Synergetic toxicity of DATR, a recombinant soluble human TRAIL mutant, in combination with traditional chemotherapeutics in rats.

ABSTRACT

The recombinant soluble human TRAIL mutant (DATR), derived from tumour necrosis factor-related apoptosis-inducing ligand (TRAIL), is a promising agent for cancer therapy. The present study evaluated the synergetic toxicity of DATR in combination with traditional chemotherapeutics, including irinotecan, polyene paclitaxel and oxaliplatin in rats. Rats treated with polyene paclitaxel alone or in combination with DATR showed severe diarrhea, appetite inhibition, increasing sodium (Na(+)), potassium (Cl(-)) and glucose (GLU) and serious disorders in the haematological system. Increasing total bilirubin (TBIL) and blood urea nitrogen (BUN) were detected in the rats treated with oxaliplatin alone or in combination with DATR. Furthermore, except that the BUN and Crea of male rats treated with irinotecan in combination with DATR were higher than those of treated with irinotecan, the addition of DATR does not increase the toxicity induced by irinotecan, polyene paclitaxel and oxaliplatin. In conclusion, DATR probably increases kidney lesions of rat with irinotecan, but does not increase the toxicity induced by polyene paclitaxel and oxaliplatin. This indicated that DATR has promising potential in clinical combination therapies. Furthermore, the toxicity induced by DATR on the liver, kidneys and haematological system should be considered carefully if DATR is used in combination with traditional chemotherapeutics.