Anti-VEGF Therapy Overexpression of vascular endothelial growth factor (VEGF), which plays a role in the regulation of angiogenesis contributing to the survival of newly formed blood vessels, is seen in 30% to 60% of patients with esophageal cancer, and has been linked with advanced stage at diagnosis and reduced survival.16
Bevacizumab, a humanized IgG1 monoclonal antibody that targets VEGF, was studied in combination with irinotecan and cisplatin in a phase 2 trial of patients with metastatic or unresectable gastroesophageal junction cancer (n=23) or gastric cancer (n=24).23 Cisplatin 30 mg/m2 and irinotecan 65 mg/m2 were given on Days 1 and 8, and bevacizumab 15 mg/kg was given on Day 1 of each 21-day cycle.23 After a median follow-up of 12.2 months, median time to progression was 8.3 months (95% CI 5.5, 9.9) with a 75% improvement over historical control.23 In the 34 patients with measurable disease, the overall response rate was 65% (95% CI 46%, 80%); median overall survival was 12.3 months (95% CI 11.3, 17.2).23 During treatment with bevacizumab, 13 patients (28%) developed grade 3 hypertension, and three experienced a gastric perforation or near-perforation.23
Sunitinib, an oral tyrosine kinase inhibitor with activity against VEGF receptors and platelet-derived growth factors, was investigated in combination with paclitaxel in a phase 2 trial of 28 patients with advanced esophageal or gastroesophageal junction cancer, with disappointing results.24 The 24-week progression-free survival rate of 25% was not superior to those of historical controls treated with paclitaxel alone, and there was a high rate of serious toxicity.
A limited number of trials have found benefit from targeted therapy for esophageal cancer, but most did not determine whether subjects’ tumors overexpressed the signaling pathway targeted by the study drug. Better matching of patient to therapy may eventually lead to truly individualized cancer treatment, where a drug is chosen for its ability to disrupt a specific signaling pathway that is overexpressed in the patient’s tumor.
1. Gethins M. International Cancer Conference: targeted therapies boom expected in 3-5 years. J Natl Cancer Inst. 2011;103(20):1491-1493.
2. Kleinberg LR, Brock MV, Jagannath SB, Forastiere AA. Cancer of the esophagus. In: Abeloff MD, Armitage JO, Niederhuber JE, Kastan MB, McKenna WG, eds. Abeloff’s Clinical Oncology. 4th ed. Philadelphia, PA: Churchill Livingstone Elsevier; 2008.
3. Lagergren J, Bergström R, Lindgren A, Nyrén O. Symptomatic gastroesophageal reflux as a risk factor for esophageal adenocarcinoma. N Engl J Med. 1999;340(11):825-831.
4. Duan L, Wu AH, Sullivan-Halley J, Bernstein L. Antacid drug use and risk of esophageal and gastric adenocarcinomas in Los Angeles County. Cancer Epidemiol Biomarkers Prev. 2009;18(2):526-533.
5. Adams R, Morgan M, Mukherjee S, et al. A prospective comparison of multidisciplinary treatment of oesophageal cancer with curative intent in a UK cancer network. Eur J Surg Oncol. 2007;33(3):307-313.
6. Scarpa M, Valente S, Alfieri R, et al. Systematic review of health-related quality of life after esophagectomy for esophageal cancer. World J Gastroenterol. 2011;17(42):4660-4674.
7. Tytgat GN. Recent developments in gastroesophageal reflux disease and Barrett’s esophagus: ANNO 2012. J Dig Dis. 2012;13(6):291-295.