The Emperor of All Maladies: A Biography of Cancer (61 page)

William Peters was trying to convince himself, using a strict randomized trial, that megadose chemotherapy worked. But others were already convinced. Many oncologists had long assumed that the regimen was so obviously effective that no trial could possibly be needed. After all, if the deepest reservoirs of the marrow could be depleted by the searing doses of drugs, how could cancer possibly resist?

By the late 1980s, hospitals and, increasingly, private clinics offering marrow transplantation for breast cancer had sprouted up all around America, Great Britain, and France with waiting lists that stretched into several hundreds of women. Among the most prominent and successful of the megadose transplanters was Werner Bezwoda, an oncologist at the University of Witwatersrand in Johannesburg, South Africa, who was recruiting dozens of women into his trial every month. Transplant was big business: big medicine, big money, big infrastructure, big risks. At large academic centers, such as the Beth Israel hospital in Boston, entire floors were refitted into transplant units, with case volumes that ran into several dozens each week. Minimizing the risks of the procedure using creative phrasing became a cottage industry. As private clinics lined up to perform transplants on women, they christened the procedure a “minitransplant” or “transplant lite” or even “drive-thru transplant.”
Transplanters, as one oncologist
put it, “became gods at hospitals.”

This frantic landscape was tipped into further disarray as patients began to file requests for insurance providers to pay for the procedure, priced anywhere between $50,000 to $400,000 per patient. In the summer of 1991, a public-school teacher named Nelene Fox in Temecula, California, was diagnosed with advanced breast cancer. Fox was thirty-eight years old, the mother of three children. When she relapsed with
metastatic breast cancer after exhausting all conventional therapies, her doctors suggested an autologous bone marrow transplant as a last resort. Fox lunged at the suggestion. But when she applied to Health Net, her insurance provider, to pay for the transplant, Health Net refused, stating that the procedure was still “investigational” and thus not covered by the HMO’s standard list of clinically proven protocols.

In another decade and with any other disease, Fox’s case may have garnered scarcely any public attention. But something fundamental about the relationship between patients and medicine had changed in the aftermath of AIDS. Until the late 1980s, an experimental drug or procedure had been considered precisely that, experimental, and therefore unavailable for general public use. But AIDS activism had transformed that idea. An investigational agent, AIDS activists insisted, was no longer a hothouse flower meant to be cultivated only in the rarefied greenhouses of academic medicine, but rather a public resource merely waiting in the warming antechamber of science while doctors finished clinical trials that would, in the end, prove the efficacy of said drugs or procedures anyway.

Patients, in short, had lost patience. They did not want trials; they wanted drugs and cures. ACT UP, parading on the streets of New York and Washington, had made the FDA out to be a woolly bureaucratic grandfather—exacting but maddeningly slow, whose sole purpose was to delay access to critical medicines. Health Net’s denial of Nelene Fox’s transplant thus generated a visceral public reaction. Furious and desperate, Fox decided to raise the money privately by writing thousands of letters. By mid-April 1992, an enormous fund-raising effort to pay for Fox’s transplant had swung into gear. Temecula, a quiet hamlet of golf courses and antique shops, was gripped by a mission. Money poured in from softball matches and pie sales; from lemonade stands and car washes; from a local Sizzler restaurant; from a yogurt shop that donated a portion of its profits.
On June 19, a retinue
of Fox’s supporters, chanting, “Transplant, transplant,” and Fox’s name, staged a rally outside Health Net’s corporate headquarters. A few days later, Fox’s brother, an attorney named Mark Hiepler, filed a lawsuit against Health Net to force the HMO to pay for his sister’s transplant. “
You marketed this coverage to her
when she was well,” Hiepler wrote. “Please provide it now that she is ill.”

In the late summer of 1992, when Health Net refused yet another request for coverage, once again citing lack of clinical evidence, Fox chose to go ahead on her own. By then, she had raised $220,000 from nearly
twenty-five hundred friends, neighbors, relatives, coworkers, and strangers—enough to afford the transplant on her own.

In August 1992, Nelene Fox
thus underwent high-dose chemotherapy and a bone marrow transplant for metastatic breast cancer, hoping for a new lease on her life.

In the gleaming new wards of the Norris Center in Los Angeles, where Fox was undergoing her transplant, the story of Werner Bezwoda’s remarkable success with megadose chemotherapy was already big news. In Bezwoda’s hands, everything about the regimen seemed to work like a perfectly cast spell. A stocky, intense, solitary man capable, Oz-like, of inspiring both charm and suspicion, Bezwoda was the self-styled wizard of autologous transplantation who presided over an ever-growing clinical empire at Witwatersrand in Johannesburg with patients flying in from Europe, Asia, and Africa. As Bezwoda’s case series swelled, so, too, did his reputation. By the mid-1990s, he was regularly jetting up from South Africa to discuss his experience with megadose chemotherapy at meetings and conferences organized all around the world. “
The dose-limiting barrier
,” Bezwoda announced audaciously in 1992, had been “overcome”—instantly rocketing himself and his clinic into stratospheric fame.

