Lung cancer advances expand market

Lung cancer, currently one of the most common cancers in the United States, accounts for almost 15% of all cancer cases. Each year, 170,000 new cases of this disease are diagnosed. As a result, there is a great deal of research being conducted. In 1998, the American Cancer Society awarded 57 grants totalling $13.5 million for lung cancer research alone.

According to CenterWatch, a publishing company that reports on the clinical trials industry, 39 new lung cancer drugs are in the pipeline.

The general definition of lung cancer is the uncontrolled growth of abnormal cells in the lung. There are two main types of lung cancer: small cell and non-small cell (epidermoid carcinoma, adenocarcinoma and large cell carcinoma). These terms describe the type of cell a doctor sees under the microscope, not the actual size of the tumor. According to the American Cancer Society, non-small cell lung cancer accounts for almost 75% of newly diagnosed United States lung cancer cases annually. The five-year survival rate for advanced non-small cell lung cancer is less than 10%.

Both types of cancer are often found in patients who smoke or have a history of smoking. Unfortunately, lung cancer can go unnoticed, because the symptoms mirror those of bronchitis (coughing or chest pain, wheezing and shortness of breath). If the tumor is detected early and occurs in only one lung, surgery may be recommended and can be successful.

But cancer is often found in both lungs, requiring a combination of surgery and other treatments. In later stage cases, high-dose radiation that kills cancer cells is often the treatment of choice. Chemotherapy is sometimes used in conjunction with radiation treatment, depending on the stage of the cancer.

Chemotherapy

Chemotherapy, used to kill the cancer cells in the lungs, can either be taken orally or by injection. The treatment often produces strong side effects such as nausea, vomiting, temporary hair loss and increased risk of infection due to a lowered white blood cell count.

The Food and Drug Administration recently approved chemotherapeutics for lung cancer: two for the treatment of non-small cell lung cancer and one for small cell lung cancer.

In March 1998, Bristol-Myers Squibb's Taxol (paclitaxel) was approved for first-line treatment of non-small cell lung cancer in combination with cisplatin, a platinum agent. Taxol was previously indicated in the United States as a second-line treatment of AIDS-related Kaposi's sarcoma.

The Food and Drug Administration approved Eli Lilly's Gemzar (gemcitabine) in August 1998 to treat non-small cell lung cancer. Like Taxol, this drug is also administered with cisplatin. The data reported that with the use of Gemzar plus cisplatin, the one-year survival probability for cancer patients who take the product is approximately 60%. Previously, Gemzar was marketed for the treatment of metastatic pancreatic cancer only.

A new drug for small cell lung cancer, SmithKline Beecham's Hycamtin (topotecan), was approved in June 1998 as a second-line treatment. The high probability of relapse for small cell lung cancer patients creates a need for second-line treatment. Hycamtin is a topoisomerase I inhibitor that kills cancer cells by inhibiting topoisomerase I, an enzyme needed for DNA synthesis.

Soon, Matrix will begin phase II trials for its drug MDL 101,731 (FMdC) a treatment for non-small cell lung cancer. FMdC is an inhibitor of ribonucleoside diphosphate reductase, an enzyme also involved in DNA synthesis

Vaccines

Research partners ImClone Systems and Merck are currently in phase III trials with the small cell lung cancer vaccine BEC2. BEC2 is genetically engineered to mimic the shape of GD3, an antigen that is overly expressed in small cell lung cancer carcinomas. The vaccine would then stimulate an immune response to the antigen cancer marker and prevent the tumor from forming.

Progenics Pharmaceuticals and Bristol-Myers Squibb are testing the MGV vaccine for small cell lung cancer and are currently in phase I/II. This vaccine contains GD2 and GM2 antigens, which stimulate the production of antibodies and destroy the cancer cells.

New advances

Another research focus is the use of monoclonal antibodies to destroy cancer cells. ImClone and Merck are researching C225, a drug currently in Phase IIb/IIa. This drug is a monoclonal antibody that inhibits the activity of epidermal growth factor receptor, a compound associated with cancer cell growth in epidermoid carcinoma.

Agouron Pharmaceuticals is currently evaluating the effectiveness of its phase II compound, AG3340, for non-small cell lung cancer. AG3340 inhibits the invasion and growth of solid tumors by inactivating a group of enzymes known as matrix metalloproteases, which are believed to be involved in tumor progression. AG3340 also inhibits angiogenesis, the formation of new blood vessels that feed growing tumors. PR