By By Amy D'Orazio, PhD

Breast Cancer

“ATAC”-ing Early Stage Breast Cancer: Tamoxifen, Arimidex, or Both?
Ask a group of breast cancer survivors what treatment they received after surgery for breast cancer and chances are a good proportion of them will answer “tamoxifen.” And for good reason: for many years tamoxifen was the only therapy with proven ability to prevent breast cancer from recurring.

Tamoxifen has its drawbacks, including the important fact that some patients can become resistant to it. Doctors are uncertain how this happens, but it appears that the breast cancer cell changes the way it sees tamoxifen: instead of a stop sign, the breast cancer sees a go signal, and begins to grow again.
Arimidex® (anastrozole) was developed as an alternative anti-estrogen therapy. Arimidex leads to an almost complete shut-down of estrogen production, which in turn leads to “starvation” of any breast cancer cells in the patient’s body after surgery. But is Arimidex as effective as tamoxifen in preventing breast cancer?
The “ATAC” Trial (Arimidex or Tamoxifen Alone and in Combination) compared the two agents in postmenopausal women who had completed their initial treatment (ie, surgery, radiation therapy, and chemotherapy). The preliminary results showed that Arimidex was more effective than tamoxifen in lowering the risk of relapsing or developing a new tumor in the opposite breast. Arimidex also had a lower incidence of some side effects such as hot flashes, vaginal bleeding, weight gain, blood clot formation, and endometrial cancer.

These results, , presented at the San Antonio Breast Cancer Symposium in December 2001, are only the preliminary results and could change as the patients are followed for longer periods of time. At this time however, it appears that Arimidex could be as good or better than tamoxifen in decreasing the risk of a breast cancer recurrence after surgery and or radiation as well as in developing a new tumor in the other breast.

New Drug Can Lower Risk of Infection Without Need For Daily Injections
Chemotherapy can sometimes decrease the numbers of infection fighting white blood cells (WBC), putting the cancer patient at risk of fever and infection. Chemotherapy patients face high risk of these complications because many chemotherapy agents can lower the number of infection-fighting WBC whose primary role is to ward off infections. In patients with low white blood cell counts, even common infections can become life-threatening.

To stimulate the growth of the white blood cells, physicians frequently prescribe Neupogen® (filgrastim) injections. However, the administration of Neupogen required daily injections, sometimes for up to 14 consecutive days, which can be both uncomfortable and inconvenient.

The February, 2002 FDA approval of a new drug called Neulasta™ (pegfilgrastim) could change that. Neulasta, a form of Neupogen that has been chemically modified, can be given only once every three weeks, or about once to read once per cycle of chemotherapy. This means fewer office visits, fewer painful injections, and less disruption of the patients’ lives. Moreover, Neulasta is just as effective as Neupogen at reducing the risk of infection and hospitalizations. The most common side effect of Neulasta is bone pain, which is seen in about 1 in 4 patients taking Neulasta and can be alleviated by over the counter pain relievers. For more information, visit www.neulasta.com.

Should You Get More Chemotherapy Before Your Operation for Breast Cancer?
Doctors used to think that the best strategy for treating a breast tumor was like the strategy for moving out of your house: take out the big pieces first, and then go back for the lamps and things. So most women get surgery to remove the breast tumor then chemotherapy for anything that was left. However, this opinion may soon change, and your doctor might recommend that you have chemotherapy before your operation.

The National Surgical Adjuvant Breast and Bowel Project (NSABP) is a coalition of surgical oncologists who are dedicated to finding the best treatment options for cancers in the breasts and bowels. Several years ago, the NSABP reported that giving patients chemotherapy before surgery, instead of afterwards, resulted in less need for mastectomy and, in some patients, complete remission.

NSABP is currently conducting another trial that makes use of an intensive chemotherapy regimen before surgery. In their first trial, patients received “AC” chemotherapy, which stands for the combination of Adriamycin® (doxorubicin) and Cytoxan® (cyclophosphamide). In the second trial, researchers added a
second step to the regimen, meaning patients received AC every three weeks for a total of 12 weeks and then received four courses of Taxotere® (docetaxel), which was also given every three weeks. At the most recent San Antonio Breast Cancer Symposium, which was attended by approximately 4,000 doctors and breast cancer patient advocates, a representative of NSABP reported that giving patients Taxotere after AC chemotherapy resulted in more tumor shrinkage.

