**2. Treatment results with adjuvant chemotherapy**

Treatment results of adjuvant chemotherapy may depend on the interaction between residual tumor and anticancer drugs. The tumor burden should be reduced as much as possible to obtain the most optimal survival benefit of adjuvant chemotherapy [10]. As compared to Western countries, the high survival rate in East Asia might have resulted from a selection of early-stage patients and radical operations, including systematic lymph node dissection [10]. The Southwestern Oncology Group (SWOG) conducted a two-armed prospective, randomized trial of adjuvant chemotherapy for patients with gastric adenocarcinoma surgically resected to negative margins (**Table 1**). Most patients (54%) had undergone a D0 dissection, which is less than a complete dissection of the N1 nodes. The chemotherapy regimen included fluorouracil, 425 mg/m<sup>2</sup> of body-surface area per day, and leucovorin, 20 mg, followed by radiotherapy of 4500 cGy of radiation at 180 cGy/day. The median survival time in the surgery group was 27 months as compared with 36 months in the chemoradiotherapy group [5]. The 3-year survival rates were 50% in the chemoradiotherapy group and 41% in the surgeryonly group [5, 11]. The 503-patient United Kingdom National Cancer Research Institute (NCRI) Medical Research Council Adjuvant Gastric Infusional Chemotherapy (MAGIC) trial was the first randomized trial to demonstrate the survival benefit from the use of perioperative chemotherapy for patients with resectable gastric cancer compared with surgery alone.


**Table 1.** Adjuvant chemotherapy compared to the surgical control of curative resection of stomach cancer.

However, in the Western world, D2 gastrectomy is not as widely performed as in Japan and Korea [5]. Western surgical studies have shown that most patients present with tumors that penetrated the submucosa; they have a 5-year survival rate of 20–30% [6]. Postoperative chemotherapy is a standard treatment component of resectable gastric cancer and has improved patient outcomes [3, 4]. Treatment results of adjuvant chemotherapy may depend on the interaction between residual cancers and anticancer drugs. The Japanese recommendation for adjuvant chemotherapy is based on the Adjuvant Chemotherapy Trial of TS-1 for Gastric Cancer (ACTS-GC) study, which showed a survival benefit with adjuvant chemotherapy after D2 gastrectomy compared with surgery alone [4]. This study showed a survival benefit for stage II and IIIA gastric cancer [4]. However, the FLAGS trial for advanced gastric cancer or gastroesophageal cancer that compared cisplatin and S-1 versus cisplatin and fluorouracil in non-Asian countries did not prolong overall survival [7]. In Korea, adjuvant immunochemotherapy in advanced gastric cancer patients, who had undergone radical subtotal gastrectomy for stage III gastric cancer has been performed. For immunotherapy, a *Streptococcus pyogenes* preparation (picibanil) was followed by MF (mitomycin C and 5-FU) in the late 1990s and early 2000s [3, 8]. The Capecitabine and Oxaliplatin Adjuvant Study in Stomach Cancer (CLASSIC) study was designed to compare the effect of adjuvant capecitabine plus oxaliplatin after D-2 gastrectomy with stage II or III gastric cancer [1]. Although adjuvant chemotherapy is a standard treatment option for operable gastric cancer, there have been some differences concerning methods of chemotherapy and survival data between the Western world (Europe and North America) and East Asia (Korea and Japan). Therefore, this article summarizes the adjuvant chemotherapy for resectable gastric cancer

Treatment results of adjuvant chemotherapy may depend on the interaction between residual tumor and anticancer drugs. The tumor burden should be reduced as much as possible to obtain the most optimal survival benefit of adjuvant chemotherapy [10]. As compared to Western countries, the high survival rate in East Asia might have resulted from a selection of early-stage patients and radical operations, including systematic lymph node dissection [10]. The Southwestern Oncology Group (SWOG) conducted a two-armed prospective, randomized trial of adjuvant chemotherapy for patients with gastric adenocarcinoma surgically resected to negative margins (**Table 1**). Most patients (54%) had undergone a D0 dissection, which is less than a complete dissection of the N1 nodes. The chemotherapy regimen included

radiotherapy of 4500 cGy of radiation at 180 cGy/day. The median survival time in the surgery group was 27 months as compared with 36 months in the chemoradiotherapy group [5]. The 3-year survival rates were 50% in the chemoradiotherapy group and 41% in the surgeryonly group [5, 11]. The 503-patient United Kingdom National Cancer Research Institute (NCRI) Medical Research Council Adjuvant Gastric Infusional Chemotherapy (MAGIC) trial was the first randomized trial to demonstrate the survival benefit from the use of perioperative chemotherapy for patients with resectable gastric cancer compared with surgery alone.

of body-surface area per day, and leucovorin, 20 mg, followed by

using a medical literature review.

