| General information |
| Database: | DB00439 |
| Objective: | At presentation, most cases of adenocarcinoma of the esophagus (ACE) are inoperable. Although chemotherapy can prolong survival, patients eventually die as a result of refractory disease. Epidermal growth factor receptor (EGFR) is almost universally expressed in ACE and is a negative prognostic factor. |
| Authors: | Ferry DR, et al |
| Title: | a phase II study of gefitinib monotherapy in advanced esophageal adenocarcinoma: evidence of gene expression, cellular, and clinical response. |
| Journal: | Clin Cancer Res. |
| Year: | 2007 |
| PMID: | 17908981 |
| Trial Design |
| Clinical Trial Id: | NA |
| Agent: | gefitinib
|
| Target: | Epidermal growth factor receptor
|
| Cancer Type: | esophagusgastroesophageal junction cancer |
| Cancer Subtype: | adenocarcinoma of the esophagus (ACE) or adenocarcinoma of the esophagogastric junction |
| Therapy Type: | mono |
| Therapeutic Combination Type: | NA |
| Therapeutic Combination Content: | NA |
| Study Type: | open label, two center, non comparative, two part phase II trial |
| Key Patients Feature: | All patients provided written, informed consent.ACE was classified according to the WHO classification of esophagealtumors (16). Barrett's esophagus was also confirmed histologically, inassociation with endoscopic findings using accepted criteria (17-19).Inclusion criteria were histologically confirmed ACE or adenocarcinoma of the esophagogastric junction, locally advanced or metastaticdisease that was incurable with surgery, measurable disease accordingto Response Evaluation Criteria In Solid Tumors standards, the abilityto swallow tablets (patients with dysphagia could have dilation ormetal stent insertion prior to trial entry), and those aged z18 years. |
| Biomarker: | NA |
| Biomark Analysis: | NA |
| Control Group Info: | single arm |
| Treatment Info: | The protocol consisted of oral gefitinib 250 mg daily for 1 year plus intravenous oxaliplatin 85 or 100 mg/m(2) on days 1, 15, and 29, and RT (50.4 Gy in 28 1.8Gy fractions). Fourquadrant biopsies were obtained at 1cm intervals along the length of the tumor before and after treatment and the specimens were immunostained for EGFR, Erk, Akt, and their phosphorylated (activated) forms. |
| Primary End Point: | PFS, OS |
| Secondary End Point: | NA |
| Patients Number: | 27 |
| Trial Results |
| DLT_MTD: | NA |
| Objective Response Rate: | Three patients had a partial response and seven had stable disease, giving a disease control rate(partial response + stable disease) of3 7%. |
| Disease Control Rate: | 0.37 |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | 1.9 months (95% confidence interval, 1.02.7) |
| Median OS A vs. C: | 4.5 months |
| Adverse Event(agent arm): | Drugrelated adverse events were generally mild: diarrhea in 19 (grade 3 in three) and rash in 19 (grade 3 in five) patients, and there were no grade 4 drugrelated adverse events. |
| Conclusions: | Gefitinib (500 mgd) is an active and generally welltolerated treatment for ACE. Studies on endoscopic biopsies are feasible and indicate that gefitinib inhibits both gene expression and cellular biology at 500 mgd, and these may provide surrogate end points for predictive biomarkers. Further trials of gefitinib are warranted, particularly as patient response seems to be durable and current secondline chemotherapy options have no proven ability to prolong life. |