This study compared two different types of chemotherapy for patients with metastatic (spread to other parts of the body) colorectal cancer (mCRC). Researchers suggested that FOLFOXIRI plus bevacizumab (Avastin) is associated with better outcomes in these patients.

Colorectal cancer is the third most common cancer worldwide. Many patients present mCRC at the time of diagnosis. Chemotherapy treatments for mCRC are of limited effectiveness, therefore the discovery of new therapies is necessary.

Chemotherapy such as FOLFOXIRI consists of a combination of drugs (fluorouracil, leucovorin, oxaliplatin, and irinotecan) that target and kill tumor cells. However, at the expense of a high rate of side effects. Bevacizumab is a type of immunotherapy that prevents tumor growth. This treatment is the first-line recommended therapy for advanced mCRC. However, its effectiveness after disease progression is still not clear.

This study included information about 679 patients with mCRC, previously untreated. Patients were assigned to 2 different groups. Group 1 (340) received mFOLFOX6 (oxaliplatin, leucovorin, fluorouracil) combined with bevacizumab followed by FOLFIRI (irinotecan, leucovorin, fluorouracil) plus bevacizumab after progression. Group 2 (339) received FOLFOXIRI plus bevacizumab followed by the same therapy after progression. Treatments were repeated every 14 days for up to 8 cycles. The average follow-up period was 35.9 months.

Average progression-free survival (PFS; time from treatment to cancer worsening) was 19.2 months in group 2 and 16.4 months in group 1. Patients from group 2 had a 26% improvement in the odds of a better PFS. 62% of patients in group 2 responded to treatment as compared to 50% in group 1. 

The most common moderate side effects were diarrhea, neutropenia (decrease in blood white cells), and hypertension (high blood pressure). Severe events were seen in 25% of patients from group 2 and 17% from group 1. 8 treatment-related deaths were reported in group 2 and 4 in group 1. The most common side effect after progression was neurotoxicity (arms and legs numbness) seen only in group 2 (6).

Severe side effects after progression were seen in 15% of patients from group 2 and in 12% from group 1. 3 treatment-related deaths after progression were reported in group 2 and 4 in group 1.

This study concluded that FOLFOXIRI plus bevacizumab followed by the same therapy after progression seems to be a preferable therapy for mCRC.

This study was funded by F. Hoffmann–La Roche, the bevacizumab manufacturers.

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