Skip to main content
Top
Published in: Annals of Surgical Oncology 9/2012

01-09-2012 | Gastrointestinal Oncology

Pilot Feasibility Study of Neoadjuvant Chemoradiotherapy with S-1 in Patients with Locally Advanced Gastric Cancer Featuring Adjacent Tissue Invasion or JGCA Bulky N2 Lymph Node Metastases

Authors: Tatsushi Inoue, MD, Shinichi Yachida, MD, PhD, Hisashi Usuki, MD, PhD, Tomoki Kimura, MD, PhD, Masanobu Hagiike, MD, PhD, Keiichi Okano, MD, PhD, Yasuyuki Suzuki, MD, PhD

Published in: Annals of Surgical Oncology | Issue 9/2012

Login to get access

Abstract

Background

To improve the prognosis of locally advanced gastric cancer, clinical trials of neoadjuvant chemotherapy (NAC) are being performed. Although neoadjuvant chemoradiotherapy (NACRT) generally achieves superior local tumor control to NAC, its efficacy for locally advanced gastric cancers remains unclear. Therefore, a prospective trial was conducted to explore the feasibility and safety of NACRT with oral S-1 in a series of cases.

Methods

Patients who had Japanese Gastric Cancer Association (JGCA) cStage IIIB gastric cancer were enrolled onto this study and received oral S-1 (65 mg/m2/day) administration and 50-Gy radiotherapy followed by radical surgery. The primary end points were completion of therapy and safety.

Results

Between October 2005 and September 2008, 12 eligible patients were enrolled. Two could not complete the chemotherapy because of grade 3 toxicity. R0 resections were performed in 11 patients (91.7 %) (95 % confidence interval 61.5–99.8). Although operative morbidity was observed in two cases, there were no postoperative deaths. A pathologic response was observed in 10 patients (83.3 %). In five (62.5 %) of eight gastric cancers with invasion to adjacent structures, microscopic tumor deposits were not found in the affected organs. The 3-year survival rate was 58.3 % during a median follow-up period of 36 months.

