| General information |
| Database: | DB00452 |
| Objective: | Esophageal and gastric cancers often present at an advanced stage. Systemic chemotherapy is the mainstay of treatment, but survival with current regimens remains poor. They evaluated the safety, tolerability, and efficacy of the combination capecitabine, oxaliplatin, and bevacizumab in the treatment of metastatic esophagogastric adenocarcinomas. |
| Authors: | Uronis HE, et al |
| Title: | a phase II study of capecitabine, oxaliplatin, and bevacizumab in the treatment of metastatic esophagogastric adenocarcinomas. |
| Journal: | Oncologist. |
| Year: | 2013 |
| PMID: | 23485624 |
| Trial Design |
| Clinical Trial Id: | NCT00447330 |
| Agent: | bevacizumab
|
| Target: | Vascular endothelial growth factor
|
| Cancer Type: | esophageal cancer |
| Cancer Subtype: | advanced esophagogastric cancer |
| Therapy Type: | com |
| Therapeutic Combination Type: | 2 |
| Therapeutic Combination Content: | capecitabine, oxaliplatin, and bevacizumab |
| Study Type: | a phase II Study |
| Key Patients Feature: | patients with metastatic or unresectablegastric/gastroesophageal junction tumors |
| Biomarker: | Neuropilin1 (NRP1) and 2 (NRP2) mRNA expression |
| Biomark Analysis: | NRP2 mRNA levels significantly correlated with PFS (p = 0.042) and showed a trend toward significance with OS (p = 0.051). Nonsignificant trends for NRP1 were noted for higher expression levels and worse outcome. |
| Control Group Info: | single arm |
| Treatment Info: | patients were enrolled and treated with capecitabine 850 mg/m(2) BID on days 114, and oxaliplatin 130 mg/m(2) with bevacizumab 15 mg/kg on day 1 of a 21day cycle. |
| Primary End Point: | PFS |
| Secondary End Point: | response rate (RR) and overall survival (OS). Neuropilin1 (NRP1) and 2 (NRP2) mRNA expression was evaluated in archived tumor. |
| Patients Number: | 35 |
| Trial Results |
| DLT_MTD: | NA |
| Objective Response Rate: | RR was estimated at 51.4% (95% CI: 35.5-67.1%), including one complete response and 17 partial responses. |
| Disease Control Rate: | NA |
| Median Time to Progression: | 7.2 months (95% C.I.: 6.5- 8.5). |
| Median PFS A vs. C: | 7.2 months(95% C.I.: 5.4 - 8.5) |
| Median OS A vs. C: | 10.8 months(95% C.I.: 8.7-14.5) |
| Adverse Event(agent arm): | Overall, this regimen was generally well tolerated. Toxicity was assessed via NCI Common Toxicity Criteria version 3.0. Expected chemotherapyrelated toxicities were common, including fatigue, handfoot syndrome, anorexia, and peripheral neuropathy. These toxicities were readily manageable with standard dose adjustments and supportive care. Grade 3-5 events included grade 3 hypertension (n=2), grade 3 hemorrhage (n=1), grade 3 venous thrombosis (n=4), grade 3 duralcutaneous fistula (n=1), grade 4 perforation/fistula (n=1) and grade 5 perforation/fistula. |
| Conclusions: | Bevacizumab can be given safely with chemotherapy in patients with metastatic esophagogastric adenocarcinomas. The combination of capecitabine, oxaliplatin, plus bevacizumab has activity comparable to other bevacizumabcontaining regimens in metastatic gastroesophageal cancer. |