Relationships between drug activity in NCI preclinical in vitro and in vivo models and early clinical trials.

An analysis of the activity of compounds tested in pre-clinical in vivo and in vitro assays by the National Cancer Institute's Developmental Therapeutics Program was performed. For 39 agents with both xenograft data and Phase II clinical trials results available, in vivo activity in a particular histology in a tumour model did not closely correlate with activity in the same human cancer histology, casting doubt on the correspondence of the pre-clinical models to clinical results. However, for compounds with in vivo activity in at least one-third of tested xenograft models, there was correlation with ultimate activity in at least some Phase II trials.

The taxol supply crisis. New NCI policies for handling the large-scale production of novel natural product anticancer and anti-HIV agents.

Over the past 30 years, the National Cancer Institute has been involved in the preclinical and/or clinical evaluation of the majority of those agents approved for the treatment of cancer. Many of the new agents under consideration in the NCI program are either natural products or derivatives of natural product leads, and of critical importance to their development is the issue of drug supply. In responding to the drug supply crisis which emerged with the demonstration of the clinical efficacy of taxol, the NCI has identified several important lessons for those interested in natural product drug discovery and development.

The National Cancer Institute: cancer drug discovery and development program.

The discovery and development of novel therapeutic products for the treatment of malignancy is vitally important to those physicians responsible for the management of cancer patients. A description of the ongoing efforts at the National Cancer Institute (NCI) is intended to provide insight into those complex processes necessary to accomplish this mission. An update on the NCI's revised cancer screen is accompanied by a brief summary of those new agents scheduled to be entered into clinical investigation in the near future.

Historical overview of the National Cancer Institute Fermentation Program.

The background of the National Cancer Institute fermentation program is placed into the historical perspective of the entire NCI drug development program, which began as the Cancer Chemotherapy National Service Center and metamorphosed into the Chemotherapy Program and ultimately into the Division of Cancer Treatment.

Antitumor screening procedures of the National Cancer Institute.

From the time of its inception in 1955, the Drug Development Program of the National Cancer Institute has relied primarily on transplanted rodent tumor systems in vivo for the evaluation and selection of potential antitumor agents. Although greater emphasis has been placed in recent years on rationally designed drugs, the major effort throughout the history of the program has involved the empirical screening of a wide variety of chemical structures and natural products of varying sources. The initial screening spectrum consisted of three mouse tumors, Sarcoma 180, Carcinoma 755 and Leukemia 1210, based on the retrospective analysis presented in the GELLHORN-HIRSCHBERG Report.