A drug that works -- for some

CONCORD -- Early last year, Kate Robbins started her death journal. It was meant to guide her two children after lung cancer killed her. Robbins poured out advice: on dating, on morality, on family. The things a mother explains to her teens. She also memorialized quiet, poignant moments. One rainy day, watching 10-year-old Hillary board the school bus, Robbins began weeping. She wrote simply, "You looked really pretty today." The kids would read the journal years later, she hoped, and feel their mother's love.

Advanced lung cancer patients rarely live one year. Robbins had months left. Then, last autumn, she began taking an experimental drug called Iressa, as did hundreds of other patients in the United States. Most continued to worsen.

But a small group, including Robbins, thrived. Doctors were stunned because lung cancer, the speediest and most widespread killer among cancers, had resisted virtually every treatment.

Now researchers are racing to unravel why Iressa -- the first significant new lung cancer drug in a generation -- appears to help only select patients. They are studying the DNA of patients for clues, hoping to develop a genetic screening test that would enable them to get the drug to the right people quickly. If they succeed, a small portion of lung cancer victims would get extra years of life. Given that 157,000 Americans die annually from the disease, the impact could be considerable.

The effort is part of an emerging area of medicine seeking to genetically match patients to drugs. Such personally-tailored medicating promises to be a hallmark of 21st-century health care.

Robbins's doctor, Thomas Lynch of Massachusetts General Hospital, said he has other lung cancer patients who also are doing well as many as three years after starting on Iressa.

"I've been treating this cancer since 1989, 500 patients a year, and this is the most significant development I've seen," he said.

Last week, Robbins, 46, had her first checkup in five months: Out of 16 once-bulging tumors scattered throughout her organs, there appeared to be none.

"It's the most amazing thing," she said.

Robbins has big eyes and a round, girlish face. She talks with energy and enthusiasm, her Boston accent occasionally poking through. Robbins was raised in Chelmsford and moved to Concord from rural Connecticut four months ago to be near MGH. She worked as a nurse but stopped to raise her children, Tom, now 13, and Hillary, 11. Her husband, Mark, is a cancer doctor at Emerson Hospital.

Attentive to her health, Robbins was an unlikely candidate for lung cancer in her 40s. About 85 percent of the disease's victims are current or former smokers, but Robbins has never smoked. She rarely drinks, and, moved by the suffering of animals, became a vegetarian at age 10. But one day in January 2002, she developed an intense headache. "I thought it was post-holiday stress," she said.

An MRI revealed a small brain tumor. Robbins went in for more scans. After one appointment, her husband came out holding the results, and "I could tell he was upset," she said.

Robbins had an 8-centimeter tumor on the upper lobe of her right lung. With a tumor there, and one in her brain, it was clear she had advanced lung cancer that was spreading. The prognosis: eight to 10 months to live. More Americans die annually of lung cancer than of breast, colon, and prostate cancers combined.

Robbins decided to ignore these daunting statistics, girding herself to fight the disease. The devout Catholic thought: "I believe in miracles. I am a miracle."

In February 2002, surgeons removed her brain tumor. A month later, she started traditional chemotherapy. She began her death journal, jotting down wisdom culled from Emerson, Thoreau, and others. From Martin Luther King Jr., she urged her son to constantly consider, "What is the content of my character?"

During that time, she contacted Lynch at MGH, determined to tap the hospital's expertise in lung cancer treatment. Lynch placed her on different chemotherapy drugs and daily blasts of radiation to her chest. Her hair fell out, terrifying her son.

In July 2002, Robbins had part of her lung removed, a dangerous operation involving an incision starting at the top of her neck, down her back, then around front to her abdomen. Complications kept her hospitalized the entire summer.

After all this, the worst news: Scans found tumors in her liver and pancreas. Nothing had worked.

"This has been a great fight," she told her husband one night, "but this is not going away. I am going to die."

Another round of chemotherapy failed, and her tumors kept ballooning. Lynch placed her name in a lottery, run by the British drug company AstraZeneca, to get free treatment with its experimental drug, Iressa.

The first "smart drug" approved by the federal government for lung cancer, Iressa is one of a slew of new medicines that combine the pinpoint targeting of cancer cells with minimal side effects. At least two similar drugs are in the early stages of testing on lung cancer. Other smart drugs have helped thousands of breast cancer patients and are under review for use against virtually every cancer type.

Robbins started the once-daily pill regimen last November, "planning for the worst, hoping for the best."

In January of this year, she went for her first checkup after starting Iressa. The tumors were still there, only smaller. In March, more shrinkage. In June, more.

Meanwhile, the US Food and Drug Administration approved Iressa in May for lung cancer patients who have failed two attempts at treatment with other drugs or radiation. The approval was partly based on the large-scale trial that Robbins participated in, which found that 13.6 percent of patients saw their tumors shrink by 50 percent or more. Hardly a blockbuster, but given the dire condition of these patients and moved by testimony from 15 patients once at death's door, FDA officials approved the drug.

Fitting like the missing piece of a jigsaw puzzle, Iressa grabs onto the epidermal growth-factor receptor on the surface of lung cancer cells, blocking a cascade of biological signals that stimulate tumors to grow and spread. It works on patients with nonsmall-cell lung cancer, which accounts for about 80 percent of all cases.

"The good news is that there is this real group of patients that has done well for long periods of time, we're talking years," said Dr. Roy Herbst, a lung cancer specialist at MD Anderson Cancer Center in Houston, where the first Iressa studies were done in the late 1990s.

Early evidence seems to indicate that women respond better to the drug, as do nonsmokers and those with a tumor type called bronchioloalveolar carcinoma. But these are imprecise measures. Lynch noted, "I've had men who were smokers who responded to the drug."

With more than 15,000 patients now on Iressa, researchers hope to find answers in the DNA of those who respond to the drug, part of a burgeoning field known as pharmacogenetics that seeks to genetically match patients with precision drugs.

"My own personal belief is that it's likely to happen" that Iressa's target population will be pinpointed, said Dr. Bruce Johnson of Dana Farber Cancer Institute in Boston.

Researchers such as Johnson do not see Iressa as a cure; it's not clear how long its benefits last. They view the drug as an important component in an emerging arsenal of precision drugs that lung cancer patients, who have had few options in the past, could combine to live on for years. The drugs Erbitux and Avastin, now in clinical trials, are considered prime candidates.

For Robbins, Iressa allowed her to resume her life, slowed only by occasional diarrhea and rashes, which are typical side effects of the drug. She ferried her children to activities and spent precious time with her family.

"There comes a time in your life when you have to let go of the life you planned and live the life you were meant to live," she said. "Love is truly the essence of life."

Last week, she learned her tumors had disappeared. Robbins refuses to use the word "cure," because there are no data on how many patients will relapse. Lynch calls it "uncharted territory."

Robbins has already doubled her postcancer life expectancy. Now, she has a new goal: "I want to see my son graduate from high school in four years."

And she has stashed her death journal in the closet.

Raja Mishra can be reached at rmishra@globe.com.