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Published in: International Journal of Clinical Oncology 5/2014

01-10-2014 | Original Article

Efficacy of S-1 plus cisplatin combination chemotherapy in patients with HER2-positive advanced gastric cancer

Authors: Yoshitaka Honma, Yasuhiro Shimada, Atsuo Takashima, Satoru Iwasa, Ken Kato, Tetsuya Hamaguchi, Yasuhide Yamada, Hirokazu Taniguchi, Shigeki Sekine, Ryoji Kushima

Published in: International Journal of Clinical Oncology | Issue 5/2014

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Abstract

Background

Combination chemotherapy with trastuzumab and cisplatin plus capecitabine or 5-fluorouracil has been used as a standard regimen for HER2-positive gastric cancer (GC) since the Trastuzumab for Gastric Cancer (ToGA) trial. Before the ToGA trial, HER2-positive GC in Japan was treated with S-1 plus cisplatin (SP). The primary objective of this retrospective study was to explore the efficacy of SP in HER2-positive GC.

Methods

We reviewed patients who had received SP as first-line chemotherapy at our institute between April 2007 and March 2011 and from whom we had enough samples to examine HER2 status. Seventy-seven patients fulfilled the selection criteria and were tested for HER2 status with immunohistochemical staining (IHC) and fluorescence in situ hybridization. The patients’ backgrounds were investigated to evaluate the clinicopathologic features of their HER2-positive GC, including survival.

Results

Seven (9.1 %) of 77 patients were judged to be IHC3+, and all of these had predominantly differentiated histology. HER2 positivity was associated with differentiated histology (P = 0.016) and liver metastasis (P = 0.025). Median overall survival was 23.6 months [95 % confidence interval (CI) 0.8–44.7] in HER2-positive GC and 12.9 months (95 % CI 8.3–17.5) in HER2-negative disease, but the difference was not statistically significant (P = 0.615). In multivariate analysis, HER2 status was not associated with survival outcomes.

