Violation (26 page)

Cell biologists and cancer researchers may spend an entire career focusing on a particular gene expressed at a particular phase in the cycle of a particular kind of cell. They study things like the tumor-suppressor gene Smad4/DPC4 and how gelatinase B affects the growth of tumors' circulatory systems, and they study them for years, from every angle. But for all the time, money, and words spent on cancer, many of the basic questions are largely
unanswered. Walter Urba, director of the Robert W. Franz Cancer Research Center, says, “We don't really know how all these drugs work. We
think
we know.”

Tumors are heterogeneous, made up of cancer cells dividing and behaving in different ways. For unknown reasons, cancer also tends to become resistant to the killing action of a given drug. To combat tolerance and attack these differently behaving cells, most chemotherapy is given in combinations. Combinations also allow a higher kill rate without overwhelming side effects. Few drugs are used alone, and most are used for several diseases.

Many combinations exist in standard practice. My handy laminated booklet from
Pharmacy Practice News
lists four different regimens for Hodgkin's disease, fifteen for non-Hodgkin's lymphoma, and thirty-two for breast cancer. Well and good—except that with thirty-two regimens in use, which one would be right for me? This is where it gets tricky. The order in which the drugs are given, the rate at which they are given, and the amount of time between drugs are partly a matter of opinion. Any known genetic markers of the cancer and current research matter. But so do factors that can only be called political in nature: where and when a physician trained, the proximity of a teaching hospital, and insurance compensation can all affect the choice of a regimen.

One of the reasons for choosing a specific regimen over another is the patient, not the cancer. The therapeutic index of a drug is the difference between the dose required to have a therapeutic effect and the dose that causes harm. Cytotoxic drugs have one of the lowest therapeutic indices found; there is often a very fine distinction between getting results and causing harm. In fact, taking patients as close as possible to the edge of tolerance often seems to increase survival rates, though some drugs have lifetime cumulative dose limits. A person with heart disease will not be able to tolerate the same doses and drugs as a person with a healthy heart. Moreover, the drugs are given to patients with stressed kidneys and livers, who may be recovering from surgery, who are taking many other strong drugs, who are malnourished,
who are still suffering the lingering effects of prior chemotherapy and radiation. (They are given, after all, to people with cancer.) No one can predict how a patient will respond to any given drug; it may be genetically determined.

There have been many disappointments in the research. Interferon, a cell protein, is one; monoclonal antibodies are another. IL-2, which is curative for a small percentage of patients, isn't much help to the rest.

“We're disappointed that we don't have a vaccine yet,” says Walter Urba. “But there will be vaccines.” Many will be tailored to an individual, at a cost of many thousands of dollars. “If we figure out how to cure cancer,” he adds, “we'll figure out how to pay for it.”

The hope in oncology is for more targeted therapies using drugs that interfere with cell growth in much more precise ways than cytotoxic drugs. For example, a whole new class of drugs that affect estrogen synthesis has changed the treatment of breast cancer dramatically. A close friend of mine was diagnosed with widely metastasized breast cancer more than two years ago. This disease is generally considered terminal, usually within a year or two. She has not had traditional chemotherapy at all. Her tumors have been controlled by a single oral drug, anastrozole, and one course of radiation. It won't work forever, but right now, with metastatic cancer, she feels healthy and well.

The nature of discovery is surprise, points out Menashe. “We're in the fog still, and we don't know when we're going to break through. It could be tomorrow.” Until then, cytotoxic chemotherapy is the cornerstone. The foundation, the bedrock, the core. The whole damned house, for a lot of people.

LIANA MARTIN IS
the nurse manager of the oncology unit, where everyone knows her as Lee. She hired me to work on 5-K. She is fifty-five years old and has been a nurse for a long time, an oncology nurse for twelve years.

Three years ago, Lee had her first routine colonoscopy.
“When I woke up, the G.I. specialist said, ‘Okay, we need to find you a surgeon.' I looked at her and said, ‘Are you saying I have
cancer
?'” As soon as possible, she went to see Walter Urba, whom she counts as a good friend. “I said the worst possible thing I could say to him. I grabbed his hand and said, ‘Walter, don't let me die!'”

