Study Shows Timing is Key to Killing Lung Cancer Cells

March 07, 2003

A Strong Memorial Hospital doctor who specializes in treating lung cancer discovered a new way of combining radiation and chemotherapy to kill tumor cells when they are most vulnerable. Her observations began in the laboratory, but quickly moved to clinical trials involving patients with advanced lung cancer. Of the 33 patients who completed the new regimen, 98 percent saw their large chest tumors shrink or disappear a result that is capturing the attention of oncologists nationwide.

"I am very excited about this study because it truly illustrates how research can improve patient care," says Yuhchyau Chen, M.D., Ph.D., associate professor of Radiation Oncology, at the James P. Wilmot Cancer Center of the University of Rochester. "And, because we were able to use lower doses of chemotherapy in a more strategic way to enhance the radiation effects, many patients felt good enough to go about their normal activities during treatment."

Chen's study is published in the March 7, 2003 issue of Clinical Cancer Research. She also was invited to present her findings to a group of top oncologists at the M.D. Anderson Cancer Center at the University of Texas.

Lung cancer remains the No. 1 killer of all types of cancer in men and women. The biology of lung cancer is lethal, and unfortunately by the time it is discovered the tumors are often quite large (grapefruit-sized or larger) or have begun to spread outside of the chest, Chen says.

Historically, radiation was the best treatment for most inoperable lung cancer. But in the last decade, new standards arose using combinations of radiation and chemotherapy, given in different sequences at different doses. The drawback to combination therapy, however, is that many patients cannot withstand the toxicity. They develop low blood counts, pneumonia, infections, or other life-threatening side effects. In addition, no one has discovered the optimum dose schedule for all situations. 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.

Chen's research focused on timing the treatments precisely to target cancer cells. She started with a laboratory analysis of lung cancer cells and the cycles they go through every 24 and 48 hours. Using that evidence, Chen designed a treatment regimen based on the precise hours, within the 48-hour period, that lung cancer cells would most likely die when hit with radiation. By pinpointing the timing, Chen was able to repeat low doses of paclitaxel, a widely prescribed chemotherapy drug with many toxic side effects, to work in tandem with radiation.

Patients enrolled in Chen's clinical study received low doses of chemotherapy on Mondays, Wednesdays and Fridays before 11 a.m., followed by radiation five hours later, when the cells had progressed to the critical point in their life cycle. On Tuesdays and Thursdays, the patients also received radiation, timed again to the correct cell phase. "The degree of primary chest tumor shrinkage was impressive," Chen says. "This demonstrates that this drug may enhance the tumor's response to radiation if the timing of the chemotherapy and radiation is right."

The survival rates in Chen's clinical trial were equal to or better than the survival rates reported in several of large, randomized clinical trials of patients with advanced lung cancer treated with a combination of chemotherapy/radiation, the study reports. In addition, Chen's study showed better primary tumor control than other studies, and her patients experienced fewer harmful side effects.

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 in patients with heart disease, kidney problems, or other health conditions that render them too ill for aggressive chemo-radiation treatments.

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