Conclusion

Because of the retrospective nature of this study, we cannot conclude whether HER2 status influences the survival of patients who receive SP as first-line chemotherapy. Our study provides important historical data for prospective phase II studies of SP plus trastuzumab.
Literature
1.
go back to reference Ferlay J, Shin HR, Bray F et al (2010) Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer 127:2893–2917PubMedCrossRef Ferlay J, Shin HR, Bray F et al (2010) Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer 127:2893–2917PubMedCrossRef
2.
go back to reference Glimelius B, Hoff man K, Haglund U et al (1994) Initial or delayed chemotherapy with best supportive care in advanced gastric cancer. Ann Oncol 5:189–190PubMed Glimelius B, Hoff man K, Haglund U et al (1994) Initial or delayed chemotherapy with best supportive care in advanced gastric cancer. Ann Oncol 5:189–190PubMed
3.
go back to reference Pyrhonen S, Kuitunen T, Nyandoto P et al (1995) Randomised comparison of fluorouracil, epidoxorubicin and methotrexate (FEMTX) plus supportive care with supportive care alone in patients with non-resectable gastric cancer. Br J Cancer 71:587–591PubMedCrossRefPubMedCentral Pyrhonen S, Kuitunen T, Nyandoto P et al (1995) Randomised comparison of fluorouracil, epidoxorubicin and methotrexate (FEMTX) plus supportive care with supportive care alone in patients with non-resectable gastric cancer. Br J Cancer 71:587–591PubMedCrossRefPubMedCentral
4.
go back to reference Vanhoefer U, Rougier P, Wilke H et al (2000) Final results of a randomized phase III trial of sequential high-dose methotrexate, fluorouracil, and doxorubicin versus etoposide, leucovorin, and fluorouracil versus infusional fluorouracil and cisplatin in advanced gastric cancer: a trial of the European Organization for Research and Treatment of Cancer Gastrointestinal Tract Cancer Cooperative Group. J Clin Oncol 18:2648–2657PubMed Vanhoefer U, Rougier P, Wilke H et al (2000) Final results of a randomized phase III trial of sequential high-dose methotrexate, fluorouracil, and doxorubicin versus etoposide, leucovorin, and fluorouracil versus infusional fluorouracil and cisplatin in advanced gastric cancer: a trial of the European Organization for Research and Treatment of Cancer Gastrointestinal Tract Cancer Cooperative Group. J Clin Oncol 18:2648–2657PubMed
5.
go back to reference Ohtsu A, Shimada Y, Shirao K et al (2003) Randomized phase III trial of fluorouracil alone versus fluorouracil plus cisplatin versus uracil and tegafur plus mitomycin in patients with unresectable, advanced gastric cancer: the Japan Clinical Oncology Group Study (JCOG9205). J Clin Oncol 21:54–59PubMedCrossRef Ohtsu A, Shimada Y, Shirao K et al (2003) Randomized phase III trial of fluorouracil alone versus fluorouracil plus cisplatin versus uracil and tegafur plus mitomycin in patients with unresectable, advanced gastric cancer: the Japan Clinical Oncology Group Study (JCOG9205). J Clin Oncol 21:54–59PubMedCrossRef
6.
go back to reference Findlay M, Cunningham D, Norman A et al (1994) A phase II study in advanced gastro-esophageal cancer using epirubicin and cisplatin in combination with continuous infusion 5-fluorouracil (ECF). Ann Oncol 5:609–616PubMed Findlay M, Cunningham D, Norman A et al (1994) A phase II study in advanced gastro-esophageal cancer using epirubicin and cisplatin in combination with continuous infusion 5-fluorouracil (ECF). Ann Oncol 5:609–616PubMed
7.
go back to reference Cutsem EV, Moiseyenko VM, Tjulandin S et al (2006) Phase III study of docetaxel and cisplatin plus fluorouracil compared with cisplatin and fluorouracil as first-line therapy for advanced gastric cancer: a report of the V325 Study Group. J Clin Oncol 24:4991–4997PubMedCrossRef Cutsem EV, Moiseyenko VM, Tjulandin S et al (2006) Phase III study of docetaxel and cisplatin plus fluorouracil compared with cisplatin and fluorouracil as first-line therapy for advanced gastric cancer: a report of the V325 Study Group. J Clin Oncol 24:4991–4997PubMedCrossRef
8.
