By Michael E. Miller
By Allie Conti
By Keegan Hamilton and Francisco Alvarado
By Jake Rossen
By Allie Conti
By Kyle Swenson
By Chris Joseph
By Michael E. Miller
Temi Linzner wheels her sleek, cobalt blue Mercedes into a parking lot near Holy Cross Hospital.Dark glasses shroud her intense brown eyes; a round-brimmed straw hat covers her sparse crop of short, silver hair. When she first started chemotherapy for her lymphatic cancer in the late 1970s, all her hair fell out. Linzner was mortified. While she waited for her hair to grow back, she tried covering her baldness with a wig but hated it.
"I am very vain," admits the 70-year-old former fashion model and professional bridge player. "But I refuse to wear a wig now. People will just have to accept it or not. I don't have time to worry about that."
Her headgear today is both practical and aesthetic, shading her from the noontime September sun as she steps onto the blacktop. The sprawling, four-story hospital complex overlooking North Federal Highway in Fort Lauderdale looms before her; rising circles of steel form the skeleton of the new wing at the Michael and Dianne Bienes Comprehensive Cancer Center. She walks across a side street and enters an adjacent medical building where about 20 doctors maintain offices. One of them is Dr. Howard R. Abel, her Harvard-educated hematologist and oncologist.
Linzner enters the elevator, where she presses a button for the second floor. She's made this trip periodically for four years. The visits have become more frequent as her disease has progressed; Since July she's been forced to see the doctor weekly. After nearly two decades of remission, her cancer reappeared in 1996, first as a low-grade sarcoma -- a malignant tumor -- and later in a more aggressive form. She now harbors a grape-size tumor close to her heart.
Linzner takes a seat with about ten other patients in Abel's nondescript waiting room. They are men and women, mostly Linzner's age or older, all but one of them white. They wear resigned expressions; though they are at various points in their treatment, they know that the long-term odds are against them. As a veteran of this war, Linzner maintains an outward calm, but she knows the enemy is close, and she's low on ammunition.
Six weeks ago Abel prescribed a regimen of Rituxan injections, which contain cancer-fighting antibodies. This treatment is the latest option the federal Food and Drug Administration has approved for combating Linzner's particular form of lymphatic-system cancer.
Linzner feels better for the first time in months, but today she will schedule a series of tests to determine if the antibodies are actually working to eradicate her cancer. If they are, she will likely continue taking them. If not, she might still have one final hope.
This month Holy Cross will become the first community hospital in the United States to conduct clinical trialsof cancer vaccines created by federal researchers, using local patients. The vaccines are the newest and most promising treatment in the fight against many forms of the deadly disease. In testing the effectiveness of these vaccines, patients and doctors at Holy Cross will work directly with researchers at the National Cancer Institute (NCI), part of the National Institutes of Health in Bethesda, Maryland, through real-time computerized links.
Linzner knows she could become a candidate for the trials if the Rituxan fails her or shows only limited success. No one with cancer can be considered truly lucky, but she is nevertheless grateful that she has ended up in Abel's care right now. "This is the greatest thing, the greatest," she says of the research. "I mean, I hope I don't have to use it, but if I do, I won't have to travel."The idea of a cancer vaccine is nearly 30 years old, growing with a generation of research born when the federal government began pouring money into medical research. In the early '70s in Albany, New York, doctors discovered that lung-cancer patients who developed infections following surgery, despite the apparent danger, tended to live longer. Physicians theorized that the infections triggered an attack by the body's immune system, which killed both bacteria and cancer cells.
Meanwhile the NCI, benefiting from Pres. Richard Nixon's "war on cancer," led a broad-based, well-funded research assault that included the training of many young doctors who subsequently staffed the country's university research hospitals. The offensive also included generous government funding for those hospitals.
Before the war on cancer, Abel recalls, very few medical students sought careers in oncology. "It was depressing, there was little progress, and it was a field in which the patients always died," Abel says. "And the universities just weren't interested."
Then the money came, and so did the interest and the research.
In cancer vaccines, noteworthy advances have occurred only recently, explains Dr. Ralph Volgler, an Atlanta-based spokesperson for the American Cancer Society. "They've now identified a protein that's unique to cancer cells and [have] been able to link it to antibodies," he says. "These research studies use it as a vaccine, applying it earlier and earlier [in the course of the disease]."
