| General information |
| Database: | DB00453 |
| Objective: | Perioperative chemotherapy and surgery is a standard treatment of localised oesophagogastric adenocarcinoma; however, the outcomes remain poor. |
| Authors: | Okines AF, et al |
| Title: | Bevacizumab with perioperative epirubicin, cisplatin and capecitabine (ECX) in localised gastrooesophageal adenocarcinoma: a safety report. |
| Journal: | Ann Oncol. |
| Year: | 2013 |
| PMID: | 23108952 |
| 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: | 5 |
| Therapeutic Combination Content: | Bevacizumab with perioperative epirubicin, cisplatin and capecitabine (ECX) |
| Study Type: | multicentre, randomised, phase II/III study |
| Key Patients Feature: | Eligible patients hadhistologically verified gastric or oesophagogastric junction (OGJ)adenocarcinoma (Sietheyrt type II or III), stage IbIV (T4N12M0 only usingTNM 6th edition) assessed by computed tomography (CT) scan andlaparoscopy. World Health Organisation performance status (PS) 0-1, adequate bone marrow, liver and renal function, LVEF more than and equal to 50% measured byechocardiogram (echo) or multigated acquisition (MUGA) scan andabsence of proteinuria were required |
| Biomarker: | NA |
| Biomark Analysis: | NA |
| Control Group Info: | perioperative ECX with or without bevacizumab (ECXB). |
| Treatment Info: | ECX comprises 3weekly epirubicin 50 mg/m2 and cisplatin 60 mg/m2 i.v. (day 1), with capecitabine 1250 mg/m2/day (divided doses days 1-21), plus bevacizumab 7.5 mg/kg i.v. (day 1) added in the ECXB arm. Surgery was scheduled 5 to 6 weeks after the last capecitabine dose of the third cycle and postoperative chemotherapy (three cycles) restarted 6-10 weeks after surgery. ECXB patients then received six 3weekly cycles of maintenance bevacizumab 7.5 mg/kg i.v. |
| Primary End Point: | safety, specifically gastrointestinal (GI) perforation rates and cardiotoxicity. |
| Secondary End Point: | NA |
| Patients Number: | 200 |
| Trial Results |
| DLT_MTD: | NA |
| Objective Response Rate: | NA |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | NA |
| Median OS A vs. C: | NA |
| Adverse Event(agent arm): | 175 of the 200 patients (90 ECX and 85 ECXB) had more than and equal to 2 LVEF measurements and these data are presented. Two ECX patients and one (1.0%, 80%CI 0.1%-3.9%) ECXBpatient experienced a gastric perforation at the primary site. One ECX patient had a gastric perforation 10 days postoesophagectomy. VTEs occurred at similar rates in both the arms. ATEs (MI/CVA) were more frequent with bevacizumab (1 ECX, 5 ECXB). Woundhealing complications defined as wound infections (8 ECX, 6 ECXB), delayed woundhealing including wound dehiscence and delayed woundhealing without documented infection (2 ECX, 4 ECXB) and suture line leaks (5 ECX, 5 ECXB) and GI haemorrhages (4 ECX, 1 ECXB) were not increased by bevacizumab. Other frequently occurring (more than and equal to 10%) and/or grade more than and equal to 3 adverse events are similar in the two groups. |
| Conclusions: | Addition of bevacizumab to perioperative ECX chemotherapy is feasible with acceptable toxicity and no negative impact on surgical outcomes. |