Delaying Chemotherapy May Compromise Distant Control

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

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

A randomized trial conducted by investigators at The Joint Center forRadiotherapy and the Dana-Farber Cancer Institute, including Dr. Henderson,and published last year, found no significant difference in the frequencyof failure, regardless of which adjuvant therapy was given first afterlumpectomy. Local or distant failure occurred in 38% of women who had radiotherapyfirst, 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 morelikely to have recurrence of breast cancer at a distant site (36%) thanthose who had immediate adjuvant chemotherapy (24%), a highly significantdifference. In contrast, women who had chemotherapy immediately after surgerywere more likely to have local recurrence (14%) than those who had radiotherapyfirst (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 achievinglocal control, even when the patient has had mastectomy and chemotherapy."

And, he pointed out, another Dana-Farber study suggests that delayingradiotherapy after mastectomy to give chemotherapy first does not significantlyincrease the rate of local failure, even if the delay is as long as eightmonths.

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

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

Or it may be due to the lower doses of chemotherapy that were givento patients who went immediately to radiotherapy. Women who had radiotherapyfirst 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 doseof methotrexate while those who had chemotherapy first received 75% ofthe dose. "These possible explanations seem more plausible than apure issue of timing," Dr. Henderson said.