Article thumbnail

Critical appraisal of trastuzumab in treatment of advanced stomach cancer

By Judith Meza-Junco, Heather-Jane Au and Michael B Sawyer

Abstract

Advanced or metastatic gastric cancer constitutes the majority of patients in clinical practice. In North America, about 70% of cases are advanced or metastatic when diagnosed, which is higher than the 50% reported in Japan. This difference in presentation is reflected in 5-year overall survival, which is about 20% in North America and 40%–60% in Japan. Despite numerous efforts of randomized studies on advanced gastric cancer, no globally accepted standard regimen has yet been established. Systemic chemotherapy provides palliation and prolongs survival, but the prognosis remains poor. Several monotherapies and combined regimens are currently available and vary around the world. Additionally, several molecular targeting agents are under evaluation in international randomized studies. Human epidermal growth factor receptor-2 (HER-2) is overexpressed or amplified in approximately 22% of patients with gastric cancer. Trastuzumab, a recombinant humanized anti-HER-2 monoclonal antibody, is the first biological therapy that has showed a survival improvement by nearly three months (reduced risk of death by 26%). Therefore, trastuzumab in combination with cisplatin is a reasonable treatment option for patients with advanced gastric cancer who are HER-2 positive. This paper will focus on trastuzumab, its chemical and pharmacological characteristics, and the relevant efficacy, safety, and tolerability studies

Topics: Review
Publisher: Dove Medical Press
OAI identifier: oai:pubmedcentral.nih.gov:3085240
Provided by: PubMed Central

To submit an update or takedown request for this paper, please submit an Update/Correction/Removal Request.

