부산대학교 도서관

Background: To date, anthracyclines are the most active drugs against breast tumors, and the taxane paclitaxel (Taxol) looks very promising. Both classes of drugs are affected by cellular multidrug-resistance mechanisms, and therefore their sequential use raises the possibility of clinical cross-resistance. It is therefore important to assess the activity of paclitaxel in patients with clinical resistance to anthracyclines. Purpose: We assessed the safety and efficacy of paclitaxel administered by the logistically convenient 3-hour infusion to breast cancer patients who had disease progression within 12 months since prior therapy with anthracyclines. Methods: Fifty-one patients with metastatic breast cancer who had all relapsed or whose disease had progressed within 12 months from completion of an anthracycline-containing chemotherapy protocol (six receiving adjuvant therapy, 19 receiving neoadjuvant therapy, and 26 receiving treatment for metastatic disease) were enrolled in this phase II trial from June 1992 to May 1994. After medication to prevent type I acute hypersensitivity reactions, paclitaxel was given intravenously over 3 hours at 175 mg/[m.sup.2] to the first 15 patients and at 225 mg/[m.sup.2] to the next 36 patients. The median age was 50 years (range, 31-62 years), and the median Eastern Cooperative Oncology Group performance status was 0 (range, 0-2). Results: Patients received a median of five cycles (range, one to 11 cycles). After initial doses of 175 and 225 mg/[m.sup.2], paclitaxel could be increased by 25 mg/[m.sup.2] in 73% and 58% of cycles, respectively. Among 50 assessable patients, seven achieved a complete response and 12 achieved a partial response (response rate, 38% [95% confidence interval = 25%-53%]). The median duration of response was 7 months (range, 4-16 months), and the median time to disease progression for all patients was 5 months. Grade 4 neutropenia occurred in 3% of the cycles and in 12% of the patients and was never associated with fever and infection. Common toxic effects were myalgia and arthralgia (94% of the patients; 4% grade 3), peripheral neuropathy (92% of the patients; 8% grade 3), and alopecia (all patients). Pruritus and neuropathy were significantly more frequent and severe, respectively, with the higher dose (P