Samuel C. Augustine

High-dose therapy with iodine-131-labeled monoclonal antibody CC49 in patients with gastrointestinal cancers: a phase I trial.

PURPOSE A phase I trial that evaluated for extrahematopoietic toxicity was conducted with iodine-131 (131I) labeled monoclonal antibody (MAb) CC49. Correlative studies included pharmacokinetic and biodistribution analyses, estimates of absorbed radiation dose, and measurement of human antimonoclonal antibodies (HAMA). PATIENTS AND METHODS After collection and cryopreservation of hematopoietic stem cells, 15 patients with gastrointestinal cancers were administered a tracer dose of 131I-MAb CC49. Within 5 to 6 days, 14 patients (two to three per activity level) underwent a single treatment with 131I-MAb CC49 (50, 100, 150, 200, 250, and 300 mCi/m2). Biodistribution was determined using planar and single photon emission computer tomographic (SPECT) imaging. Pharmacokinetic studies were performed by measuring radioactivity in serial blood samples. In some patients, biopsies of metastases and related normal tissues were obtained for radioactivity measurements. Radiation dosimetry estimates were calculated using available biodistribution, pharmacokinetic, and tissue biopsy data. Toxicity was evaluated using the National Cancer Institute (NCI) Common Toxicity Criteria. RESULTS No dose-limiting extrahematopoietic toxicity was identified. Twelve patients experienced grade IV myelosuppression and met criteria for infusion of hematopoietic stem cells. Radioimmunolocalization was excellent. The T1/2 for 131I-MAb CC49 after diagnostic and therapeutic administration was 39.7 +/- 10.4 and 46.1 +/- 10.6 hours, respectively. The percent injected dose per killigram of tumor ranged from 0.2 to 2.1. Absorbed radiation dose in metastatic tumor sites ranged from 630 to 3300 cGy. CONCLUSION Although extrahematopoietic dose-limiting toxicity was neither observed or predicted, suboptimal absorbed dose estimates suggested that further escalation of 131I-MAb CC49 would not be useful. Future studies should focus on the use of radionuclides with high energy beta emissions, such as yttrium 90, and on strategies to optimize access of antibody to target antigens.

Antiidiotypic Response Against Murine Monoclonal Antibodies Reactive with Tumor-Associated Antigen TAG-72

The immune response of 42 gastrointestinal and ovarian cancer patients at 1 month after exposure to murine monoclonal antibodies (B72.3 and CC49) reactive with the tumor-associated antigen TAG-72 was studied. The incidence of human anti-mouse antibody response was 89% to B72.3 and 70% to CC49. To evaluate the antiidiotypic immune response, we developed a serological assay based on affinity chromatography to remove the interference due to the presence of TAG-72, antiisotypic, and antiallotypic immunoglobulins in the serum. Seventy-eight percent of patients who received B72.3 developed an antiidiotypic response; in 33% of the patients, this was the only immune response detected. The antiidiotypic immune response after treatment with CC49 was present in 54% of the patients. Twelve percent of the patients who received CC49 developed an antiidiotypic response in the absence of antiisotypic or antiallotypic immune response. The lower immunogenicity of the variable region of CC49 is encouraging when considering the use of chimeric or humanized antibodies derived from the murine monoclonal antibody CC49 in clinical studies.

Medication therapy management training using case studies and the MirixaPro platform.

