PARIS--Paclitaxel (Taxol), the flagship of the new taxanes, has been hailed as a pharmacologic breakthrough, but its ideal use in the treatment of breast cancer is still a matter of debate. Speaking at the Sixth International Congress on Anti-Cancer Treatment (ICACT), National Cancer Institute oncologist Joyce O'Shaughnessy attempted to answer the most compelling unanswered questions about paclitaxel(Drug information on paclitaxel) use.
Dose and Infusion Duration
"Paclitaxel is a very active single agent in previously untreated patients with metastatic breast cancer, as well as in those previously exposed to doxorubicin(Drug information on doxorubicin), although complete responses occur primarily in minimally pretreated patients," Dr. O'Shaughnessy said.
Doses of 200 to 250 mg/m² have generally been used as first-line treatment, she said, but there does not appear to be any evidence that doses over 175 mg/m² are superior as salvage therapy.
Scheduling of single-agent paclitaxel can be "tricky," she said. In a recent randomized multicenter European trial of previously untreated women, a 24-hour infusion yielded a response rate minimally superior to that of a 3-hour infusion, but at the cost of greater toxicity.
On the other hand, she said, side-by-side comparison of data from Memorial Sloan-Kettering and the NCI indicates that, in patients given previous chemotherapy, a 24-hour infusion of 175 mg/m² offers no advantages over a 3-hour infusion. However, a growing experience suggests that 96-hour infusions might be beneficial in patients who fail to respond to 1- to 3-hour taxane infusions.
Dr. O'Shaughnessy and her colleagues at the NCI are now finishing up a phase I study of 14-day outpatient infusions of paclitaxel. "What we have found to date is that patients who were started at doses lower than the maximum tolerated dose of 175 mg/m² developed a tolerance phenomenon and could be escalated all the way to dose level 9 (273 mg/m²) without significant dose-limiting toxicity," Dr. O'Shaughnessy said.