High-Risk Hope For Children's Cancer

Of the various types of cancer that afflict children, few are more fearsome than osteogenic sarcoma, a tumor that originates in the bone and spreads rapidly. By the time doctors can tell that the pain in a youngster's arm or leg is the product of such a tumor, the odds are strong that microscopic clusters of malignant cells have already reached the lungs. Removing the primary tumor by amputation saves the patient from early death. But in 80% of the 150 cases of this cancer reported among patients under age 15 in the U.S. annually, a secondary tumor appears in the lungs within a year. In most of the cases, death follows six to nine painful months later.

Until recently, all doctors could do in most of these cases was to try to slow the cancer's fatal course with chemotherapy. Now a new--though risky --way of using an old drug called methotrexate is improving the outlook for victims of osteogenic sarcoma.

One of the oldest of the anti-cancer drugs, methotrexate has been around since 1948. It works by interrupting the cells' reproductive cycle. In low dosages, it has long been effective in controlling leukemia and certain other cancers.

But doctors were frustrated for years by the fact that standard doses of the highly toxic drug had no effect on osteogenic sarcoma cells, yet left patients suffering various unpleasant and even dangerous side effects--anemia, impaired liver and kidney function, mouth ulcers, nausea and hair loss.

In the 1960s, doctors devised a new technique. Instead of reducing dosage to decrease toxicity, they increased it. Reasoning that only enormous amounts of the drug could attack bone cancer cells effectively, they began administering potentially lethal doses of methotrexate, following those with an antidote called citrovorum factor, which protects normal cells from methotrexate's deadly action. Since then, massive doses of methotrexate followed by a citrovorum-factor "rescue" (CFR) have become an accepted method of treatment for bone cancer at several cancer centers.

Rescue Effort. At the Children's Cancer Research Foundation in Boston, Drs. Emil Frei III and Norman Jaffe have used the methotrexate-CFR treatment on Edward Kennedy Jr. (TIME, Dec. 3), and on 20 other patients. Methotrexate-CFR treatment is begun soon after amputation. Patients enter the hospital and receive a continuous intravenous infusion of methotrexate for six hours, during which they may be given more than 100 times the standard dose of the drug. Two hours after the methotrexate infusions are completed, the rescue effort begins. The patient is given citrovorum factor, first by injection, then by mouth every six hours for three days, while doctors monitor the patient's condition carefully and check the level of methotrexate in his blood. When it has dropped below the danger point, the patient can go home. He returns to the hospital in another three weeks, after his system has recovered, for more treatment.

The treatments, which continue for two years, have thus far produced few of methotrexate's more dangerous side effects--many patients have survived far longer than the usual year or less after amputation. Of 10 patients with metastatic disease treated at Boston since 1971, two have had complete recoveries and two have had partial ones; one patient, who has been off treatment for a year, is still totally free of cancer.

Of 20 others treated since 1972, only two have developed lung metastases.

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