Potential cost savings by dose down-rounding of monoclonal antibodies in a community cancer center.

Purpose Increasing new cancer cases and approval of effective but expensive new drugs extending survival have led to unsustainable cancer care costs. Potential cost savings by a hypothetical dose down-rounding project of monoclonal antibodies at a community-based cancer center is presented. Methods From October 2014 through October 2015, metastatic cancer patients receiving monoclonal antibodies at CHI-Health St Francis Cancer Treatment Center in Grand Island, Nebraska, were identified through electronic health records. A total of 11 different types of monoclonal antibodies that were administered during the study period were identified. Trastuzumab, ofatumumab, and obinutuzumab did not require dose-rounding; thus, they were excluded from the analyses. Available vial size(s) and costs per milligram per average wholesale price for each monoclonal antibody were recorded. Costs of actual amounts prescribed were compared to the costs of theoretically reduced ≤5% and ≤10% doses rounded to the nearest vial sizes. Reduced doses resulting in a decreased number of opened vials qualified for meaningful dose down-rounding and were included in the analysis. Average actual dose reduction percentage resulting in cost savings for both groups was also calculated. Results A total of 728 doses of eight monoclonal antibodies suitable for dose down-rounding were identified. Vial sizes of pembrolizumab and ipilimumab did not allow for a meaningful dose down-rounding. At the ≤5% dose down-rounding, 255 of 728 doses (35%) qualified with a potential annual cost savings of $220,793.80. At the ≤10% dose down-rounding, 526 of 728 doses (72%) qualified with a potential annual cost savings of $454,461.00. The average actual dose reduction was 2.4% for the ≤5% dose reduction group and 4.9% for the ≤10% dose reduction group. Overall average cost savings per qualifying dose reduction was around $865.00. More doses qualified for cost savings in the ≤10% dose reduction group. Significant differences between different monoclonal antibodies for dose rounding at either ≤5% (p = 0.002) or ≤10% (p < 0.001) were observed. Conclusion A practical dose down-rounding procedure may allow significant cost reduction in metastatic cancer setting, where the cure is not the goal. Drug waste can be avoided by convenient vial sizes or can even be eliminated by lyophilized forms like in trastuzumab. Our data reflect the monoclonal antibody use and potential cost savings with the proposed dose down-rounding approach in a community-based cancer program.

Successful treatment of severe thrombocytopenia with the use of thrombopoeitin receptor agonist eltrombopag in a patient with chronic myelomonocytic leukemia.

Chronic myelomonocytic leukemia (CMML) is a clonal disorder of hematopoietic stem cells often occurring in elderly patients. The combination of CMML with autoimmune manifestations, including immune-mediated thrombocytopenia, has been described before in a number of case reports. To our knowledge, this is the first reported case of the successful treatment of CMML-related thrombocytopenia with a thrombopoeitin receptor agonist, eltrombopag.

Normalization of Elevated Tumor Marker CA27-29 After Bilateral Lung Transplantation in a Patient With Breast Cancer and Idiopathic Pulmonary Fibrosis.

Solid tumors involving glandular organs express mucin glycoprotein that is eventually shed into the circulation. As a result, these proteins can easily be measured in the serum and be used as potential tumor markers. The most commonly used tumor markers for breast cancer are CA27-29 and CA15-3, which both measure the glycoprotein product of the mucin-1 (MUC1) gene. CA27-29 has been approved by the US Food and Drug Administration for monitoring disease activity in breast cancer patients. Most oncology clinical practice guidelines do not recommend the use of tumor markers for routine surveillance of early stage disease but recognize their utility in the metastatic setting. We present a patient with stage IIIA breast cancer and preexisting hypersensitivity pneumonitis who was found to have an elevated serum tumor marker CA27-29. After successful curative intent treatment of her early stage breast cancer, she developed gradual and progressive worsening of her lung disease with eventual development of severe pulmonary fibrosis requiring bilateral lung transplantation. As part of the pretransplant evaluation, she was found to have an elevation of serum tumor marker CA27-29. While the diagnostic evaluation, including imaging studies, was negative for the presence of recurrent disease, the serial serum tumor marker CA27-29 levels remained persistently elevated. The decision was made for her to undergo bilateral lung transplantation. Shortly after surgery, her CA27-29 tumor marker level returned to normal range, and it has continued to remain in the normal range with no evidence of breast cancer recurrence.

