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**Chapter 4**

**Provisional chapter**

**Adjuvant Chemotherapy of Gastric Cancer**

**Adjuvant Chemotherapy of Gastric Cancer**

DOI: 10.5772/intechopen.79824

Adjuvant chemotherapy is a standard treatment for operable gastric cancer. However, the preferred treatment varies by geographical region. Southwestern Oncology Group (SWOG) conducted a, randomized trial of adjuvant chemotherapy for patients with surgically resected gastric cancer. The 3-year survival rates were 50% in the chemoradiotherapygroup and 41% in the surgery group. The Medical Research Council Adjuvant Gastric Infusional Chemotherapy (MAGIC) trial that compared perioperative chemotherapy with the ECF regimen (epirubicin, cisplatin, and 5-fluorouracil) and patients with surgery alone had a 5-year survival rate of 36 and 23%. The Adjuvant Chemotherapy Trial of TS-1 for Gastric Cancer (ACTS-GC) showed that the 3-year overall survival rate was 80.1% in the S-1 group and 70.1% in the surgery-only group in stage II or III gastric cancer patients who underwent a D2 gastrectomy. An analysis of the Capecitabine and Oxaliplatin Adjuvant Study in Stomach Cancer (CLASSIC) study showed 3-year disease-free survival, 74% in the chemotherapy and surgery group and 59% in the surgery-only group in the patients with stage II–IIIB gastric cancer who had D2 gastrectomy. In conclusion, for all patients with stage II and III gastric cancer, standard D2 gastrectomy and adjuvant chemotherapy are

Gastric cancer is the second most common cause of cancer-related death worldwide [1]. Radical operation is the main treatment for gastric cancer, but the recurrence rate following surgery is high due to the early dissemination of cancer cells via the lymphatic system (about 40–80% in advanced gastric cancer) [1, 2]. In East Asia, especially Japan and Korea, D2 lymph node dissection is the standard treatment for operable gastric cancer [3, 4].

> © 2016 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

© 2018 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use,

distribution, and reproduction in any medium, provided the original work is properly cited.

Additional information is available at the end of the chapter

Additional information is available at the end of the chapter

strongly recommended for improved survival rates.

**Keywords:** gastric cancer, D2 lymph node dissection, chemotherapy

http://dx.doi.org/10.5772/intechopen.79824

Byoung Jo Suh

Byoung Jo Suh

**Abstract**

**1. Introduction**

#### **Adjuvant Chemotherapy of Gastric Cancer Adjuvant Chemotherapy of Gastric Cancer**

DOI: 10.5772/intechopen.79824

#### Byoung Jo Suh Byoung Jo Suh

Additional information is available at the end of the chapter Additional information is available at the end of the chapter

http://dx.doi.org/10.5772/intechopen.79824

#### **Abstract**

Adjuvant chemotherapy is a standard treatment for operable gastric cancer. However, the preferred treatment varies by geographical region. Southwestern Oncology Group (SWOG) conducted a, randomized trial of adjuvant chemotherapy for patients with surgically resected gastric cancer. The 3-year survival rates were 50% in the chemoradiotherapygroup and 41% in the surgery group. The Medical Research Council Adjuvant Gastric Infusional Chemotherapy (MAGIC) trial that compared perioperative chemotherapy with the ECF regimen (epirubicin, cisplatin, and 5-fluorouracil) and patients with surgery alone had a 5-year survival rate of 36 and 23%. The Adjuvant Chemotherapy Trial of TS-1 for Gastric Cancer (ACTS-GC) showed that the 3-year overall survival rate was 80.1% in the S-1 group and 70.1% in the surgery-only group in stage II or III gastric cancer patients who underwent a D2 gastrectomy. An analysis of the Capecitabine and Oxaliplatin Adjuvant Study in Stomach Cancer (CLASSIC) study showed 3-year disease-free survival, 74% in the chemotherapy and surgery group and 59% in the surgery-only group in the patients with stage II–IIIB gastric cancer who had D2 gastrectomy. In conclusion, for all patients with stage II and III gastric cancer, standard D2 gastrectomy and adjuvant chemotherapy are strongly recommended for improved survival rates.

**Keywords:** gastric cancer, D2 lymph node dissection, chemotherapy

#### **1. Introduction**

Gastric cancer is the second most common cause of cancer-related death worldwide [1]. Radical operation is the main treatment for gastric cancer, but the recurrence rate following surgery is high due to the early dissemination of cancer cells via the lymphatic system (about 40–80% in advanced gastric cancer) [1, 2]. In East Asia, especially Japan and Korea, D2 lymph node dissection is the standard treatment for operable gastric cancer [3, 4].

© 2016 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. © 2018 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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 using a medical literature review.

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>

**patients**

**3-YSR (%)**

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

**5-YSR (%)**

63

**Study Regimen (surgery + chemotherapy surgery alone) No. of** 

YSR, year survival rate.

Macdonald et al. [5] 5FU + leucovorin + radiotherapy 281 50 40

Cunningham et al. [6] Epirubicin + cisplatin +5FU 250 45 36

Sakuramoto et al. [4, 9] S-1 529 80 71

Bang et al. [1, 2] Capecitabine + oxaliplatin 520 83 78

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

Control 275 41 30

Control 253 30 23

Control 530 61 70

Control 515 78 69

twice daily on days 1–14 of each cycle) plus intravenous oxaliplatin (130 mg/m<sup>2</sup>

each cycle) for 6 months or surgery only. The 3-year disease-free survival was 74% in the

on day 1 of