Lee had colorectal cancer, which was already present in the lymph nodes. Urba prescribed a regimen of chemotherapy and radiation. Even with her experience, she was surprised at the uncertainty involved in the doses and in what to expect. “I wasn't supposed to lose my hair,” she says. “It came out in handfuls. I expected to have some nausea, but we couldn't control it—I lost thirty-five pounds. The radiation oncologist said, ‘Oh, it's the chemo,' and the medical oncologist said, ‘Oh, it's the radiation.'”

She had severe diarrhea. She developed peripheral neuropathy, damage to the fine nerves of the extremities, which causes numbness, tingling, and pain. Then she also developed an unusual side effect called hand-foot syndrome, in which the hands and feet become red, swollen, and burning. The side effects were so severe that Urba had to interrupt her treatment several times to let her recover. On the one hand, she knew the drugs were dangerous. “The nurses hung up a bottle, and I knew it was poison; I was letting them put poison in me.” On the other hand, she wanted those drugs.

“It was really hard to stop. It felt like a failure.
My
failure,” she says now. “I really was hindering my care in some ways. I had eighteen bouts of diarrhea in one day and I didn't call the radiation oncologist, I didn't tell him until after the treatment. And he was livid. I knew he would have held the treatment. That's how panicky I was.” More than once, 5-K nurses called Urba themselves, because Lee was obviously sick and refusing to admit it.

Finally, Urba dropped her doses by 20 percent. “That was really hard,” she recalls now. “I wanted it,
all
of it,
every
bit, as much as possible.” She wanted that poison, but she was out there, skirting the edge.

PREDICTED SIDE EFFECTS
are based on averages and on research, just like doses, and of extremes are averages made. The side effects are caused by the collateral damage of a treatment designed to kill fast-growing cells. Side effects can be immediate or delayed, brief or enduring, but they are almost inevitable. The picture window will shatter as the cockroach dies. I find that many people fear chemotherapy in an almost supernatural way; they have heard so many things about it; they tell one another tales about it, and some of the tales are true.

Unlike most drugs, chemotherapy is hard to keep secret; it makes itself known in painfully visible ways. Losing one's hair is the biggest fear most people have. They know it is an irrational fear—it won't kill them, it's temporary. But hair is iconic and relational, a symbol of youth and sex and status, almost as important to the self-image as the face. To suddenly be without it is horrifying to many people, and to be without it because of a deadly disease is worse. Losing the hair means sickness, it means weakness, it means you are in danger of losing your life, and you see it in the mirror every day.

No one really knows why chemotherapy makes hair fall out, a process called alopecia. The drugs damage the dividing cells of the follicles in ways not well understood, so that the hair shaft weakens and breaks. Alopecia is not confined, as many people believe, to the scalp. People may also lose their beards, eyebrows, eyelashes, the hair under the arms, the pubic hair, even the fine hairs of the forearms and legs. (I've heard this large-scale baldness called “the total Yul Brynner.”) We may not be covered in fur, but hair is protective. People get sunburns on their scalps or find they are cold all the time without hair's insulation. Without eyebrows and eyelashes, it's easy to get specks in your eyes, and when you cry, the tears spill out like water over a dam. After treatment, when the hair grows back (rarely, it doesn't) it may be a different texture, even a different color.

I've seen women weeping in grief over this dreaded loss, refusing to leave their rooms, but most people get used to it quickly.
Perhaps it is easier when one goes to the clinic week after week, or spends time in the hospital and sees so many others—men and women, young and old—who all look the same.

Nausea and vomiting is the other great fear before treatment and, unlike hair loss, may be more distressing than expected. Some drugs stimulate various, complex neurochemical pathways as they work, leading to activation of what is bluntly known as the vomiting center located in the brain stem. The retching that follows can be violent, sudden, and long-lasting. The surprise for many people is that only some of the drugs do this. Cisplatin, one of the most common drugs in use, causes nausea in more than 90 percent of patients; vincristine, another common drug, rarely causes nausea.