Objective. To implement and assess a medication therapy management (MTM) training program for pharmacy students using the MirixaPro (Mirixa Corporation, Reston, VA) platform and case studies. Design. Students received lectures introducing MTM and were given a demonstration of the MirixaPro platform. They were divided into teams and assigned cases and times to interview patients portrayed by faculty members. Using the MirixaPro system, students performed 2 comprehensive medication reviews during the semester, recording the patients current medications, indications, side effects, allergies, health conditions, and laboratory test recommendations and developed a personal medication record and medication action plan. Assessment. Based on a rubric with a rating scale of 0-10, campus and distance pathway students received mean scores ranging from 6.3-7.4 for their performance on the second MTM exercise, an increase of 47%-54% over the first MTM exercise. In qualitative assessments, the majority of students believed that their confidence in providing MTM was enhanced by the activity, while faculty members recognized the advantage of using MirixaPro, which allowed students to experience what is required in processing a pharmacist led, billable MTM encounter. Conclusions. Use of the MirixaPro system and patient cases provides students with a “hands-on” experience that may encourage them to promote MTM during their APPEs and provide MTM services as practicing pharmacists.

Establishing an institutional model for the administration of tositumomab and iodine I 131 tositumomab.

Radioimmunotherapy with radiolabeled anti-CD20 antibodies is a promising new treatment approach for low-grade non-Hodgkins lymphoma. However, the administration of radiolabeled antibodies presents some added complexity. At the University of Nebraska Medical Center (Omaha, NE), an institutional model has been developed that ensures the efficient and safe delivery of tositumomab and iodine I 131 tositumomab (Bexxar; Corixa Corp, South San Francisco, CA and GlaxoSmithKline, Philadelphia, PA). An integrated, multidisciplinary treatment team is responsible for managing all aspects of treatment. Using this model, it is possible to administer tositumomab and iodine I 131 tositumomab safely and effectively in the outpatient setting. Patients can usually be released immediately after treatment. Guidelines and instructions for patient release have been developed and validated and are provided herein. These instructions ensure that radiation exposure of family members and caregivers who are exposed to the patient is maintained as low as reasonably achievable and well within regulatory limits.

Exercise for low-income patients with diabetes: A continuous quality improvement project

Purpose The specific aim of this project was to form a partnership between a community health center (CHC) to improve access to exercise for low-income patients with type 2 diabetes. Methods Eligible participants were members of the Siouxland Community Health Center (SCHC), 19 years of age or older, with a diagnosis of type 2 diabetes. Patients were medically waived and received an invitation to exercise at the Siouxland YMCA. An exercise coach (pharmacist, registered nurse, or medical assistant) met with each patient and scheduled and conducted exercise visits for participating patients 2 times each week. Patients’ baseline clinical variables were taken and assessed quarterly over a 12-month period. Results This collaboration established an ongoing exercise program with a total of 1297 exercise encounters in a 12-month period. Forty-eight of 130 eligible patients (36.9%) visited theYMCA on at least 1 occasion. Patients were categorized as experimental (56.3%), involved (25%), and regular (18.8%) exercisers. Nine (18.8%) of the 48 patients attended supplementary YMCA exercise encounters. Five (11%) of the 48 patients renewed and purchased a membership at the YMCA and adopted a self-management approach to regular exercise. Conclusion The creation of a partnership between a community health center and an exercise organization permitted disadvantaged patients with diabetes an affordable exercise program and contributed to improved clinical measurements. The exercise program can be used as a model for other community health centers and health professionals who desire to improve the implementation of an exercise program for patients with diabetes.

Assessment and recommendations of compounding education in AACP member institutions.

In August 2009, the American Association of Colleges of Pharmacy (AACP) Council of Sections established a Task Force to assess the current status of compounding education at its member institutions and to provide recommendations for future direction. The Task Force conducted a survey in late June 2010 of faculty members enrolled in the AACP Pharmaceutics and Pharmacy Practice sections to gain qualitative information of the current state of compounding education. The survey results were then organized around eight curricular topics for which the Task Force members provided interpretations and recommendations. A final report was sent to the AACP Council of Sections on February 15, 2011. This publication provides the information contained in that final report to the professional community.

