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A moving target

New, 'smart' drugs offer hope, but so far, benefits are limited and costs are high

The drug had been heralded as a potential "cure" for cancer, but by the time Avastin won federal approval for treatment of advanced lung cancer last fall, the drug's maker made only this modest claim: Desperately ill patients will typically live two months more than if they hadn't taken it.

The much-anticipated "smart," or targeted, cancer treatments are joining the war on cancer -- four were approved last year alone -- but scientists are discovering that cancer is a tougher foe than they realized even a few years ago when stunning results in mice raised expectations sky high.

At least a dozen targeted drugs like Avastin, designed to attack tumors' molecular weaknesses without harming the patient, have been approved since 1998, but only three are dramatic improvements over conventional treatment, and most measure their success in extra weeks or months of life for people with advanced cancer.

What's more, the new drugs are expensive -- a month's supply of Avastin for lung cancer costs about $8,000 -- raising concerns among some observers that the rapidly escalating cost of cancer care is already preventing some patients from getting the best treatment.

Yet targeted treatment remains perhaps the brightest light in cancer research because of patients like Fred Holper , who has lived five years longer than doctors expected thanks to, in his words, "faith, love, and Avastin."

Researchers believe that as they learn to better match each patient's cancer with the right targeted drugs, there will be many more Fred Holpers. They also believe that the life-saving benefits of "smart" treatments will become clearer once the Food and Drug Administration permits them to be given to people who are less sick: Herceptin, for instance, is expected to extend many breast cancer patients' lives more than 1.5 years now that the FDA allows it to be prescribed to women whose cancer has not spread to other parts of their bodies.

"I'm not sure that we should be particularly discouraged by the progress that we've made," said Dr. Eric Winer , director of the breast oncology center at Dana-Farber Cancer Institute, who has done pioneering research on Herceptin. "We may not have a lot of home runs, but singles and doubles are better than what we were doing before."

The emergence of targeted cancer treatments comes at a historic moment in the fight against cancer. The number of people dying from the disease declined slightly in both 2003 and 2004 -- the latest years available -- even as the baby boom generation moves into its cancer-prone years. Credit goes mainly to antismoking campaigns, better screening, and improvements in conventional treatment. But the quickening pace of cancer research -- including a 50 percent increase in cancer drugs under development since 2005 -- has raised hopes of much steeper declines in cancer deaths to come.

"We are still at a very early phase of harvesting the benefits of all the new generation of drugs," said Dr. Pier Paolo Pandolfi , who is leaving Memorial Sloan-Kettering Cancer Center in New York to direct cancer research at Beth Israel Deaconess Medical Center this summer. "The gut feeling that many of us have is that this is only the tip of the iceberg. We have to find many more targets" for new drugs.

"Smart" drugs are the most heralded part of the movement toward "personalized medicine," in which cancer is understood to be not one disease but hundreds, each with its own unique molecular structure that can be deliberately attacked and destroyed. Children's Hospital researcher Judah Folkman drew widespread attention to the field in 1998 when his drugs proved remarkably successful at shutting down tumors in mice by cutting off the blood supply they needed to grow. The drugs, one of which would later become Avastin, seemed to hold out the promise of stopping cancer in its tracks without the toxic side effects that patients suffer from traditional chemotherapy and radiation.

Though Folkman's work generated more buzz, another drug, Gleevec, demonstrated the potential of the targeted approach in 2001: Ninety percent of patients with early-stage chronic myelogenous leukemia went into remission while taking it. Gleevec essentially shut down cancer's communication system, preventing the cells from getting a chemical signal directing them to grow.

Unfortunately, Gleevec's success was somewhat misleading because chronic myelogenous leukemia has a single, clear Achilles' heel, while other cancers may not be so vulnerable, said Dr. Lowell Schnipper , chief of hematology and oncology at Beth Israel Deaconess Medical Center. In fact, he said, many forms of cancer turn out to be living proof of the old Harvard Medical School wisdom: "If you throw a stone at nature, it comes back at you with a pitchfork." Eventually, cancer finds a way to resist even cleverly designed treatments, meaning there may never be one cure for cancer.

However, many observers believe that the benefits of the targeted drugs will become clearer as the Food and Drug Administration approves them for use in less advanced cancers, before the disease spirals out of control. Herceptin proved dramatically successful when given to women in the early stages of one type of breast cancer, called HER2-positive, helping many to live disease-free for years. Genentech, the company that makes both Herceptin and Avastin, is sponsoring 150 human trials of Avastin on earlier stages of 25 kinds of cancer in hopes of finding more Herceptin-like success.

In addition, cancer specialists are improving their ability to get the right drugs to the right patients. In his first Herceptin experiments, Winer said, about a quarter of the women who got Herceptin did not have HER2-positive cancers -- because scientists didn't know how to identify such cancers. Today, he says, the test for HER2 positive is accurate 90 to 95 percent of the time.

If the track record of the targeted drugs has fallen short of earlier hopes, their performance has been good enough that cancer patients fight for them. Kara Herynk of Texas was willing to pay the $3,000-a-month price of Herceptin to treat her cervical cancer after the insurance company initially refused coverage and she was too weakened from chemotherapy to take more toxic medications. Eventually, the insurance company covered the treatment, and Herynk, now 33, got eight months of remission for her body to recover before the treatment stopped working. But she was not disappointed.

"Even if it didn't cure me, I had eight months of letting my bone marrow rest so I can do it again," she said.

So far, insurers have balked at paying for targeted therapies mainly when they're prescribed for cancers that the FDA has not approved; in Herynk's case, Herceptin was approved for breast cancer treatment but not her type of cancer. But people with limited or no insurance may already be missing out on some high-priced treatments. Schnipper of Beth Israel Deaconess said he recently consulted with a Florida doctor who said he might not offer a patient Avastin "because the insurance wouldn't cover it."

Dr. Bruce E. Hillner of Virginia Commonwealth University warns that the price of cancer care is rising so rapidly that governments, healthcare providers, insurers, and patients alike have to consider what they're getting for the money. He noted that a year's supply of Herceptin -- price $50,000 -- costs more than all the treatment a breast cancer patient typically would have received in the early 1990s. Herceptin may be effective enough to justify the price, he said, but many other new drugs fall short.

"Unless we want to bankrupt future generations," Hillner wrote recently in the Journal of Clinical Oncology, "cost-effectiveness assessments will have an increasing role in determining . . . how we spend or allocate our precious healthcare dollars."

Schnipper worries that if cost issues aren't addressed now, cancer patients of the future may be divided into "haves" and "have-nots." Currently, patients who don't get targeted therapies may miss out on a few months of life, but in the years to come, he said, the life-saving benefits will grow.

"I'm very bullish, not on the next year or two, but I think in my children's lifetime this disease will be a skeleton of what it used to be," he said, as long as patients can get targeted therapies to keep the disease in check.

Scott Allen can be reached at allen@globe.com.

(Correction: Because of a reporting error, a story in yesterday's Health/Science section about "smart" drugs for cancer treatment incorrectly said Dr. Judah Folkman developed the drug Avastin. Genentech researchers created Avastin.)

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