Effects of CI-921, an analogue of amsacrine, on advanced Lewis lung tumours in mice: relevance to clinical trials.
The 4-methyl-5-N-methylcarboxamide derivative of amsacrine (CI-921; NSC 343 499), which is now undergoing clinical trial, has been used to treat advanced Lewis lung tumours in mice. The response of the tumours was monitored by physical measurement, histological examination and flow cytometric analysis. The latter technique demonstrated that a single dose of CI-921 induced an efficient blockade of the tumour cell cycle in G2 phase. Histological assessment of lung nodules indicated a progressive increase in the cross-sectional area of both tumour cells and lung nodules after drug treatment. Under conditions providing a growth delay equivalent to a 6 log10 cell kill, and demonstrable histological destruction of tumour cells, the sizes of subcutaneous tumours did not decrease below the pre-treatment volumes, suggesting, at least for subcutaneous tumours, that changes in tumour size do not provide a good criterion for appraisal of drug effects. Schedule dependence studies on advanced lung tumours were carried out in an effort to provide information of specific relevance to clinical trials. A significant correlation of total dose with response was found, suggesting that clinical schedules allowing the total administered dose to be maximal should be used.
Baguley
B C
BC
Cancer Research Laboratory, University of Auckland School of Medicine, New Zealand.
Calveley
S B
SB
Harvey
V J
VJ
D000677:Amsacrine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry; D008168:Lung / Q000473:pathology; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D051379:Mice; D013997:Time Factors; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D000677:Amsacrine; C042315:asulacrine