LOS ANGELESTwice-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.
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.