Conclusions

Although this study is preliminary, the present regimen seems to be feasible and safe as a treatment for locally advanced gastric cancers featuring adjacent tissue invasion or JGCA bulky N2 disease. This treatment approach should now be tested using the new tumor, node, metastasis staging system in a large clinical trial.
Literature
1.
go back to reference Ferlay J, Shin HR, Bray F, et al. Estimates of worldwide burden of cancer in 2008:GLOBOCAN 2008. Int J Cancer. 2010;127:2893–917.PubMedCrossRef Ferlay J, Shin HR, Bray F, et al. Estimates of worldwide burden of cancer in 2008:GLOBOCAN 2008. Int J Cancer. 2010;127:2893–917.PubMedCrossRef
2.
go back to reference Maruyama K, Kaminishi M, Hayashi K, et al. Gastric cancer treated in 1991 in Japan: data analysis of nationwide registry. Gastric Cancer. 2006;9:51–66.PubMedCrossRef Maruyama K, Kaminishi M, Hayashi K, et al. Gastric cancer treated in 1991 in Japan: data analysis of nationwide registry. Gastric Cancer. 2006;9:51–66.PubMedCrossRef
3.
go back to reference Cheng CT, Tsai CY, Hsu JT, et al. Aggressive surgical approach for patients with T4 gastric carcinoma: promise or myth? Ann Surg Oncol. 2011;18:1606–14.PubMedCrossRef Cheng CT, Tsai CY, Hsu JT, et al. Aggressive surgical approach for patients with T4 gastric carcinoma: promise or myth? Ann Surg Oncol. 2011;18:1606–14.PubMedCrossRef
4.
go back to reference Yoshikawa T, Sasako M, Yamamoto S, et al. Phase II study of neoadjuvant chemotherapy and extended surgery for locally advanced gastric cancer. Br J Surg. 2009;96:1015–22.PubMedCrossRef Yoshikawa T, Sasako M, Yamamoto S, et al. Phase II study of neoadjuvant chemotherapy and extended surgery for locally advanced gastric cancer. Br J Surg. 2009;96:1015–22.PubMedCrossRef
5.
go back to reference Kinoshita T, Sasako M, Sano T, et al. Phase II trial of S-1 for neoadjuvant chemotherapy against scirrhous gastric cancer (JCOG 0002). Gastric Cancer. 2009;12:37–42.PubMedCrossRef Kinoshita T, Sasako M, Sano T, et al. Phase II trial of S-1 for neoadjuvant chemotherapy against scirrhous gastric cancer (JCOG 0002). Gastric Cancer. 2009;12:37–42.PubMedCrossRef
8.
go back to reference Yoshikawa T, Omura K, Kobayashi O, et al. A phase II study of preoperative chemotherapy with S-1 plus cisplatin followed by D2/D3 gastrectomy for clinically serosa-positive gastric cancer (JACCRO GC-01 study). Eur J Surg Oncol. 2010;36:546–51.PubMedCrossRef Yoshikawa T, Omura K, Kobayashi O, et al. A phase II study of preoperative chemotherapy with S-1 plus cisplatin followed by D2/D3 gastrectomy for clinically serosa-positive gastric cancer (JACCRO GC-01 study). Eur J Surg Oncol. 2010;36:546–51.PubMedCrossRef
10.
go back to reference Japanese Gastric Cancer Association. Japanese classification of gastric carcinoma. 2nd English ed. Gastric Cancer. 1998;1:10–24.PubMedCrossRef Japanese Gastric Cancer Association. Japanese classification of gastric carcinoma. 2nd English ed. Gastric Cancer. 1998;1:10–24.PubMedCrossRef
11.
go back to reference Japanese classification of gastric carcinoma—2nd English edition—response assessment of chemotherapy and radiotherapy for gastric carcinoma: clinical criteria. Gastric Cancer. 2001;4:1–8. Japanese classification of gastric carcinoma—2nd English edition—response assessment of chemotherapy and radiotherapy for gastric carcinoma: clinical criteria. Gastric Cancer. 2001;4:1–8.
12.
go back to reference Ajani JA, Winter K, Okawara GS, et al. Phase II trial of preoperative chemoradiation in patients with localized gastric adenocarcinoma (RTOG 9904): quality of combined modality therapy and pathologic response. J Clin Oncol. 2006;24:3953–8.PubMedCrossRef Ajani JA, Winter K, Okawara GS, et al. Phase II trial of preoperative chemoradiation in patients with localized gastric adenocarcinoma (RTOG 9904): quality of combined modality therapy and pathologic response. J Clin Oncol. 2006;24:3953–8.PubMedCrossRef
13.
go back to reference Fujitani K, Ajani JA, Crane CH, et al. Impact of induction chemotherapy and preoperative chemoradiotherapy on operative morbidity and mortality in patients with locoregional adenocarcinoma of the stomach or gastroesophageal junction. Ann Surg Oncol. 2007;14:2010–7.PubMedCrossRef Fujitani K, Ajani JA, Crane CH, et al. Impact of induction chemotherapy and preoperative chemoradiotherapy on operative morbidity and mortality in patients with locoregional adenocarcinoma of the stomach or gastroesophageal junction. Ann Surg Oncol. 2007;14:2010–7.PubMedCrossRef