The term cancer vaccine is a bit misleading: No cancer vaccine has yet been developed to prevent the disease. Instead the injections are often used in conjunction with traditional chemotherapy or radiation treatments in patients who already have cancer. The vaccines appear to work better, says Volgler, on smaller tumors or in patients whose disease has been reduced by other therapies.
To develop a vaccine, doctors use thriving cancer cells taken from the patient, cells culled from either a tumor or the blood. They must identify proteins in the tumor cells known as polypeptides; such proteins are common in many cancers. Then the doctors will manufacture a vaccine that contains those proteins but that can also be identified immediately by the body's immune system.
The hope, explains Abel, who has followed but not conducted research in vaccines, is to "paint" prominent targets on cells that stimulate a ferocious immune-system response and to inject the patient with such cells. The immune system, recognizing and reacting to the vaccine, will then destroy anycell that carries a similar marking or target, thus killing the cancer.
For some patients whose tumors or conditions do not produce sufficient cells to create vaccines from their own bodies, researchers can also produce synthetic proteins, made in the lab from amino acids.
Early studies suggest sometimes significant promise. In the case of CancerVax, a vaccine still about two years shy of FDA approval, the survival rate of patients is about 40 percent. Only about 16.5 percent of those who endure traditional chemotherapy for the same lymphatic cancers survive.
But some doctors are already referring to CancerVax as "steam engine technology," because it is made from whole cells and not the tiny proteins doctors have more recently learned to isolate and define. They theorize it is less precise and less effective than protein-based vaccines will be.
No clinical proof exists that vaccines either prolong survival or cure cancer, only that they can help the body produce promising antibodies. But that proof is likely to come, Abel believes. "Five years, or maybe ten, and the science will be much more refined," he says. "[Cancer vaccines] will be used much more commonly."
In addition to building upon existing cancer-vaccine research, the trials at Holy Cross will have an advantage no other such experiment can now boast: a direct link with the NCI.
The Telesynergy Center is the heart of this effort. In this conference room on the first floor of Holy Cross, doctors in Fort Lauderdale and Bethesda will simultaneously examine patients, study high-resolution displays of medical tests, and control microscopes and cameras from either room. In a single examination, they will be able to focus the full force of the government's best medical minds on a given case. Patients selected for a trial will be examined at a station in the room, which also contains the expensive Telesynergy equipment and a round table with chairs for the medical team.
Only patients selected for clinical trials will benefit from the almost unheard-of consultation of 15 to 20 highly educated doctors. These professionals can draw from a distressingly large pool of potential candidates. In Broward County, doctors this year will diagnose nearly 10 percent of all new cancer cases in Florida, about 9000 people, according to the American Cancer Society. With an estimated 88,000 new cases in the state this year, Florida ranks second behind California for the highest incidence of the disease. Almost 40,000 Floridians will die from cancer in 2000, a majority from lung cancer, breast cancer, pancreatic cancer, or prostate cancer. African-Americans suffer higher mortality rates than whites because their cancers are often detected later, doctors say, and can thus prove more difficult to treat.
For patients at Holy Cross, entry into a clinical trial could alter those grim statistics. Research doctors at NCI, in turn, will gain valuable research data from patient reactions to the vaccines. "One of their problems in the past has been a lack of patients," Abel points out. "They've had the researchers, they've had the research, and now they're seeking a broader patient base. As it is now, only about 2 percent of Americans receiving treatment are engaged in clinical trials."
The "Partnership in Science," as NCI describes it, is happening at Holy Cross first in part because of the successful lobbying of Abel and two colleagues, oncologists Leonard Seigel and Martin Gutierrez. The three doctors are the point men of the venture, which also benefited from good timing, says Maureen Mann, executive director of the cancer center. "We had the doctors who had spent time [at the NCI], and we asked at the right time, so it was partly luck and partly our own ambition."
When Holy Cross decided to beef up its cancer center a couple of years ago, administrators followed the advice of the hospital oncologists and sought guidance from the NCI. Coincidentally, says Mann, NCI researchers were searching for ways to introduce new patients into their program of clinical trials.
