Is BCG an “Orphan” Drug Suffering from Chemotherapists' Overkill?

Modern interest in cancer immunotherapy emerged in 1969 following the pioneer reports of George Mathe on the effect of Bacillus Calmette-Guerin (BCG) in suppressing murine cancer and apparently increasing survival of children with acute lymphatic leukemia (1). Mathe employed intensive repeated weekly multisite scarifications with BCG during both the induction and maintenance phases of the steadily improving chemotherapy in vogue in the late 1960s. His favorable but uncontrolled studies stimulated a number of “historically controlled” trials of intensive heavy weekly BCG treatment. In the last eight years, at least 60 randomized controlled trials and many other nonrandomized studies have been completed. These employ diverse immunomodulators including various formulations of BCG (2) and BCG derivatives [BCG-MER, BCG cell wall skeletons (CWS)], as well as Corynebacterium parvumlevamisole, thymosin, poly A-poly U, and other agents. A vast array of confusing fragmentary observations and generally nonsignificant borderline findings have been summarized in several published international symposia.