Comparison of two drug combinations for treating colorectal cancer that has spread

The authors compared two drug combinations for the treatment of metastatic colorectal cancer.

Metastatic colorectal cancer indicates the cancer has spread from the colon or rectum to other parts of the body. Treatment often includes a combination of chemotherapy drugs such as FOLFOX (5-fluorouracil [Efudex], leucovorin [folinic acid], and oxaliplatin [Eloxatin]). However, this is not a very convenient treatment option as 5-fluorouracil must be injected very slowly into patients’ veins (infusion). Tefagur–uracil (UFT) is a very similar drug that can be swallowed, making it more convenient. UFT has been found to be effective for metastatic colorectal cancer when combined with leucovorin and oxaliplatin [UFOX]) 

Adding cetuximab (Erbitux), another anti-cancer drug, to FOLFOX improves the outcome of patients with metastatic colorectal cancer and a normal-KRAS gene (wild-type KRAS). It is unclear whether UFOX plus cetuximab is as effective and safe as FOLFOX plus cetuximab.

The study included 302 patients with metastatic colorectal cancer to examine whether UFOX or FOLFOX plus cetuximab was a better treatment. Patients were divided into two groups. Group 1 (150 patients) received cetuximab plus FOLFOX and group 2 (152 patients) received cetuximab plus UFOX. Reponse to the treatment (such as tumor shrinkage), progression-free survival (time until the cancer progressed) and overall survival (time until death from any cause) were compared between groups. Adverse events were also recorded for each patient.

It took longer for patients in group 1 to progress than patients in group 2, 8.2 compared to 6.6 months. 51.3% of patients in group 1 showed a response to treatment, compared to 37.5% of group 2. There was no significant difference in overall survival between the two groups. Patients in group 1 survived for an average of 18.4 months compared to 16.8 months for group 2.

80% of patients in group 1 experienced severe adverse events compared to 72% of patients in group 2.  The most common adverse events included acne-like rash (23% of group 1, 13% of group 2), diarrhea (9% of group 1, 19% of group 2) and vomiting (3% of group 1, 7% of group 2). 29% of patients in group 1 also suffered from neutropenia (low count of a type of white blood cell that helps fight off infections). None of the patients in group 2 experienced neutropenia.

The authors concluded that FOLFOX led to slower progression of the cancer. They suggest that tefagur–uracil plus cetuximab should not be used as the first treatment option for metastatic colorectal cancer.

Funding was provided by Merck KGaA, they are also responsible for manufacturing tefagur–uracil.