| General information |
| Database: | DB00446 |
| Objective: | To determine the overall survival for patients with locally advanced, human epidermal growth factor receptor 2 overexpressing, esophageal adenocarcinoma receiving trastuzumab, paclitaxel, cisplatin, and radiation on a phase III study. |
| Authors: | Safran H, et al |
| Title: | Phase I/II study of trastuzumab, paclitaxel, cisplatin and radiation for locally advanced, human epidermal growth factor receptor 2 overexpressing, esophageal adenocarcinoma. |
| Journal: | Int J Radiat Oncol Biol Phys. |
| Year: | 2007 |
| PMID: | 17097832 |
| Trial Design |
| Clinical Trial Id: | NA |
| Agent: | trastuzumab
|
| Target: | Receptor proteintyrosine kinase erbB2
|
| Cancer Type: | esophageal cancer |
| Cancer Subtype: | advanced esophagogastric cancer |
| Therapy Type: | com |
| Therapeutic Combination Type: | 3 |
| Therapeutic Combination Content: | trastuzumab, paclitaxel, cisplatin and radiation |
| Study Type: | PHASE I/II STUDY |
| Key Patients Feature: | Eligible patients included those with histologically documentedadenocarcinoma of the esophagus and T3, T4, or nodal disease.Patients with extensive locoregional disease such as gastric extension, and adenopathy that included mediastinal, celiac, portal, andretroperitoneal disease were eligible Required laboratory parameters included: granulocyte count 1, 500 cells/ L, platelet count 100, 000 cells/ L, bilirubin 2mg/dL, and creatinine 2 mg/dL. patients were required to have aleft ventricular ejection fraction 45% and be without uncontrolled cardiac disease. |
| Biomarker: | human epidermal growth factor receptor 2overexpressing |
| Biomark Analysis: | Evaluation of human epidermal growth factor receptor 2 status should be performed infuture trials for patients with adenocarcinoma of the esophagus that investigate therapies targeting the HERfamily. |
| Control Group Info: | single arm |
| Treatment Info: | All patients received cisplatin 25 mg/m2 and paclitaxel 50 mg/m2 weekly for 6 weeks with radiation therapy (RT) 50.4 Gy. Patients received trastuzumab at dose levels of 1, 1.5, or 2 mg/kg weekly for 5 weeks after an initial bolus of 2, 3, or 4 mg/kg. |
| Primary End Point: | overall survival |
| Secondary End Point: | NA |
| Patients Number: | 19 |
| Trial Results |
| DLT_MTD: | NA |
| Objective Response Rate: | The complete clinical response for patients with 3 IHCor an increase in human epidermal growth factor receptor 2 gene copy number was 8 of 14(57%). Of the 8 patients with clinical complete response, 2refused surgery and 6 underwent surgical exploration (3 hada pathologic complete response, 1 had microscopic residualcancer, and 2 had distant metastases).One of 5 patients (20%) who were 2 IHC and FISHnegativehad a complete clinical response |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | NA |
| Median OS A vs. C: | 24 months |
| Adverse Event(agent arm): | 7 (37%) had celiac adenopathy, and 7 (37%) had retroperitoneal, portal adenopathy, or scalene adenopathy. |
| Conclusions: | Assessment of the effect of trastuzumab in the treatment of patients with esophageal adenocarcinoma overexpressing human epidermal growth factor receptor 2 is limited by the small number of patients in this study. Overall survival, hotheyver, was similar to prior studies without an increase in toxicity. Evaluation of human epidermal growth factor receptor 2 status should be performed in future trials for patients with adenocarcinoma of the esophagus that investigate therapies targeting the HER family. |