BACKGROUND It has been demonstrated that the humanized clivatuzumab tetraxetan (hPAM4) antibody targets pancreatic ductal carcinoma selectively. After a trial of radioimmunotherapy that determined the maximum tolerated dose of single-dose yttrium-90-labeled hPAM4 (90Y-hPAM4) and produced objective responses in patients with advanced pancreatic ductal carcinoma, the authors studied fractionated radioimmunotherapy combined with low-dose gemcitabine in this disease. METHODS Thirty-eight previously untreated patients (33 patients with stage IV disease and 5 patients with stage III disease) received gemcitabine 200 mg/m2 weekly for 4 weeks with 90Y-hPAM4 given weekly in Weeks 2, 3, and 4 (cycle 1), and the same cycle was repeated in 13 patients (cycles 2–4). In the first part of the study, 19 patients received escalating weekly 90Y doses of 6.5 mCi/m2, 9.0 mCi/m2, 12.0 mCi/m2, and 15.0 mCi/m2. In the second portion, 19 additional patients received weekly doses of 9.0 mCi/m2 or 12.0 mCi/m2. RESULTS Grade 3/4 thrombocytopenia or neutropenia (according to version 3.0 of the National Cancer Institute’s Common Terminology Criteria for Adverse Events) developed in 28 of 38 patients after cycle 1 and in all retreated patients; no grade >3 nonhematologic toxicities occurred. Fractionated dosing of cycle 1 allowed almost twice the radiation dose compared with single-dose radioimmunotherapy. The maximum tolerated dose of 90Y-hPAM4 was 12.0 mCi/m2 weekly for 3 weeks for cycle 1, with ≤9.0 mCi/m2 weekly for 3 weeks for subsequent cycles, and that dose will be used in future trials. Six patients (16%) had partial responses according to computed tomography-based Response Evaluation Criteria in Solid Tumors, and 16 patients (42%) had stabilization as their best response (58% disease control). The median overall survival was 7.7 months for all 38 patients, including 11.8 months for those who received repeated cycles (46% [6 of 13 patients] ≥1 year), with improved efficacy at the higher radioimmunotherapy doses. CONCLUSIONS Fractionated radioimmunotherapy with 90Y-hPAM4 and low-dose gemcitabine demonstrated promising therapeutic activity and manageable myelosuppression in patients with advanced pancreatic ductal carcinoma.
Blood volume studies using the indicator dilution technique and radioactive tracers have been performed in nuclear medicine departments for over 50 y. A nuclear medicine study is the gold standard for blood volume measurement, but the classic dualisotope blood volume study is time-consuming and can be prone to technical errors. Moreover, a lack of normal values and a rubric for interpretation made volume status measurement of limited interest to most clinicians other than some hematologists. A new semiautomated system for blood volume analysis is now available and provides highly accurate results for blood volume analysis within only 90 min. The availability of rapid, accurate blood volume analysis has brought about a surge of clinical interest in using blood volume data for clinical management. Blood volume analysis, long a low-volume nuclear medicine study all but abandoned in some laboratories, is poised to enter the clinical mainstream. This article will first present the fundamental principles of fluid balance and the clinical means of volume status assessment. We will then review the indicator dilution technique and how it is used in nuclear medicine blood volume studies. We will present an overview of the new semiautomated blood volume analysis technique, showing how the study is done, how it works, what results are provided, and how those results are interpreted. Finally, we will look at some of the emerging areas in which data from blood volume analysis can improve patient care. The reader will gain an understanding of the principles underlying blood volume assessment, know how current nuclear medicine blood volume analysis studies are performed, and appreciate their potential clinical impact.
Clinical studies of (90)Y-clivatuzumab tetraxetan combined with low-dose gemcitabine appear feasible in metastatic pancreatic cancer patients beyond 2nd line and a Phase III trial of this combination is now underway in this setting.
As hospital nuclear medicine departments were established in the 1960s and 1970s, each department developed detailed policies and procedures to meet the specialized and specific handling requirements of radiopharmaceuticals. In many health systems, radiopharmaceuticals are still unique as the only drugs not under the control of the health system pharmacy; however, the clear trend-and now an accreditation requirement-is to merge radiopharmaceutical management with the overall health system medication management system. Accomplishing this can be a challenge for both nuclear medicine and pharmacy because each lacks knowledge of the specifics and needs of the other field. In this paper we will first describe medication management standards, what they cover, and how they are enforced. We will describe how we created a nuclear medicine and pharmacy team to achieve compliance, and we will present the results of their work. We will examine several specific issues raised by incorporating radiopharmaceuticals in the medication management process and describe how our team addressed those issues. Finally, we will look at how the medication management process helps ensure ongoing quality and safety to patients through multiple periodic reviews. The reader will gain an understanding of medication management standards and how they apply to nuclear medicine, learn how a nuclear medicine and pharmacy team can effectively merge nuclear medicine and pharmacy processes, and gain the ability to achieve compliance at the reader's own institution. Modernnucl ear medicine was born about 50 y ago with patenting of the Anger scintillation camera (1961) and introduction of 99m Tc as an ideal medical tracer (1960) (1,2). Most of the growth in nuclear medicine over the last half century has been the direct result of the introduction of new radiopharmaceuticals. Many of these agents (hepatobiliary agents, bone tracers, sestamibi, macroaggregated albumin, 18 F-FDG, and others) were revolutionary advances in functional imaging, leading to clinical use of multiple radiopharmaceuticals in most nuclear medicine departments. Many nuclear medicine procedures also use a variety of nonradioactive drugs (pharmacologic stress agents, cholecystokinin analog, furosemide, and others). As a result, most health system nuclear medicine departments today routinely dispense dozens of different radiopharmaceuticals and other medications (Fig. 1).Historically, radiopharmaceuticals have been managed separately from other medications in many health systems. Because of their radioactivity, radiopharmaceuticals require special handling within the medication use process and their own special procedures and safeguards to ensure safe and effective use. As nuclear medicine departments were established and evolved, many developed their own radiopharmaceutical policies and procedures intended to avoid improper administration and ensure safe use. Concurrently, many health system pharmacy departments, working hard to meet increasingly rigorous and expanding standards, have ...
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.