In fact, almost one fifth of the patients had no evidence of breast cancer after chemotherapy with AC and Taxotere. The other important finding from this trial is that fewer patients who received AC and Taxotere had cancer detected in their lymph nodes. Will these patients have less chance of relapse and/or live longer? At this time it is unknown, but the possibility exists.

Ovarian Cancer

Teaching Your Body to Fight Off Cancer
Almost everyone is familiar with the concept of a vaccine: you’ve probably received several yourself, and if you are parent, reassured your children that it might pinch for a moment, but that it would protect them from all sorts of nasty disease like measles, mumps, and polio. But what about a vaccine for cancer? Based on the results of a trial with ovarian cancer at various stages, a vaccine for ovarian cancer might soon become a reality. This new vaccine, called OvaRex® (oregovomab) is different from other treatments for ovarian cancer in that it teaches the immune system to eliminate ovarian cancer cells.
Ovarian cancer cells are distinguished from normal cells because they make higher amounts of the CA125 protein, which can be measured in blood tests to determine the status of the disease. CA125 serves as a flag, advertising to the immune system that it is a cancer cell. And OvaRex serves as a priming agent to rev up your immune system to fight.

But does it work? So far, the answer seems to be yes. In a recent Phase II trial with OvaRex over half the patients treated developed antibodies and other immune cells that attack cancer cells, because the immune system attacks ONLY the cancer cells, there are few side effects. It is not known yet what effect the vaccine will have on disease relapse or survival. Similar vaccines are being developed for prostate cancer, multiple myeloma, and other cancers.
For more information on OvaRex or other vaccines that fight cancer, see the company’s web site at www.altarex.com.

Leukemia

A Potential Wonder Drug for Leukemia
Gleevec burst onto the cancer scene only last year, and the news of its prowess in treating chronic myeloid leukemia (CML) spread like wildfire: remissions occurred in the majority of those treated with Gleevec, even in some patients who had reached the later advanced phase that can be rapidly fatal. In addition, Gleevec had few side effects. In essentially every patient treated with Gleevec, researchers were able to decrease the cancer to very low levels, and it is hoped that patients may live longer with such low levels of disease.
Although the success of Gleevec is promising, researchers are not satisfied and continue to search for still better treatments. Now, less than a year since the approval of Gleevec, a successor might already be in the works. The new drug is currently known only as PD-173955. Like Gleevec, it is an inhibitor of a cellular

protein that stimulates the cell to grow. Found in both noncancerous and cancerous cells; however, in cancerous cells the protein is like a car whose gas pedal is stuck permanently to the metal, causing the car to run continuously. Inhibitors like Gleevec and the new drug, PD-173955, serve as stop signals to the cells by turning off the protein.

Will the new drug be as effective as Gleevec for CML? At this point it is too early to tell. But researchers are hopeful that PD-173955 may be an effective alternative to Gleevec or might be used in those patients whose tumors prove resistant to Gleevec.

Myeloma

Got Zometa®?
Cancer cells have the ability to stimulate the breakdown of the patient’s bones, which leads to the release of calcium into the bloodstream. Once the levels of calcium in the bloodstream reach a certain point, severe complications can occur, including dehydration, fatigue, vomiting, confusion, or coma. In addition, the breakdown of the bones causes them to become brittle, leading to pain and the increased risk of fractures or immobility. This condition occurs in more than 10% of all cancer patients and is most common in patients with advanced breast cancer, multiple myeloma, lung cancer, or prostate cancer that has spread to the bones.

To protect patients from bone density loss, doctors have often prescribed Aredia® (pamidronate), one of a group of drugs known as bisphosphonates. Bisphosphonates stop the work of natural “bone-eating” cells, called osteoclasts, which can be stimulated by cancer cells. Zometa, a newer kind of bisphosphonate, was approved by the Food and Drug Administration in August 2001. In studies of more than 600 patients with prostate cancer, Zometa was more effective than Aredia at stopping the breakdown of the patients’ bones. In breast cancer and multiple myeloma patients, Zometa had the same efficacy as Aredia. Zometa may be preferred because it can be administered in the clinic setting in 15 minutes, compared to two hours for Aredia. Lung cancer patients treated with Zometa experienced fewer fractures than those given a placebo. Zometa was approved by the FDA in early 2002.