Twice-Weekly Paclitaxel, RT for Locally Advanced Disease

LOS ANGELES—Twice-weekly paclitaxel (Taxol) combined with radiation therapy constitutes a “promising primary management” strategy for locally advanced breast cancer, California oncologists reported at the San Antonio Breast Cancer Symposium.

The strategy achieved pathologic responses prior to surgery in 6 of 14 evaluable patients in the ongoing investigation. The combination of paclitaxel and irradiation proved both feasible and tolerable, said Silvia C. Formenti, MD, associate professor of radiation oncology and medicine, University of Southern California.

Ongoing Study

“The results compare favorably with the 36% response rate we achieved in a similar population at our institution using continuous infusion fluorouracil and radiation therapy,” she said. “We plan to continue the investigation until we have enrolled a total of 80 patients who have locally advanced breast cancer.”

The study involves patients with stage III locally advanced breast cancer. After pretreatment biopsies, patients begin a regimen that consists of twice-weekly paclitaxel doses of 1 hour and radiation therapy that begins a week after the start of chemotherapy and continues for 5 weeks until a total radiation dose of 45 Gy has been administered.

Following completion of radiation therapy, patients continue paclitaxel for an additional 2 weeks. In all cases, surgery is modified radical mastectomy.

Patients who achieve a pathologic complete response or partial response receive four cycles of doxorubicin and paclitaxel. Nonresponders get four cycles of doxorubicin and cyclophosphamide.

Pretreatment core biopsies are collected from each tumor. “Our hypotheses are that a pathologic response of primary breast cancer can be used as an in vivo human model to assess response to chemoradiation and that biological markers from the original tumor can predict pathologic response,” Dr. Formenti stated.

The San Antonio report encompassed efficacy and toxicity data on 14 of the first 22 patients enrolled in the trial. The paclitaxel chemoradiation regimen resulted in pathologic complete responses in four patients and partial responses in two. Major objective clinical responses occurred in 13 of the 14 patients.

Grade 3-4 toxicity associated with the regimen consisted of leukopenia in two patients, and esophagitis, skin desquamation, nausea, and myalgia in one patient each.