Cancer Treatment Today

Herceptin is indicated, in combination with cisplatin and capecitabine or 5-fluorouracil, for the treatment of patients with HER2 overexpressing metastatic gastric or gastroesophageal junction adenocarcinoma, who have not received prior treatment for metastatic disease.

22% of patients with advanced gastric cancer overexpress human epidermal growth-factor receptor 2 (HER2), and these patients had significantly improved overall survival when trastuzumab (Herceptin) is added to chemotherapy, compared with chemotherapy alone. In a study presented in 2009 ASCO, the improvement in overall survival was 2.7 months, from 11.1 months in the chemotherapy group to 13.8 months in the trastuzumab group (hazard ratio, 0.74, P = .0046).  Similar results were shown by ToGA, a large international Phase III trial investigating the benefit of Herceptin as the first therapy for patients with advanced and inoperable stomach cancer (first line).

Several phase II trials have investigated second-line chemotherapy in esophago-gastric cancers using irinotecan and taxanes, but phase III data and data with trastuzumab are currently lacking. NCCN recommends irinotecan with cisplatin in teh peri-operative settings but for systemic and recurrent disease it does nto specifically list irinotecan. However, it would be included under trastuzumab with other chemotherapy as category 2A for second line. It considers irintoecan with cisplatin, mitomycin, fluoropyrimindines or docetaxe, or by itself to be category 2B recommendation for second line and it lists irinotecan with fluoropyrimidines or docetaxel for fist line.

Information about previous therapy has not been provided. It is possible that some of the current drugs had already been used, which would fartehr make this coimbination not medically appropriate. In addition, there is no documentation of HER positivity.
Van Cutsem E, Kang Y, Chung H et al. Efficacy results from the ToGA trial: a Phase III study of trastuzumab added to standard chemotherapy (CT) in first-line human epidermal growth factor receptor 2 (HER2)-positive advanced gastric cancer (GC). Presented at the 2009 annual meeting of the American Society of Clinical Oncology, May 29-June 2, 2009, Orlando, FL. Abstract LBA4509.

Y. Kang, Y. Bang, F. Lordick, S. Park, A. Sawaki, H. Chung, L. Shen, J. M. Xu, J. Leon-Chong, E. Van Cutsem Incidence of gastric and gastro-esophageal cancer in the ToGA trial: Correlation with HER2 positivity 2008 Gastrointestinal Cancers Symposium , Ab. 11

 M. MacKenzie, MD, K. Spithoff, MSc, D. Jonker, MD Systemic therapy for advanced gastric cancer: a clinical practice guidelineOncology Vol 18, No 4 (2011)

Thuss-Patience PC, Kretzschmar A, Deist T, et al. Irinotecan versus best supportive care (BSC) as second-line therapy in gastric cancer:
a randomized phase III study of the Arbeitsgemeinschaft Internistische Onkologie (AIO). J Clin Oncol. 2009;27(Suppl 15):Abstr 4540.

Cunningham D, Park S, Kang Y, et al. Randomized phase II study of PEP02, irinotecan, or docetaxel as a second-line therapy in gastric
or gastroesophageal junction adenocarcinoma. J Clin Oncol. 2011;29(Suppl 4):Abstr 6.

nccn, gastric, GAST-E, 2012