Combination Treatment Boosts Efficacy of Widely-Used Chemotherapy Drug

Adding an investigational diabetes drug to anti-cancer regimen may reduce cardiotoxicity.

The combination of an investigational diabetic neuropathy drug with doxorubicin was found to boost the efficacy of the anti-cancer drug, showing promise in the treatment of colon cancer.

Doxorubicin is widely-used to treat multiple cancer types, such as breast and lung, because of its cost-effectiveness and efficacy. Unfortunately, colon cancers often develop resistance, requiring higher doses that are toxic to the heart.

To address this issue, investigators combined doxorubicin with an aldose reductase (AR) inhibitor. The results of the study, published in Scientific Reports, found that the inhibitor increased the efficacy of doxorubicin and significantly lowered cardiotoxic adverse events (AEs).

In the study, investigators showed that earlier exposure to cancer-causing agents triggers oxidative stress, a known driver of cancer growth. Additionally, oxidative signals help grow new blood vessels that the cancer tissues need.

“We’ve shown that oxidative signals can be blocked by aldose reductase, or AR, inhibitors,” said lead author Satish Srivastava. “If we could prevent development of the new blood vessels in the cancer tissue driven by these signals, tumor growth and metastasis can be slowed down or prevented.”

The investigators used the AR inhibitor fidarestat to determine its efficacy in preventing the growth and spread of cancer cells.

“In the study, using human colon cancer cell lines, we showed that the growth of cancer cells can be largely prevented using a combination of both drugs in a petri dish as well as in mouse models,” Srivastava said. “Since doxorubicin is one of the cheapest drugs that is effective against many types of cancer but rarely used in colon cancer, the combination therapy could be highly effective in combating colon cancer while drastically lowering risk of cardiotoxic [AEs].”

To date, fidarestat has completed phase 2 clinical trials in the United States and a phase 3 trial in Japan to prevent diabetic neuropathy. No major fidarestat-induced AEs were observed.

The investigators hope that the combination therapy will eventually be used to combat different types of cancer, requiring smaller doses of doxorubicin and ultimately reducing toxicity.