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Delaying Chemotherapy May Compromise Distant Control

Delaying Chemotherapy May Compromise Distant Control

CHICAGO--When a breast cancer patient is to receive both adjuvant chemotherapy and radiotherapy after surgery, the question remains as to which should be given first.

In a presentation at the Society of Surgical Oncology cancer symposium, I. Craig Henderson, MD, said that a delay in administering radiotherapy may modestly reduce local control of breast cancer, but a delay in giving chemotherapy decreases distant control of the disease, which may adversely affect survival.

A randomized trial conducted by investigators at The Joint Center for Radiotherapy and the Dana-Farber Cancer Institute, including Dr. Henderson, and published last year, found no significant difference in the frequency of failure, regardless of which adjuvant therapy was given first after lumpectomy. Local or distant failure occurred in 38% of women who had radiotherapy first, and 31% of women who had chemotherapy first.

The sequence of therapy also did not significantly affect survival: Overall survival was 73% for women who had radiotherapy first versus 81% for women who had chemotherapy first.

The Take-Home Point

Differences were found, however, in the type of failure that occurred. Women who underwent radiotherapy immediately after lumpectomy were more likely to have recurrence of breast cancer at a distant site (36%) than those who had immediate adjuvant chemotherapy (24%), a highly significant difference. In contrast, women who had chemotherapy immediately after surgery were more likely to have local recurrence (14%) than those who had radiotherapy first (5%).

"Chemotherapy first results in a lower rate of distant failure. I think that is the important take-home point," Dr. Henderson said. Nevertheless, he added, "radiotherapy still is important in achieving local control, even when the patient has had mastectomy and chemotherapy."

And, he pointed out, another Dana-Farber study suggests that delaying radiotherapy after mastectomy to give chemotherapy first does not significantly increase the rate of local failure, even if the delay is as long as eight months.

In this study, breast cancer recurred locally in 17% of women who had chemotherapy only after surgery, compared with 7% of women who had chemotherapy followed by radiotherapy. These figures can be compared with 10-year historical control data from Brigham & Women's Hospital, which show a 6% local recurrence rate in high-risk women who received adjuvant radiotherapy only.

Dr. Henderson cautioned that the effect on distant failure of giving chemotherapy first may be due to the shorter interval between surgery and the start of chemotherapy in patients who receive chemotherapy before radiotherapy. In the lumpectomy study, the interval was 119 days when radiotherapy was given first, but only 52 days when chemotherapy was initiated first.

Or it may be due to the lower doses of chemotherapy that were given to patients who went immediately to radiotherapy. Women who had radiotherapy first received 81% of the standard dose of doxorubicin, compared with 88% of the dose given to chemotherapy-first patients.

Similarly, women who had radiotherapy first received 50% of the dose of methotrexate while those who had chemotherapy first received 75% of the dose. "These possible explanations seem more plausible than a pure issue of timing," Dr. Henderson said.

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