| General information |
| Database: | DB00994 |
| Objective: | The FOLFOXIRI (irinotecan, oxaliplatin, fluorouracil, and folinate) regimen has been shown to be better than FOLFIRI (fluorouracil, folinate, and irinotecan) in a phase 3 trial in patients with metastatic colorectal cancer. Results of various studies have shown that the addition of bevacizumab to chemotherapy increases treatment efficacy. they therefore assessed the safety and activity of the combination of FOLFOXIRI plus bevacizumab in patients with colorectal cancer |
| Authors: | Masi G, et al |
| Title: | Bevacizumab with FOLFOXIRI (irinotecan, oxaliplatin, fluorouracil, and folinate) as firstline treatment for metastatic colorectal cancer: a phase 2 trial. |
| Journal: | Lancet Oncol. |
| Year: | 2010 |
| PMID: | 20702138 |
| Trial Design |
| Clinical Trial Id: | NCT01163396 |
| Agent: | bevacizumab
|
| Target: | Vascular endothelial growth factor
|
| Cancer Type: | colorectal cancer |
| Cancer Subtype: | advanced colorectal cancer |
| Therapy Type: | com |
| Therapeutic Combination Type: | 2 |
| Therapeutic Combination Content: | Bevacizumab with FOLFOXIRI (irinotecan, oxaliplatin, fluorouracil, + folinate) |
| Study Type: | a phase II trial. |
| Key Patients Feature: | patients (aged 1875 years) with colorectal cancer, which was judged to be unresectable for metastatic disease |
| Biomarker: | NA |
| Biomark Analysis: | NA |
| Control Group Info: | single arm |
| Treatment Info: | pts were given the combination of intravenous bevacizumab (5 mg/kg on day 1) and intravenous FOLFOXIRI (irinotecan 165 mg/m(2) on day 1, oxaliplatin 85 mg/m(2) on day 1, folinate 200 mg/m(2) on day 1, and fluorouracil 3200 mg/m(2) for 48 h continuous infusion starting on day 1 and repeated every 2 weeks) as firstline treatment in seven centres in Italy. Induction treatment (FOLFOXIRI and bevacizumab) was administered for a maximum of 6 months, followed by maintenance treatment with bevacizumab (5 mg/kg intravenously on day 1, repeated every 2 weeks). |
| Primary End Point: | progression free survival (PFS) at 10 months from study entry in the intentiontotreat population |
| Secondary End Point: | NA |
| Patients Number: | 57 |
| Trial Results |
| DLT_MTD: | NA |
| Objective Response Rate: | 77% |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | PFS at 10 months was 74% (95% CI 62-85). Median PFS 13.1 months (10.9-15.2) |
| Median OS A vs. C: | 30.9 months (24.9-35.2) |
| Adverse Event(agent arm): | Main grade 3 or 4 adverse events during induction treatment were neutropenia (n=28 [49%], including one case of febrile neutropenia), diarrhoea (n=8 [14%]), stomatitis (n=2 [4%]), neurotoxicity (n=1 [2%]), deepvein thrombosis (n=4 [7%]), and hypertension (n=6 [11%]). No treatmentrelated deaths occurred. Six serious adverse events occurred during the induction treatment: febrile neutropenia (n=1 [2%]), grade 3 diarrhoea with dehydration (n=2 [4%]), grade 4 stomatitis (n=1 [2%]), grade 4 hypertension (n=1 [2%]), and fluorouracilrelated cardiac ischaemia (n=1 [2%]). The most common grade 3 or 4 adverse events noted in the 37 patients who received maintenance treatment were hypertension (n=5 [14%]) and neurotoxicity (n=3 [8%]). One case of acute myocardial infarction due to coronary thrombosis was noted during the maintenance treatment. |
| Conclusions: | Bevacizumab can be safely used with FOLFOXIRI without causing unforeseen adverse events. Treatment achieved promising results in terms of PFS. Aphase 3 study for the comparison of FOLFOXIRI plus bevacizumab with FOLFIRI plus bevacizumab is in progress |