Xelox + Avastin for metastatic CRC – pro

Avastin has been shown to be more effective with Folfox than Folfox alone. Preliminary results from a large, randomized clinical trial for patients with advanced colorectal cancer who had previously received treatment show that those who received bevacizumab (Avastin™) in combination with an oxaliplatin (Eloxatin™) regimen known as FOLFOX4 lived longer than patients who received FOLFOX4 alone.

The Data Monitoring Committee overseeing the trial (known as E3200)* recommended that the results of a recent interim analysis be made public because the study had met its primary endpoint of demonstrating improved overall survival. Researchers found that the patients in the trial who received bevacizumab in combination with FOLFOX4 (a regimen of oxaliplatin, 5-fluorouracil and leucovorin) had a median overall survival of 12.5 months compared to patients treated with FOLFOX4 alone, who had a median overall survival of 10.7 months. This difference is statistically significant and corresponds to a 17 percent improvement in median overall survival. There was a 26 percent reduction in the risk of death (hazard ratio of 0.74) for patients in this study who received bevacizumab plus FOLFOX4 compared to those who received FOLFOX4 alone.

The plan resricts Avastin for colorectal cancer to 5FU based regimens, in accordance with the FDA indication. Xeloda is generally considered to be eqivalent to 5Fu and it is a 5FU pro-drug. A number of studies suggest that it is as effective as Folfox. A Phase III study showed the chemotherapy combination XELOX (Xeloda + oxaliplatin) to be as effective — in terms of progression-free survival (PFS) — as the current standard treatment, FOLFOX-4 (infused 5-FU/leucovorin + oxaliplatin), in the treatment of advanced (metastatic) colorectal cancer. However, a Phase III trial NCT00349336 is currenlty looking at this question. This study will compare the pharmacokinetics and safety of Avastin at steady state under 2 different dosing regimens, in combination with XELOX (oxaliplatin + Xeloda) or FOLFOX-4 (oxaliplatin, leucovorin and 5-fluorouracil). Patients randomized to the XELOX arm will receive Avastin (7.5mg/kg iv) on Day 1 of each 3 week cycle; patients randomized to the FOLFOX-4 arm will receive Avastin (5mg/kg iv) on Day 1 of each 2 week cycle. The anticipated time on study treatment is 3-12 months, and the target sample size is <100 individuals.
Hurwitz H, Fehrenbacher L, Novotny W, et al. Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. N Engl J Med. 2004;350:2335-42.

nccn.org, Colorectal cancer

[3]Giantonio BJ, Catalano PJ, Meropol NJ, et al. High-dose bevacizumab improves survival when combined with FOLFOX4 in previously treated advanced colorectal cancer: Results from the Eastern Cooperative Oncology Group E3200. Proceedings of American Society of Clinical Oncology. Orlando FL. 2005. Abstract #2.


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