Placebo Effects in Oncology

BACKGROUND: Previous studies have suggested that placebo treatment can have positive effects on a variety of disorders and disease-related symptoms. However, the methodology used to collect and interpret the data may not have been ideal, because the studies were not double-blinded or the endpoints were not properly validated. The purpose of the present study was to determine the probability of improvement in symptoms or quality of life and tumor response in cancer patients treated with placebos in randomized controlled trials. We hypothesized that administration of placebos would improve symptom control and quality of life but would not lead to tumor response. METHODS: We reviewed reports of randomized controlled trials in which there was a placebo arm (37 trials) or a best supportive care (BSC) arm (10 trials). RESULTS: In trials that assessed average responses for patients in the placebo arm, improvements in average levels of pain were reported in two of six trials and in appetite, in one of seven trials. No improvements in average levels of weight gain (six trials), in quality of life (as assessed by patients; 10 trials), or in performance status (as assessed by physicians; nine trials) were reported. In trials that assessed response to a placebo in individual patients, 0%-21% of patients showed reduced pain or decreased analgesic intake, 8%-27% of patients showed appetite improvement, 7%-17% of patients showed weight gain, and 6%-14% of patients showed improvement in performance status. Quality of life for individual patients was not reported in any trial. Tumor response assessed by World Health Organization criteria was observed in 10 (2.7%) of 375 patients (seven trials total). Response as assessed by a serum marker was observed in 1 (1.7%) of 60 patients (two trials total). The probability of symptom improvement in patients receiving BSC was generally similar to that in patients receiving placebo, although no improvement in pain and only one tumor response among 191 patients (five trials) were reported. CONCLUSION: In randomized double-blinded, placebo-controlled trials, presumably with minimum sources of bias, placebos are sometimes associated with improved control of symptoms such as pain and appetite but rarely with positive tumor response. Substantial improvements in symptoms and quality of life are unlikely to be due to placebo effects.