SAN ANTONIO—A weekly outpatient paclitaxel (Taxol) regimen led to rapid responses in more than 40% of a group of heavily pretreated women with metastatic breast cancer, said Dr. Hans-Joachim Luck, of the Medical University of Hannover, Germany. [See page 30 for a commentary on single-agent taxanes in this setting.]

After 6 weeks of treatment, 15 of 41 evaluable patients had a partial response, and four others had a minor objective response. An additional 18 patients had disease stabilization. Duration of response exceeded 300 days.

“These results show that a weekly paclitaxel schedule is feasible in the outpatient setting and leads to a substantial response rate in heavily pretreated patients,” Dr. Luck said at a poster presentation at the 20th Annual San Antonio Breast Cancer Symposium. “The weekly regimen induced a remarkable time to progression.”

The findings confirm previous evidence of high activity with weekly paclitaxel in heavily pretreated patients presented last year at the American Society of Clinical Oncology meeting (Proc Am Soc Clin Oncol 16:597, 1997), he added.

Typically, paclitaxel regimens entail a 3-hour infusion every 3 weeks. Shorter, more frequent infusions might be more comfortable and convenient for patients treated in the outpatient setting, he said.

The Hannover investigators evaluated a weekly regimen in 53 patients with advanced metastatic breast cancer. About 80% of patients had two or more metastatic sites. Half had been treated previously with anthracyclines, and 30% had previously received taxane-based therapy. Ten had received combination therapy with an anthracycline and a taxane.

The weekly regimen included paclitaxel dosages that ranged from 60 to 90 mg/m2, infused over an hour. Twelve patients received the lowest dose, eight received 70 mg/m2, and 30 received 90 mg/m2. Premedication consisted of dexamethasone, clemastine and raniti-dine. Patients completed a median of 12 weekly cycles (range, 1 to 21).

In addition to the partial and minor responses achieved after 6 weeks, 18 patients had stable disease. At 12 weeks, 10 evaluable patients had a partial response, 3 had a minor response, and 7 had stable disease.

Among responding patients, the median duration of response was 320 days. In patients with disease stabilization, duration of status was 300 days. Prolonged responses also were seen in patients who had a history of anthracycline therapy (312 days) or taxane therapy (262 days).

The regimen was associated with a favorable toxicity profile, Dr. Luck said. No patient developed grade 3-4 neutro-penia, anemia, thrombocytopenia, or febrile neutropenia. With respect to non-hematologic toxicity, 60% of patients had alopecia. The regimen caused no nausea, vomiting, mucositis, or grade 3-4 neuropathy. Grade 2 neuropathy occurred in 15% of the patient population.

“The overall quality of life was improved in patients, compared to the 3-hour infusion,” Dr. Luck said. “In particular, patients who had bone metastases reported decreased bone pain and a reduced use of analgesics.”

The response rates are at least comparable to those observed in early paclitaxel clinical trials in similar populations of heavily pretreated breast cancer patients, he added. Those early trials employed a 3-hour infusion, which was associated with increased toxicity.

“The toxicity may be dependent on the peak drug level,” Dr. Luck said. “We observed no severe neutropenia with the 1-hour paclitaxel schedule, but grade 3-4 neutropenia is very common with a 3-hour, 3-week schedule.”