Drug combo shows promise against advanced, metastatic breast cancer

Dec. 15 (UPI) -- A new drug combination is effective at slow disease progression in people with advanced or metastatic breast cancer resistant to conventional chemotherapy, a study published Wednesday by Science Translational Medicine found.

In a phase 1-2 clinical trial, the combined treatment led to response rates as high as 82% in participants with advanced tumors confined to the breast and 15% in those with metastatic triple-negative breast cancer, or disease that has spread to other parts of the body, the data showed.

The treatment -- a combination of the approved chemotherapy drug docetaxel and the experimental drug L-NMMA -- was effective at reducing the size of tumors or slowing their spread, the researchers said.

L-NMMA is intended to target nitric oxide in tumor tissue, which is known to promote cancer growth.

The results suggest that the combination could provide a badly needed treatment option for patients with these often fatal, advanced forms of breast cancer, they said.

"We report on a novel first-in-class drug that targets inducible nitric oxide that appears to be effective in combination with standard chemotherapy for women with triple negative breast cancer," study co-author Dr. Jenny C. Chang told UPI in an email.

The combination works "by changing the immune landscape of cancers," or how they evade the human immune system to develop and grow, said Chang, chair of cancer research at Houston Methodist Hospital.

Triple-negative breast cancer is an aggressive form of the disease that has a high risk of metastasis -- spread to other parts of the body -- and for developing resistance to chemotherapy, meaning that the drugs no longer work to slow tumor growth, according to the National Cancer Institute.

As a result, people with this form of the disease, which accounts for about 8% of all breast cancer cases in the United States, the agency estimates, typically have a poor prognosis.

Earlier studies in animals have found that L-NMMA, or nitro monomethyl L-arginine acetate, a molecule that inhibits the cancer-supporting nitric oxide signaling pathway, can slow the growth of triple-negative breast cancers.

For this study, Chang and her colleagues assessed the new drug in combination with the commonly used chemotherapy docetaxel, sold under the brand name Taxotere, in 35 patients with advanced or metastatic breast cancer tumors resistant to chemotherapy.

The researchers gave the drug combination to 11 patients with advanced triple-negative breast cancer and 24 patients with metastatic triple-negative breast cancer, most of whom had already failed to respond to multiple chemotherapy regimens, they said.

Although 21% of the patients showed some side effects to the treatment, none of the adverse effects were linked with L-NMMA, the researchers said.

Just under 46% of the participants' tumors responded to the treatment, and the combination shrank tumor volumes and improved skin ulcerations in many of the participants, according to the researchers.

Phase 1 and 2 trials initially assess the safety and effectiveness of a new treatment, while phase 3 studies, the final step in the drug evaluation process, test them in a larger population of patients.

The new combination treatment for advanced or metastatic breast cancer still needs to pass through phase 3 trials before it could become widely available for use.

The researchers are "planning a global phase 3 now, as well as a separate trial for metaplastic breast cancer," Chang said.