Suggested articles

Citations

  1. A phase I, dose-finding study of sunitinib (su) in combination with cisplatin (p) and 5-fluorouracil (5-fu) in patients (pts) with advanced gastric cancer (gc). Ann Oncol. 2010;21 Suppl 8:S818.
  2. (2008). A phase II study of bevacizumab, docetaxel, and oxaliplatin in gastric and gastroesophageal junction (GEJ) cancer.
  3. A phase II SWOG study of GW572016 (lapatinib) as first line therapy in patients (pts) with advanced or metastatic gastric cancer.
  4. (2008). A phase III randomized comparison of lapatinib plus capecitabine versus capecitabine alone in women with advanced breast cancer that has progressed on trastuzumab: Updated efficacy and biomarker analyses. Breast Cancer Res Treat.
  5. (2009). A prospective phase II study of cetuximab in combination with XELOX (capecitabine and oxaliplatin) in patients with metastatic and/or recurrent advanced gastric cancer. Invest New Drugs.
  6. Advances in the treatment of patients with gastric adenocarcinoma.
  7. (2005). Amplification of HER-2 in gastric carcinoma: Association with topoisomerase II alpha gene amplification, intestinal type, poor prognosis and sensitivity to trastuzumab. Ann Oncol.
  8. Association of ERBB2 gene status with histopathological parameters and disease-specific survival in gastric carcinoma patients.
  9. (2008). ATTAX2: Docetaxel plus cetuximab as second-line treatment for docetaxel refractory oesophago-gastric cancer – final results of a multicentre phase II trial by the AGITG. J Clin Oncol.
  10. (2010). Cancer Facts and Figures
  11. Cardiac dysfunction in the trastuzumab clinical trials experience.
  12. Cetuximab plus oxaliplatin/ leucovorin/5-fluorouracil in first-line metastatic gastric cancer: A phase II study of the Arbeitsgemeinschaft Internistische Onkologie (AIO).
  13. (2008). Cetuximab with irinotecan as salvage therapy in heavily pretreated patients with metastatic gastric cancer.
  14. Chemotherapy for metastatic gastric cancer in Japan.
  15. Chemotherapy for metastatic gastric cancer: Past, present, and future.
  16. Chemotherapy in advanced gastric cancer: A systematic review and meta-analysis based on aggregate data.
  17. Chemotherapy in gastric cancer: A review and updated meta-analysis.
  18. Cisplatin (P) in patients (pts) with advanced or metastatic gastric cancer (CG). Ann Oncol. 2010;21 Suppl 8:S816.
  19. Clinical benefit with docetaxel plus fluorouracil and cisplatin compared with cisplatin and fluorouracil in a phase III trial of advanced gastric or gastroesophageal cancer adenocarcinoma: The V-325 Study Group.
  20. (2006). Comparison of HER2 gene amplification assessed by fluorescence in situ hybridization and HER2 protein expression assessed by immunohistochemistry in gastric cancer. Oncol Rep.
  21. Current perspective – trastuzumab.
  22. Effect of trastuzumab on health-related quality of life in patients with HER2-positive metastatic breast cancer: Data from three clinical trials.
  23. Effects on quality of life of combined trastuzumab and chemotherapy in women with metastatic breast cancer.
  24. (2003). Efficacy, tolerability and pharmacokinetics of gefitinib (ZD1839) in pretreated patients with metastatic gastric cancer. Proc Am Soc Clin Oncol.
  25. Epidemiology of gastric cancer in Japan.
  26. Epirubicin, oxaliplatin, and capecitabine with or without panitumumab for advanced esophagogastric cancer: Dose-finding study for the prospective multicenter, randomized, phase II/III REAL-3 trial.
  27. (2007). Evaluation of HER-2 gene status in gastric carcinoma using immunohistochemistry, fluorescence in situ hybridization, and real-time quantitative polymerase chain reaction. Hum Pathol.
  28. Final results of the intergroup FFCD-GERCOR-FNCLCC 03-07 phase III study comparing two sequences of chemotherapy in advanced gastric cancers. Ann Oncol. 2010;21 Suppl 8:S8010.
  29. (2008). FOLFOX6 and bevacizumab (FOLFOX6/B) for metastatic esophageal (E), gastroesophageal (GE), and gastric (G) adenocarcinoma: A single institution’s initial clinical experience.
  30. Gastric cancer in the era of molecularly targeted agents: current drug development strategies.
  31. Gastric cancer: Pathogenesis, screening, and treatment.
  32. Growth inhibitory effects of trastuzumab and chemotherapeutic drugs in gastric cancer cell lines.
  33. (2009). HER-2 amplification is highly homogenous in gastric cancer. Hum Pathol.
  34. (1992). Humanization of an antip185HER2 antibody for human cancer therapy.
  35. Irinotecan versus best supportive care (BSC) as second-line therapy in gastric cancer: A randomized phase
  36. Lapatinib 1 capecitabine in advanced gastric cancer: An open-label phase II study of non ERBB2-targeted disease. Ann Oncol. 2010;21 Suppl 8:S817.
  37. Lapatinib plus capecitabine for HER2-positive advanced breast cancer.
  38. Matuzumab plus epirubicin, cisplatin and capecitabine (ECX) compared with epirubicin, cisplatin and capecitabine alone as first-line treatment in patients with advanced oesophago-gastric cancer: A randomised, multicentre open-label phase II study.
