TAMPERE, FinlandAdjuvant treatment with the nonsteroidal
estrogen inhibitor toremifene (Fareston) proved equivalent to
tamoxifen (Nolvadex) for prevention of breast cancer recurrence but
was associated with fewer embolic events, investigators in an ongoing
Finnish trial reported at the San Antonio Breast Cancer Symposium.
Over a mean follow-up of 2.7 years, patients treated with toremifene
had an 18.3% recurrence rate, compared with 21.6% for tamoxifen (P =
.26). Toremifene patients had a lower overall incidence of embolic
events and a significantly lower incidence of cerebrovascular events.
At this point, we really dont have a good explanation for
the difference in embolic events, said Kaija Holli, MD, an
oncologist at Tampere University Hospital. We have started an
additional trial to learn more about the effects of toremifene on the
clotting system.
Dr. Holli reported findings on the first 900 patients enrolled in a
study that ultimately will accrue a total of 1,460 patients.
All the patients are postmenopausal and have histologically verified
invasive breast cancer with spread to the axillary lymph nodes. More
than 60% of the women are estrogen-receptor positive. Patients
undergo segmental mastectomy and axillary lymph node dissection.
Patients are randomized to receive 40 mg of toremifene daily or 20 mg
of tamoxifen daily. Treatment continues for 3 years.
At the interim follow-up, the two agents proved equivalent in their
ability to prevent breast cancer recurrence. Dr. Holli said that 84
of 459 evaluable toremifene patients have had recurrences (11
locoregional, 73 distant) vs 95 of 440 tamoxifen patients (7
locoregional, 88 distant).
Analysis of cardiovascular events showed a trend in favor of
toremifene-treated patients. Overall, 19 toremifene patients have had
events, resulting in an incidence of 4.1%, compared with a 6.4%
incidence in the tamoxifen group. The major difference related to
cerebrovascular events, which occurred in 0.4% of toremifene patients
and 2.5% of tamoxifen patients (P = .01).
There were fewer cardiovascular events in the toremifene
patients, Dr. Holli said. We carefully recorded all
possible adverse events. There is something going on with respect to
these events, but we cannot say what the reason is. We found the
difference between toremifene and tamoxifen very interesting.
The Finnish investigators have planned other comparative trials
involving toremifene and tamoxifen. The trials will incorporate
careful scrutiny of lipid levels, endometrial changes, bone density,
and ocular changes. Dr. Holli said results could be available within
a year.
Dual Action
Tamoxifen has been shown to reduce recurrences and subsequent
mortality from breast cancer but also has emerged with a variety of
unexpected effects, some of which are adverse, she commented.
Part of the effects have been explained by the dual antiestrogenic
and estrogenic action of tamoxifen, she said. Toremifene has
similar antiestrogenic and estrogenic effects, but it has a lower
estrogenic-to-antiestrogenic ratio than tamoxifen, which might help
explain differences between the two drugs, including the differences
we observed in this study.
