November 2004

University of Texas M. D. Anderson Cancer Center

No link found between pneumonitis in breast cancer patients and taxane-based chemotherapies

HOUSTON - Researchers at The University of Texas M. D. Anderson Cancer Center have shown that breast cancer patients treated with taxane-based chemotherapies and radiation are not at increased risk of developing a dangerous lung condition involving the inflammation of lung tissue, pneumonitis, according to a study published in the Nov. 17 issue of the Journal of the National Cancer Institute.

These results are vitally important, says Thomas Buchholz, M.D., the study's corresponding author, because both radiation and taxanes-based chemotherapies, including Taxotere and Taxol, have proven effective in the treatment and improved survival of selected patients with breast cancer.

In addition, these results disprove a previous smaller study that had suggested the dangerous correlation between taxanes, radiation treatment and lung injury.

"We had the unique opportunity to investigate and clearly focus on the question of whether or not taxanes increase radiation induced lung complications," says Buchholz, professor in the Department of Radiation Oncology at M. D. Anderson. "Both taxanes and radiation therapy are critically important in the treatment of patients whose disease has spread beyond the breast.

"The first study showed higher rates of toxicity and received a great deal of attention within the medical community. We were concerned that oncologists might have some reluctance in giving these appropriate treatments. With this study, we wanted to try and determine if we could alleviate the fears of both the physicians administering, and the patients receiving these potentially life-saving treatments."

The research, led by Tse-Kuan Yu, M.D., Ph.D., a resident in radiation oncology at M. D. Anderson and the study's principal investigator, analyzed 189 breast cancer patients who had been enrolled in a prospective Phase III randomized trial. The patients had received either four cycles of paclitaxel (Taxol) followed by four cycles of 5-flourouracil, doxorubicin and clyclophsphamide (FAC) and then radiation therapy; or eight cycles of FAC followed by radiation.

The researchers were able to review chest X-rays of the women in both groups and could directly evaluate the rates of lung injury. They concluded that there was statistically no difference in the rate of radiation-induced lung toxicity between the two groups of patients; 5 percent in those treated with the paclitaxel-FAC and radiation, compared with 4.5 percent in those treated with FAC and radiation. In addition, the researchers reported that no patients were hospitalized and/or died as a result of pneumonitis.

"Fortunately, we discovered that the rates of seriously related lung injury were very, very low in both groups of patients, making us more comfortable in using these potentially curative treatments without any reservations," says Buchholz.

Buchholz and Yu both point out a key difference between the M. D. Anderson research and the earlier study that suggested the lung damage correlation was, in the M. D. Anderson study, chemotherapy and radiation were given sequentially, compared to simultaneous delivery in the smaller study.

"It is possible that taxanes and radiation given simultaneously interact to cause increased lung toxicity, but with our delivery, which is more standard practice, we did not see any clinically-relevant damage," says Yu. "Additionally, the sequencing and extended time between the delivery of paclitaxel and the radiation might be of great importance. In our study, four cycles of paclitaxel and then four cycles of FAC were given, followed by surgery and then radiation. Having the buffer window between the Taxol and the radiation might be, in part, cause for why we did not see any lung injury."

Other researchers collaborating on the M. D. Anderson study include: Gary J. Whitman, M.D.; Howard D. Thames, Ph.D.; Aman U. Buzdar, M.D.; Eric A. Strom, M.D.; George H. Perkins, M.D.; Naomi R. Schechter, M.D.; Marsha D. McNeese, M.D.; Shu-Wan Kau; Eva S. Thomas, M.D.; and Gabriel Hortobagyi, M.D.






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