Hyperthermia and paclitaxel-epirubicin chemotherapy: enhanced cytotoxic effect in a murine mammary adenocarcinoma

Multimodality therapy is considered of great interest in the treatment of locally advanced solid tumours. In previous experiments, paclitaxel (TX) and epirubicin (EP) were combined with different schedules, obtaining a superadditive effect on the growth of a murine mammary carcinoma. In the present study, the authors have analysed the possible use of hyperthermia (HT) to increase the efficacy of TX and EP combinations. Tumours were transplanted into the right hind foot of female hybrid (C3D2F1) mice. Both TX and EP were administered i.p in two different doses. Hyperthermia was applied using a water bath at 43.2 degrees C for 1 h. Results were analysed in terms of Tumour Growth Delay (TGD). The maximum tolerated doses in combined protocols were TX 45 mg/kg and EP 9 mg/kg, with an interval time of 24 h between the two administrations. TGDs of some of the schedules performed are reported: EP+HT=11 days, TX+HT=16 days, TX+EP (with an interval time of 24h)=14 days, and TX+EP+HT=22 days. In the experimental model, HT significantly increases the effects of both TX and EP. TX+EP+HT treatment is the most effective (significantly different from TX+EP), but not in a significant way when compared to TX+HT treatment. These results suggest the possible use of a TX+HT protocol for local tumour response, whereas EP could be added in order to achieve a better systemic control.