Oncologists, scientists, and patients who thronged to his packed seminars found themselves mesmerized by his results. Bezwoda lectured slowly and dispassionately, in a bone-dry, deadpan drone, looking occasionally at the screen with his characteristic sideways glance, delivering the most exhilarating observations in the world of clinical oncology as if reading the Soviet evening news. At times the ponderous style seemed almost deliberately mismatched, for even Bezwoda knew that his results were astounding. As the lights flickered on for the poster session at the annual oncology meeting held in San Diego in May 1992, clinicians flocked around him, flooding him with questions and congratulations.
In Johannesburg, more than 90 percent
of women treated with the megadose regimen had achieved a complete response—a rate that even the powerhouse academic centers in the United States had been unable to achieve. Bezwoda, it seemed, was going to lead oncology out of its decades-long impasse with cancer.

Nelene Fox, though, was not so fortunate. She soldiered through the punishing regimen of high-dose chemotherapy and its multiple compli
cations. But less than one year after her transplant, breast cancer relapsed explosively all over her body, in her lungs, liver, lymph nodes, and, most important, in her brain.
On April 22, eleven months after
Bezwoda’s poster was hung up in nearby San Diego, Fox passed away in her home in a shaded cul-de-sac in Temecula. She was only forty years old. She left behind a husband and three daughters, aged four, nine, and eleven. And a lawsuit against Health Net, now winding its way through the California court system.

Juxtaposed against Bezwoda’s phenomenal results, Fox’s agonizing struggle and untimely death seemed an even more egregious outcome. Convinced that the
delayed
transplant—not cancer—had hastened his sister’s demise, Hiepler broadened his claims against Health Net and vigorously pushed for a court trial. The crux of Hiepler’s case rested on the definition of the word “investigational
.”
High-dose chemotherapy could, he argued, hardly be considered an “investigational” procedure if nearly every major clinical center in the nation was offering it to patients, both on and off trial.
In 1993 alone
, 1,177 papers in medical journals had been written on the subject. In certain hospitals, entire wards were dedicated to the procedure. The label “experimental” was slapped on, Hiepler contended, by HMOs to save money by denying coverage. “If all you have is a cold or the flu, sure, they will take good care of you. But when you get breast cancer, what happens? Out comes ‘investigative.’ Out comes ‘experimental.’”

On the morning of December 28, 1993
, Mark Hiepler spent nearly two hours in the courtroom describing the devastating last year of his sister’s life. The balconies and benches overflowed with Fox’s friends and supporters and with patients, many of them weeping with anger and empathy. The jury took less than two hours to deliberate.
That evening, it returned a verdict
awarding Fox’s family $89 million in damages—the second-highest amount in the history of litigation in California and one of the highest ever awarded in a medical case in America.

Eighty-nine million dollars was largely symbolic (the case was eventually settled out of court for an undisclosed smaller amount), but it was also the kind of symbolism that any HMO could readily understand. In 1993, patient advocacy groups urged women to battle similar cases around the country. Understandably, most insurers began to relent.
In Massachusetts, Charlotte Turner
, a forty-seven-year-old nurse diagnosed with metastatic
breast cancer, lobbied ferociously for her transplant, rushing on a wheelchair from one legislator’s office to another with sheaves of medical articles in her arms. In late 1993, as a result of Turner’s efforts, the Massachusetts state legislature enacted the so-called Charlotte’s Law, mandating coverage for transplantation for eligible patients within the state. By the mid-1990s, seven states required HMOs to pay for bone marrow transplantation, with similar legislation pending in seven additional states.
Between 1988 and 2002
, eighty-six cases were filed by patients against HMOs that had denied transplants. In forty-seven instances, the patient won the case.

That this turn of events—aggressive chemotherapy and marrow transplantation
mandated
by law—was truly extraordinary was not lost on many observers. It was, at face value, a liberating moment for many patients and patient advocates. But medical journals ran rife with scorching critiques of the protocol. It is a “
complicated, costly and potentially dangerous
technology,” one article complained pointedly. The litany of complications was grim: infections, hemorrhage, blood clots in the arteries and the liver, heart failure, scarring of lungs, skin, kidneys, and tendons. Infertility was often permanent. Patients were confined to the hospital for weeks, and most ominous perhaps, between 5 and 10 percent of women ran the risk of developing a second cancer or precancerous lesion as a result of the treatment itself—cancers doggedly recalcitrant to any therapy.

But as autologous transplantation for cancer exploded into a major enterprise, the scientific evaluation of the protocol fell further and further behind. Indeed the trials were caught in an old and perverse quagmire. Everyone—patients, doctors, HMOs, advocacy groups—wanted trials in principle. But no one wanted to be
in
trials, in practice. The more health insurance plans opened their floodgates for bone marrow transplantation, the more women fled from clinical trials, fearing that they might be assigned to the nontreatment arm by what amounted to a coin flip.

Between 1991 and 1999, roughly forty thousand
women around the world underwent marrow transplantation for breast cancer, at an estimated cost of between $2 billion and $4 billion (at the higher estimate, about twice the yearly budget of the NCI). Meanwhile, patient accrual for the clinical trials, including Peters’s trial at Duke, nearly trickled to a halt. The disjunction was poignant. Even as clinics overflowed with women being treated with high-dose chemotherapy and wards filled their beds with transplanted patients, the seminal measure to test the efficacy of that regimen was pushed aside, almost as if it were an afterthought.
“
Transplants, transplants, everywhere
,” as Robert Mayer put it, “but not a patient to test.”