Journal List > Korean J Gastroenterol > v.68(5) > 1007576

Kim, Kang, Moon, Sung, Jeong, and Sul: Clinical Outcome of Doublet and Triplet Neoadjuvant Chemotherapy for Locally Advanced Gastric Cancer

Abstract

Background/Aims

In gastric cancer, the rate of recurrence and metastasis following radical resection is high, necessitating improvement in survival and cure rates. Neoadjuvant chemotherapy (NAC) has potential benefits for locally advanced gastric cancer; however, the surgical benefits and effects on survival are unclear. This study evaluates the effectiveness of NAC in locally advanced gastric cancer and compares clinical outcomes of doublet and triplet regimens.

Methods

We reviewed patient medical records of 383 patients who underwent NAC (n=41) or surgery only (n=342) for treatment of locally advanced gastric cancer. The baseline characteristics and clinical outcomes were compared between the groups. Chemotherapy patients were classified according to regimen, doublet (n=28) and triplet (n=13), and NAC-related clinical response, safety, and toxicity were analyzed.

Results

The baseline characteristics did not differ significantly between groups. After NAC, the tumor downstage rate was 51.2% (21/41); however, overall survival (p=0.205) and disease-free survival (p=0.415) were not significantly different between the groups. On subgroup analysis, no significant differences in drug toxicity (p=0.604) or clinical response (p=0.374) were found between outcomes of doublet and triplet chemotherapy regimens.

Conclusions

In patients with locally advanced gastric cancer, NAC showed tolerable drug toxicity and increased tumor downstage, but NAC failed to increase the survival rate, which may be caused by a high D2-lymphadenectomy rate. Therefore, NAC was found to be a therapeutic option for select gastric cancer patients.

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Fig. 1.
Kaplan-Meier estimates of overall survival rate.
kjg-68-245f1.tif
Fig. 2.
Kaplan-Meier estimates of disease-free survival rate.
kjg-68-245f2.tif
Table 1.
Patiens Baseline Characteristics
Characteristic NAC group (n=41) Surgery only group (n=342) pvalue
Age (yr) 61.90±10.09 63.59±9.16 0.270
Gender (male) 36 (87.8) 253 (74.0) 0.079
WHO performance status     0.671
 0 30 (73.2) 265 (77.5)  
 1 11 (26.8) 77 (22.5)  
Tumor location     0.425
 Upper third 8 (19.5) 58 (17.0)  
 Middle third 14 (34.1) 121 (35.4)  
 Lower third 19 (46.3) 163 (47.7)  
Pretreatment T stage     0.012
 T1 0 (0) 0 (0)  
 T2 1 (2.4) 32 (9.4)  
 T3 13 (31.7) 174 (50.9)  
 T4 27 (65.9) 136 (39.8)  
Pretreatment N status     0.000
 N0 1 (2.4) 72 (21.1)  
 N1 2 (4.9) 82 (24.0)  
 N2 26 (63.4) 123 (36.0)  
 N3 12 (29.3) 65 (19.0)  
Pretreatment M status     0.254
 M0 38 (92.7) 331 (96.8)  
 M1 0 (0) 0 (0)  
 Mx 3 (7.3) 11 (3.2)  

Values are presented as mean±SD or n (%).

NAC, neoadjuvant chemotherapy; WHO, World Health Organization.

Table 2.
Grade 3 or 4 Toxicity and Clinical Response Assessment during Neoadjuvant Chemotherapy
Variable Total (n=41) Doublet (n=28) Triplet (n=13) pvalue
Toxicity (total) 15 (36.6) 9 (32.1) 6 (46.2) 0.604
 Neutropenia 5 (12.2) 4 (14.3) 1 (7.7)  
 Thrombocytopenia 3 (7.3) 1 (3.6) 2 (15.4)  
 Anemia 2 (4.9) 1 (3.6) 1 (7.7)  
 Nausea/vomiting 2 (4.9) 2 (7.1) 0 (0)  
 Mucositis 1 (2.4) 0 (0) 1 (7.7)  
 Fever 1 (2.4) 0 (0) 1 (7.7)  
 Nephrotoxicity 1 (2.4) 1 (3.6) 0 (0)  
Clinical response       0.374
 Complete response 5 (12.2) 3 (10.7) 2 (15.4)  
 Partial response 14 (34.1) 9 (32.1) 5 (38.5)  
 Stable disease 19 (46.3) 15 (53.6) 4 (30.8)  
 Progressive disease 3 (7.3) 1 (3.6) 2 (15.4)  

Values are presented as n (%).

Table 3.
Surgical and Pathologic Results
Characteristic NAC group (n=41) Surgery only group (n=342) pvalue
Type of surgery     0.726
 Total gastrectomy 6 (14.6) 39 (11.4)  
 Distal gastrectomy 35 (85.4) 303 (88.6)  
Resection margin     0.829
 R0 38 (92.7) 321 (93.9)  
 R1 2 (4.9) 20 (5.8)  
 R2 0 (0) 1 (0.3)  
 Open & closure 1 (2.4) 0 (0)  
Postoperative complication 6 (14.6) 61 (17.8) 0.770
Pathologic results      
 Tumor stage     0.001
  T1 6 (14.6) 0 (0)  
  T2 4 (9.8) 8 (2.3)  
  T3 3 (7.3) 128 (37.4)  
  T4 28 (68.3) 206 (60.2)  
 Nodal status     0.000
  N0 12 (29.3) 4 (1.2)  
  N1 8 (19.5) 72 (21.1)  
  N2 5 (12.2) 96 (28.1)  
  N3 16 (39.0) 170 (49.7)  
 Metastasis status     0.127
  M0 39 (95.1) 338 (98.8)  
  M1 2 (4.9) 4 (1.2)  

Values are presented as n (%).

NAC, neoadjuvant chemotherapy.

Table 4.
Stage Change of the Pretreatment vs. Post Neoadjuvant Chemotherapy
Characteristic Pretreatment (clinical stage) Post NAC (pathologic stage) pvalue
Tumor stage     0.000
 T1 0 (0) 6 (14.6)  
 T2 1 (2.4) 4 (9.8)  
 T3 13 (31.7) 3 (7.3)  
 T4 27 (65.9) 28 (68.3)  
Nodal status     0.000
 N0 1 (2.4) 12 (29.3)  
 N1 2 (4.9) 8 (19.5)  
 N2 26 (63.4) 5 (12.2)  
 N3 12 (29.3) 16 (39.1)  
Change of overall stage      
 Downstage   21 (51.2)  
 Upstage   9 (22.0)  
 No change   11 (26.8)  

Values are presented as n (%).

NAC, neoadjuvant chemotherapy.

Table 5.
Pattern of Recurrence, Survival Status, and Cause of Death
Characteristic NAC group (n=41) Surgery only group (n=342) pvalue
Recurrence 20 (48.8) 218 (63.7) 0.119
 Locoregional only 1 (2.4) 30 (8.8)  
 Distant only 5 (12.2) 36 (10.5)  
 Both 14 (34.1) 152 (44.4)  
Death 17 (41.5) 182 (53.2) 0.209
 Cancer related 13 (31.7) 161 (47.1)  
 Surgery related 2 (4.9) 12 (3.5)  
 Others 2 (4.9) 9 (2.6)  

Values are presented as n (%).

NAC, neoadjuvant chemotherapy.

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