Lung Cancer Treatment Improves with Better Timing

Doctors have devised a new way to use chemotherapy and radiation on lung cancer that relies on precise timing to zap cancer cells when they're most vulnerable. Patients receive less toxic amounts of chemotherapy, causing fewer side effects, in tandem with daily radiation treatments.

The research by University of Rochester Medical Center oncologists is published in the March 7, 2003 issue of Clinical Cancer Research.

Lung cancer is the No. 1 killer of all types of cancer in men and women. Historically, radiation alone was the best treatment for most inoperable lung cancer. But in the last decade, doctors have used combinations of radiation and chemotherapy. Still, it is not clear what types of chemotherapy drugs work best in tandem with radiation. Also, these treatments are usually very harsh: Patients often develop low blood counts, pneumonia, infections, and other life-threatening side effects. Sometimes the treatments themselves are fatal. Today, only 15 to 25 percent of patients with locally advanced lung cancer survive three to five years after diagnosis and aggressive chemo-radiation treatment.

Yuhchyau Chen, M.D., Ph.D., associate professor of Radiation Oncology at the university's James P. Wilmot Cancer Center, Rochester, N.Y., has been investigating new combinations that might be less toxic to patients and but more effective on the cancer. Her observations began in the laboratory, and quickly moved to clinical trials involving patients with advanced disease. Of the 33 people who completed Chen's new regimen, 98 percent saw their large chest tumors shrink or disappear in four to six weeks - a result that's capturing the attention of oncologists nationwide.

Chen began by analyzing the life cycle of lung cancer cells while they were exposed to paclitaxel, a common chemotherapy drug. Every 48 hours, she noticed, the cells went through phases in which the drug seemed to set the cells up to be most radiosensitive. She theorized that by administering paclitaxel to patients on alternate days to coincide with this cycle, the cells would remain in a position to be zapped by radiation.

Patients enrolled in Chen's study received lower doses than usual of the chemotherapy on Mondays, Wednesdays and Fridays before 11 a.m., followed by radiation five hours later, when the cells had progressed to a critical point in their life cycle. On Tuesdays and Thursdays, the patients received more radiation, timed again to the correct cell phase.

Chen's patients experienced fewer harmful side effects, and superior tumor shrinkage, compared with other published studies. The overall survival rates in Chen's clinical trial also were equal to or better than the survival rates reported in several large, randomized trials of patients with advanced lung cancer who were treated with a combination therapy.

"The degree to which we were able to control the cancer in the chest was quite impressive," Chen says. "This demonstrates that this drug may enhance the tumor's response to radiation if the timing of the chemotherapy is right.

"I am very excited about this study because it truly illustrates how research can improve patient care," she says. "And because we were able to use lower doses of chemotherapy in a more strategic way, many patients felt good enough to go about their normal activities during treatment."

The National Institutes of Health and Bristol-Myers Squibb, maker of paclitaxel, funded the research. Chen was supported by Kishan Pandya, M.D., professor, Hematology/Oncology at the Wilmot Cancer Center. She is continuing her research to find a combination therapy that will prevent the cancer from spreading outside of the chest. In addition, she is exploring whether other drugs might work with radiation for patients with heart disease, kidney problems, or other health conditions that render them too ill for aggressive chemo-radiation treatments.