Looks like we've got some new treatments on the way

Drugs Show New Hope in Fighting Cancer

By ANDREW POLLACK, The New York Times

NEW ORLEANS (June 6) - Several new drugs are showing unprecedented promise in treating kidney cancer, a form of cancer that has been particularly hard to treat, doctors said on Sunday.
"I think they are a leap above anything we've seen previously," said Dr. Walter M. Stadler, a kidney cancer expert at the University of Chicago, who gave a talk about new drugs here at the annual meeting of the American Society of Clinical Oncology.

Separately, a study presented at the conference suggested that statins, the drugs widely used to lower cholesterol, might also help prevent colon cancer. Experts said that it would be premature, however, for healthy people to take such a drug just for that purpose.

The kidney drugs are all so-called targeted therapies, which are changing cancer treatment by attacking particular molecular mechanisms that spur cancer growth. More than that, however, the drugs are examples of the latest trend: trying to inhibit more than one such mechanism at a time. That appears to work better than inhibiting just one, just as roadblocks at multiple locations will disrupt traffic more than a single roadblock.

Two of the kidney drugs discussed block two or more mechanisms. Another trial involved two drugs used in combination, each blocking a single mechanism. Only one of the four drugs is available now, but the others are expected to reach the market over the next two or three years.

There are 30,000 to 36,000 new cases of kidney cancer a year in the United States and about 12,500 deaths, doctors said. Only 10 to 20 percent of people live more than two years after diagnosis.

The disease has been particularly resistant to chemotherapy. There is only one drug approved for kidney cancer, interleukin-2. While it can cause a complete remission in 3 to 10 percent of patients treated, it is so toxic that most patients do not receive it and those who do are often placed in a hospital intensive care unit. Another drug, alpha interferon, is also frequently used.

The data presented Sunday were mainly from small trials without placebo controls, and doctors cautioned that the results might not hold up in larger, randomized trials. The data do not yet show that the drugs prolong lives. But for the majority of patients they either shrank tumors or at least stopped them from growing.

For kidney cancer, even that is an accomplishment. Dr. Robert J. Motzer of Memorial Sloan-Kettering Cancer Center in New York City, who led the trial of one drug, said it was the first drug he had worked with in 20 years that had such activity.

The drug, known as SU11248, shrank tumors by at least half in 21 of the 63 patients treated and stopped tumor growth in 23 others. The trial, sponsored by Pfizer, the drug's manufacturer, involved 63 patients whose tumors had continued to worsen despite previous treatment with interleukin-2 or interferon.

Another drug called BAY 43-9006 caused tumor shrinkage or stopped tumor growth in 82 of 106 patients, most of whom had also had previous unsuccessful treatment. Tumors shrank by half in 13 of those patients. The drug is being developed by Bayer and Onyx Pharmaceuticals of Richmond, Calif.

The two drugs used in concert were Avastin, which is already approved to treat colon cancer, and Tarceva, which has been shown in a trial to extend the lives of lung cancer patients. Avastin blocks the flow of blood to tumors while Tarceva blocks a growth-spurring protein called epidermal growth factor receptor.

In that trial, tumors shrank by at least half in 12 of 58 patients and shrank by a lesser amount, or stopped growing, in 38 others.

The newer targeted therapies generally have fewer side effects than older chemotherapy drugs. But right now, old and new drugs are often used together, so patients do not avoid toxicity. Combinations of targeted agents could change that.

"What we're trying to do is treat patients in a meaningful way with targeted therapy that doesn't include chemotherapy," said Dr. Susan Desmond-Hellmann, the top medical officer at Genentech, which developed Avastin and is developing Tarceva along with Roche and OSI Pharmaceuticals of Melville, N.Y. The combination of the two drugs is also being tested in other cancers.

But trying to arrange a trial combining two drugs can be "extraordinarily difficult," said Dr. John D. Hainsworth of the Sarah Cannon Cancer Center in Nashville, the principal investigator of the trial involving Avastin and Tarceva. Companies do not like to cooperate because the trial might not make clear which company's drug causes which effects. In this case, he said, the trial was possible because the same company is developing both drugs.

Other doctors and analysts said that combining two drugs would be expensive and that a single drug attacking multiple targets, like those being developed by Pfizer, Bayer and Onyx, would be preferable.

Financial analysts here were scrutinizing the results, in particular comparing the Bayer and Onyx drug to the Pfizer drug. Some analysts said the Pfizer drug appeared to work better but had more serious side effects. The stock of Onyx, which has no drugs on the market yet, could rise or fall Monday based on their sentiment. But doctors said that both agents seemed to work and that it was too early to tell which was better.

The study on statins involved a comparison of statin use in about 1,600 Israelis with colon cancer and a similar number without colon cancer who were matched for age, gender and ethnicity. Use of the drugs was associated with a roughly 50 percent lower risk of colon cancer, said the author, Dr. Stephen B. Gruber of the University of Michigan. Some previous studies have also showed evidence of reduced cancer risk from the drugs, which include Lipitor, Zocor and Pravachol.

Still Dr. Gruber and some other experts said it was too early to recommend that people take statins, since the Israeli study was not a clinical trial, but rather a look back at patient records.

"To say to an otherwise healthy person to go start taking statins right now would be imprudent," said Dr. Monica Morrow of Northwestern Memorial Hospital in Chicago.

In another study discussed on Sunday, new data showed that the osteoporosis drug Evista, also known as raloxifene, reduced the risk of breast cancer in post-menopausal women who took it for eight years. But investigators said it was premature for women to take that drug for cancer prevention. Another trial is under way to assess whether Evista is as effective as the frequently used tamoxifen in reducing the risk of breast cancer.


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