Fatigue in Cancer Treatment Studies: Analysis of Placebo Arms

Fatigue and asthenia are common in patients with cancer; and identifying the cause as drug toxicity versus cancer progression is difficult, particularly in clinical trials without control arms.

We carried out a systematic literature review of fatigue in placebo arms of randomized cancer trials reported in PubMed from 2000 to 2021.

Fatigue/asthenia were reported in 100 out of 134 placebo cohorts, and the average of reported frequencies was 22.8%, with a range of 0-83%. Grade 3 or higher fatigue/asthenia was reported in 2.3% (0-17%). Fatigue/asthenia was positively correlated with nausea (R=0.683) Conclusion: For detection of drug toxicity, observations should be flagged when they are higher than the maximum reported in the placebo arm, and the assessment should be supplemented by comparing observations in early oncology trials to literature placebo arms, including both sample sizes and event numbers.