A Lottery of Life, Death--and Hope
She remembers the doctor opening his office door and not looking at her.
“You don’t even have to say it,” she told him. “It’s bad, isn’t it?”
“Yeah, it’s pretty bad.”
They agreed that he would perform exploratory surgery on her left breast, where the tumor was, and that he would decide whether to remove just the lump or take more tissue. When she awoke from the operation, she found layers of gauze where the breast had been.
That was the spring of 1992, and Valli Lopez-Lasker, then 42, figured the worst was over. But the cancer spread further into her lymph system, and also to her backbone and liver.
Over three years, she underwent a barrage of treatments, including radiation therapies, chemotherapies and a $150,000 bone marrow transplant that left her with a scorched lung, impaired hearing and arthritis, she says. “And it didn’t work.”
Then, while in such despair she sought out a spiritual healer, she heard about a new drug being tested by Dr. Dennis Slamon at the UCLA Medical School.
The study involved women with advanced breast or ovarian cancer of an especially aggressive type: The tumors are spurred by overproduction of the so-called HER2/neu receptor, a protein structure on the cancer cells that appears to regulate their growth.
Among the most innovative cancer medicines ever devised, the drug is a genetically engineered antibody that sticks to the HER2/neu receptor, interfering with the cancer cells’ life cycle.
Cancer researchers view the HER2 antibody drug as a hint of cancer treatments to come, the advance guard of an approach called immunotherapy. The way proponents see it, if radiation, chemotherapy and surgery are like battering down cancer’s door, immunotherapy is like picking the lock.
“We believe that’s the paradigm that’s going to be coming on board in the next few years in cancer therapy,” Slamon said.
The drug is so specific for this form of cancer that it has much the same name: MAb HER2, “MAb” being short for “monoclonal antibody.” It is suitable only for the 30% of women with breast or ovarian tumors abetted by an excess of the HER2/neu receptor, Slamon says.
As it happened, Lopez-Lasker was one of them. She started receiving the drug in December.
She lives on a steep Santa Barbara hillside in a stucco house with priceless views of the ocean. Avocado trees range across an adjacent hill. Swallows wheel in the rosemary-scented air. And four cats and 13 dogs make chaos of the sun-washed chaparral.
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Yes, the dogs are excessive--she was once arrested for, in effect, running a kennel without a license--but perhaps it is not really so bizarre for someone clinging to life to immerse herself in a howling abundance of animal spirit. Many mornings, she said, she can hardly get out of bed, she feels so hopeless; but the dogs rouse her, and as she walks and feeds them she is grateful to be needed.
When the local pound and humane society chapter are about to put a mutt down, they call Lopez-Lasker, and often enough she has gone to the rescue. She has always been that way, she says, but allows that cancer has deepened her feel for the underdog.
Last summer, when Lopez-Lasker’s health was bottoming out, her husband, Lawrence Lasker, a screenwriter, got her to call Dr. Mark Renneker, a physician in San Francisco almost as well known for his surfing exploits as for the care he provides. Besides being a founder of the Surfer’s Medical Assn. and seeing patients at clinics in Oakland and San Francisco, he steers seriously ill people into experimental treatments that might help them.
Recalling his first impression of Lopez-Lasker, he said: “It was hard for her to even use the word ‘cancer.’ She was frightened.”
He lobbied to get Lopez-Lasker into the UCLA study. It had been set up to test the HER2 antibody in combination with another drug, cisplatin, which often has serious side effects, including kidney damage and hair loss. Lopez had taken cisplatin before and wanted no more of it.
To help persuade UCLA to give her the antibody drug alone, Renneker invoked her in-laws’ golden name. Perhaps no family in U.S. history has done more for medical research than the Laskers. Her husband’s step-grandmother was Mary Lasker, a grand patroness of biomedical research. Each year the family foundation honors several medical researchers with the Lasker Awards, surpassed in prestige only by the Nobel.
But in the end, Slamon said, the family connection was not important. “Absolutely not,” he said. Lopez-Lasker got into the study because she had the exact cancer being studied. All the legwork and paperwork done to enroll her was simply aimed at ensuring she would receive the antibody drug without cisplatin, he said.
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Slamon is more than an advocate of HER2 therapy--he helped invent it. A decade ago he established the role of the previously discovered HER2/neu gene in especially aggressive breast cancer tumors. And he laid the groundwork for using an antibody directed against the HER2/neu receptor to hinder the cancer cells’ growth.