go back to reference Bang YJ, Van Cutsem E, Feyereislova A et al (2010) ToGA trial investigators. Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): a phase 3, open-label, randomized controlled trial. Lancet 376:687–697PubMedCrossRef Bang YJ, Van Cutsem E, Feyereislova A et al (2010) ToGA trial investigators. Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): a phase 3, open-label, randomized controlled trial. Lancet 376:687–697PubMedCrossRef
9.
go back to reference Cunningham D, Starling N, Rao S et al (2008) Capecitabine and oxaliplatin for advanced esophagogastric cancer. N Engl J Med 358:36–46PubMedCrossRef Cunningham D, Starling N, Rao S et al (2008) Capecitabine and oxaliplatin for advanced esophagogastric cancer. N Engl J Med 358:36–46PubMedCrossRef
10.
go back to reference Bang YJ, Van Cutsem E, Feyereislova A et al (2010) Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): a phase 3, open-label, randomised controlled trial. Lancet 376(9742):687–697PubMedCrossRef Bang YJ, Van Cutsem E, Feyereislova A et al (2010) Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): a phase 3, open-label, randomised controlled trial. Lancet 376(9742):687–697PubMedCrossRef
11.
go back to reference Boku N, Yamamoto S, Fukuda H, Gastrointestinal Oncology Study Group of the Japan Clinical Oncology Group et al (2009) Fluorouracil versus combination of irinotecan plus cisplatin versus S-1 in metastatic gastric cancer: a randomized phase 3 study. Lancet Oncol 10:1063–1069PubMedCrossRef Boku N, Yamamoto S, Fukuda H, Gastrointestinal Oncology Study Group of the Japan Clinical Oncology Group et al (2009) Fluorouracil versus combination of irinotecan plus cisplatin versus S-1 in metastatic gastric cancer: a randomized phase 3 study. Lancet Oncol 10:1063–1069PubMedCrossRef
12.
go back to reference Koizumi W, Narahara H, Hara T et al (2008) S-1 plus cisplatin versus S-1 alone for first-line treatment of advanced gastric cancer (SPIRITS trial): a phase III trial. Lancet Oncol 9:215–221PubMedCrossRef Koizumi W, Narahara H, Hara T et al (2008) S-1 plus cisplatin versus S-1 alone for first-line treatment of advanced gastric cancer (SPIRITS trial): a phase III trial. Lancet Oncol 9:215–221PubMedCrossRef
13.
go back to reference Wang YK, Gao CF, Yun T et al (2011) Assessment of ERBB2 and EGFR gene amplification and protein expression in gastric carcinoma by immunohistochemistry and fluorescence in situ hybridization. Mol Cytogenet 4(1):14CrossRef Wang YK, Gao CF, Yun T et al (2011) Assessment of ERBB2 and EGFR gene amplification and protein expression in gastric carcinoma by immunohistochemistry and fluorescence in situ hybridization. Mol Cytogenet 4(1):14CrossRef
14.
go back to reference Wu HM, Liu YH, Lin F et al (2011) Association of HER2 protein expression with clinicopathologic features and prognosis in Chinese patients with gastric carcinoma. Zhonghua Bing Li Xue Za Zhi (Chin J Pathol) 40(5):296–299 Wu HM, Liu YH, Lin F et al (2011) Association of HER2 protein expression with clinicopathologic features and prognosis in Chinese patients with gastric carcinoma. Zhonghua Bing Li Xue Za Zhi (Chin J Pathol) 40(5):296–299
15.
go back to reference Hofmann M, Stoss O, Shi D et al (2008) Assessment of a HER2 scoring system for gastric cancer: results from a validation study. Histopathology 52:797–805PubMedCrossRef Hofmann M, Stoss O, Shi D et al (2008) Assessment of a HER2 scoring system for gastric cancer: results from a validation study. Histopathology 52:797–805PubMedCrossRef
16.
go back to reference García I, Vizoso F, Martin A et al (2003) Clinical significance of the epidermal growth factor receptor and HER2 receptor in resectable gastric cancer. Ann Surg Oncol 10:234–241PubMedCrossRef García I, Vizoso F, Martin A et al (2003) Clinical significance of the epidermal growth factor receptor and HER2 receptor in resectable gastric cancer. Ann Surg Oncol 10:234–241PubMedCrossRef
17.
go back to reference Allgayer H, Babic R, Gruetzner KU et al (2000) C-erbB-2 is of independent prognostic relevance in gastric cancer and is associated with the expression of tumor-associated protease systems. J Clin Oncol 18:2201–2209PubMed Allgayer H, Babic R, Gruetzner KU et al (2000) C-erbB-2 is of independent prognostic relevance in gastric cancer and is associated with the expression of tumor-associated protease systems. J Clin Oncol 18:2201–2209PubMed
18.
