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

R. L. Page, D. W. Macy, G. K. Ogilvie, G. L. Rosner, M. W. Dewhirst, D. E. Thrall, S. J. Withrow, M. C. Mcentee, J. M. Cline, G. L. Heidner, C. A. Novotney, E. L. Gillette

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25 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)187-197
Number of pages11
JournalInternational Journal of Hyperthermia
Issue number2
StatePublished - 1992
Externally publishedYes


  • Canine
  • Doxorubicin
  • Lymphoma
  • Whole body hyperthermia

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)
  • Cancer Research


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