum tumor markers before and after treatment

Marker	Baseline	After treatment	P value
CEA (ng/mL)
Median (range)	15.2 (1.5-180.5)	6.1 (0.5-55.0)	< 0.001
CA19-9 (U/mL)
Median (range)	60.5 (10.5-1000.0)	26.4 (5.0-400.0)	< 0.001
CA72-4 (U/mL)
Median (range)	8.0 (1.5-300.0)	2.8 (0.5-80.0)	< 0.001

CEA: Carcinoembryonic antigen; CA19-9: Cancer antigen 19-9; CA72-4: Cancer antigen 72-4.

Table 3 Changes in T lymphocyte subsets before and after treatment

Subset	Baseline	After treatment	P value
CD3+ (%)
Median (range)	62.5 (45.0-75.0)	70.0 (50.0-85.0)	< 0.05
CD4+ (%)
Median (range)	30.0 (20.0-45.0)	40.0 (25.0-55.0)	< 0.05
CD8+ (%)
Median (range)	28.5 (15.0-40.0)	22.0 (10.0-35.0)	< 0.05
CD4+/CD8+ ratio
Median (range)	1.2 (0.6-2.5)	1.8 (0.8-3.5)	< 0.05

Table 4 Association between biomarker changes and clinical response

Biomarker change	Clinical response rate (CR + PR)	P value
CEA
≥ 50% reduction	70.0%	< 0.05
< 50% reduction	40.0%
CA19-9
≥ 50% reduction	75.0%	< 0.05
< 50% reduction	42.9%
CA72-4
≥ 50% reduction	72.2%	< 0.05
< 50% reduction	38.5%
CD4+ /CD8+ ratio
≥ 1.5-fold increase	71.4%	< 0.05
< 1.5-fold increase	41.7%

CR: Complete response; PR: Partial response; CEA: Carcinoembryonic antigen; CA19-9: Cancer antigen 19-9; CA72-4: Cancer antigen 72-4.

Table 5 Univariate and multivariate analyses for progression-free survival and overall survival

Factor	Univariate analysis, HR (95%CI)	P value	Multivariate analysis, HR (95%CI)	P value
PFS
CEA (≥ 50% vs < 50% reduction)	0.45 (0.23-0.88)	0.020	0.40 (0.20-0.82)	0.012
CA19-9 (≥ 50% vs < 50% reduction)	0.50 (0.26-0.97)	0.040	0.58 (0.29-1.16)	0.123
CA72-4 (≥ 50% vs < 50% reduction)	0.48 (0.24-0.94)	0.032	0.55 (0.27-1.12)	0.098
CD4+ /CD8+ ratio (≥ 1.5 vs < 1.5)	0.42 (0.21-0.84)	0.014	0.45 (0.22-0.92)	0.028
OS
CEA (≥ 50% vs < 50% reduction)	0.52 (0.25-1.08)	0.080	0.60 (0.28-1.30)	0.197
CA19-9 (≥ 50% vs < 50% reduction)	0.55 (0.27-1.13)	0.103	0.70 (0.33-1.50)	0.361
CA72-4 (≥ 50% vs < 50% reduction)	0.43 (0.20-0.92)	0.030	0.38 (0.17-0.85)	0.018
CD4+ /CD8+ ratio (≥ 1.5 vs < 1.5)	0.40 (0.18-0.87)	0.021	0.42 (0.19-0.93)	0.033

PFS: Progression-free survival; OS: Overall survival; HR: Hazard ratio; CEA: Carcinoembryonic antigen; CA19-9: Cancer antigen 19-9; CA72-4: Cancer antigen 72-4.

Table 6 Adverse events (≥ grade 3)

Adverse events	n (%)
Neutropenia	21 (35.0)
Thrombocytopenia	12 (20.0)
Anemia	9 (15.0)
Fatigue	6 (10.0)
Nausea/vomiting	4 (6.7)
Diarrhea	3 (5.0)
Neuropathy	2 (3.3)
Elevated transaminases	2 (3.3)