go back to reference Kim KC, Koh YW, Chang HM et al (2011) Evaluation of HER2 protein expression in gastric carcinomas: comparative analysis of 1414 cases of whole-tissue sections and 595 cases of tissue microarrays. Ann Surg Oncol 18(10):2833–2840PubMedCrossRef Kim KC, Koh YW, Chang HM et al (2011) Evaluation of HER2 protein expression in gastric carcinomas: comparative analysis of 1414 cases of whole-tissue sections and 595 cases of tissue microarrays. Ann Surg Oncol 18(10):2833–2840PubMedCrossRef
19.
go back to reference Terashima M, Kitada K, Ochiai A et al (2012) Impact of expression of human epidermal growth factor receptors EGFR and ERBB2 on survival in stage II/III gastric cancer. Clin Cancer Res 18(21):5992–6000PubMedCrossRef Terashima M, Kitada K, Ochiai A et al (2012) Impact of expression of human epidermal growth factor receptors EGFR and ERBB2 on survival in stage II/III gastric cancer. Clin Cancer Res 18(21):5992–6000PubMedCrossRef
20.
go back to reference Yoshida M, Ohtsu A, Boku N et al (2004) Long-term survival and prognostic factors in patients with metastatic gastric cancers treated with chemotherapy in the Japan Clinical Oncology Group (JCOG) study. Jpn J Clin Oncol 34(11):654–659PubMedCrossRef Yoshida M, Ohtsu A, Boku N et al (2004) Long-term survival and prognostic factors in patients with metastatic gastric cancers treated with chemotherapy in the Japan Clinical Oncology Group (JCOG) study. Jpn J Clin Oncol 34(11):654–659PubMedCrossRef
21.
go back to reference Thuss-Patience PC, Kretzschmar A, Bichev D et al (2011) Survival advantage for irinotecan versus best supportive care as second-line chemotherapy in gastric cancer––a randomised phase III study of the Arbeitsgemeinschaft Internistische Onkologie (AIO). Eur J Cancer 15:2306–2314CrossRef Thuss-Patience PC, Kretzschmar A, Bichev D et al (2011) Survival advantage for irinotecan versus best supportive care as second-line chemotherapy in gastric cancer––a randomised phase III study of the Arbeitsgemeinschaft Internistische Onkologie (AIO). Eur J Cancer 15:2306–2314CrossRef
22.
go back to reference Kang JH, Lee SI, Lim do H et al (2012) Salvage chemotherapy for pretreated gastric cancer: a randomized phase III trial comparing chemotherapy plus best supportive care with best supportive care alone. J Clin Oncol 30:1513–1518PubMedCrossRef Kang JH, Lee SI, Lim do H et al (2012) Salvage chemotherapy for pretreated gastric cancer: a randomized phase III trial comparing chemotherapy plus best supportive care with best supportive care alone. J Clin Oncol 30:1513–1518PubMedCrossRef
23.
go back to reference Grabsch H, Sivakumar S, Gray S et al (2010) HER2 expression in gastric cancer: rare, heterogeneous and of no prognostic value: conclusions from 924 cases of two independent series. Cell Oncol 32:57–65PubMed Grabsch H, Sivakumar S, Gray S et al (2010) HER2 expression in gastric cancer: rare, heterogeneous and of no prognostic value: conclusions from 924 cases of two independent series. Cell Oncol 32:57–65PubMed
24.
go back to reference Lee EY, Cibull ML, Strodel WE et al (1994) Expression of HER-2/neu oncoprotein and epidermal growth factor receptor and prognosis in gastric carcinoma. Arch Pathol Lab Med 118:235–239PubMed Lee EY, Cibull ML, Strodel WE et al (1994) Expression of HER-2/neu oncoprotein and epidermal growth factor receptor and prognosis in gastric carcinoma. Arch Pathol Lab Med 118:235–239PubMed
25.
go back to reference Marx AH, Tharun L, Muth J et al (2009) HER-2 amplification is highly homogenous in gastric cancer. Hum Pathol 40:769–777PubMedCrossRef Marx AH, Tharun L, Muth J et al (2009) HER-2 amplification is highly homogenous in gastric cancer. Hum Pathol 40:769–777PubMedCrossRef
Metadata
Title
Efficacy of S-1 plus cisplatin combination chemotherapy in patients with HER2-positive advanced gastric cancer
Authors
Yoshitaka Honma
Yasuhiro Shimada
Atsuo Takashima
Satoru Iwasa
Ken Kato
Tetsuya Hamaguchi
Yasuhide Yamada
Hirokazu Taniguchi
Shigeki Sekine
Ryoji Kushima
Publication date
01-10-2014
Publisher
Springer Japan
Published in
International Journal of Clinical Oncology / Issue 5/2014
Print ISSN: 1341-9625
Electronic ISSN: 1437-7772
DOI
https://doi.org/10.1007/s10147-013-0629-3

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