Irinotecan combined with capecitabine-based chemoradiotherapy before surgery improves the outcomes of patients with rectal cancer

This study investigated the effectiveness of treatment with irinotecan (Camptosar) combined with capecitabine (Xeloda) chemotherapy (ICC) before rectal cancer surgery. Researchers suggested that this combined therapy significantly improved the treatment outcomes in these patients.

Rectal cancer is a common cancer with an occurrence of 30% of all colorectal cancers. Chemotherapy and radiation therapy followed by surgery is the standard treatment for this type of cancer. However, the tumor response rate after chemotherapy in rectal cancer is only 10 to 15%, and the progression rate is 30%. Therefore, adding a second drug to the treatment might increase the effectiveness of the treatment.

The effectiveness of irinotecan has only been studied with small population sizes. However, it has been associated with negative side effects such as diarrhea. Prior studies showed that even with higher rates of side effects irinotecan and capecitabine chemotherapy (ICC) was associated with longer overall and disease-free survival.

More recently, UGT1A1 protein has been associated with irinotecan activity. If a mutation (permanent change) is present in the gene, UGT1A1 is unable to inactivate irinotecan, which increases toxicity. The maximum tolerated dose of irinotecan decreases with increased numbers of UGT1A1 mutations. However, the effectiveness of this drug in the treatment of rectal cancer patients with different UGT1A1 status is still not clear.

This study included 356 patients with rectal cancer and different UGT1A1 status. All patients had pelvic radiation and chemotherapy. Half of the participants (group 1) were assigned to receive chemotherapy with capecitabine and oxaliplatin (Eloxatin) and half had ICC (group 2). Irinotecan dose was 80 mg/m² for those with UGT1A1 *1*1 and 65 mg/m² for those with UGT1A1*1*28. The main outcome was a complete treatment response meaning no cancer cells left after surgery.

Surgery was performed in 87% of patients from group 1 and in 88% of patients from group 2. The treatment response rates were 15% in group 1 and 30% in group 2. Group 2 had a 1.96 times increase in the odds of improved treatment response when compared to group 1.

Moderate side effects were recorded in 11 (6%) patients in group 1 and in 68 (38%) in group 2. The most common side effects were decreased white blood cells and diarrhea. The rate of complications after surgery was not significantly different between the two groups. 

This study concluded that ICC guided by UGT1A1 status and radiotherapy before surgery improve treatment response in patients with rectal cancer.

In this study, not all UGT1A1 mutations were considered to determine the irinotecan dosage to use. Further studies, including all different UGT1A1 mutation status, are necessary.