| General information |
| Database: | DB00456 |
| Objective: | Bevacizumab improves survival in several solid tumor malignancies when combined with chemotherapy. they evaluated the efficacy and safety of the addition of bevacizumab to chemotherapy in the treatment of gastric and gastroesophageal junction (GEJ) adenocarcinoma. |
| Authors: | Shah MA, et al |
| Title: | Multicenterphase II study of irinotecan, cisplatin, and bevacizumab in patients with metastatic gastric or gastroesophageal junction adenocarcinoma. |
| Journal: | J Clin Oncol. |
| Year: | 2006 |
| PMID: | 17114652 |
| Trial Design |
| Clinical Trial Id: | NA |
| Agent: | bevacizumab
|
| Target: | Vascular endothelial growth factor
|
| Cancer Type: | esophagusgastroesophageal junction cancer |
| Cancer Subtype: | adenocarcinoma of the stomach or gastroesophageal junction |
| Therapy Type: | com |
| Therapeutic Combination Type: | 2 |
| Therapeutic Combination Content: | irinotecan, cisplatin, and bevacizumab |
| Study Type: | Multicenterphase II Study |
| Key Patients Feature: | patients were eligible if they were 18 years of age or older with a pathologically confirmed diagnosis of gastric or GEJ adenocarcinoma.patients wererequired to have previously untreated metastatic or unresectable disease. Patients may have received prior adjuvant or neoadjuvant treatment for locoregional resectable disease, but any prior therapy could not have includedirinotecan or cisplatin and must have been completed at least 3 weeks beforestudy initiation (6 weeks for mitomycinc). patients were required to have aKarnofsky performance status of at least 60%, and adequate organ function asdefined as: total neutrophil count (absolute neutrophil count) 1, 500/mm3, platelet count 75, 000/mm3, serum creatinine 1.5 mg/dL, proteinuria 500 mg/d, total serum bilirubin 1.5 mg/dL, and serum AST and ALT three times the upper limit of normal or five times the upper limit ofnormal in the case of known liver metastases. Full or partialdose anticoagulation was allowed, although patients not on anticoagulation were required tohave a prothrombin time (international normalized ratio) 1.5 and a partialthromboplastin time 3 seconds above the upper limits of normal. Patientswere required to have radiographically assessable, nonmeasurable diseaseor measurable disease as per Response Evaluation Criteria in Solid Tumors(RECIST) criteria.1 |
| Biomarker: | NA |
| Biomark Analysis: | NA |
| Control Group Info: | single arm |
| Treatment Info: | patients with metastatic or unresectable gastric/GEJ adenocarcinoma were treated with bevacizumab 15 mg/kg on day 1, irinotecan 65 mg/m2, and cisplatin 30 mg/m2 on days 1 and 8, every 21 days. |
| Primary End Point: | a 50% improvement in time to progression over historical values. |
| Secondary End Point: | safety, response, and survival. |
| Patients Number: | 47 |
| Trial Results |
| DLT_MTD: | NA |
| Objective Response Rate: | Response to therapy was assessable in all 47 enrolledpatients. Of 34 patients with measurable disease, 20 patients achieveda partial response and two patients achieved a complete response foran overall response rate of 65% (exact 95%CI, 46% to 80%). Forpatients with assessable, nonmeasurable disease, 12 patients had stabledisease, and one patient had disease progression. Including these nonmeasurablepatients, the overall response rate was 46.8% (exact 95%CI, 38% to 68%) |
| Disease Control Rate: | NA |
| Median Time to Progression: | 8.3 months (95% CI, 5.5 to 9.9 months) |
| Median PFS A vs. C: | NA |
| Median OS A vs. C: | 12.3 months (95% CI, 11.3 to 17.2 months) |
| Adverse Event(agent arm): | Possible bevacizumabrelated toxicity included a 28% incidence of grade 3 hypertension, two patients with a gastric perforation and one patient with a near perforation (6%), and one patient with a myocardial infarction (2%). Grade 3 to 4 thromboembolic events occurred in 25% of patients. |
| Conclusions: | Bevacizumab can be safely given with chemotherapy even with primary gastric and GEJ tumors in place. The response rate, time to disease progression (TTP), and overall survival are encouraging, with TTP improved over historical controls by 75%. Further development of bevacizumab in gastric and GEJ cancers is warranted. |