| General information |
| Database: | DB00455 |
| Objective: | To evaluate the safety and efficacy of a modified administration schedule of docetaxel, cisplatin, and fluorouracil (mDCF) with bevacizumab in patients with advanced gastroesophageal malignancies. |
| Authors: | Shah MA, et al |
| Title: | Phase II study of modified docetaxel, cisplatin, and fluorouracil with bevacizumab in patients with metastatic gastroesophageal adenocarcinoma. |
| Journal: | J Clin Oncol. |
| Year: | 2011 |
| PMID: | 21189380 |
| Trial Design |
| Clinical Trial Id: | NCT00390416 |
| Agent: | bevacizumab
|
| Target: | Vascular endothelial growth factor
|
| Cancer Type: | esophagusgastroesophageal junction cancer |
| Cancer Subtype: | adenocarcinoma of the lower oesophagus, oesophagealjunction or stomach |
| Therapy Type: | com |
| Therapeutic Combination Type: | 2 |
| Therapeutic Combination Content: | modified docetaxel, cisplatin, and fluorouracil with bevacizumab |
| Study Type: | phase II clinical trial |
| Key Patients Feature: | patients were required to be age 18 years orolder with pathologically confirmed gastric, GEJ, or distal esophageal adenocarcinoma, previously untreated for metastatic disease. Histologic documentation of metastasis or confirmation on two independent imaging modalitieswas required. Prior chemotherapy or chemoradiotherapy for locoregionaldisease was allowed if more than 6 months had elapsed following completionof prior therapy and registration on the clinical trial. Patients could not havereceived prior cisplatin, docetaxel, bevacizumab, or any biologic antiangiogenic agent. Radiographically evaluable disease per Response Evaluation Criteria in Solid Tumors (RECIST) criteria25 was required. The primary tumorwas not considered radiographically evaluable. Anticoagulation therapy was allowed. Patients not being given anticoagulation therapy were required tohave a prothrombin time (international normalized ratio) 1.5 and a partialthromboplastin time 3 seconds above upper limit of normal (ULN). patients were required to have a Karnofsky performance status of at least 70%and adequate organ function defined as absolute neutrophil count 1, 500/ L, hemoglobin 9.0 g/dL, platelet count 100, 000/ L, serum creatinine 1.5 mg/dL, urinalysis 2 proteinuria, urine protein (mg/dL):urine creatinine (mg/dL) ratio 1.0, total bilirubin ULN, and AST, ALT, andalkaline phosphatase within the eligible range (per Appendix Table A1, onlineonly). Women of childbearing potential were required to have a negativepregnancy test. |
| Biomarker: | NA |
| Biomark Analysis: | NA |
| Control Group Info: | single arm |
| Treatment Info: | Previously untreated patients with metastatic gastroesophageal adenocarcinoma received bevacizumab 10 mg/kg, docetaxel 40 mg/m2, fluorouracil 400 mg/m2, leucovorin 400 mg/m2 on day 1, fluorouracil 1, 000 mg/m2/d ¡Á 2 days intravenous continuous infusion beginning on day 1, and cisplatin 40 mg/m2 on day 3. |
| Primary End Point: | improve 6month progression free survival (PFS) from 43% (historical DCF control) to 63% with the addition of bevacizumab. |
| Secondary End Point: | NA |
| Patients Number: | 44 |
| Trial Results |
| DLT_MTD: | Treatmentrelated grade 3 to 4 toxicity was as follows: neutropeniawithout fever (50%), fatigue (25%), venous thromboembolism (39%), and nausea, vomiting, mucositis, neuropathy, and febrile neutropenia less than 10% each. |
| Objective Response Rate: | In 39 patients with measurabledisease, the confirmed response rate was 67% (95% CI, 50% to 81%). Sixmonth PFS was 79%(95% CI, 63% to 88%), and median PFS was 12 months (95% CI, 8.8 to 18.2 months). |
| Disease Control Rate: | 31% (95% CI, 17% to 48%) |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | 12 months (95% CI, 8.8 to 18.2 months) |
| Median OS A vs. C: | 16.8 months (95% CI, 12.1 to 26.1 months) |
| Adverse Event(agent arm): | Treatmentrelated grade 3 to 4 toxicity was as follows: neutropenia without fever (50%), fatigue (25%), venous thromboembolism (39%), and nausea, vomiting, mucositis, neuropathy, and febrile neutropenia less than 10% each. |
| Conclusions: | mDCF with bevacizumab appears tolerable and has notable patient outcomes in patients with advanced gastroesophageal adenocarcinoma. Sixmonth PFS was 79%, surpassing our predefined efficacy end point, and median and 2year OS they were 16.8 months and 37%, respectively. |