Correlation between sensitivity in vitro of patient chronic lymphocytic leukemia cells and clinical systemic exposure at the maximum tolerated dose for cell cycle phase-specific (type 2) anticancer drugs.
Previously in Anti-cancer Drugs we have reported a high correlation between clinical plasma concentration-time products (C x T) and the concentration of cytotoxic drugs giving 50% cell survival (IC50) in primary cultures of human lymphatic cells. In the present study we investigated the relationship separately for cell cycle-specific (type 1) and cell cycle non-specific (type 2) drugs in chronic lymphatic leukemia cells. A high correlation (R = 0.92) was observed between C x T and IC50 for cell cycle non-specific drugs, while for cell cycle-specific, or C x T-dependent, drugs, the relationship was much weaker (R = 0.58). Since the opposite pattern has been observed for the relationship between clinical C x T and LD10 in mice, these results further imply that drug sensitivity assays may be a useful complement to animal data in the selection of starting dose and dose escalation procedure in phase I clinical trials of new cytotoxic drugs.
Fridborg
H
H
Department of Oncology, University Hospital, Uppsala University, Sweden.
Nygren
N
N
Larsson
R
R
D000818:Animals; D002453:Cell Cycle; D002470:Cell Survival; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D066298:In Vitro Techniques; D007928:Lethal Dose 50; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy* / Q000473:pathology; D051379:Mice; D014407:Tumor Cells, Cultured