Abstract
Radiopharmaceuticals, meaning drugs that hold a radionuclide intended for use in cancer patients for treatment of their disease or for palliation of their disease-related symptoms, have gained new interest for clinical development in adult patients with relapsed or refractory leukemia. About one-third of adult patients outlive their leukemia, with the remainder unable to attain complete remission status following the first phase of treatment due to refractory bone marrow or blood residual microscopic disease. The National Cancer Institute (NCI) Cancer Therapy Evaluation Program conducted 49 phase 1-1b trials in adult patients with leukemia between 1986 and 2017 in an effort to discover tolerated and effective therapeutic drug combinations intended to improve remission and mortality rates. None of these trials involved radiopharmaceuticals. In this article, the NCI perspective on the challenges encountered in and on the future potential of radiopharmaceuticals alone or in combination for adult patients with relapsed or refractory leukemia is discussed. An effort is underway already to build-up the NCI's clinical trial enterprise infrastructure for radiopharmaceutical clinical development.
Highlights
In 2018, adult leukemias collectively forecast as the eighth most common any-type cancer in Americans [1]
Biospecimens are fully releasable for shipment without radioactive labeling when conditions under 48 CFR 52.223–7 are met (≤ 0.002 microcuries per gram, www.govinfo.gov). This perspective article examines the scope of radiopharmaceutical clinical development as related to use in adult leukemias; the evaluation of radionuclide and ligand toxicities as related to targeted radiopharmaceuticals; and guidance on the acquisition, handling, processing, and shipment of biomarker samples after radiopharmaceutical administration
The current National Cancer Institute (NCI) position does not address radiopharmaceuticals that might be considered for leukemia treatment that are intended for a local route of administration
Summary
In 2018, adult leukemias collectively forecast as the eighth most common any-type cancer in Americans [1]. A desire to meet therapeutic needs of adult patients with relapsed or refractory leukemias has incentivized one phase of NCI’s radiopharmaceutical clinical development plan. The second NCI phase 1b trial enrolled 25 adult patients with relapsed or refractory leukemia for treatment by cytarabine (1,000 mg m−2) on days 1–5 in combination with dose-escalated triapine (50–100 mg m−2) on days 2–5, repeated on a 28-day cycle [18]. The NCI is interested in fatigue as a patient-reported outcome [30], and, it might possibly be listed as a special interest dose-limiting toxicity in its future radiopharmaceutical trials, because of the complex relationship of nucleoside demand-supply responses among normal cells and skeletal muscle is presumably unknown. Biospecimens are fully releasable for shipment without radioactive labeling when conditions under 48 CFR 52.223–7 are met (≤ 0.002 microcuries per gram, www.govinfo.gov)
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