  39. Modified therapy with 5-fluorouracil, doxorubicin, and methotrexate in advanced gastric cancer.
  40. Multicenter phase II study of irinotecan, cisplatin and bevacizumab in patients with metastatic gastric or gastroesophageal junction adenocarcinoma.
  41. (2009). Novel anticancer targets: Revisiting ERBB2 and discovering ERB3. Nat Rev Cancer.
  42. Novel chemotherapy combinations in advanced gastric cancer: An updated meta-analysis. Ann Oncol.
  43. Our experience in the use of trastuzumab in patients with advanced stomach cancer. Ann Oncol. 2010;21 Suppl 8:S839.
  44. Overexpression of Grb2/HER2 signaling in Chinese gastric cancer: their relationship with clinicopathological parameters and prognostic significance.
  45. (2009). Pathological features of advanced gastric cancer (GC): Relationship to human epidermal growth factor receptor 2 (HER2) positivity in the global screening programme of the ToGA trial. J Clin Oncol.
  46. Pharmacology and therapeutic use of trastuzumab in breast cancer.
  47. Phase I study of epirubicin, cisplatin and capecitabine plus matuzumab in previously untreated patients with advanced oesophagogastric cancer.
  48. Phase II of trastuzumab and cisplatin in patients (pts) with advanced gastric cancer (AGC) with HER2/ neu overexpression/amplification.
  49. (2006). Phase II study of bevacizumab and docetaxel in metastatic esophageal and gastric cancer.
  50. Phase II study of cetuximab in combination with cisplatin and docetaxel in patients with untreated advanced gastric or gastro-oesophageal junction adenocarcinoma (DOCETUX study).
  51. (2007). Phase II study of cetuximab in combination with FOLFIRI in patients with untreated advanced gastric or gastroesophageal junction adenocarcinoma (FOLCETUX study). Ann Oncol.
  52. Phase II study of everolimus in patients with advanced gastric cancer refractory to chemotherapy including fluoropyrimidine and platinum. Ann Oncol. 2010;21 Suppl 8:S725.
  53. Phase II study of sorafenib in combination with docetaxel and cisplatin in the treatment of metastatic or advanced gastric and gastroesophageal junction adenocarcinoma: ECOG 5203.
  54. (2010). Phase II study of sunitinib as second-line treatment for advanced gastric cancer. Invest New Drugs.
  55. Phase III study of docetaxel and cisplatin plus fluorouracil compared with cisplatin and fluorouracil as first-line therapy for advanced gastric cancer:
  56. (2008). Post-marketing safety of antineoplasic MAb: Rituximab and trastuzumab. Pharmacoepidemiol Drug Saf.
  57. Prospective randomized trial comparing mitomycin, cisplatin, and protracted venous-infusion fluorouracil (PVI 5-FU) with epirubicin, cisplatin, and PVI 5-FU in advanced esophagogastric cancer.
  58. Randomised comparison of fluorouracil, epidoxorubicin and methotrexate (FEMTX) plus supportive care with supportive care alone in patients with non-resectable gastric cancer.
  59. (1997). Randomized comparison between chemotherapy plus best supportive care with best supportive care in advanced gastric cancer. Ann Oncol.
  60. Randomized phase II evaluation of irinotecan plus high-dose 5-fluorouracil and leucovorin (ILF) versus 5-fluorouracil, leucovorin, and etoposide (ELF) in untreated metastatic gastric cancer.
  61. Randomized phase III study of 5-fluorouracil (5-FU) alone versus combination of irinotecan and cisplatin (CP) versus S-1 alone in advanced gastric cancer (JCOG9912). J Clin Oncol. 2007;25 Suppl 18:SLBA4513T.
  62. (2008). Randomized phase III study of irinotecan plus S-1 (IRIS) versus S-1 alone as first-line treatment for advanced gastric cancer (GC0301/TOP-002). Poster A5 presented at the ASCO Gastrointestinal Cancers Symposium,
  63. Randomized phase III trial of irinotecan (CPT 11) 5-FU/folinic acid (FA) vs CDDP–5-FU in first line advanced gastric cancer patients.
  64. Review of second-line chemotherapy for advanced gastric adenocarcinoma.
  65. (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.
  66. (2010). Second-line chemotherapy with irinotecan plus cisplatin after the failure of S-1 monotherapy for advanced gastric cancer. Gastric Cancer.
  67. Sunitinib (su) with cisplatin (p) and capecitabine (x) or oxaliplatin (o) and x (xelox) in advanced gastric cancer (gc) – a phase I, dose-finding study.
  68. Sunitinib as second line treatment for advanced gastric cancer: Preliminary results from a phase II study.
  69. SWOG 0127 phase II trial of erlotinib in GEJ and gastric adenocarcinoma.
  70. 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.
  71. Trastuzumab – mechanism of action and use in clinical practice.
  72. (2007). Trastuzumab: Mechanism of action, resistance and future perspectives in HER2-overexpressing breast cancer. Ann Oncol.
  73. Upper Gastrointestinal Clinical Studies Group of the National Cancer Research Institute of the United Kingdom. Capecitabine and oxaliplatin for advanced esophagogastric cancer.
  74. (2009). Weekly paclitaxel for heavily treated advanced or recurrent gastric cancer refractory to fluorouracil, irinotecan, and cisplatin. Gastric Cancer.