NCI looked at other hospitals, including cancer centers in California. Then its managers performed a due-diligence analysis of Holy Cross. They found a successful hospital with an established cancer center and a growing population of patients. But NCI did require some changes: Hospital administrators would have to acquire $250,000 of telecommunications equipment and add a new wing to the cancer center. The soon-to-be-completed wing will provide beds to accommodate patients entering the clinical trials.
Abel keeps an aerial photo of Harvard Medical School, his alma mater, framed on his wall. He uses the picture one day to explain his own compulsion to help create the partnership between NCI and Holy Cross.
"Harvard," he muses. "Such an elegant place, such elegant academics, such elegant science. And so distant from the rest of the world." He and his team, he says, will try to narrow that distance. "It's fair to say this [joint venture] is what now makes the work exciting to me -- the chance to palliate, to alleviate, or potentially to cure disease."
Though he, Seigel, and Gutierrez lobbied hard for this opportunity, Abel tries to shrug off credit, admitting only that he used his connections by calling researchers he knew at NCI. He says the hospital's willingness to spend money on technology and construction was a more important factor in bringing the vaccine trials here.
"All this helps people here, which is good," he says.
The first patient will begin to benefit as early as October 15, the doctors say. Temi Linzner might eventually qualify for the trials too, but she won't be the first in line. That honor will go to an as-yet-unnamed sufferer of a rare and deadly form of cancer known as mantle-cell lymphoma. The reason: Abel's colleague, Gutierrez, specialized in mantle-cell lymphoma at NCI and may help design the vaccine that researchers there will create. Linzner came close to entering a clinical trial earlier this year during two weeklong visits to one of the nation's most renowned private cancer clinics, M.D. Anderson Cancer Center in Houston, Texas. She received good advice, she says, but no treatment from a doctor who said he would not prescribe trial drugs because she wasn't his patient. She left the clinic in frustration.
Linzner has no such complaint about Abel. "I never feel rushed, not ever," she notes, describing a common complaint made by patients in community oncology centers. Nor does she have to suffer through long waits for an appointment. His office is extremely well organized, staffed by veteran nurses who have been with him for many years.
Her doctor is a formal man. He always addresses patients as Mr., Mrs., or Ms. The 62-year-old, balding Abel dresses meticulously: a lightly starched, long-sleeve dress shirt and crisply knotted tie under his doctor's smock. Linzner has never seen his cool professionalism waver. One time earlier this year when Linzner felt particularly demoralized, she told Abel she needed a hug. "He told me he didn't do hugs," she recalls with a grin. "But you won't find a doctor who cares more."
Linzner has completed her four-week therapy of one Rituxan injection per week. Today, two weeks after the last injection, the therapy seems to be working. For the first time in many months, she feels a spark of energy, and her cough is at least manageable. She has been feeling dizzy, though.
Linzner's 45-year-old daughter, Beth, slips quietly through the waiting room door, greeting her mother with a soft "hi." These days Beth spends as much time with her mom as possible, especially at medical appointments.
When a nurse calls her name, Linzner all but springs from her seat. Her daughter follows close behind as Linzner moves past the doctor's collection of framed posters, signed by Joan Sutherland and celebrating spectacular performances at the Metropolitan Opera. The pair enters a long hallway, where a nurse leads Linzner to the examining room. She offers a gown, but Linzner squashes the idea. "I don't do gowns," she says. "I'm not wearing a bra, so I can just slip off the jersey."
She sees Connie Wienants, Abel's top nurse, and the two share a quick, friendly hug.
The patient hoists herself onto the examination table, where she must wait for only a minute before Abel sweeps through the door in a dramatic rush, like a character appearing on stage in the Wagnerian operas he enjoys. Poised and trim, Abel appears to be curious about nearly everything.
"Did you hear about Deion Sanders?" he quickly asks. "He dropped the ball!" Abel is delighted by the lousy play the Washington Redskins' notoriously cocky cornerback committed the night before. Seems he doesn't like braggarts. "And so the mighty are humbled," he announces.
The obligatory chitchat completed, Abel gets down to business with a warm, encouraging smile. Earlier he fretted aloud that, even with the Rituxan, Linzner's chances of beating the disease are only about fifty-fifty.
