Colon cancers that are caused by defects in genes that repair damaged DNA don’t respond well to 5-FU treatment after surgery.
However, a new analysis of patients treated with FOLFOX (oxaliplatin, leucovorin, and 5-FU) found no differences between patients with deficient mismatch repair tumors and those with normal gene expression.
In this small study of 135 patients, the research team concluded that adding oxaliplatin to 5-FU and leucovorin may overcome resistance to chemotherapy in mismatch repair deficient and microsatellite instable (MSI) colon cancer.
South Korean researchers analyzed tumors from patients with stage II, III, or IV colorectal cancer, all of whom had surgery that completely removed all visible signs of cancer. The 14 patients with stage IV cancer had liver metastases only, which were successfully removed.
They studied two genes related to deficient DNA repair — MLH1 and MSH2. They also used genotyping to determine microsatellite instability (MSI), and stained tumors for the expression of p53 protein.
They found that:
- About 1 in 10 tumors were MSI-high (MSI-H); 9 out of 10 were MSI-low or microsatellite stable (MSI-L/S).
- Similarly, almost 10 percent showed deficient mismatch repair gene expression (MMR-D).
- There was almost complete agreement (94.7 percent) between the MSI-high and deficient mismatch repair specimens.
Comparing results to disease-free and overall survival, the study showed:
- There was no difference between patients with deficient and intact DNA mismatch repair for either disease-free or overall survival.
- p53 expression made no difference in either disease-free or overall survival.
- For patients with agreement between genotyping and immunohistochemical tests, microsatellite instability — either high or low/stable — also made no difference in disease-free or overall survival.
Seung Tae Kim and the team in Seoul concluded,
The MMR status or p53 positivity was not significantly associated with outcomes to FOLFOX as adjuvant chemotherapy in colon cancer patients with R0 resection. Adding oxaliplatin in adjuvant chemotherapy may overcome negative impact of 5-FU on colon cancers with MSI-H/MMR-D.