First, Pinkel reasoned that while combinations of drugs were necessary to induce remissions, combinations were insufficient in themselves. Perhaps one needed combinations of combinations - six, seven, or even eight different chemical poisons mixed and matched together for maximum effect.
Second, since the nervous system relapses had likely occurred because even these highly potent chemicals could not breach the blood-brain barrier, perhaps one needed to instill chemotherapy directly into the nervous system by injecting it into the fluid that bathes the spinal cord.
Third, perhaps even that instillation was not enough. Since X-rays could penetrate the brain regardless of the blood-brain barrier, perhaps, one needed to add high-dose radiation to the skull to kill residual cells in the brain.
And finally, As Min Chiu Li had seen with choriocarcinoma, perhaps one needed to continue chemotherapy not just for weeks and months as Frei and Freireich had done, but for month after month, stretching into two or even three years.
The treatment protocol that emerged from these guiding principles could only be described as, as one of Pinkel's colleagues called it, "an all-out combat." To start with, the standard antileukemic drugs were given in rapid-fire succession. Then, at defined intervals, methotrexate was injected into the spinal canal using a spinal tap. The brain was irradiated with high doses of X-rays. Then, chemotherapy was bolstered even further with higher doses of drugs and alternating intervals, "in maximum tolerated doses." Antibiotics and transfusions were usually needed, often in succession, often for weeks on end. The treatment lasted up to two and a half years; it involved multiple exposures to radiation, scores of blood tests, dozens of spinal taps, and multiple intravenous drugs - a strategy so precise and demanding that one journal refused to publish it, concerned that it was impossible to even dose it and monitor it correctly without killing several patients in the trials. Even at St. Jude's, the regimen was considered so overwhelmingly toxic that the trial was assigned to relatively junior physicians under Pinkel's supervision because the senior researchers, knowing its risks, did not want to run it. Pinkel called it "total therapy."
As fellows, we called it "total hell."引自 Part 2 An Impatient War 105
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