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

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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.

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References

  1. Ferlay J, Shin HR, Bray F et al (2010) Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer 127:2893–2917

    Article  PubMed  CAS  Google Scholar 

  2. Glimelius B, Hoff man K, Haglund U et al (1994) Initial or delayed chemotherapy with best supportive care in advanced gastric cancer. Ann Oncol 5:189–190

    PubMed  CAS  Google Scholar 

  3. 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 71:587–591

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  4. 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 18:2648–2657

    PubMed  CAS  Google Scholar 

  5. 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 21:54–59

    Article  PubMed  CAS  Google Scholar 

  6. 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 5:609–616

    PubMed  CAS  Google Scholar 

  7. 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 24:4991–4997

    Article  PubMed  Google Scholar 

  8. 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 376:687–697

    Article  PubMed  CAS  Google Scholar 

  9. Cunningham D, Starling N, Rao S et al (2008) Capecitabine and oxaliplatin for advanced esophagogastric cancer. N Engl J Med 358:36–46

    Article  PubMed  CAS  Google Scholar 

  10. 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):687–697

    Article  PubMed  CAS  Google Scholar 

  11. 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 10:1063–1069

    Article  PubMed  CAS  Google Scholar 

  12. 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 9:215–221

    Article  PubMed  CAS  Google Scholar 

  13. 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):14

    Article  Google Scholar 

  14. 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

    CAS  Google Scholar 

  15. Hofmann M, Stoss O, Shi D et al (2008) Assessment of a HER2 scoring system for gastric cancer: results from a validation study. Histopathology 52:797–805

    Article  PubMed  CAS  Google Scholar 

  16. 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 10:234–241

    Article  PubMed  Google Scholar 

  17. 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 18:2201–2209

    PubMed  CAS  Google Scholar 

  18. 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):2833–2840

    Article  PubMed  Google Scholar 

  19. 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):5992–6000

    Article  PubMed  CAS  Google Scholar 

  20. 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):654–659

    Article  PubMed  Google Scholar 

  21. 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 15:2306–2314

    Article  Google Scholar 

  22. 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 30:1513–1518

    Article  PubMed  CAS  Google Scholar 

  23. 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 32:57–65

    PubMed  Google Scholar 

  24. 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 118:235–239

    PubMed  CAS  Google Scholar 

  25. Marx AH, Tharun L, Muth J et al (2009) HER-2 amplification is highly homogenous in gastric cancer. Hum Pathol 40:769–777

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

We thank Ms. Hiromi Orita and Ms. Emiko Usami for data collection. This study was supported by the National Cancer Center Research and Development Fund (grant no. 23-A-19).

Conflict of interest

The authors declare that they have no conflict of interest.

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Correspondence to Yoshitaka Honma.

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Honma, Y., Shimada, Y., Takashima, A. et al. Efficacy of S-1 plus cisplatin combination chemotherapy in patients with HER2-positive advanced gastric cancer. Int J Clin Oncol 19, 863–870 (2014). https://doi.org/10.1007/s10147-013-0629-3

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  • DOI: https://doi.org/10.1007/s10147-013-0629-3

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