By Amy D'Orazio, PhD and Kavita Maung, PhD

Breast Cancer

Cancer Growth Loses Steam With Zarnestra™
The ras gene was among the first cancer-causing genes discovered that seemed to play a crucial role in how tumors developed from normal cells. About 30% of all human cancers contain an abnormal form of this gene, which allows the cell to grow uncontrollably. But until recently, researchers didn’t know how to stop it.

Zarnestra (tipifarnib, R115777) is a new drug in clinical development at Johnson & Johnson for patients with breast and lung cancers as well as leukemia. At the 2002 American Society of Clinical Oncology (ASCO) meeting, Stephen Johnston, MD, and his colleagues from the United Kingdom reported the first phase II trial using Zarnestra to treat breast cancer patients. Nearly 25% of patients given Zarnestra, most of whom had relapsed after treatment with chemotherapy, showed tumor reduction or stoppage of growth. There were very few side effects, especially in patients who were given short breaks during the course of treatment.

Sarasar™(lonafarnib), another inhibitor of ras, is also being tested in lung cancer. For more information, visit www.sch-plough.com.

Lymphoma

Unwinding a Cure
If the DNA in a normal human cell were unwound, it would stretch out to more than 6 feet in length. Compacting this DNA into a tiny cell requires the help of proteins known as histones, which serve as spools around which the DNA thread is wound when not in use–to be unwound when specific genes are needed. The winding and unwinding of the DNA is a highly regulated process.

A new agent, depsipeptide, controls one of the enzymes that controls the histone activity called histone deacetylase. T-cell lymphomas are an aggressive subtype of non-Hodgkin’s lymphoma. In a phase I trial, depsipeptide was able to cause complete resolution of disease in one T-cell lymphoma patient. The trial was then expanded to include more T-cell lymphoma patients. At the 2002 ASCO meeting, Richard Piekarz, MD, National Cancer Institute, reported that more than half of these patients achieved tumor regression with depsipeptide.

Although these results are very preliminary and more studies are needed to determine the safety of this agent, investigators feel depsipeptide has the potential to be one of the more active agents for T-cell lymphoma, which will affect about 15% of the 53,900 persons diagnosed with non-Hodgkin’s lymphoma in 2002.

Colon Cancer

Colon Cancer’s Newest Enemy
On August 8, 2002 a new drug was approved for those with colorectal cancer in the United States. Eloxatin® (oxaliplatin), approved in Europe for a number of years, was approved in the U.S. following results from a trial which showed that, when given with fluorouracil and folinic acid, it delayed tumor recurrence in patients who had failed treatment with standard chemotherapy drugs.

Eloxatin has manageable side effects such as diarrhea and vomiting, although it can result in nerve damage (neuropathy). It is administered as a short infusion every 2 or 3 weeks. Another NCI-sponsored trial, led by the North Central Cancer Treatment Group, suggests that Eloxatin with fluorouracil and folinic acid could also be a good option in previously untreated colorectal cancer patients, with good results seen in tumor shrinkage and in prolonging survival.

For more information about the results of the NCCTG clinical trial visit www.cancer.gov under Colon and Rectal Cancer Updates or see the ASCO web site at www.asco.org.

Leukemia & Lymphoma

When Chemotherapy Works Too Well
Everyone wants effective therapeutic regimens that act quickly and completely, but in some patients, fast and effective treatments can have a dangerous side effect called tumor lysis syndrome. This emergency situation is caused by the release of the contents of the tumor cell as it is destroyed by chemotherapy treatment. One compound within the tumor cell is uric acid, a substance which, when released at high levels, can overwhelm the kidneys and crystallize, leading to kidney failure. Patients with lymphoma or leukemia are most likely to develop tumor lysis syndrome although cases have been seen in patients with breast and lung cancer as well.

Elitek™ (rasburicase) is a new agent that increases the metabolism of uric acid by preventing it from crystallizing in the kidneys. In three studies recently presented to the FDA, Elitek was effective at controlling uric acid levels in the patients, most of whom were children with lymphoma or leukemia. None of these patients experienced life-threatening tumor lysis syndrome, although some did experience a rash. Based on these studies, the FDA approved Elitek in July 2002 for the prevention of increased uric acid levels in pediatric cancer patients.

Additional studies have shown that Elitek can control uric acid levels in adults as well and more studies in both adult and pediatric cancer patients are ongoing to determine whether this will lower the risk of tumor lysis syndrome.

To learn more about Elitek, visit www.sanofi-synthelabo.com.

Sarcoma

Marine Drug for Patients With Sarcoma
Sea squirts, found in oceans in the Caribbean and Mediterranean seas, could contain an effective treatment for sarcoma, a characteristically hard-to-treat cancer.

The new drug, called ET-743 or ecteinascidin, which is extracted from these marine animals, acts by interfering with the DNA of cancer cells.

Four phase II trials involving more than 300 sarcoma patients were reported at the 2002 ASCO meeting. The trials showed that ET-743, which is given once every three weeks, could cause tumor shrinkage or at least inhibit further growth in as many as 25% of the patients. Most of the patients had already received multiple chemotherapy regimens before receiving ET-743. The main side effects of this drug appear to be low white blood cell count and, in some patients, liver toxicity.

Studies with this new drug have also been undertaken in breast, lung, and ovarian cancer. To learn more, visit www.pharmamar.es.

Kidney & Breast Cancer

Putting the Brakes on Cell Division
Normal cells have a carefully regulated process for growing and dividing that cancer cells have managed to circumvent. Drugs that stop the process of cancer cell division, or even slow it down, are likely to be good antitumor agents. CCI-779, one such agent, is showing exciting effectiveness against kidney and breast cancers.

A study involving 110 patients across the United States showed that CCI-779 was able to halt growth or cause tumor shrinkage in as many as three quarters of patients with kidney cancer. A rash was the most common side effect seen in these patients.

There is evidence that CCI-779 could also be effective for patients with breast cancer. In another trial conducted in the United Kingdom and Germany, treatment with CCI-779 of patients whose breast tumors were resistant to chemotherapy resulted in tumor shrinkage or growth cessation in about half of the patients. Trials are ongoing to determine if this new agent will be effective for lymphoma, brain tumors, and lung cancer.

Visit www.wyeth.com to learn more about CCI-779.