Phase I Clinical Trials in Patients ≥80.

Phase I clinical trials play a crucial role in development of therapeutics for cancer patients. During phase I clinical trials common toxicities are delineated, dose limiting toxicities (DLT) are determined and a dose for phase II studies is recommended. However, reviews of the phase I population indicate a younger group of participants with a median age of 50-55. No data exists on the performance of octogenarians on phase I trials. Concerns for enrollment of this patient population, relates to presence of comorbidities and possibly altered pharmacokinetics in the setting of unknown potential toxicities. We present herein the largest review of octogenarians on phase I trials. Twenty-two octogenarian patients with a median age of 83 were enrolled on phase I clinical trials. More than 50% of them were chemotherapy-naïve most likely indicative of the fact that treating physicians believed standard therapy to be potentially toxic to this population. These 22 patients were otherwise matched in terms of performance status and other parameters to a control group of participants < 80. This includes a similar number of cycles administered. Patients ≥80 had a 3 fold higher rate of achieving DLT (p=0.06) compared to the control group enrolled at the same dose level. The toxicities observed include cardiovascular, gastrointestinal and infectious complications. Three patients were enrolled on molecular targeted treatments with no significant toxicities. We conclude that enrollment of patients ≥80 on phase I trials of chemotherapy agents is most likely associated with higher risk of DLT.