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Breast Cancer Patients Need Alternatives to Dose Escalation

Breast Cancer Patients Need Alternatives to Dose Escalation

TOWSON, Md—Evidence 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. Wolff’s answer to that is that many patients and physicians seemed to be convinced of its value.

“I’m 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. That’s why clinical trials are important.”

Novel Agents

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 it’s 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 future.

 
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