The Emperor of All Maladies: A Biography of Cancer (38 page)

It took Fisher a full ten years to actually gather that data. Recruiting patients for his study was an uphill task. “
To get a woman to participate in a clinical trial
where she was going to have her breast off or have her breast not taken off, that was a pretty difficult thing to do. Not like testing Drug A versus Drug B,” he recalled.

If patients were reluctant, surgeons were almost impossibly so. Immersed in the traditions of radical surgery, many American surgeons put up such formidable barriers to patient recruitment that Canadian
surgeons and their patients were added to complete the study. The trial recruited 1,765 patients in thirty-four centers in the United States and Canada. Patients were randomized into three groups: one treated with the radical mastectomy, the second with simple mastectomy, and the third with surgery followed by radiation. Even with all forces in gear, it still took years to recruit adequate numbers. Crippled by forces within surgery itself, the NSABP-04 trial barely hobbled to its end.

In 1981, the results of the trial were finally made public. The rates of breast cancer recurrence, relapse, death, and distant cancer metastasis were statistically identical among all three groups. The group treated with the radical mastectomy had paid heavily in morbidity, but accrued no benefits in survival, recurrence, or mortality.

Between 1891 and 1981, in the nearly one hundred years of the radical mastectomy, an estimated five hundred thousand women underwent the procedure to “extirpate” cancer. Many chose the procedure. Many were forced into it. Many others did not even realize that it
was
a choice. Many were permanently disfigured; many perceived the surgery as a benediction; many suffered its punishing penalties bravely, hoping that they had treated their cancer as aggressively and as definitively as possible. Halsted’s “cancer storehouse” grew far beyond its original walls at Hopkins. His ideas entered oncology, then permeated its vocabulary, then its psychology, its ethos, and its self-image. When radical surgery fell, an entire culture of surgery thus collapsed with it. The radical mastectomy is rarely, if ever, performed by surgeons today.

Few doctors in this country
seem to be involved with the non-life-threatening side effects of cancer therapy. . . . In the United States, baldness, nausea and vomiting, diarrhea, clogged veins, financial problems, broken marriages, disturbed children, loss of libido, loss of self-esteem, and body image are nurses’ turf.

—Rose Kushner

And it is solely by risking life
that freedom is obtained.

—Hegel

The ominous toppling of radical surgery off its pedestal may have given cancer chemotherapists some pause for reckoning. But they had their own fantasy of radicalism to fulfill, their own radical arsenal to launch against cancer. Surgery, the traditional battle-ax against cancer, was considered too primitive, too indiscriminate, and too weary. A “
large-scale chemotherapeutic attack
,” as one doctor put it, was needed to obliterate cancer.

Every battle needs its iconic battleground, and if one physical place epitomized the cancer wars of the late 1970s, it was the chemotherapy ward. It was “
our trench and our bunker
,” a chemotherapist recalls, a space marked indelibly in the history of cancer. To enter the ward was to acquire automatic citizenship—as Susan Sontag might have put it—into the kingdom of the ill.

The journalist Stewart Alsop was confined to one such ward at the NIH in 1973 for the treatment of a rare and unidentifiable blood cancer. Crossing its threshold, he encountered a sanitized vision of hell. “
Wandering about the NIH clinical center
, in the corridors or in the ele
vator, one comes occasionally on a human monster, on a living nightmare, on a face or body hideously deformed,” he wrote. Patients, even disguised in “civilian” clothes, could still be identified by the orange tinge that chemotherapy left on their skin, underneath which lurked the unique pallor of cancer-related anemia. The space was limbolike, with no simple means of egress—no exit. In the glass-paneled sanatorium where patients walked for leisure, Alsop recalled, the windows were covered in heavy wire mesh to prevent the men and women confined in the wards from jumping off the banisters and committing suicide.

A collective amnesia prevailed in these wards. If remembering was an essential requisite for survival, then so was forgetting. “
Although this was a cancer ward
,” an anthropologist wrote, “the word ‘cancer’ was actively avoided by staff and patients.” Patients lived by the regulations—“
accepted roles, a predetermined
routine, constant stimuli.” The artifice of manufactured cheer (a requirement for soldiers in battle) made the wards even more poignantly desolate: in one wing, where a woman lay dying from breast cancer, there were “
yellow and orange walls in the corridors
; beige and white stripes in the patients’ rooms.” At the NIH, in an attempt to inject optimism into the wards,
the nurses wore uniforms with plastic yellow buttons
with the cartoonish outline of a smiling face.

These wards created not just a psychological isolation chamber but also a physical microenvironment, a sterile bubble where the core theory of cancer chemotherapy—eradicating cancer with a death-defying bombardment of drugs—could be adequately tested. It was, undeniably, an experiment. At the NIH, Alsop wrote pointedly, “
Saving the individual patient
is not the essential mission. Enormous efforts are made to do so, or at least to prolong the patient’s life to the last possible moment. But the basic purpose is not to save that patient’s particular life but to find means of saving the lives of others.”