14.
go back to reference Saikawa Y, Kubota T, Takahashi T, et al. Is chemoradiation effective or harmful for stage VI gastric cancer patients? Oncol Rep. 2005;13:865–70.PubMed Saikawa Y, Kubota T, Takahashi T, et al. Is chemoradiation effective or harmful for stage VI gastric cancer patients? Oncol Rep. 2005;13:865–70.PubMed
15.
go back to reference Shirasaka T, Nakano K, Takechi T, et al. Antitumor activity of 1 M tegafur-0.4 M 5-chloro-2,4-dihydroxypyridine-1 M potassium oxonate (S-1) against human colon carcinoma orthotopically implanted into nude rats. Cancer Res. 1996;56:2602–6.PubMed Shirasaka T, Nakano K, Takechi T, et al. Antitumor activity of 1 M tegafur-0.4 M 5-chloro-2,4-dihydroxypyridine-1 M potassium oxonate (S-1) against human colon carcinoma orthotopically implanted into nude rats. Cancer Res. 1996;56:2602–6.PubMed
16.
go back to reference Shirasaka T, Shimamato Y, Ohshimo H, et al. Development of a novel form of an oral 5-fluorouracil derivative (S-1) directed to the potentiation of the tumor selective cytotoxicity of 5-fluorouracil by two biochemical modulators. Anticancer Drugs. 1996;7:548–57.PubMedCrossRef Shirasaka T, Shimamato Y, Ohshimo H, et al. Development of a novel form of an oral 5-fluorouracil derivative (S-1) directed to the potentiation of the tumor selective cytotoxicity of 5-fluorouracil by two biochemical modulators. Anticancer Drugs. 1996;7:548–57.PubMedCrossRef
17.
go back to reference Sugimachi K, Maehara Y, Horikoshi N, et al. An early phase II study of oral S-1, a newly developed 5-fluorouracil derivative for advanced and recurrent gastrointestinal cancers. The S-1 Gastrointestinal Cancer Study Group. Oncology. 1999;57:202–10.PubMedCrossRef Sugimachi K, Maehara Y, Horikoshi N, et al. An early phase II study of oral S-1, a newly developed 5-fluorouracil derivative for advanced and recurrent gastrointestinal cancers. The S-1 Gastrointestinal Cancer Study Group. Oncology. 1999;57:202–10.PubMedCrossRef
18.
go back to reference Koizumi W, Kurihara M, Nakano S, et al. Phase II study of S-1, a novel oral derivative of 5-fluorouracil, in advanced gastric cancer. For the S-1 Cooperative Gastric Cancer Study Group. Oncology. 2000;58:191–7.PubMedCrossRef Koizumi W, Kurihara M, Nakano S, et al. Phase II study of S-1, a novel oral derivative of 5-fluorouracil, in advanced gastric cancer. For the S-1 Cooperative Gastric Cancer Study Group. Oncology. 2000;58:191–7.PubMedCrossRef
19.
go back to reference Sakuramoto S, Sasako M, Yamaguchi T, et al. Adjuvant chemotherapy for gastric cancer with S-1, an oral fluoropyrimidine. N Engl J Med. 2007;357:1810–20.PubMedCrossRef Sakuramoto S, Sasako M, Yamaguchi T, et al. Adjuvant chemotherapy for gastric cancer with S-1, an oral fluoropyrimidine. N Engl J Med. 2007;357:1810–20.PubMedCrossRef
20.
go back to reference Basch E, Iasonos A, McDonough T, et al. Patient versus clinician symptom reporting using the National Cancer Institute Common Terminology Criteria for Adverse Events: results of a questionnaire-based study. Lancet Oncol. 2006;7:903–9.PubMedCrossRef Basch E, Iasonos A, McDonough T, et al. Patient versus clinician symptom reporting using the National Cancer Institute Common Terminology Criteria for Adverse Events: results of a questionnaire-based study. Lancet Oncol. 2006;7:903–9.PubMedCrossRef
21.
go back to reference Kim YH, Lee KH, Park SH, et al. Staging of T3 and T4 gastric carcinoma with multidetector CT: added value of multiplanar reformations for prediction of adjacent organ invasion. Radiology. 2009;250:767–75.PubMedCrossRef Kim YH, Lee KH, Park SH, et al. Staging of T3 and T4 gastric carcinoma with multidetector CT: added value of multiplanar reformations for prediction of adjacent organ invasion. Radiology. 2009;250:767–75.PubMedCrossRef
22.
go back to reference Ikeguchi M, Katano K, Saitou H, et al. Pre-operative serum levels of CA72-4 in patients with gastric adenocarcinoma. Hepatogastroenterology. 1997;44:866–71.PubMed Ikeguchi M, Katano K, Saitou H, et al. Pre-operative serum levels of CA72-4 in patients with gastric adenocarcinoma. Hepatogastroenterology. 1997;44:866–71.PubMed
