Cancer Treatment Today

Bevacizumab was approved by the FDA in February 2004 for use in metastatic colorectal cancer when used with standard chemotherapy treatment (as first-line treatment) and with 5-fluorouracil-based therapy for second-line metastatic colorectal cancer. This recommendation was based on the E3200 trial  addition of bevacizumab to oxaliplatin/5-FU/leucovorin (FOLFOX4) therapy. Subsequently it was also approved for second line therapy and it is often used for metastatic colorectal cancer with Folfiri and capecitabine based regimens, for which there is guideline and literature support.

Unfortunately, there comes a point in treatment, after which chemotherapy is poorly tolerated. This is particularly true of oxaliplatin containing combinations, but also is true of others. Maintenance treatments can be considered but there is no consensus on how and whether to deliver it. Maintenance treatment with a fluoropyrimidine alone prolongs the progression-free survival compared with a complete treatment break, after an initial period of combination chemotherapy.  OPTIMOX 2 study randomized patients to six cycles of modified FOLFOX7 followed by 5-FU/leucovorin maintenance until progression, or six cycles of modified FOLFOX7 followed by cessation of therapy until tumor progression; in both groups, modified FOLFOX7 was reintroduced at disease progression. The duration of disease control and progression-free survival was significantly higher in patients receiving maintenance therapy, but the overall survival was similar in both groups.

It is tempting to use Avastin as a single agent for maintenance, because it is generally well tolerated. Thus far,t eh results are not encouraging. The MACRO study indicated included 480 patients with metastatic colorectal cancer randomized to first-line XELOX plus bevacizumab for six cycles followed by XELOX plus bevacizumab or single-agent bevacizumab as maintenance therapy. The study found no difference in PFS between the two arms and acceptable toxicity in both arms Hopefully, the ongoing CAIRO3 study, by the Dutch Colorectal Cancer Group, will provide more definitive answers. In that study, patients with stable disease after induction therapy for advanced colorectal cancer are being randomized to observation or maintenance therapy with low-dose capecitabine and bevacizumab.