The Emperor of All Maladies: A Biography of Cancer (59 page)

In 1982, Frei recruited William Peters
, a young doctor from New York, as a fellow at the institute. Peters was an academic all-star. He had graduated from Pennsylvania State University with three majors, in biochemistry, biophysics, and philosophy, then steamrollered his way through the College of Physicians and Surgeons at Columbia, earning both an M.D. and a Ph.D. Affable, determined, enthusiastic, and ambitious, he was considered the most able corporal among the troops of junior faculty at the Farber. The relationship between Frei and Peters was almost instantly magnetic, perhaps even parental. Peters was instinctually drawn to Frei’s reputation, creativity, and unorthodox methods; Frei, to Peters’s energy and enthusiasm. Each saw in the other an earlier or later incarnation of himself.

On Thursday afternoons, fellows and faculty at the Farber gathered in a conference room on the sixteenth floor. The room was symbolically set on the highest floor of the building, its large windows, overlooking the evergreen fens of Boston, and its wood-paneled walls, blond and reflective, creating a light-immersed casket suspended midair. Lunch was catered. The doors were closed. It was a time dedicated to academic thinking, sealed away from the daily whir of labs and clinics in the floors below.

It was at these afternoon conferences that Frei began to introduce the idea of megadose combination chemotherapy with autologous marrow
support to the fellows and junior faculty.
In the fall of 1983, he invited Howard Skipper
, the soft-spoken “mouse doctor” who had so deeply influenced Frei’s early work, to speak. Skipper was inching toward higher and higher doses of cytotoxic drugs in his mouse models and spoke enthusiastically about the possibility of curative treatment with these megadose regimens. He was soon after followed by Frank Schabel, another scientist who had demonstrated that combining agents, in doses lethal for the marrow, possessed synergistic effects on mouse tumors. Schabel’s lecture was particularly galvanizing,
a “seminal event
,” as Peters described it. After the talk, as Frei recalled, the room was abuzz with excitement; Schabel was surrounded by young, eager investigators mesmerized by his ideas. Among the youngest, and by far the most eager, was Bill Peters.

Yet the surer Frei became about megadose chemotherapy, the less sure some others around him seemed to get.
George Canellos, for one, was wary
, right from the outset. Wiry and tall, with a slight stoop and a commanding basso-profundo voice, Canellos was the closest to Frei’s equal at the institute, an original member of the NCI from its heady early days in the mid-1960s. Unlike Frei, though, Canellos had turned from advocate to adversary of megadose chemo regimens, in part because he had been among the first to notice a devastating long-term side effect: as doses escalated, some chemotherapeutic drugs damaged the marrow so severely that, in time, these regimens could precipitate a premalignant syndrome called myelodysplasia, a condition that tended to progress to leukemia. The leukemias that arose from the ashes of chemotherapy-treated marrows carried such grotesque and aberrant mutations that they were virtually resistant to any drugs, as if their initial passage through that fire had tempered them into immortality.

With Canellos arguing one side and Frei the other, the institute split into bitterly opposing camps. But Peters and Frei were unstoppably enthusiastic. By late 1982, with Frei’s guidance, Peters had written a detailed protocol for the STAMP regimen. A few weeks later, the Institutional Review Board at the Farber approved STAMP, giving Peters and Frei the green light to begin their trial. “
We were going to swing and go for the ring
,” Peters recalled. “That drove us. You had to believe you were going to pull off something that was going to change history.”

The first patient to “change history” with STAMP
was a thirty-year-old
commercial driver from Massachusetts with breast cancer. A grim, determined, hefty woman hardened by the gritty culture of truck stops and highways, she had been treated and re-treated with multiple standard and escalating regimens of chemotherapy. Her tumor, a friable, inflamed disk of tissue, was nearly six centimeters wide, hanging visibly off her chest wall. But having “failed” all the conventional treatments, she had become virtually invisible to the institute. Her case was considered so terminal that she had been written off from every other experimental protocol. When she signed on to Peters’s protocol, no one objected.

Marrow transplantation begins, of course, by “harvesting” bone marrow. On the morning of the first harvest, Peters went down to the leukemia clinic and gathered his arms full of bone marrow needles. He wheeled his first patient over to the operating room at the neighboring Beth Israel hospital (the Farber had no operating rooms) and began pulling out the marrow, plunging a steel trocar repeatedly into the hip and drawing out the cells, leaving a hip pockmarked with red bruises. Each time he pulled, a few droplets of reddish sludge gathered in the syringe.

Then disaster struck. As Peters pulled out a specimen, the marrow needle broke, leaving a piece of steel buried deeply in his patient’s hip. For a few minutes, pandemonium broke out in the operating room. Nurses made frantic phone calls to the floors, asking for surgeons to step in to help. An hour later, using a pair of orthopedic pliers to dig into the hip, Peters recovered the needle.

