Soluble irinotecan as a treatment for colorectal cancer

This study investigated the efficacy and safety of EZN-2208, an anti-cancer agent, in patients with advanced colorectal cancer.

Colorectal cancer is cancer in the colon and rectum that has high tendency to metastasize (spread into distant organs) or to spread locally. Cancer results from uncontrolled cell growth, and therefore one treatment approach is to inhibit cellular growth by using a drug called irinotecan (Campto). This drug has contributed to notable survival rates among patients with colorectal cancer. Due to its poor water solubility it is difficult  to achieve an effective blood concentration, therefore higher doses are administered. In order to solve this problem, a more soluble form of irinotecan called EZN-2208 has recently been developed. Compared to irinotecan, EZN-2208 has a longer treatment effect, and produces greater therapeutic exposure.

This study examined the efficacy and safety of EZN-2208 by comparing it with different treatment regimens including irinotecan and cetuximab (Erbitux; used to prevent metastasis formation). Cetuximab is known to be effective only in colorectal cancers that lack a mutation in a gene called KRAS.

The study included 292 patients with unresectable (unable to be removed through surgery) colorectal cancer. Patients with a KRAS mutation (group A) were assigned to receive 9 mg/m² EZN-2208 monotherapy (single drug therapy). Patients with normal KRAS were divided into two groups: Group B received 9 mg/m² EZN-2208 plus cetuximab and group C received 125 mg/m² irinotecan plus cetuximab.

Results showed that overall response rates (the percentage of patients whose cancer decreased in size or disappeared after treatment) were 0% in group A, 10.7% in group B and 14.3% in group C. The response duration for group B was 5.6 months versus 9.5 months in group C. Group B had a higher progression-free survival (time during and after treatment in which the disease does not get worse) of 4.9 months versus group C who had 3.7 months. The 6-month progression-free survival rate in group B was 37% versus 29% in group C.

EZN-2208 was well tolerated, both as monotherapy and when combined with cetuximab. Some common side effects of EZN-2208 were low white blood cell count, fatigue and diarrhea. However, these had approximately the same frequency in each group.

In summary, for patients with KRAS mutation-free colorectal cancer, there was no statistically significant difference in survival rates between EZN-2208 + cetuximab and irinotecan + cetuximab treatment groups. However, as EZN-2208 has a longer treatment effect than irinotecan, it can be administered in lower doses. 

This study was funded by Enzon Pharmaceuticals, the manufacturer of EZN-2208. Furthermore, in order to determine the efficacy of EZN-2208 in patients with mutant KRAS, further investigations are essential.