New treatment plan might improve the outcome of advanced colorectal cancer patients

This study evaluated how cetuximab (Erbitux) might be safely and effectively added to intermittent (a planned interruption in the treatment) chemotherapy regimens.

Advanced colorectal cancer is treated with a combination of cytotoxic drugs and novel treatments. Cytotoxic drugs, including chemotherapy, work by killing tumor cells. Unfortunately, they can also kill our healthy cells. Cells that are growing and dividing are more likely to be killed during chemotherapy; skin cells, hair cells, immune cells and blood cells. The death of healthy cells can lead to some of the adverse events experienced by patients during treatment.

Cetuximab is a new anti-cancer drug: it blocks proteins that are involved in cancer cell growth and invasion (spread). As a result of this it can slow the growth and spread of cancer. Introducing cetuximab to patients’ treatment plans might improve patient outcome.

This study included 169 patients with KRAS wild-type advanced colorectal cancer (the cancer has spread to other parts of the body and has a normal, non-mutated, KRAS gene). Patients were divided into two groups, both groups received FOLFOX (5-fluorouracil [Efudex], leucovorin, oxaliplatin [Eloxatin]) chemotherapy and weekly cetuximab for 12 weeks, then either had a planned interruption in chemotherapy (group 1; 66 patients) or an interruption in cetuximab and chemotherapy (group 2; 64 patients). After the break the initial therapy began again for 12 weeks followed by another break.

The most important outcome was failure-free survival at 10 months. Failure was defined as stopping the maximum dose of treatment due to cancer progression or death. After 10 months the rate of failure-free survival was similar for both groups, 52% of group 1 compared to 50% of group 2. The average failure-free survival time was 14.3 months in group 1 and 12.2 months in group 2.

Average overall survival was longer for patients who did not have a break in cetuximab therapy. Average survival was 22.2 months in group 1 and 16.8 months in group 2. Progression-free survival (time following treatment before the disease progresses) was also longer for patients who did not have a break in cetuximab. Average progression-free survival time was 5.8 months for group 1 and 3.1 months for group 2.

The treatment was stopped because of toxicity in 12% of patients from both groups. The most common moderate to severe adverse events were similar in both groups. Adverse events included skin rash (22-27%), neutropenia (29-33%; low levels of specific white blood cells involved in fighting infection), diarrhea (18-25%), and lethargy (21-26%; lack of energy).

The authors concluded that cetuximab can be safely and effectively incorporated into two intermittent chemotherapy strategies. Continuous cetuximab was associated with a higher failure-free survival, higher overall survival, and longer time to progression.