| General information |
| Database: | DB00438 |
| Objective: | Overexpression of epidermal growth factor receptor (EGFR) in esophageal cancer is associated with poor prognosis. Preclinical studies indicate synergism between the EGFR inhibitor gefitinib and oxaliplatin or radiotherapy (RT). They report here early results of a plannedphase I/II study of gefitinib, oxaliplatin, and RT for locally advanced, unresectable esophageal cancer. |
| Authors: | Javle M, et al |
| Title: | Pilot study of gefitinib, oxaliplatin, and radiotherapy for esophageal adenocarcinoma: tissue effect predicts clinical response. |
| Journal: | Am J Clin Oncol. |
| Year: | 2008 |
| PMID: | 18845990 |
| Trial Design |
| Clinical Trial Id: | NA |
| Agent: | gefitinib
|
| Target: | Epidermal growth factor receptor
|
| Cancer Type: | esophageal cancer |
| Cancer Subtype: | advanced esophageal adenocarcinomaor squamous cell carcinoma |
| Therapy Type: | com |
| Therapeutic Combination Type: | 3 |
| Therapeutic Combination Content: | gefitinib, oxaliplatin, and radiotherapy |
| Study Type: | Pilot Study (early results of a planned phase I/II study) |
| Key Patients Feature: | Eligibility criteria included a histologic diagnosis of esophageal adenocarcinomaor squamous cell carcinoma that was American Joint Committee on Cancer stage III-IVA and inoperable. Additionaleligibility requirements were age older than 18 years, anEastern Cooperative Oncology Group performance statusscore of 0 to 1, life expectancy of more than 4 months, andadequate organ and bone marrow function, as indicated byleukocyte levels 3000/ L, granulocytes 1500/ L, platelets 100, 000/ L, normal values of bilirubin, alkaline phosphatase, and alanine and aspartate aminotransferases 2.5the upper limits of normal. |
| Biomarker: | EGFR, Erk, Akt, and their phosphorylated (activated) forms |
| Biomark Analysis: | EGFR was expressed by tumor in 5 cases and Erk and Akt in 6 cases before treatment; no changes were noted after treatment. EGFR expression did not correlate with survival or response. |
| 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: | best response, toxicities, PFS, OS |
| Secondary End Point: | NA |
| Patients Number: | 6 |
| Trial Results |
| DLT_MTD: | no grade 4 toxicities were noted; 2 patients experiencedgrade 3 toxicities at dose level 1 (Table 3); and the mostcommon grade 1 or 2 toxic effects were skin rash (n=5), fatigue (n=5), dehydration (n=3), neuropathy (n=3), dysphagia (n=3), and nausea (n=2). No dose modificationswere needed for toxicity from oxaliplatin |
| Objective Response Rate: | 1 patient experiencedmucosal complete response, 1 showed a partial response, and1 had stable disease. Two enrolled patients could not beevaluated, one for not completing the first treatment cycle and the other for having had a change in diagnosis to nonHodgkin lymphoma. |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | 8.4 months |
| Median OS A vs. C: | 10.8 months |
| Adverse Event(agent arm): | No grade 4 toxicities were noted; grade 3 toxicities were diarrhea (n=1), vomiting (n=1), fatigue (n=1), and constipation (n=2). |
| Conclusions: | Gefitinib in combination with oxaliplatin and RT was tolerable, but had limited clinical activity and did not downregulate total or activated EGFR, Akt, or Erk in esophageal tumor samples. |