Antitumor activity of the two epipodophyllotoxin derivatives VP-16 and VM-26 in preclinical systems: a comparison of in vitro and in vivo drug evaluation.

摘要: The epipodophyllotoxines VP-16 and VM-26 are chemically closely related. has been found to be considerably more potent than in vitro a number of investigations. Although the drugs have known for >20 years, they not compared at clearly defined equitoxic doses on an optimal schedule vivo it clarified as whether therapeutic difference exists between them. A prolonged is both drugs; accordingly we determined toxicity mice using 5-day schedule. dose killing 10% (LD10) was 9.4 mg/kg daily (95% confidence limits, 7.4–11.8) 3.4 (2.5–4.5) VM-26. In vitro, 6–10 times clonogenic assay murine tumors P388 L1210 leukemia Ehrlich ascites. This pattern also demonstrated multidrug-resistant subline selected resistance daunorubicin (Ehrlich/DNR+), 30 less sensitive cells Using 90%, 45%, 22% LD10 same vivo, that effect two equal evaluated by increase life span cures. were nude inoculated with human small-cell lung cancer lines OC-TOL CPH-SCCL-123; however, toxic only limited observed. conclusion, complete cross-resistance suggests identical antineoplastic spectrum. vitro; this correlated advantage over