Later that evening, the full impact of that moment struck Peters. It had been a close shave. “
The ultimate trial of chemotherapeutic intensification
,” Peters said, “almost broke its back on an old needle.” For Peters and Frei, it was an all-too-obvious metaphor for the rustiness and obsolescence of the status quo. The War on Cancer was being waged by timorous doctors (unwilling to maximize chemotherapy) with blunt, outmoded weapons.

For a few weeks after that initial tumult, Peters’s life fell into a reasonably stable routine. Early mornings, dodging Canellos and other muttering skeptics, he rounded on his patients on the far corner of the twelfth floor, where a few rooms had been set aside for the trial. Evenings were spent at home with
Masterpiece Theatre
playing in the background as he sharpened needles physically and sharpened the trial intellectually. As the trial gathered speed, it also gained visibility. Peters’s first few patients had been last-ditch, hopeless cases, women with tumors so deeply recalcitrant
to all drugs that they were readily enrolled in experimental trials as a last resort in the hope of obtaining even a minor remission. But as rumors of the trial coursed through networks of patients and friends, cancer patients began to contact Peters and Frei to try the megadose strategy
up front
—not after they had failed more conventional regimens, but before they had even tried anything else. In the late summer of 1983, when a previously untreated woman with metastatic breast cancer enrolled in STAMP, as Peters recalled, the institute stood up to take notice. “
Suddenly, everything broke loose
and things came apart.”

The woman was thirty-six years old
—charming, sophisticated, intense, coiled and tightened into a spring by her yearlong battle with illness. She had watched her mother die of an aggressive breast cancer that had been fiercely resistant to conventional therapy. Instinctually, she was convinced that hers would be just as virulent and just as resistant. She wanted to live and wanted the most aggressive therapy up front, without soldiering through trials that would, she was convinced, fail anyway. When Peters offered her STAMP, she grasped at it without hesitation.

Her clinical course was among the most closely watched in the history of the institute. Fortunately for Peters, chemotherapy and transplantation went smoothly. On the seventh day after megadose chemotherapy, when Frei and Peters hurried down to the basement to look at the first chest X-ray after treatment, they found that they had been beaten to it. An entire congregation of curious doctors had gathered in the room like a jury and was huddled around the films. Against the sharp, fluorescent light, her chest X-ray showed a marked response. The metastatic deposits peppered around in her lung had shrunk visibly, and even the swollen lymph nodes around it had visibly recessed. It was, as Peters recalls, “
the most beautiful remission you could have imagined
.”

As the year drew on, Peters treated and transplanted more cases and obtained beautiful remissions. By the summer of 1984, the database of transplanted cases was large enough to begin to discern patterns. The medical complications of the STAMP regimen had, of course, been predictably ghastly: near-lethal infections, severe anemia, pneumonias, and hemorrhages in the heart. But under the clouds of X-rays, blood tests, and CT scans, Peters and Frei saw a silvery inkling. The remissions produced by STAMP, they were convinced, had all been more durable than those produced by conventional chemotherapy. It was only an impression—at best, a guess. To prove that point, Peters needed a randomized
trial. In 1985, with Frei’s encouragement, he left Boston to set up a STAMP program at Duke University in North Carolina. He wanted to leave the Farber’s “pressure cooker” behind for a quiet and stable academic place where he could run a trial in peace.

As William Peters dreamed of a quiet and stable environment to test megadose chemotherapy, the world of medicine was overturned by an unexpected and seemingly unrelated event.
In March 1981, in the journal
Lancet
, a team of doctors reported eight cases of a highly unusual form of cancer called Kaposi’s sarcoma in a cohort of men in New York. The disease was not new: named after a nineteenth-century Hungarian dermatologist, Kaposi’s sarcoma had long been recognized as a slow-growing, violet-colored, indolent tumor that crept along the skin of elderly Italian men that, while occasionally serious, was often considered a somewhat glorified form of a mole or carbuncle. But all the
Lancet
cases were virtually unrecognizable forms of the disease, violent and aggressive variants that had exploded into bleeding, metastatic, blue-black macules spread all over the bodies of these young men. All eight of the men were homosexual. The eighth case drew particular alarm and interest: this man, with lesions on his head and back, was also diagnosed with a rare pneumonia called PCP caused by the organism
Pneumocystis carinii.
An outbreak of one obscure illness in a cluster of young men was already outlandish. The confluence of two suggested a deeper and darker aberration—not just a disease, but a syndrome.

Far away from New York, the sudden appearance of
Pneumocystis carinii
was also raising eyebrows at the Centers for Disease Control in Atlanta, Georgia. The CDC is the nation’s medical radar screen, an agency that tracks emerging diseases to discern patterns and contain their spread.
Pneumocystis
pneumonia only occurs in humans when the immune system is severely compromised. The principal victims had been cancer patients whose white blood cells had been decimated by chemotherapy. (DeVita had encountered it in Hodgkin’s patients treated with four-drug chemo.) The new cases of PCP made little sense: these were young, previously healthy men who had suddenly succumbed to PCP with their immune systems on the verge of collapse.