In some cases, the experiment worked. In 1976, the year that the NSABP-04 trial struggled to its midpoint, a novel drug, cisplatin, appeared in the cancer wards. Cisplatin—short for
cis-platinum
—was a new drug forged out of an old one. Its molecular structure, a central planar plati
num atom with four “arms” extending outward, had been described back in the 1890s. But chemists had never found an application for cisplatin: the beautiful, satisfyingly symmetric chemical structure had no obvious human use. It had been shelved away in the laboratory in relative obscurity. No one had bothered to test its biological effects.

In 1965, at Michigan State University
, a biophysicist, Barnett Rosenberg, began to investigate whether electrical currents might stimulate bacterial cell division. Rosenberg devised a bacterial flask through which an electrical current could be run using two platinum electrodes. When Rosenberg turned the electricity on, he found, astonishingly, that the bacterial cells stopped dividing entirely. Rosenberg initially proposed that the electrical current was
the active
agent in inhibiting cell division. But the electricity, he soon determined, was merely a bystander. The platinum electrode had reacted with the salt in the bacterial solution to generate a new growth-arresting molecule that had diffused throughout the liquid. That chemical was cisplatin. Like all cells, bacteria need to replicate DNA in order to divide. Cisplatin had chemically attacked DNA with its reactive molecular arms, cross-linking and damaging the molecule irreparably, forcing cells to arrest their division.

For patients such as
John Cleland
, cisplatin came to epitomize the new breed of aggressive chemotherapeutics of the 1970s. In 1973, Cleland was a twenty-two-year-old veterinary student in Indiana. In August that year, two months after his marriage, he discovered a rapidly expanding lump in his right testis. He saw a urologist on a Tuesday afternoon in November. On Thursday, he was whisked off to the operating room for surgery. He returned with a scar that extended from his abdomen to his breastbone. The diagnosis was metastatic testicular cancer—cancer of the testes that had migrated diffusely into his lymph nodes and lungs.

In 1973, the survival rate from metastatic testes cancer was less than 5 percent. Cleland entered the cancer ward at Indiana University and began treatment with a young oncologist named Larry Einhorn. The regimen, a weather-beaten and toxic three-drug cocktail called ABO that had been derived from the NCI’s studies in the 1960s—was only marginally effective. Cleland lived in and out of the hospital. His weight shrank from 158 to 106 pounds. One day in 1974, while he was still receiving chemo, his wife suggested that they sit outside to enjoy the afternoon. Cleland real
ized, to his utter shame, that he was too weak to stand up. He was carried to his bed like a baby, weeping with embarrassment.

In the fall of 1974, the ABO regimen was stopped. He was switched to another equally ineffective drug. Einhorn suggested a last-ditch effort: a new chemical called cisplatin. Other researchers had seen some responses in patients with testicular cancer treated with single-agent cisplatin, although not durable ones. Einhorn wanted to combine cisplatin with two other drugs to see if he could increase the response rate.

There was the uncertainty of a new combination and the certainty of death. On October 7, 1974, Cleland took the gamble: he enrolled as “patient zero” for BVP, the acronym for a new regimen containing bleomycin, vinblastine, and cisplatin (abbreviated
P
for “platinum”). Ten days later, when he returned for his routine scans, the tumors in his lungs had vanished. Ecstatic and mystified, he called his wife from a hospital phone. “I cannot remember what I said, but I told her.”

Cleland’s experience was typical.
By 1975, Einhorn had treated
twenty additional patients with the regimen and found dramatic and sustained responses virtually unheard of in the history of this disease. Einhorn presented his data at the annual meeting of oncologists held in Toronto in the winter of 1975. “
Walking up to that podium
was like my own walk on the moon,” he recalled. By the late winter of 1976, it was becoming progressively clearer that some of these patients would not relapse at all. Einhorn had cured a solid cancer by chemotherapy. “
It was unforgettable
. In my own naive mind I thought this was the formula that we had been missing all the while.”

Cisplatin was unforgettable in more than one sense. The drug provoked an unremitting nausea, a queasiness of such penetrating force and quality that had rarely been encountered in the history of medicine: on
average
, patients treated with the drug vomited twelve times a day. (In the 1970s, there were few effective antinausea drugs. Most patients had to be given intravenous fluids to tide them through the nausea; some survived by smuggling marijuana, a mild antiemetic, into the chemotherapy wards.) In
Margaret Edson’s play
Wit
, a scathing depiction of a woman’s battle with ovarian cancer, an English professor undergoing chemotherapy clutches a nausea basin on the floor of her hospital ward, dry-heaving in guttural agony (prompting her unforgettable aside, “
You may think
my vocabu
lary has taken a turn for the Anglo-Saxon”). The pharmacological culprit lurking unmentioned behind that scene is cisplatin. Even today, nurses on oncology floors who tended to patients in the early 1980s (before the advent of newer antiemetics that would somewhat ease the effect of the drug) can vividly recollect the violent jolts of nausea that suddenly descended on patients and brought them dry-heaving to the ground. In nursing slang, the drug came to be known as “cisflatten.”