The observation in the 1950s that nitrogen mustard and other toxic
chemicals could induce antitumor responses in patients with refractory
lymphoma initiated a massive search for active chemotherapeutic agents.
The initial observations stimulated a search for new chemotherapeutic
agents which might have increased antitumor activity with less toxicity
for normal tissues. To aid in the search for these new chemicals and to
attempt to distinguish among the many toxic chemicals which might be
candidates for clinical studies, the National Cancer Institute, the
pharmaceutical industry, and the cancer research laboratories of most
Western nations developed systems for "screening" drugs for antitumor
activity. Perhaps the most extensive screening program was established
by the National Cancer Institute (1). This screening program has evolved
over the last two decades, an evolution which has been repeatedly
reviewed (2-5). Various screening programs in use have examined over
500,000 compounds as potential anticancer agents. From these, there are
now approximately forty anticancer drugs in clinical use. The utiliy of
these compounds and their toxicities have been reviewed on many
occasions. It is now apparent that more active and less toxic anticancer
drugs are needed. It is also clear that the current screening programs
are identifying compounds with similar levels of activity and with
continuing moderate to severe toxicity (6).