title: Digitoxin medication and cancer; case control and internal dose-response studies.
abstract: BACKGROUND
  Digitoxin induces apoptosis in different human malignant cell lines in vitro. In this paper we investigated if patients taking digitoxin for cardiac disease have a different cancer incidence compared to the general population.
  
  
  METHODS
  Computer stored data on digitoxin concentrations in plasma from 9271 patients with cardiac disease were used to define a user population. Age and sex matched controls from the Norwegian Cancer Registry were used to calculate the number of expected cancer cases.
  
  
  RESULTS
  The population on digitoxin showed a higher incidence of cancer compared to the control population. However, an additional analysis showed that the population on digitoxin had a general increased risk of cancer already, before the start on digitoxin. Leukemia/lymphoma were the cancer types which stood out with the highest risk in the digitoxin population before starting on digitoxin. This indicates that yet unknown risk factors exist for cardiovascular disease and lymphoproliferative cancer. An internal dose-response analysis revealed a relationship between high plasma concentration of digitoxin and a lower risk for leukemia/lymphoma and for cancer of the kidney/urinary tract.
  
  
  CONCLUSIONS
  Morbidity and mortality are high in the population on digitoxin, due to high age and cardiac disease. These factors disturb efforts to isolate an eventual anticancer effect of digitoxin in this setting. Still, the results may indicate an anticancer effect of digitoxin for leukemia/lymphoma and kidney/urinary tract cancers. Prospective clinical cancer trials have to be done to find out if digitoxin and other cardiac glycosides are useful as anticancer agents.
authors.affiliation: Department of Oncology, University Hospital, N-7006, Trondheim, Norway. jhaux@operamail.com
authors.forename: J
authors.initials: J
authors.lastname: Haux
authors.forename: O
authors.initials: O
authors.lastname: Klepp
authors.forename: O
authors.initials: O
authors.lastname: Spigset
authors.forename: S
authors.initials: S
authors.lastname: Tretli
mesh_terms: D000367:Age Factors; D000368:Aged; D000889:Anti-Arrhythmia Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use; D016022:Case-Control Studies; D015331:Cohort Studies; D004074:Digitoxin / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006331:Heart Diseases / Q000150:complications / Q000188:drug therapy; D006801:Humans; D015994:Incidence; D008297:Male; D009369:Neoplasms / Q000097:blood / Q000139:chemically induced / Q000453:epidemiology*
chemical_list: D000889:Anti-Arrhythmia Agents; D004074:Digitoxin