Medicine: Mister Sam’s Drug

The more a drug is touted as a cure for cancer, the more likely it is to be an example of fraud or quackery. But a few drugs do slow or even halt, for varying periods, the course of some kinds of cancer. The manufacturers of these products firmly specify that they have no cure; they do not want to raise false hope. And even among the most useful of cancer palliative drugs, most are not available for general prescription by all doctors; they are limited to ”investigational” use by research physicians.

Such a drug is 5-fluorouracil (pronounced floo-or-oh-you’re-a-sill), which Dallas physicians started giving, at the beginning of last week, to House Speaker Sam Rayburn. It is usually given only to selected patients who have already had surgery, radiation or both. Mister Sam’s body was so riddled with spreading cancer (probably from a growth in the pancreas) that surgery was not possible. All the doctors could do at first was try to slow the march of the disease by chemical warfare against cancer cells.

Phony Food. The theory behind 5-fluorouracil is disarmingly simple. Rapidly multiplying cancer cells consume a more than average supply of ”metabolites”—foods that have been altered chemically in the body. In some types of leukemia it had been shown that malignant cells can be fooled into accepting a phony metabolite, or “antimetabolite.” When it was shown in 1954 that solid cancers have an abnormal appetite for the metabolite called uracil, the University of Wisconsin’s Dr. Charles Heidelberger set about making a phony variant of uracil. With Dr. Robert Duschinsky of Hoffmann-La Roche, Inc., he quickly found a way to make one by substituting an atom of fluorine for one of hydrogen at the No. 5 position on the molecular ring—hence, 5-fluorouracil. Many of the cancer cells accept 5-fluorouracil in place of the real thing, and cannot multiply.

But the practical use of 5-fluorouracil is by no means so simple as the theory. There are other body cells that multiply about as fast as cancer cells, and therefore need a lot of uracil, notably those in the bone marrow, which makes blood cells, and those in the lining of the digestive tract. Soon after 5-fluorouracil has attacked the cancer, it damages these vital, normal cells. Patients begin to suffer from vomiting. At the first sign of inflammation and ulceration in the mouth, doctors stop the drug. Usually they try to give heavy doses (injected into an arm vein) for three to five days, followed by smaller doses on alternate days until they have to stop. Then they lay off for a month, to spare the bone marrow and gut lining, and start again.

Dr. Ralph Tompsett. spokesman for Dallas’ Baylor University Medical Center, said that Mister Sam tolerated the first big doses well, and had no nausea. A midweek bout of pneumonia interrupted the treatment, but Rayburn rallied quickly. After that he was given FUDR (5-fluoro-2′-deoxyuridine), which is a close chemical kin of 5-fluorouracil and works the same way.

Still Too Soon. On the average, one-fifth of all 5-fluorouracil patients with cancer of the large bowel, and a few with cancer of the liver or other organs, show worthwhile benefit. Their most distressing symptoms subside, and they live more comfortably. In unpredictable cases the improvement is more marked. A few patients have been able to tolerate repeated treatments and have stayed reasonably well for more than a year.

But no cure by 5-fluorouracil has ever been claimed. This year the Food and Drug Administration decided that it was still too soon, because of hazards and unpredictable results, to license 5-fluorouracil for general prescription.