By Amy D'Orazio, PhD

Multiple Myeloma

Waiting for the Thumbs Up on a New Drug
Millennium Pharmaceuticals, Inc., recently announced that the U.S. Food and Drug Administration (FDA) has accepted for review and granted priority review designation to the new drug application for Velcade™ (bortezomib), which appears to be effective for patients with advanced multiple myeloma (MM) who have failed prior treatments. Priority review was granted only six weeks after the drug received fast-track status and means that the FDA will expedite the approval process from 10 to six months.

Velcade is the first of a new type of drugs called proteasome inhibitors. Proteasomes, the “digestive system” of the cell, breaks down and eliminates proteins made by the cell, including many of the proteins that control cell growth. Inhibiting the proteasome function with Velcade has been shown to shut down cell growth and, in many cases, has led to the death of the cancer cells.
At the December 2002 American Society of Hematology meeting in Philadelphia, researchers reported that 33-50% of MM patients treated with Velcade had decrease in their myeloma tumor burden. At the same meeting, another group showed this drug might have activity in lymphoma patients as well. Velcade is also being tested in lung and colorectal cancer.

For more information about Velcade, visit Millennium Pharmaceuticals at www.mlnm.com.

Lymphoma

A Silver Bullet for Lymphoma
Two effective treatments for lymphoma patients are radiation therapy and monoclonal antibody therapies targeted specifically to lymphoma cells. A new agent called Bexxar® (tositumomab) combines these ideas: a monoclonal antibody that delivers radiation directly to lymphoma cells. The result is a high level of activity with fewer side effects similar to traditional radiation therapy.
A recent FDA advisory committee voted that Bexxar appeared to benefit low-grade (slow-growing) lymphoma patients based on data from clinical trials, which showed that 30% of lymphoma patients achieved a response to the drug.

There was also data showing that this drug was beneficial for patients who had previously received treatment with Rituxan® (rituximab), another widely used antibody for lymphoma. The most common side effects seen with Bexxar are low blood cell count and low platelet count. Data also showed that a small number of patients were at risk of developing radiation-associated leukemias following treatment.

The purpose of this committee was to make a recommendation to the FDA. Based on this recommendation, the FDA is now considering approving Bexxar for use in the United States. A decision is expected later in 2003.

A similar drug called Zevalin™ (ibritumomab) is already on the market for patients with lymphoma. Zevalin was approved in February 2002 for lymphoma patients who had progressed on prior chemotherapy or Rituxan therapy.

To learn more about combined radiation/antibody therapies, visit www.corixa.com or www.zevalin.com.

Lung Cancer

Doubling Up On Lung Cancer
The treatment of advanced lung cancer relies on the use of “doublets,” two chemotherapy drugs given together, one of which is usually Platinol® (cisplatin) or Paraplatin® (carboplatin). Various drugs have been paired with either cisplatin or carboplatin, including Navelbine® (vinorelbine), Gemzar® (gemcitabine), and Taxol® (paclitaxel) with similar results.

Recently, researchers compared the combination of Taxotere® (docetaxel) and cisplatin and found that it appeared to lead to an increased number of remissions and extend survival rates compared to Navelbine/cisplatin. The patients given this treatment also enjoyed a good quality of life with less pain and less nausea and vomiting than in patients given the control treatment of Navelbine/cisplatin. Even patients over age 65 benefited from treatment with Taxotere/cisplatin.

The results of this study led to FDA approval of Taxotere/cisplatin as an option for first-line therapy for lung cancer patients in December 2002. Taxotere has been approved by the FDA for some time for treatment of lung cancer patients who relapsed after first treatment with cisplatin. With this approval, more patients can receive Taxotere and at earlier stages in their treatment.

Most patients treated in this trial had metastatic disease and had never before received chemotherapy. Cisplatin can be hard to tolerate because of nausea, vomiting, and diarrhea. In some patients, it can also cause hearing loss.

To learn more about this new option for lung cancer patients, visit www.taxotere.com.

Colorectal Cancer

Erbitux™ Available for Compassionate Use
Makers of the drug Erbitux (cetuximab or C225) announced in February 2003 that this new drug will be available through a compassionate use program for patients with colorectal cancer who have progressed on standard chemotherapy treatment. Erbitux is an antibody that targets epidermal growth factor receptor (EGFR), which is expressed at high levels in up to 77% of colorectal cancers.

The high levels of EGFR contribute to the uncontrolled growth seen in these tumors, and preclinical studies have shown that blocking EGFR with Erbitux helps halt tumor cell growth. Erbitux also might sensitize the cells to the effects of chemotherapy, especially Camptosar® (irinotecan) and Eloxatin™ (oxaliplatin).

Erbitux has been surrounded by controversy as the former chief executive officer of ImClone Systems, Inc., the company that makes Erbitux, pled guilty to accusations of insider trading. Despite the controversy, however, benefit for colorectal cancer patients has been seen in terms of disease control and tumor shrinkage. Erbitux is very tolerable with its primary side effect being an acne-like rash.

For more information visit, www.imclone.com.