The Years of Creativity: 1953-1965. Clinical

During the 1950s and early 1960s, several principles of chemotherapy were established, principally from methodical studies in childhood acute lymphocytic leukemia carried out within the setting of cooperative oncology groups. Combination chemotherapy, first initiated at the National Cancer Institute, led to a protocol comparing two drugs versus one; the results showed that two drugs given together were better than their sequential administration. The dose-schedule principle and first-order kinetic action of chemotherapeutic drugs were successfully studied in the clinic. A leap forward occurred with the demonstration that the effects of new chemotherapeutic agents could be tested in patients in clinical remission. Imaginative study designs were conceived leading to the identification of different phases of therapy: induction, maintenance and periodic reinduction. A continuous-flow blood cell separator was developed; granulocye and platelet transfusions were used to effectively reduce death from infections and hemorrhages; methods of treating meningeal leukemia became available. With these advances, long-term duration of unmaintained remission was seen in children with acute lymphocytic leukemia. Also, for the first time, the cure of a metastatic solid tumor in human, choriocarcinoma, was achieved.

Keywords: Acute lymphocytic leukemia, combination chemotherapy, induction, maintenance, reinduction, granulocyte and platelet transfusions, meningeal leukemia, choriocarcinoma.