Etoposide prior to cis-diamminedichloroplatinum in combination chemotherapy: in vitro and in vivo studies.

Antitumor effect and toxicity of etoposide (VP 16) in combination with cis-diamminedichloroplatinum (DDP) were studied on the in vitro C108 line and its in vivo counterpart, the M1087 line, both deriving from Lewis lung carcinoma. A colony-forming assay was used to assess the in vitro cytotoxicity of each drug and, on the basis of survival curve shape indications, different drug sequences were analyzed in order to find the optimal combination. Tumor growth inhibition, growth delay, metastasis reduction and percentage increase in lifespan were considered as parameters of therapeutic effect. From the present work it can be derived that the VP 16-DDP combination produces a poor antitumour effect against the Lewis lung carcinoma lines, otherwise associated with a highly acute toxicity. The sequence in which VP 16 is given before DDP induces a significant antimetastatic effect together with acceptable toxicity.