High Rates of Adverse Events Lead to Earlier Dropouts in Phase 1 Cancer Trials

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Disease progression and adverse effects were common reasons that patients left clinical trials.
Disease progression and adverse effects were common reasons that patients left clinical trials.

Participants enrolled in phase 1 cancer trials who experience adverse events (AE) are more likely to withdraw from the study, a study published in Supportive Care in Cancer has shown.

Phase 1 trials, which determine the safety profiles of treatment regimens, are of particular importance in the development of cancer therapeutics as they determine phase 2 dosing and dose-limiting toxicities. While there is supporting evidence for reasons as to why patients enroll in phase 1 studies, motivations to withdraw are unclear.

For this retrospective review, investigators analyzed the records of 255 patients with solid tumors who enrolled in phase 1 clinical trials from the Oncore clinical trials database. Baseline characteristics including race, age, gender, cancer type, performance status, and whether trials were evaluating cytotoxic or noncytotoxic therapies were recorded. The frequency, nature, and grades of adverse events (AE) experienced by patients were also reviewed.

Patients were enrolled in phase 1 studies for a mean duration of 78.4 days, and 23% of patients were on study for 30 days or less.

Patients on average experienced 25.1 AEs, which included constitutional (29.3%), gastrointestinal (24%), and pain (12.8%); 46.9% of AEs were nonlaboratory (events that presented as symptoms and not only as abnormal laboratory results).

The most common reason for withdrawal from studies was disease progression (57.6%), followed by adverse effects (16.5%). Approximately 13% of patients cited other reasons as cause for discontinuation, but upon further review 41.7% of these cases were associated with symptom burden. Greater AE rates had a significant positive association with shorter study duration (r = -0.331; P <.01).

The authors concluded that “[d]esigning interventions to reduce AE burden may extend duration on trial, affect the recommended phase II dose, and benefit the quality of life of participants on phase I trials.”


1. Treasure M, Daly B, Fu P, Kerpedjieva S, Dowlati A, Meropol NJ. Relationship between phase I study duration and symptom burden [published online October 4, 2017]. Support Care Cancer. doi: 10.1007/s00520-017-3879-1

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