23.
go back to reference Hwang GI, Yoo CH, Sohn BH, et al. Predictive value of preoperative serum CEA, CA19-9 and CA125 levels for peritoneal metastasis in patients with gastric carcinoma. Cancer Res Treat. 2004;36:178–81.PubMedCrossRef Hwang GI, Yoo CH, Sohn BH, et al. Predictive value of preoperative serum CEA, CA19-9 and CA125 levels for peritoneal metastasis in patients with gastric carcinoma. Cancer Res Treat. 2004;36:178–81.PubMedCrossRef
24.
go back to reference Harada K, Kawaguchi S, Supriatno, et al. Enhancement of apoptosis in salivary gland cancer cells by the combination of oral fluoropyrimidine anticancer agent (S-1) and radiation. Int J Oncol. 2004;25:905–11.PubMed Harada K, Kawaguchi S, Supriatno, et al. Enhancement of apoptosis in salivary gland cancer cells by the combination of oral fluoropyrimidine anticancer agent (S-1) and radiation. Int J Oncol. 2004;25:905–11.PubMed
25.
go back to reference Harada K, Kawaguchi S, Supriatno, et al. Combined effects of the oral fluoropyrimidine anticancer agent, S-1 and radiation on human oral cancer cells. Oral Oncol. 2004;40:713–9.PubMedCrossRef Harada K, Kawaguchi S, Supriatno, et al. Combined effects of the oral fluoropyrimidine anticancer agent, S-1 and radiation on human oral cancer cells. Oral Oncol. 2004;40:713–9.PubMedCrossRef
26.
go back to reference Harada H, Omura K. Preoperative concurrent chemotherapy with S-1 and radiotherapy for locally advanced squamous cell carcinoma of the oral cavity: phase I trial. J Exp Clin Cancer Res. 2010;29:33.PubMedCrossRef Harada H, Omura K. Preoperative concurrent chemotherapy with S-1 and radiotherapy for locally advanced squamous cell carcinoma of the oral cavity: phase I trial. J Exp Clin Cancer Res. 2010;29:33.PubMedCrossRef
27.
go back to reference Roth AD, Allal AS, Brundler MA, et al. Neoadjuvant radiochemotherapy for locally advanced gastric cancer: a phase I–II study. Ann Oncol. 2003;14:110–5.PubMedCrossRef Roth AD, Allal AS, Brundler MA, et al. Neoadjuvant radiochemotherapy for locally advanced gastric cancer: a phase I–II study. Ann Oncol. 2003;14:110–5.PubMedCrossRef
28.
go back to reference Lowy AM, Feig BW, Janjan N, et al. A pilot study of preoperative chemoradiotherapy for resectable gastric cancer. Ann Surg Oncol. 2001;8:519–24.PubMedCrossRef Lowy AM, Feig BW, Janjan N, et al. A pilot study of preoperative chemoradiotherapy for resectable gastric cancer. Ann Surg Oncol. 2001;8:519–24.PubMedCrossRef
29.
go back to reference Balandraud P, Moutardier V, Giovannini M, et al. Locally advanced adenocarcinomas of the gastric cardia: results of pre-operative chemoradiotherapy. Gastroenterol Clin Biol. 2004;28:651–7.PubMedCrossRef Balandraud P, Moutardier V, Giovannini M, et al. Locally advanced adenocarcinomas of the gastric cardia: results of pre-operative chemoradiotherapy. Gastroenterol Clin Biol. 2004;28:651–7.PubMedCrossRef
30.
go back to reference Klautke G, Foitzik T, Ludwig K, et al. Neoadjuvant radiochemotherapy in locally advanced gastric carcinoma. Strahlenther Onkol. 2004;180:695–700.PubMedCrossRef Klautke G, Foitzik T, Ludwig K, et al. Neoadjuvant radiochemotherapy in locally advanced gastric carcinoma. Strahlenther Onkol. 2004;180:695–700.PubMedCrossRef
31.
go back to reference Emami B, Lyman J, Brown A, et al. Tolerance of normal tissue to therapeutic irradiation. Int J Radiat Oncol Biol Phys. 1991;21:109–22.PubMedCrossRef Emami B, Lyman J, Brown A, et al. Tolerance of normal tissue to therapeutic irradiation. Int J Radiat Oncol Biol Phys. 1991;21:109–22.PubMedCrossRef
32.
go back to reference Becker K, Mueller JD, Schulmacher C, et al. Histomorphology and grading of regression in gastric carcinoma treated with neoadjuvant chemotherapy. Cancer. 2003;98:1521–30.PubMedCrossRef Becker K, Mueller JD, Schulmacher C, et al. Histomorphology and grading of regression in gastric carcinoma treated with neoadjuvant chemotherapy. Cancer. 2003;98:1521–30.PubMedCrossRef
33.
