Answers About L-Asparaginase

Among almost a dozen chemicals which have a selective damaging effect on cancer cells, L-asparaginase is unique in one respect: its action is so much more selective that it appears to do no harm whatever to normal cells. Since L-asparaginase was erroneously reported to have cured a case of childhood leukemia (TIME, April 14; July 7), researchers have been trying to answer three main questions: 1) Against what types of cancer is it effective?; 2) Will a laboratory test show in advance whether a particular patient's disease will respond?; and 3) Even though L-Asparaginase spares normal cells, how severe are its other harmful effects?

Partial and partly reassuring answers are being reported this week to hematologists meeting in Toronto by Dr. Herbert F. Oettgen speaking for a research team at Manhattan's Memorial Sloan-Kettering Cancer Center. L-asparaginase is so scarce, besides being forbiddingly expensive,-o that Dr. Oettgen could report on only 14 patients. Even this small number of cases made it clear that the enzyme is likely to be effective mainly, against only one common form of "blood cancer" -- acute lymphatic leukemia. All seven patients with this type of disease showed prompt and marked improvement; among them were three children whose bone marrow stopped making abnormal white cells, at least for a while. An eighth patient, who had acute myelocytic leukemia, also enjoyed a temporary improvement, though three others with this type of disease had none. One patient with a third form of leukemia (monocytic) and two with lymphosarcoma got no benefit from the enzyme.

Hundredfold Doses. Since the patients' responses to treatment could have been predicted in nearly every case by a laboratory test devised at Sloan-Kettering, there is no need to waste L-asparaginase by trying it blindly on patients unlikely to benefit. Side effects included fever, nausea, weight loss and allergic reactions but, said Dr. Oettgen, it is uncertain whether these were due to the enzyme or to contaminants.

Despite these drawbacks, the Memorial doctors would like to be able to give L-asparaginase in vastly bigger doses. In mice, small doses will temporarily suppress leukemia, and hundredfold-greater doses result in what seems to be a permanent cure. This, said Dr. Oettgen, raises the question whether massive doses of L-asparaginase, perhaps combined with other drug treatment, might actually cure one form of human leukemia.

*It is extracted in minute quantities by highly complex processes from vats in which countless billions of colon bacteria, Escherichia coli, have been grown.

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