SAN FRANCISCO--Interim results of a major intergroup study of
paclitaxel (Taxol) as adjuvant treatment of node-positive breast
cancer "will change the standard of care for node-positive
breast cancer patients," I. Craig Henderson, MD, of the
University of California, San Francisco, said at ASCO.
The planned interim analysis showed that adding paclitaxel to
standard doxorubicin/cyclophosphamide (AC) improved survival, while
escalating the doxorubicine dose did not.
Adding paclitaxel "decreased recurrence by 22% and deaths by
26%," Dr. Henderson said. "We have not seen evidence of
dose-response for doxorubicin doses over 60 mg/m²."
No previous randomized trial had found an adjuvant chemotherapy
regimen more active than AC.
The study randomized 3,170 patients with operable node-positive
breast cancer to adjuvant therapy with cyclophosphamide (600
mg/m²) plus one of three doses of doxorubicin (60, 75, 90
mg/m²), with or without paclitaxel (175mg/m² over 3 hours),
every 3 weeks for 4 cycles. Patients with estrogen-receptor-positive
tumors also had the option of taking tamoxifen (Nolvadex), 20 mg/day
for 5 years.
At the time of the interim analysis, there had been 453 recurrences
and 200 deaths. At 18 months of follow-up, 90% of patients on AC plus
paclitaxel were estimated to be alive and free of recurrence,
compared with 86% on AC without paclitaxel (see Table).
Overall survival at 18 months was 97% on AC plus paclitaxel vs 95%
on AC alone.
Looking at the proportional rather than absolute benefit, paclitaxel
was thus responsible for about a 22% reduction in annual odds of
recurrence and a 26% reduction in annual odds of death, an effect,
Dr. Henderson said, that "may represent the largest increase in
benefit for adjuvant therapy since the first CMF trials in the 1970s."
However, he urged that this statement be taken with caution in light
of the fact that the data are not mature.
He noted that proportional effects are usually much larger than
absolute effects because they are based only on the patients who have
recurred in the control arm and those who presumably would have died
in the treated arm as well if they had not been treated.
"Thus," he said, "in a study of 100 patients where 10
have died in the control arm and 8 in the treated arm, the absolute
difference in mortality would be 2%, but the proportional reduction
would be 20%."
Although these results are preliminary, Dr. Henderson noted that
"in the past, we have found that once we establish a significant
reduction in the annual risk of recurrence or death from breast
cancer, that remains fairly constant over 10 to 15 years."
The usual toxicities associated with AC were seen. Cardiotoxicity
rates were low and did not increase with doxorubicin dose or with
addition of paclitaxel. The most common paclitaxel-associated
toxicities (grade 3) were transient myelosuppression (21%),
neuropathy (5%), pain (5%), and hyperglycemia (5%).
"The sequential addition of paclitaxel to AC as postoperative
adjuvant therapy of node-positive primary breast cancer is well
tolerated and significantly improves both disease-free survival and
overall survival," Dr. Henderson concluded. Long-term analysis
will be done to determine the durability of this effect.