Linzner has a form of non-Hodgkin's lymphoma. After exhausting the traditional prescriptions of chemotherapy and radiation earlier this year in treatments that shrank but failed to kill her tumors, and after returning without succor from M.D. Anderson, Linzner began the Rituxan. As Abel explains it, Rituxan binds itself to an antigen in the tumor cell. An antigen attracts or stimulates antibodies; the medicine can take advantage of that Achilles' heel in a tumor cell to kill it.
Though it is among a new generation of treatments, Rituxan already may be outdated. "What's coming up are antibodies that have radioactive properties," Abel reports. "Not only will they tag onto the tumor, but they will radiate nearby cells that could be infected."
Even if Rituxan is no longer the latest thing, Linzner is plenty encouraged by its results so far -- mostly because, unlike chemotherapy, it didn't nearly kill her. In fact she's feeling better and tells Abel so.
"I'm breathing better," she says. Earlier, her lungs had filled with fluid, the result of other, possibly related, medical problems she must fight. "The cough is better, but when I do cough, I get a swelling."
The doctor nods, oblivious now to everything in the room but Linzner.
"I rarely use my oxygen," she continues.
"Are you eating well?" he asks suddenly.
"What are you taking now?"
"Well," Linzner says, "there's Coumadin [an anticoagulant that helps blood flow through an artery being constricted by her tumor], and of course there's the thyroid medicine. I take iron in the morning; you know I hate taking things. I took myself off the Prevacid [for intestinal problems, not prescribed by Abel]. And I'm dizzy a lot."
"Dizzy?" repeats Abel.
"Dizzy. You think it's from the chemo?"
"No, too long ago."
"You think I'm dizzy just because I'm dizzy?" she asks, almost coquettishly. More than 20 years ago, Linzner was a medical technician. She is not afraid to ask questions or to tease the doctor. "Could it be low blood pressure?"
The conversation goes on, questions and responses snapping like synapses on both sides. Working at it together, they narrow in on Linzner's current condition. Still, the doctor doesn't have enough information to know for sure if the Rituxan is working. They'll need to do a CAT scan of her tumor areas; the scan's thin, cross-sectional images, which can reveal even minuscule tumors, will help determine her next move. If the Rituxan has failed, her chances of surviving much longer are limited -- but she might become a candidate for the vaccine trials.
She'll have to live with the question for the next few days, awaiting the results of the CAT scan. Abel also gives her a tentative diagnosis of "excellent, just excellent."
"To understand what I mean," he explains to a visitor, "you have to know where she came from."
"A bad place," Linzner finishes.
"If the Rituxan doesn't work," she later comments quietly, riding the elevator down from Abel's office and nodding toward the cancer center, "at least I've lived long enough to benefit from that." Abel finishes his morning without a break. Today he will have to work through lunch at the hospital. He walks across the road from his medical building and into the Telesynergy Center for a midday meeting. On this day doctors will discuss four patients suffering from lung cancer. Because construction is under way, a door near the cancer center at Holy Cross has become the hospital's temporary main entrance. A host of people enter the hospital, but only a few turn into the cancer care center itself.
Abel passes through the sprawling waiting room, navigating among the familiar, seated forms of aging, somber cancer patients. He slips into a hospital corridor not open to the general public, turning into the Telesynergy Center, where a crowd gathers in a midday buzz of professional energy. This is the local half of the "Partners in Science" team of doctors in Bethesda and Fort Lauderdale. The doctors come from many disciplines: The team includes a pathologist, a pulmonologist, two radiation oncologists, a hematologist, a radiologist, and a surgeon. Nurses, technicians, a dietician, center administrator Maureen Mann, and a couple of psychologists round out the team, about 15 people.
Along one wall of the conference room is the technology that makes the vaccine trials possible at Holy Cross. Nine separate instruments together provide the "telesynergy." NCI literature trumpets this bit of technobabble to describe it: "A multi-media, medical imaging workstation to be used within an electronic imaging environment, utilizing an Asynchronous Transfer Mode (ATM) tele-medicine network designed to provide for the simultaneous high-resolution display of medical images from numerous modalities."
