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.