go back to reference Hermanek P, Hutter RV, Sobin LH, et al. International Union Against Cancer. Classification of isolated tumor cells and micrometastasis. Cancer. 1999;86:2668–73.PubMedCrossRef Hermanek P, Hutter RV, Sobin LH, et al. International Union Against Cancer. Classification of isolated tumor cells and micrometastasis. Cancer. 1999;86:2668–73.PubMedCrossRef
34.
go back to reference Tsujinaka T, Fujitani K, Hirao M, et al. Current status of chemoradiotherapy for gastric cancer in Japan. Int J Clin Oncol. 2008;13:117–20.PubMedCrossRef Tsujinaka T, Fujitani K, Hirao M, et al. Current status of chemoradiotherapy for gastric cancer in Japan. Int J Clin Oncol. 2008;13:117–20.PubMedCrossRef
35.
go back to reference Sasako M, Sano T, Yamamoto S, et al. D2 lymphadenectomy alone or with para-aortic nodal dissection for gastric cancer. N Engl J Med. 2008;359:453–62.PubMedCrossRef Sasako M, Sano T, Yamamoto S, et al. D2 lymphadenectomy alone or with para-aortic nodal dissection for gastric cancer. N Engl J Med. 2008;359:453–62.PubMedCrossRef
36.
go back to reference Diaz-Gonzalez JA, Rodriguez J, Hernandez-Lizoain JL, et al. Patterns of response after preoperative treatment in gastric cancer. Int J Radiat Oncol Biol Phys. 2011;80:698–704.PubMedCrossRef Diaz-Gonzalez JA, Rodriguez J, Hernandez-Lizoain JL, et al. Patterns of response after preoperative treatment in gastric cancer. Int J Radiat Oncol Biol Phys. 2011;80:698–704.PubMedCrossRef
37.
go back to reference Kunisaki C, Akiyama H, Nomura M, et al. Comparison of surgical results of D2 versus D3 gastrectomy (para-aortic lymph node dissection) for advanced gastric carcinoma: a multi-institutional study. Ann Surg Oncol. 2006;13:659–67.PubMedCrossRef Kunisaki C, Akiyama H, Nomura M, et al. Comparison of surgical results of D2 versus D3 gastrectomy (para-aortic lymph node dissection) for advanced gastric carcinoma: a multi-institutional study. Ann Surg Oncol. 2006;13:659–67.PubMedCrossRef
38.
go back to reference Yoo CH, Noh SH, Shin DW, et al. Recurrence following curative resection for gastric carcinoma. Br J Surg. 2000;87:236–42.PubMedCrossRef Yoo CH, Noh SH, Shin DW, et al. Recurrence following curative resection for gastric carcinoma. Br J Surg. 2000;87:236–42.PubMedCrossRef
39.
go back to reference Marutsuka T, Shimada S, Shiomori K, et al. Mechanisms of peritoneal metastasis after operation for non-serosa-invasive gastric carcinoma: an ultrarapid detection system for intraperitoneal free cancer cells and a prophylactic strategy for peritoneal metastasis. Clin Cancer Res. 2003;9:678–85.PubMed Marutsuka T, Shimada S, Shiomori K, et al. Mechanisms of peritoneal metastasis after operation for non-serosa-invasive gastric carcinoma: an ultrarapid detection system for intraperitoneal free cancer cells and a prophylactic strategy for peritoneal metastasis. Clin Cancer Res. 2003;9:678–85.PubMed
40.
go back to reference Kuramoto M, Shimada S, Ikeshima S, et al. Extensive intraoperative peritoneal lavage as a standard prophylactic strategy for peritoneal recurrence in patients with gastric carcinoma. Ann Surg. 2009;250:242–6.PubMedCrossRef Kuramoto M, Shimada S, Ikeshima S, et al. Extensive intraoperative peritoneal lavage as a standard prophylactic strategy for peritoneal recurrence in patients with gastric carcinoma. Ann Surg. 2009;250:242–6.PubMedCrossRef
41.
go back to reference Nagatomo A, Abe N, Takeuchi H, et al. Microscopic cancer cell spread in gastric cancer: whole-section analysis of mesogastrium. Langenbecks Arch Surg. 2009;394:655–60.PubMedCrossRef Nagatomo A, Abe N, Takeuchi H, et al. Microscopic cancer cell spread in gastric cancer: whole-section analysis of mesogastrium. Langenbecks Arch Surg. 2009;394:655–60.PubMedCrossRef
Metadata
Title
Pilot Feasibility Study of Neoadjuvant Chemoradiotherapy with S-1 in Patients with Locally Advanced Gastric Cancer Featuring Adjacent Tissue Invasion or JGCA Bulky N2 Lymph Node Metastases
Authors
Tatsushi Inoue, MD
Shinichi Yachida, MD, PhD
Hisashi Usuki, MD, PhD
Tomoki Kimura, MD, PhD
Masanobu Hagiike, MD, PhD
Keiichi Okano, MD, PhD
Yasuyuki Suzuki, MD, PhD
Publication date
01-09-2012
Publisher
Springer-Verlag
Published in
Annals of Surgical Oncology / Issue 9/2012
Print ISSN: 1068-9265
Electronic ISSN: 1534-4681
DOI
https://doi.org/10.1245/s10434-012-2332-4

Other articles of this Issue 9/2012

Annals of Surgical Oncology 9/2012 Go to the issue