title: A Phase II dose titration study of thalidomide for cancer-associated anorexia.
abstract: BACKGROUND
  Sixty-five percent of people with advanced cancer suffers from loss of appetite. Several inflammatory cytokines appear to cause appetite loss in animal models. Thalidomide is an immunomodulatory drug that has been associated with improved appetite in those with HIV infections and cancer.
  
  
  OBJECTIVE
  We completed a two-stage Phase II dose titration study of thalidomide, the primary purpose of which was to assess appetite response to thalidomide in cancer-associated anorexia.
  
  
  METHODS
  Individuals older than 18 years of age with active cancer, loss of appetite by numerical rating scale (NRS), life expectancy of at least four weeks, and Eastern Cooperative Oncology Group performance status of 0-3 were entered into the study. Pretreatment screening included medical history, neurologic examination, and symptoms by NRS and categorical scale (CAT). Patients received 50mg of thalidomide by mouth at bedtime for two weeks. Individuals who did not respond were dose escalated to 100mg at night for two weeks. Assessment of appetite, early satiety, fatigue, insomnia, night sweats, pain, and quality of life (QOL) occurred at two-week intervals. Toxicity also was assessed. The primary outcome was appetite response defined as a two-point reduction in the NRS or a one-point improvement in the CAT.
  
  
  RESULTS
  Thirty-five patients entered the study; 33 completed 14 days of therapy and were analyzed for efficacy and toxicity. Sixty-four percent who completed at least two weeks of thalidomide had improved appetite. The CAT scores for appetite, insomnia, and QOL improved significantly. The 95% confidence intervals did not overlap. Five participants dropped out because of toxicity: two before two weeks and three later.
  
  
  CONCLUSIONS
  Thalidomide reduced multiple symptoms commonly associated with cancer-related anorexia and improved QOL. Our findings confirmed and validated a previously published single-arm trial. A recent randomized trial demonstrated greater benefits when thalidomide is used combined with other agents to treat cancer-associated anorexia and cachexia. Thalidomide helped cancer-associated anorexia in most patients. It also improved insomnia and QOL in advanced cancer.
authors.affiliation: The Harry R. Horvitz Center for Palliative Medicine, Cleveland Clinic Taussig Cancer Institute, Cleveland, Ohio, USA.
authors.forename: Mellar
authors.initials: M
authors.lastname: Davis
authors.forename: Wael
authors.initials: W
authors.lastname: Lasheen
authors.forename: Declan
authors.initials: D
authors.lastname: Walsh
authors.forename: Fade
authors.initials: F
authors.lastname: Mahmoud
authors.forename: Leslie
authors.initials: L
authors.lastname: Bicanovsky
authors.forename: Ruth
authors.initials: R
authors.lastname: Lagman
mesh_terms: D000368:Aged; D000855:Anorexia / Q000188:drug therapy* / Q000209:etiology* / Q000517:prevention & control; D017321:Clinical Trials, Phase I as Topic; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000150:complications* / Q000188:drug therapy*; D007319:Sleep Initiation and Maintenance Disorders / Q000188:drug therapy / Q000209:etiology* / Q000517:prevention & control*; D013792:Thalidomide / Q000008:administration & dosage* / Q000009:adverse effects; D016896:Treatment Outcome
chemical_list: D007166:Immunosuppressive Agents; D013792:Thalidomide