Brown Bag Simulations to Teach Drug Utilization Review

Objective. To teach drug utilization review (DUR) skills to pharmacy students and assess their abilities and confidence before and after training. Design. Profile reviews and online and live drug-utilization-review activities of increasing difficulty were incorporated into the first (P1), second (P2), and third (P3) years of the Pharmacy Skills Training Laboratory sequence in a doctor of pharmacy (PharmD) curriculum. Assessment. An online survey instrument was administered to gauge how comfortable students were with specific DUR skills before and after the activities. Students’ confidence in performing specific DUR skills improved after completing the activities. Conclusion. Profile reviews, as well as online and live medication reviews, gave students numerous opportunities to practice drug utilization review skills throughout the first 3 years of the pharmacy curriculum. Students’ confidence in performing specific drug utilization review skills improved after the activities. Students’ ability to perform the skills also improved as measured with the developed checklist in section V and VI of the Pharmacy Skills Laboratory sequence.

Combination therapy for non-Hodgkin's lymphoma: An opportunity for pharmaceutical care in a specialty practice

OBJECTIVE To describe the application of pharmaceutical care practices in the administration of new therapeutic radiopharmaceuticals used in the treatment of non-Hodgkins lymphoma (NHL). PRACTICE DESCRIPTION At the Antibody Labeling Facility at the University of Nebraska Medical Center, the nuclear pharmacist provides support in the formulation, preparation, and quality testing of radiopharmaceuticals. The nuclear pharmacist also provides direct patient care by assisting in the administration of radiopharmaceuticals, monitoring patients during their infusions, and counseling patients on radioimmunotherapy and radiation safety. PRACTICE INNOVATION Expanding the role of the nuclear pharmacist in treating patients with NHL using radiolabeled monoclonal antibodies (MABs). INTERVENTIONS The nuclear pharmacist provides specialized pharmaceutical care by being involved in planning patient care, administering diagnostic and therapeutic radiopharmaceuticals, performing individualized patient dose calculations, monitoring patients, and counseling patients. MAIN OUTCOME MEASURES Number of patients treated with radiolabeled MABs. RESULTS Since January 1996, 85 patients with NHL have been treated using 131I-tositumomab (Corixa, GlaxoSmithKline), an anti-B1 MAB, under various clinical research protocols requiring specialized pharmaceutical care. The nuclear pharmacist on the team provided direct patient care, assisting with the administration of diagnostic and therapeutic radiopharmaceuticals under a collaborative agreement with a nuclear medicine physician or a radiation oncologist. Other pharmaceutical care activities performed include calculating individual patient doses, obtaining medication histories, counseling patients on their therapy and on radiation safety after early release, and monitoring patients for adverse effects during medication infusion. Patients have responded favorably to nontraditional nuclear pharmacy activities. CONCLUSION The nuclear pharmacist has become an important member of the health care team that provides a new and unique therapy for patients with NHL. To date, the nuclear pharmacist, in collaboration with the nuclear medicine physician or the radiation oncologist, has successfully administered the tositumomab and 131I-tositumomab combination therapy without significant incident.

Impact of Prescription Drug Expense on Low-Income Women with Hypertension, Dyslipidemia, and Diabetes in the State of Nebraska

Objective: A survey was designed to assess the burden of acquiring medications in low-income Nebraska women. Methods: The survey was mailed to 23,000 women. Questions asked evaluated health status, prescription drug coverage, income, and impact associated with purchasing medications. Data was evaluated in aggregate and comparisons were made between those with and without prescription drug coverage. Results: 23,000 surveys were mailed and 8,044 (35.0%) were returned. About 85% of respondents made less than

Explanations and Unresolved Issues Pertaining to the Development of the Nuclear Pharmacy Compounding Guidelines

30,000 yearly and 57.9% lived in towns of less than 5,000. Fifty-six percent reported having hypertension, diabetes, dyslipidemia, or more than one of these diseases. More than half of the respondents had stopped drug therapy and 28% stopped buying some foods in order to purchase medications. Respondents with prescription drug coverage had lower levels of stress but 80% remained worried about drug cost. Conclusion: Low-income rural women who need medication for common chronic diseases are having difficulty meeting this need.