In plain English that means everybody in Fort Lauderdale and Bethesda can look at the patient and his or her tests at the same time using the equipment.
The workstation includes electronic view-boxes, a computer controlled by a main operator, a video monitor, and a remote-control microscope used for histopathology and cytogenetics -- the studies of microscopic changes in diseased tissue and cell formation and development respectively.
The workstation also includes a VCR that records the images doctors are studying, an x-rayfilm digitizer to present x-ray images on screens, and a hand-held camera that can be used to examine patients.
The equipment is poised and ready to go, but today the teleconferencing screens are blank. The Holy Cross team needs to settle on the first group of test subjects for vaccines. Some of the cases the team will discuss today are potential candidates for the trials, which are scheduled to begin in mid- to late October. Three of the four lung-cancer patients being considered today are Abel's.
"Patients should be categorized by their performance status," announces a doctor as the meeting gets under way. (Performance status is a euphemism for "chance of survival.")
The first patient has a performance status of one, out of a possible four. One is very good, if such a term can be used to describe a victim of lung cancer. But there is a peculiar problem. "This is a 74-year-old male who has smoked a pack a day since he was nine or ten years old," says the patient's doctor. Now the patient has a nodule in the middle lobe of his right lung.
The dilemma: Several doctors disagree about exactly what kind of tumor has appeared. The disagreement is important; if it's a small-cell tumor, tradition prohibits surgery, for a variety of reasons.
"You really don't have a diagnosis," calls out the pathologist, sparking a fusillade of opinions and suggestions.
"Can he tolerate surgery?" asks a young radiation oncologist.
"He can tolerate it," the patient's doctor declares.
The young doctor proposes a newly developed treatment that could make surgery possible, extending the patient's life significantly. "It probably wasn't being taught when you were in school," he explains impishly to no one in particular. The doctors consider this suggestion and reach a prognosis: Surgery it is. "Whack it out," prescribes the young doctor cheerfully. The team chatters briefly, smiles blooming here and there at their colleague's candor, before moving on to the next patient.
Another old man. Another heavy smoker. He has already undergone several courses of treatment, but suspicious abnormalities have now appeared in both the abdomen and the lung, and a barium enema has revealed a tumor in or near the prostate. "I wasn't sure what to do," his doctor admits.
The team studies images that appear on the computers, which are linked to an overhead screen. Tumors are clearly visible, and a radiologist uses an NFL-style pointer to circle them, à la John Madden.
One of the oncologists: "There is a big lung lesion, and a secondary in the colon. I think it's two separateprimaries."
"You think he's been skunked already?" asks another oncologist. If the man has two separate tumors, he is likely to die no matter what medical resources are brought to bear.
"The management is hard," admits the doctor, adding after a pause, "The big cancer is not going to be cured."
The men and women in the room consider the problem for no more than a minute, all of them staring at the screens. They agree: The man will be treated only to provide comfort. "Another disappointment," says the doctor.
As the meeting breaks up, Abel, Seigel, and Gutierrez gather in a corner. The men are animated, excited. Although none of the patients reviewed today will enter the cancer-vaccine trials and one is beyond help, the Telesynergy Center and the team are ready.
Exactly nine days later, September 28, the trio huddles again following a similar midday meeting. In the intervening days, Temi Linzner got her CAT scan. The Rituxan has worked but not entirely: The battle isn't over. "There is less effusion, still some manifestation," Abel says -- then explains that this means the tumor has shrunk but is still there. "But this [treatment] has definitely helped her. She has a nice prognosis."
Linzner is elated at first but ultimately settles into the more familiar terrain of doubt and fear. She says she's concerned about the many unknowns of her current treatment and worries that she's in for yet another spin on the physical and emotional roller coaster. "In the meantime I'm going on with life normally," she says gamely. "For this I am grateful."
And if the tumor doesn't respond better after another round of the Rituxan, she might yet enter the vaccine trials, Abel says.
For another of Abel's patients, the news on this day has not been so good. The woman learned from a CAT scan that she has cancer. "She has a five-centimeter breast cancer, which is very large," Abel says. "We're going to enroll her immediately in a trial." She will be the first of Abel's patients to enter a cancer vaccine trial, and one of the first at Holy Cross. Maybe, says the doctor, he can save her life.