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
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, 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.