1997-1998 indexDistributed December 6, 1997
Weekly drug strategy may lead to improved breast cancer treatment
A new weekly regimen of an intense dose of the drug paclitaxel significantly shrinks breast cancer tumors in many patients.
PROVIDENCE, R.I. -- The use of weekly high-dose paclitaxel has resulted in the highest reported response rate for a single-agent taxane regimen in patients with advanced breast cancer. Taxanes are anti-cancer compounds derived from the bark, needles and twigs of yew trees.
In 34 patients, the weekly regimen achieved response rates of 79 percent in patients with locally advanced breast cancer and 77 percent in patents with metastatic breast cancer. The findings were reported by William M. Sikov, M.D., in a poster presentation Saturday, Dec. 6, 1997, at the 20th Annual San Antonio Breast Cancer Symposium.
"Further study of this regimen in a larger number of patients, and comparison of its effectiveness to standard doses of paclitaxel given every three weeks, are planned to confirm these promising results," said Sikov, chair of the study.
Sikov is an assistant professor of medicine in the Brown University School of Medicine and chairman of the Brown University Oncology Group Breast Cancer Committee. He is based at The Miriam Hospital in Providence, R.I.
Paclitaxel is approved for treatment of breast and ovarian cancers. It is also used to treat a number of other malignancies, including bladder, lung, gastrointestinal and head and neck cancers. The most effective dose and schedule for paclitaxel in advanced breast cancer is not known, despite several years of the drug's use. The Brown research was supported in part by a grant from Bristol-Myers Squibb Oncology, Princeton, N.J., makers of the drug TAXOL(TM), which was used in the study.
To increase the dose intensity of paclitaxel, Sikov and colleagues administered the drug at a rate of 175mg/m2 weekly for six weeks, followed by a two-week break, to patients with untreated locally advanced and metastatic breast cancer. The paclitaxel dose was reduced for low blood counts or other side effects. Even with those reductions, patients in the study received twice the dose intensity of the drug compared to standard treatment with paclitaxel of 175mg/m2 every three weeks.
Patients with locally advanced breast cancer who responded to treatment underwent surgery, followed by additional chemotherapy and radiation. Response to paclitaxel often made surgery possible for previously unresectable tumors, Sikov said. Patients with metastatic disease have continued treatment until disease progression or the development of significant side effects, he said.
Toxicities associated with the high-dose weekly paclitaxel regimen were significant but manageable, Sikov said. One major side effect was low blood counts. Despite a high incidence of low white blood counts, only two patients required hospitalization for treatment of fever, he said.
The second major side effect was neurologic toxicity. The most common neurologic toxicity was numbness in the fingers and toes. Overall, 11 patients in the study developed moderately severe neurologic side effects, and four developed severe neurologic side effects, Sikov said. With interruption of treatment, followed by resumption of weekly paclitaxel at a lower dose, no patient experienced progression of neurologic toxicity, he said. Other side effects included nausea, diarrhea, rash and muscle and joint aches.
The study was a Phase II trial, designed to determine the effectiveness of the paclitaxel regimen in patients with advanced breast cancer.
"The effectiveness of taxanes in treating breast cancer has been established," Sikov said. "Now we must focus on determining which regimen achieves the most rapid and complete responses with an acceptable level of side effects. Weekly paclitaxel appears to be a promising regimen, and I look forward to moving this treatment into Phase III trials." A Phase III trial is a study that compares two or more treatments, typically performed at several locations, involving hundreds of patients.
According to the National Cancer Institute, breast cancer is the most frequently diagnosed non-skin cancer among U.S. women. It is the second leading cause of cancer deaths in women in the United States.
Sikov's colleagues in the study include Wallace Akerley, M.D., study co-chair and associate professor of medicine, based at Rhode Island Hospital; Rochelle Strenger, M.D., assistant professor of medicine, The Miriam Hospital; and Frank Cummings, M.D., associate professor, based at Roger Williams Hospital.######