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.
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North Carolina State University, College of Veterinary Medicine, Raleigh 27606.
Macy
D W
DW
Ogilvie
G K
GK
Rosner
G L
GL
Dewhirst
M W
MW
Thrall
D E
DE
Withrow
S J
SJ
McEntee
M C
MC
Cline
J M
JM
Heidner
G L
GL
D000818:Animals; D003131:Combined Modality Therapy; D004283:Dog Diseases / Q000188:drug therapy / Q000628:therapy*; D004285:Dogs; D004317:Doxorubicin / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D006321:Heart / Q000187:drug effects; D006979:Hyperthermia, Induced / Q000009:adverse effects / Q000662:veterinary*; D008228:Lymphoma, Non-Hodgkin / Q000188:drug therapy / Q000628:therapy / Q000662:veterinary*; D008297:Male; D009206:Myocardium / Q000473:pathology
D004317:Doxorubicin