Ex vivo therapeutic index by drug sensitivity assay using fresh human normal and tumor cells.

Toxicity is a major deterrent to achieving substantial improvements in cancer management, since most anticancer drugs inadequately distinguish normal and neoplastic tissues. Improving the differential between beneficial and toxic effects of therapy--therapeutic index--is a major clinical objective, but therapeutic index for cytotoxic drugs is narrow. Fresh tumor and normal cells from 59 patients with acute myeloid leukemia, non-Hodgkin's lymphoma, ovarian cancer and cancers of unknown origin were tested for ex vivo drug sensitivity using apoptosis by morphology assays.

Parameters affecting the ex vivo cytotoxic drug sensitivity of human hematopoietic cells.

The drug sensitivity of normal cells provides a baseline for determining the therapeutic index, and therefore the effectiveness, of cytotoxic drugs, yet little is known about the factors that affect normal cell chemosensitivity. Some parameters are known to have a profound effect on tumor cell sensitivity. The purpose of this study was to determine how cytotoxic drug sensitivity of hematopoietic cells isolated from cancer patients was affected by various parameters.