Oncology meeting marked by reports of drug advances

New medications, some still in clinical trials, target cancers, often in a most specific way.

By Susan J. Landers, amednews staff. June 10, 2002.

Research results presented at the 38th annual meeting of the American Society of Clinical Oncologists in Orlando, Fla., demonstrate that progress, both in treatment and prevention, is continually being made against some of the most lethal forms of cancer.

An oral cancer drug has shown success at targeting cancer cells in the lung while leaving normal cells largely unharmed.

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Researchers from Memorial Sloan-Kettering Cancer Center in New York City treated patients in whom chemotherapy was no longer working with the drug Iressa. Tumors shrank by as much as half in 12% or more of the patients taking the medication.

Patient symptoms such as shortness of breath, cough, weight loss and mental clarity also improved in 43% of patients, usually by only the second week of treatment.

Another study presented at the conference revealed that a substance that helps restore lung cells' ability to absorb vitamin A may hold the potential for preventing lung cancer in former smokers.

For three months some of the 226 former smokers in the study received either a form of vitamin A called 9-cis retinoic acid, another form of retinoic acid plus vitamin E or a pill with no active ingredients.

Gleevec shows promise against chronic myeloid leukemia and gastrointestinal stromal tumors.

Retinoic acid receptors increased significantly among those patients who were taking 9-cis-retinoic acid, according to the researchers.

Retinoic acid receptors absorb vitamin A, which is known to protect against lung cancer. Heavy smoking cuts the number of retinoic acid receptors. Researchers did warn, however, that excessive doses of Vitamin A can be toxic.

In addition, results of a phase III randomized trial of 584 patients demonstrated increased survival rates for a multidrug treatment for advanced non-small cell lung cancer. Patients who received a cisplatin-based combination therapy had a median two-month longer survival rate than did patients who received the single agent paclitaxel, or Taxol.

Although combination chemotherapy is the standard of care for patients with metastatic or recurrent non-small cell lung cancer, previous studies have not demonstrated a clear survival benefit compared with treatment with a single agent.

The study suggests that the survival benefit is still modest, but it "opens the door a crack," said Larry Norton, MD, who just completed his term as president of the oncology clinicians. "When you look at the curative therapy of all diseases, it starts with a small advance where there is an impact, and then that door gets opened a little wider."

Colorectal cancer

A combination of chemotherapy drugs that includes the new drug oxaliplatin works better and has fewer side effects than the standard treatment for advanced colorectal cancer, according to research findings. It could become the new standard of treatment for the disease.

Researchers at medical centers around the country enrolled about 800 patients in a phase III clinical trial, randomly assigning the patients to receive one of three treatments: the standard therapy of irinotecan, leucovorin and 5-FU; oxaliplatin with irinotecan; or a treatment called FOLFOX, consisting of 5-FU, leucovorin and oxaliplatin.

Bevacizumab slowed tumor growth in metastatic renal cell carcinoma.

About 38% of patients on the FOLFOX regimen responded to therapy, living for a median 18 months after beginning therapy, compared with 14 months for those on standard therapy.

Although the results were promising, they should not be overemphasized, said researchers familiar with the study.

Meanwhile, the National Cancer Institute is submitting data on oxaliplatin to the Food and Drug Administration for review.

Until the drug is commercially available, NCI is sponsoring an expanded access program to allow patients with advanced or metastatic colorectal cancer to receive oxaliplatin in the FOLFOX combination therapy.

Chronic myeloid leukemia

Gleevec has continued to live up to its early promise. The drug was first approved for use in advanced stages of chronic myeloid leukemia in May 2001.

At an average follow-up of 14 months, 68% of patients treated with Gleevec (imatinib mesylate) had no detectable leukemia, compared with 7% of interferon-treated patients. Patients also were better able to tolerate Gleevec therapy than they were the standard interferon-based therapy, said Brian J. Druker, MD, who led the team that developed the drug.

Gleevec should now be considered as the standard first-line therapy for CML, said Dr. Druker, who is a professor for medicine, division of hematology and medical oncology at the Oregon Health Sciences University in Portland.

In another study reported at the ASCO conference, Gleevec was shown to shrink or stop tumor growth for at least a year in over 60% of patients with gastrointestinal stromal tumor.

Gleevec is the best known of a new class of targeted therapies that attack targets present or abundant only on cancer cells. Gleevec interferes with the activity of one enzyme in CML and another in GIST, both of which send signals to the nucleus of cancerous cells, telling them to grow and divide, making more cancerous cells.

Kidney cancer

Another molecularly targeted drug, bevacizumab, slowed tumor growth in patients with metastatic renal cell carcinoma, the most common form of kidney cancer in adults. Like Gleevec, bevacizumab is designed to specifically interfere with a biological process that promotes tumor growth or survival.

This drug targets the angiogenic process -- the growth of new blood vessels that provide a supply of oxygen and nutrients that are necessary for a growing tumor.

In a randomized phase II clinical trial of 116 patients with advanced cancer, the time it took for the cancer to show measurable growth was two and a half times longer in patients who were given a high dose of bevacizumab.

More than 20 additional clinical trials are currently under way to evaluate bevacizumab as a treatment for various types of cancer including phase III trials for breast and colorectal cancer.