There are good, quite expensive, new drugs for nausea and some old standbys that work well for many people, but nothing is foolproof. Marijuana helps some people a lot. Many patients swear that a joint is much more effective than the pharmaceutical form, a pill called Marinol.
^3
3

Oregon has a medical-marijuana law, but the law is problematic in ways I didn't foresee when I voted for it. One lymphoma patient, an artist, casually lit up a bong in his room on his first day on 5-K. This was a mistake in several ways—not least that he was sharing it with his friends—but it is how I found out that the entire building's no-smoking rule applies to this legal medicine as well. Since the medical-marijuana law prohibits a licensed user from using it in public spaces, such as the hospital's outdoor smoking area, this patient found himself in a difficult position. One day his girlfriend began crying, begging for me to find a way for him to get some relief—“just one joint,” she said tearfully. I called security and explained the situation, and they told me the schedule of their rounds out in the parking lots. I told the patient and his girlfriend
what I'd learned; they took a walk, and we didn't talk about it anymore.

Worse than the nausea for many people is a condition called mucositis. Many drugs damage the DNA of cells in the mucus membranes of the entire digestive tract, from mouth to anus, as well as mucous membranes in the vagina. This damage and the release of inflammatory chemicals destroys tiny blood vessels and connective tissue, creating ulcers. Some patients are in such severe pain from mouth sores that they can't swallow or even speak. They require narcotics and may need days or weeks of what is called
TPN
, total parenteral nutrition, a metabolically balanced liquid given through the veins. (Now and then, if a patient has a certain sense of humor about his or her dark condition, the nurses will label the big, milky bag: “Steak, baked potatoes, apple pie,” changing the menu day by day.)

Diarrhea is common as well and usually has several causes, including changes in fluid and electrolytes and direct damage to the cells and normal enzymes. Christa described the result of her severe diarrhea as “scorched earth,” a term accurate in both metaphorical and clinical ways. She was a little indignant even two years later. “Everyone wanted to see it! You don't really want to show it to them.”

These are the side effects patients dread, but there are many more they don't even anticipate. Although vincristine rarely causes nausea, it is renowned for neurological complications, one of which is constipation; another is foot drop. Another is peripheral neuropathy, even at relatively low doses.

One class of cytotoxic drugs is the antibiotics. We don't tend to think of them that way, but antibiotics are cell-killers par excellence, and some potent ones kill cancer cells by preventing DNA synthesis. They have a tendency to color the urine—usually red, but in the case of mitoxantrone blue-green. Some drugs cause rashes, or little pustules similar to acne, or itching, or changes in pigmentation, or sensitivity to sunshine. Some drugs cause blurred vision and changes in color perception, or increased tears.
There are drugs that reduce libido or cause coughing. Paclitaxel, used for certain lung cancers, is known for causing severe joint and muscle pain. The drugs can cause sterility. They can cause cancer. I know I've told my patients these things, the physicians have told them, we've printed out the information, read through the list of possable side effects with them, and repeated ourselves, and they don't remember—they can't remember, it's all too much and too scary and too new. So their pee turns red and they think it's blood, or they forget about the sun and get a burn, and they cry, reminded. Reminded of so many things they want to forget.

People want to survive; they are willing to do much more than they would have thought they could. Years later, people who are so happy to be alive, to be well, will tell you this most difficult time was a gift, that it changed them for the better, clarified their lives. But in the midst of it? “I'd rather die than not be able to knit,” one old woman said to me, having refused any more treatment because of the risk of neuropathy in her hands. And she did die. I've seen people start puking as soon as I enter the room, hours before I bring the drug, because I am associated with it—my blue scrubs, the faint scent of soap on my hands, is enough. I've seen people so used to pain and so broken by it that they simply lie there, leaking tears, as I hurt them again. I've seen an engineer who runs a busy office, a man of authority, ashamed to silence by his diarrhea, like a bad child who cannot get to the toilet in time.