Along with UCLA, more than 100 hospitals in North America are cooperating in the HER2 antibody study, which is being funded largely by the South San Francisco biotechnology firm Genentech, producer of the HER2 antibody. The study will eventually involve 750 women with breast cancer--the third and final research phase before the drug is considered for Food and Drug Administration approval.
“HER2 is extremely important,” said Dr. Larry Norton, chief of breast cancer medicine at Memorial Sloan Kettering Institute in New York. His research team is also testing the drug and has had at least one spectacular result--complete remission of metastatic breast cancer in one woman for three years. He has also seen it have no effect on patients whatsoever.
“I don’t think anyone is saying that this is a cure for cancer,” he said. “The important thing is that at least in somebody it has been shown to work, and that is a proof of the principle.”
An editorial in March in the Journal of Clinical Oncology, a leading publication for cancer specialists, said that many questions about HER2 therapy remained to be answered. Still, it said, the therapy held enough promise that studies like the one Lopez-Lasker is involved in may someday be regarded as a “landmark” in cancer research.
Her friends congratulate her for venturing onto the frontier of research on cancer, long America’s most dreaded disease. “They say, ‘You’re so brave!’ ” Lopez-Lasker recalled. “But it’s no more brave than brushing your teeth or whatever: It’s just something you’ve got to do.”
Her progress since entering the UCLA study in December can be seen in the periodic CT scans made of her liver.
Arraying the films against a light box, Slamon pointed to scans done before the treatment started. In one image, numerous large blackish splotches--tumors--appear against the light gray of normal liver tissue. Two months later, the splotches were measurably smaller and fainter; at four months, smaller and fainter still. A few had vanished.
When Lopez-Lasker first heard that the tumors were shrinking, she was elated. She sent vases of flowers to her doctors and nurses. She spent thousands of dollars joining a swim club in Santa Barbara. She felt better than she had in memory.
And, wonderfully, the drug had no side effects except a mild fever the first time she received it. Going to the clinic once a week for treatment, she lounged on a daybed while the clear HER2 solution dripped from an IV sac into a vein in her hand.
Usually her daughter, Bianca Ryan, was there, and they joked and ate chocolates. Lopez-Lasker felt so upbeat she referred to herself as the treatment’s “poster child.”
Ryan, 29, born when Lopez-Lasker was a senior at Palisades High School, has been the person most often at her side. They are like sisters now, similarly dark-haired and brown-eyed, with siblings’ easy, wisecracking ways. “You’ll be able to take care of me when I get old,” Lopez-Lasker once said.
“Mom,” Ryan said, “when you’re old, I’ll be old.”
In late April, UCLA sent out a press release to help recruit more patients for HER2 studies. “We are extremely optimistic about these trials,” Slamon said in the release. “Our early findings are very promising, with some outstanding results.”
Of the six women that UCLA had tested by then, one had her tumors disappear completely, three (including Lopez-Lasker) had tumors shrink, one stayed the same, and one got sicker, with the tumors spreading to her brain.
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To take part in a medical experiment is to enter “no man’s land,” as Slamon said in a recent interview, where even the most dramatic progress can suddenly give way to a setback.
After Lopez-Lasker had received HER2 antibody therapy for six months, a CT scan of her liver revealed several new blackish marks--tiny blotches representing incipient tumors of less than half an inch across, Slamon said. He cannot explain why the therapy suddenly failed to hold the cancer in check. “I don’t know what to make of it,” he said. “We’re in a no man’s land. This is new ground in terms of therapy.”
Early one June evening, Slamon called Lopez to tell her about the CT scans. “I’m concerned,” he said.
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Although advances in diagnosis and care have lengthened and improved patients’ lives, the overall breast cancer death rate--which researchers view as the ultimate measure of success against the disease--has barely budged in decades. In 1993, about 26 out of every 100,000 American women died of breast cancer, just as in the 1930s, according to the American Cancer Society.
Still, breast cancer research is booming. National Cancer Institute funding for the disease has increased tenfold since 1981, to $336.8 million this year. The number of cancer medicines in development at drug companies has nearly doubled in the last few years, to more than 200, according and Manufacturers of America.
Meanwhile, the FDA, reacting to complaints from drug companies and patient advocacy groups, has both speeded up the review process for new cancer drugs and, perhaps more important, eased the criteria for approval.
