Phase III evaluation of doxorubicin and whole-body hyperthermia in dogs with lymphoma

Sixty-one dogs with histologically confirmed, untreated, high-grade lymphoma were evaluated and treated with doxorubicin (DOX, 30 mg/m2) alone. Forty-seven dogs (77%) achieved a complete response. Forty-six of the 47 dogs were randomized to receive five additional treatments with doxorubicin ± whole-body hyperthermia (WBH). Median disease-free survival for the group treated with DOX alone (n = 22) was 189 days and for the DOX plus WBH (n = 24) was 239 days (p = 0·17). After the analysis was adjusted for stratification variables (i.e. institution, weight, stage), the effect of heat on disease-free survival remained statistically insignificant (p = 0·10), but suggested a tendency towards increased disease-free survival in hyperthermic dogs. Intact male dogs had significantly shorter disease-free survival than neutered males and neutered females (178 days vs 266 days, respectively; p = 0·013). No intact females were treated. Body weight, when evaluated as a continuous variable, was found to be a negative prognostic factor (p = 0·036). Tumour volume, stage and institution were not significant. Clinical incidence of cardiac dysfunction was not increased in dogs receiving DOX and WBH; however, post-mortem histological analysis of cardiac tissue suggested that the combined therapy of DOX and WBH was associated with greater myocyte degeneration (p = 0·012) and a tendency for increased cardiac fibrosis (p = 0·08). We concluded that continued refinement of DOX-WBH protocols is warranted, and may ultimately result in significant therapeutic improvement.