Background: Phase I experts recommend revisiting dose-limiting toxicity (DLT) definition to include chronic and cumulative toxicities induced by new molecularly targeted therapies. Patient's assessment of late toxicities' tolerability is, however, unknown.
Materials and methods: A prospective survey on adverse events (AEs) tolerability on 23 National Cancer InstituteCommon Terminology Criteria for Adverse Event, Version 4 (NCI-CTCAE.v4) items was conducted at Gustave Roussy's Phase I department. Patients' maximum tolerability duration was recorded at baseline, during trial and at trial completion. Results were compared with the corresponding physicians' survey.
Results: 52 patients enrolled in 27 Phase I trials between May 2014 and November 2015 completed 102 forms. At baseline, the most feared G2/G3 AEs were haematuria (74%), vomiting (71%) and hyperglycemia (64%)/dry mouth (94%), hyperglycemia (92%) and vomiting (92%). At trial completion, the most feared G2/G3 AEs were personality change (83.3%), haematuria (82%) and fever (80%)/dry mouth, fever and dizziness (100% each). Tolerability score did not differ over time. More previous treatments and occurrence of severe AEs were associated with better tolerability at study completion (p=0.0234 and p=0.0153, respectively, in multivariate analysis). Patient's tolerability differed from physician's assessment.
Conclusion: AEs considered intolerable by patients are toxicities that directly impact their quality of life and differ from those feared by physicians or included in DLT definition. Patient-reported tolerability of AEs may help in optimising drug development.
Keywords: Dose limiting toxicity; adverse event; patient reported outcome; phase 1; tolerability.