Development of a canine multidrug chemotherapeutic model using doxorubicin, cisplatin, and ifosfamide

The purpose of this study was to develop a safe and clinically relevant canine experimental model for multidrug chemotherapy administration utilizing doxorubicin (ADR), cisplatin (CDP), and ifosfamide (IFX). Though these agents are commonly used in clinical orthopaedic oncology, their effects on orthopaedic reconstructive procedures after tumor resection have not been explored. Prior to our study, an appropriate experimental model did not exist. Our experiment was divided into 2 steps. Two dogs were used for step 1. Dosages in the first step, which were determined using single agent protocols, were as follows: ADR, 30 mg/m²; CDP, 75 mg/m²; and IFX, 450 mg/m². This combined regimen led to sepsis and death in both dogs soon after the first cycle. Therefore, in the second step, dosages were reduced as follows: ADR, 20 mg/m²; CDP, 50 mg/m²; and IFX, 300 mg/m². Four dogs were used for step 2. All 4 dogs survived three full cycles with serious myelosuppression but no other significant laboratory abnormalities. No haematuria or proteinuria occurred throughout the course, and no significant pathological findings were observed at autopsy. In conclusion, this clinically relevant regimen is tolerated by the canine and may be used as a model for further studies of chemotherapy effects.