Chemo-Drug Combo Clobbers Cancer

Lung cancer with common mutation responds to chemotherapy and selumetinib

(RxWiki News) Gene therapies to treat lung cancer are continuing to emerge. A new combination of drugs may help lung cancer patients live longer. Several gene mutations have been identified in lung cancer cells.

One of the most common is called KRAS, a gene involved with controlling cell division.

While chemotherapy alone can be effective in treating cancer, patients with non-small cell lung cancer (NSCLC) and this gene mutation may respond better when receiving chemotherapy along with a drug that blocks the function of the KRAS gene, according to a new study.

"Look into new gene therapies that target lung cancer."

Pasi A. Jänne, MD, scientific director at the Belfer Institute for Applied Cancer Science and associate professor of medicine at Harvard Medical School in Boston, led an international team of investigators comparing the effects of chemotherapy alone vs. chemo and targeted therapy on NSCLC patients.

Scientists studied 87 patients at 67 sites around the world. All patients had cancer with the KRAS-mutant gene. According to the authors, 20 percent of all NSCLC cases have this KRAS gene alteration. KRAS mutations are more common in current and former smokers than in those who have never smoked. The alterations also occur at a higher rate in Caucasians than in other races.

The subjects in this study all had cancer that was not responding after initial chemotherapy.

Participants were randomly assigned to receive either chemotherapy or the KRAS-targeting medication selumetinib along with chemo. The chemotherapy was the standard agent docetaxel (Taxotere). Selumetinib is still an investigational agent.

It is not commercially available because it has not been approved by the US Food and Drug Administration (FDA) yet, but it is undergoing many clinical tests.

Researchers reported that patients receiving selumetinib lived a median of 5.3 months before their cancer began to worsen, compared to 2.1 months for those receiving chemotherapy alone. About 37 percent of the patients in the selumetinib group experienced some shrinkage of their tumor. None of the patients in the docetaxel-only group had tumor reduction.

Patients in the selumetinib group also lived longer. On average, they lived 9.4 months compared to 5.2 months for the docetaxel-only group, but because of the small number of patients in the study, this data was not considered statistically significant.

The authors reported some side effects. Patients in the selumetinib group commonly experienced neutropenia (a white blood cell deficiency), neuropenia plus fever, shortness of breath and loss of strength. Dr. Jänne said that researchers and physicians will need to work on ways of managing these problems.

“The opportunity now is to validate this approach in further clinical trials so it can be developed into a real therapy for patients,” said Dr. Jänne. “Given that KRAS mutations are common in other cancers [found in 90 percent of pancreatic cancers and 40 percent of colon cancers], our findings may be useful in developing therapies for patients with these cancers as well.”

The study was published online in November in The Lancet Oncology. The research was sponsored by AstraZeneca, which holds the rights to the development of selumetinib.

Review Date: 
December 11, 2012