TOWSON, MdEvidence is mounting that dose escalation with
conventional cytotoxic drugs appears to have no significant advantage
over standard chemotherapy in metastatic breast cancer, said Antonio
C. Wolff, MD, assistant professor of oncology, Johns Hopkins
University School of Medicine.
Several recent studies have shown little difference in overall
survival and time to treatment failure or progression between
patients on standard chemotherapy and high-dose chemotherapy, Dr.
Wolff said at Seeking Excellence in Breast Cancer Care, a
conference sponsored by Johns Hopkins.
The findings raise the question of whether the oncology community
needed to use the heavier approach in the first place. But Dr.
Wolffs answer to that is that many patients and physicians
seemed to be convinced of its value.
Im glad that the initial results of the trials are
finally in, he said, referring to the randomized studies of
high-dose therapy with transplant support. A couple of years
ago, patients were suing their insurance companies and requesting
high-dose chemotherapy because it was billed as your only
chance of cure, he said.
Randomized studies comparing standard to high-dose chemotherapy with
transplant took forever to accrue patients because
patients, and some physicians, believed high doses were necessary, he noted.
Aside from two studies from South Africa, high-dose therapy as
given in the studies recently presented has not been shown to offer
any additional benefit, Dr. Wolff said. Much of what is
done in medicine is based on the beliefs of individual physicians,
rather than science. Thats why clinical trials are important.
Dr. Wolff and his colleagues at Hopkins have begun studies of novel
agents they hope will show far less toxicity than existing drugs for
metastatic breast cancer. So far, diethylnorspermine, or DENSPM, has
shown no significant adverse effects in a phase I study. The drug
mimics the structure of a vital molecule in growth factor pathways in
breast cancer, fooling the pathways into shutting down, he said.
Dr. Wolff is awaiting the final go-ahead from the Department of
Defense for a phase II trial. This study, which the team hopes to
begin this year, will enroll up to 34 women who have already received
at least one but no more than two chemotherapy regimens and whose
disease is advancing, but who have not reached a crisis point.
The women will receive 100 mg/m²/d for two courses of 5 days
each for just under a month; if, upon evaluation, they have at least
stable disease, they will be given the opportunity to continue the
treatment. Those who do not respond or who do not wish to
continue can move on to other therapies, he said.
Dr. Wolff has also begun a phase I study of taxoprexin (under
development by Protarga, Conshohocken, Pennsylvania), which consists
of paclitaxel (Taxol) with a fatty acid attached. The compound is
thought to improve tumor targeting by taking advantage of cancer
cells increased demand for fatty acids. Thus far, there
has been minimal toxicity, but its too early to talk about
activity, he said.
Another phase I study is assessing the effects of T138067 (being
developed by Tularik, South San Francisco, California), which seems
to disrupt microtubule function, but he said that it is too soon to
make any comment.
Dr. Wolff discussed taxoprexin and T138067 as examples of novel
compounds that may be tested against breast cancer in the near