Effect of early and delayed difluoromethylornithine pretreatment upon cyclophosphamide chemotherapy

The Dunning R3327 MAT-LyLu prostatic adenocarcinoma was utilized to study the effectiveness of an early versus delayed difluoromethylornithine (DFMO)-induced polyamine-depleted environment on cyclophosphamide (CTX) chemotherapy. DFMO (2%) was administered either at the time of tumor inoculation (early) or 36 h after tumor implantation (delayed). CTX (50 mg/kg) was administered to both DFMO groups in two doses; the first 36 h after initiation of DFMO therapy, and the second 1 week later. Each protocol (early and delayed) for combined DFMO/CTX chemotherapy significantly reduced tumor sizes with the earlier DFMO protocol appearing slightly more effective (p less than 0.001 and 0.02, respectively). DFMO administered alone was not significantly effective with either protocol.