62 Gastric Cancer - An Update

fluorouracil, 425 mg/m<sup>2</sup>

**2. Treatment results with adjuvant chemotherapy**

The patients who received perioperative chemotherapy with the ECF regimen (epirubicin, cisplatin, and 5-fluorouracil, 5FU) had a 5-year survival of 36%, compared with 23% in patients treated with surgery alone [12] (**Table 1**). Kim et al. evaluated 10,783 consecutive patients who underwent operation for gastric cancer [3]. The prognostic significance of treatment modality (surgery alone, surgery + chemotherapy, surgery + immunotherapy + chemotherapy <immunochemotherapeutic treatment>) was evaluated for stage III gastric cancer. The protocol for immunochemotherapy was as follows: Picibanil (a *Streptococcus pyogenes* preparation; Tokyo, Japan), mitomycin C 4 mg/50 kg, and 5-FU 500 mg/50 kg. They concluded that radical lymph node dissection, with more than 25 resected lymph nodes, improved survival in patients with stage II and IIIc disease; as postoperative adjuvant therapy, immunochemotherapy was most effective in patients with stage III disease. There were significant differences in survival in stage III patients; the 5-year survival rates were 44.8% for the immunochemotherapy group, 36.8% for the surgery + chemotherapy group, 36.8% for the surgery + chemotherapy group, and 27.1% for the surgery-alone group [3]. In the meta-analysis, which assessed entitled adjuvant chemotherapy after curative resection for gastric cancer in Non-Asian patients, Earle et al. concluded adjuvant chemotherapy may produce a small survival benefit of borderline statistical significance in patients with curatively resected gastric carcinoma [13]. Sakuramoto et al. reported that patients with stage II or III gastric cancer who underwent gastrectomy with extended (D2) lymph node dissection were randomly assigned to undergo surgery followed by adjuvant chemotherapy with S-1 or to undergo surgery only. The analysis of the follow-up data showed that the 3-year overall survival rate was 80.1% in the S-1 group and 70.1% in the surgery-only group [4]. Consecutive results of the ACT-GC trial showed the overall survival rate at 5 years was 71.1% in the S-1 group and 61.1% in the surgery-only group (**Table 1**) [9]. In the Capecitabine and Oxaliplatin Adjuvant Study in Stomach Cancer (CLASSIC) trial, the patients with stage II–IIIB gastric cancer who had curative D2 gastrectomy were randomly assigned to receive adjuvant chemotherapy of eight cycles of oral capecitabine (1000 mg/m<sup>2</sup> twice daily on days 1–14 of each cycle) plus intravenous oxaliplatin (130 mg/m<sup>2</sup> on day 1 of each cycle) for 6 months or surgery only. The 3-year disease-free survival was 74% in the chemotherapy and surgery group and 59% in the surgery-only group. They concluded that adjuvant capecitabine plus oxaliplatin treatment after curative D2 gastrectomy should be considered as a treatment option for patients with operable gastric cancer [1].

East Asia and the Western world. However, no significant differences in prognostic factors were reported between these two regions of the world. In conclusion, for all patients with stage II and III gastric cancer worldwide, standard D2 gastrectomy and adjuvant chemotherapy are

Adjuvant Chemotherapy of Gastric Cancer http://dx.doi.org/10.5772/intechopen.79824 65

Department of Surgery, Memorial Jin-Pok Kim Gastric Cancer Center, Haeundae Paik

[1] Bang YJ, Kim YW, Yang HK, et al. Adjuvant capecitabine and oxaliplatin for gastric cancer after D2 gastrectomy (CLASSIC): A phase 3 open-label, randomised controlled trial.

[2] Noh SH, Park SR, Yang HK, et al. Adjuvant capecitabine plus oxaliplatin for gastric cancer after D2 gastrectomy (CLASSIC): 5-year follow-up of an open-label, randomised

[3] Kim JP, Lee JH, Kim SJ, Yu HJ, Yang HK. Clinicopathologic characteristics and prognostic factors in 10783 patients with gastric cancer. Gastric Cancer. 1998;**1**(2):125-133 [4] Sakuramoto S, Sasako M, Yamaguchi T, et al. Adjuvant chemotherapy for gastric cancer with S-1, an oral fluoropyrimidine. The New England Journal of Medicine. 2007;

[5] Macdonald JS, Smalley SR, Benedetti J, et al. Chemoradiotherapy after surgery compared with surgery alone for adenocarcinoma of the stomach or gastroesophageal junc-

[6] Cunningham D, Allum WH, Stenning SP, et al. Perioperative chemotherapy versus surgery alone for resectable gastroesophageal cancer. The New England Journal of Medi-

[7] Ajani JA, Rodriguez W, Bodoky G, et al. Multicenter phase III comparison of cisplatin/S-1 with cisplatin/infusional fluorouracil in advanced gastric or gastroesophageal adenocarcinoma study: The FLAGS trial. Journal of Clinical Oncology. 2010;**28**(9):1547-1553

[8] Oh SJ, Suh BJ, Park JK, Oh SD, Yu HJ. Prognostic discrepancy of the 6th and 7th UICC N classification for lymph node staging in gastric cancer patients after curative resection.

strongly recommended for a better rate of survival.

Address all correspondence to: oltx62@hanmail.net

Lancet. 2012;**379**(9813):315-321

**357**(18):1810-1820

cine. 2006;**355**(1):11-20

Case Reports in Oncology. 2017;**10**(1):57-65

Hospital, Inje University College of Medicine, Busan, Korea

phase 3 trial. The Lancet Oncology. 2014;**15**(12):1389-1396

tion. The New England Journal of Medicine. 2001;**345**(10):725-730

**Author details**

Byoung Jo Suh

**References**