Previously, the agency required that a drug actually lengthen patients’ lives before approving it; beginning in late March, with a new initiative hailed by President Clinton, a cancer drug may be approved if it “shows evidence of tumor shrinkage for patients who have no satisfactory alternative therapy,” the agency said.
Some cancer researchers are troubled by the agency’s shift. “I think this was a big step backward,” said Dr. John Bailar, a noted cancer researcher at the University of Chicago. He said that the benefits of many highly touted experimental cancer drugs turn out to be overstated, while their often considerable side effects are understated. “I’m very much concerned about the hazards of cancer therapy, because those are immediate, real and big.”
Researchers working on the HER2 antibody drug don’t know if it will pass FDA review when the study is finished in two years or so. But the chances of its eventual approval appear quite good. In preliminary studies the drug has reduced tumors in 12% of those eligible patients who received it. And the FDA has already approved a cancer drug that is less effective than that.
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In the dusky stillness after Slamon had telephoned Lopez-Lasker with word of possible new tumors, her tears flowed and she started brooding again over who would take care of her dogs when she was gone.
But her condition wasn’t hopeless, Slamon said. There were other options. She could start taking the HER2 antibody along with cisplatin. Or, if she still didn’t want that, there is a separate study involving taxol, a newer drug used against ovarian cancer and breast cancer.
How she has grown to hate the word “options.” To her, it makes her feel she has very few options indeed. It is another one of those white-coat euphemisms, like “quality of life,” which gravely ill people realize is a signal that little quantity remains.
For days she thought it over, weighing the possible benefits of taxol and cisplatin against their side effects. Like cisplatin, taxol can cause nausea and hair loss, among other things. She settled on taxol, even though there was a catch: To test whether the HER2 antibody really boosts the effectiveness of taxol, half the women in Slamon’s study receive taxol plus antibody, while the other half receive just taxol. And to avoid skewing the study results, neither the researchers nor the subjects determine which group each patient ends up in. Lopez-Lasker would be “randomized,” as researchers call it.
A week before the treatment was to start, she learned that she was a victim of chance after all. “I’ve randomized out, I’m in the control group,” she said over the phone. She was crying. “I’m losing my mind over this.”
But she went ahead anyway, and one afternoon in late June, she sat in the day ward at UCLA’s Jonsson Comprehensive Cancer Center, a taxol IV emptying into a vein in one hand.
By the time she got home, her stomach ached and her heart seemed to strain with every beat. “I had a very, very hard time,” she said. “I felt like I was dying.” It became so hard for her to breathe she went to the emergency room at a Santa Barbara hospital for treatment.
Slamon said it was a shame she wasn’t getting the HER2 antibody, but taxol alone had a good chance of fighting the tumors, he told her. And if she took a turn for the worse, he went on, she could switch to cisplatin, and she would definitely get the HER2 antibody then.
He grapples every day with the dilemma of having to withhold a potentially useful experimental treatment from patients in need. “It’s very frustrating,” he said. “As a physician, it’s extremely frustrating because patients say, ‘I’m dying, why can’t I get this?’ There’s just no counter-argument to that.
“But from the standpoint of a new drug, whether or not it works has to be proven. No one believes in HER2/neu more than I do, but I can’t in good faith say unequivocally that it’s effective. We have to actually prove that it’s more effective than the best available therapy.”
Lopez-Lasker wearies of the struggle, naturally. “There’s something really monumentally unjust about the fact that doctors have developed all these techniques to tell you you have cancer and how long you can live, but then they can’t do anything about it. It sort of makes me long for the old days, you know, when people put their hoe down on the north forty and went in for a nap and just died two weeks later.”
Renneker cheered her up a bit the other night over dinner in Santa Barbara. “There are other things coming up”--other treatments, he meant. “They’re a year or two away and we’re going to keep you alive for that.”
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At the animal hospital a while ago, Lopez-Lasker came across a stray cat with skin cancer.
She said she would take it home. But before she could do so, it had to be returned to the pound for a while, in case its owner turned up.
After a few days, she called the pound to arrange to pick the cat up. An attendant said the cat had been put down. “It had cancer,” he explained. “It wasn’t going to live.”
“How did he know what that animal wanted?” Lopez-Lasker said, fuming. “How did he know how long it had to live?”
