History of Cancer Chemotherapy - Combination Chemotherapy

Combination Chemotherapy

In 1965, a major break-through in cancer therapy occurred. James Holland, Emil Freireich, and Emil Frei hypothesized that cancer chemotherapy should follow the strategy of antibiotic therapy for tuberculosis with combinations of drugs, each with a different mechanism of action. Cancer cells could conceivably mutate to become resistant to a single agent, but by using different drugs concurrently it would be more difficult for the tumor to develop resistance to the combination. Holland, Freireich, and Frei simultaneously administered methotrexate (an antifolate), vincristine (a Vinca alkaloid), 6-mercaptopurine (6-MP) and prednisone — together referred to as the POMP regimen — and induced long-term remissions in children with acute lymphoblastic leukaemia (ALL). With incremental refinements of original regimens, using randomized clinical studies by St. Jude Children's Research Hospital, the Medical Research Council in the UK (UKALL protocols) and German Berlin-Frankfurt-Münster clinical trials group (ALL-BFM protocols), ALL in children has become a largely curable disease.

This approach was extended to the lymphomas in 1963 by Vincent T. DeVita and George Canellos at the NCI, who ultimately proved in the late 1960s that nitrogen mustard, vincristine, procarbazine and prednisone — known as the MOPP regimen — could cure patients with Hodgkin's and non-Hodgkin's lymphoma. Currently, nearly all successful cancer chemotherapy regimens use this paradigm of multiple drugs given simultaneously.