What Is the Optimal Dose and Schedule for Dasatinib in Chronic Myeloid Leukemia: Two Case Reports and Review of the Literature.

Efficacy and safety of dasatinib in chronic phase (CP) chronic myelogenous leukemia (CML) patients has been well established. Initially approved dose and schedule of 70 mg twice daily has been changed to 100 mg once daily after demonstration of the same efficacy with less toxicity. Some patients require significant dose reductions to enable continued treatment with dasatinib. Even at a dose of 80 mg once daily, several patients may require further dose reductions due to substantial toxicity while maintaining good control of their disease. We report two CP-CML patients achieving and maintaining major molecular responses while on very low doses of dasatinib, ultimately achieving undetectable levels of BCR-ABL fusion transcript in their peripheral blood. Observations of several CP-CML cases responding remarkably well to dasatinib despite very low dose and frequent dose interruptions challenge our current understanding and the accuracy of the data regarding the optimum dose and schedule of this drug. In selected intolerant patients, low-dose dasatinib therapy may be a safe and effective alternative treatment option before a treatment discontinuation or change considered.

Impact of the National Cancer Institute Community Cancer Centers Program on Clinical Trial and Related Activities at a Community Cancer Center in Rural Nebraska.

PURPOSE: Although 85% of patients with cancer are diagnosed and treated in the community setting, only 3% are enrolled onto clinical trials. Lack of adequate time, infrastructure, resources, incentives, and reimbursement adversely affect clinical trial participation. In July 2007, Saint Francis Cancer Treatment Center (SFCTC) in Grand Island, Nebraska, was selected as one of the initial 16 sites for the National Cancer Institute Community Cancer Centers Program (NCCCP). METHODS: Clinical trial and related activities data at SFCTC 5 years before and 5 years during the NCCCP were gathered and compared. Data included information on patients in clinical trials, number and type of trials, ratio of underserved patients, staffing, collection and storage of tissue samples, availability of new cancer services, and organizational infrastructure and linkage to National Cancer Institute-designated cancer centers. RESULTS: The number and percentage of patients enrolled onto clinical trials increased from 89 (3.2%) to 640 (23%; P<.001). All enrollees were rural Nebraskans, with 70%age > 65 years. Available treatment and nontreatment (eg, prevention, biospecimen,cancer control) trials increased from eight and three per year to 28 and 12 per year (P=.012), respectively. Staffing increased from 1.2 to 3.9 full-time equivalents (P=.012). A genetic counselor, smoking cessation counselor, and outreach project coordinator and two nurse navigators were hired. The number of tissue samples collected and/or stored increased from 26 (19%) to 320 (52%; P<.001). CONCLUSION: NCCCP participation had a direct and positive impact on all activities, with enhanced access to expanded types of trials and cancer care services. Our data demonstrate the feasibility of successful implementation of an expanded spectrum of clinical trials and programs in a rural community.

Hemophagocytic Lymphohistiocytosis: A Series of Five Clinical Cases in Adult Patients at a Single Institution with a Review of the Literature.

CONTEXT: Hemophagocytic Lymphohistiocytosis or the "Hemophagocytic Syndrome" is a spectrum of disorders of regulatory immunomodulatory pathways inciting phagocytosis of hematopoietic cells resulting in end-organ damage. The condition appears in both heritable and non-heritable forms from a multitude of possible environmental triggers, most notably infection. The condition often results in a fatal outcome without prompt diagnosis and treatment. Cases in children have been reported much more frequently and classically than in adult patients. CASE REPORT: In this case series we examined five such cases in adult patients that were found at our institution in a window as small at 2 years with more cases having presented since the time of this writing. In these cases, likely triggers were found ranging from infectious, drug-inducing and even underlying malignancy. The condition can be diagnosed by a set of laboratory and physical criteria (Hemophagocytic Lymphohistiocytosis -2004). Treatment ranges from immunosuppressive agents to chemotherapeutic approaches with variable success. CONCLUSION: Clinicians must maintain a higher index of suspicion in cases presenting with ominous symptomatology to ensure a prompt diagnosis and effective treatment of this potentially deadly condition.

Radiation Recall Pneumonitis During Systemic Treatment With Everolimus.

Radiation recall syndrome is an acute inflammatory reaction developing at anatomical sites of previously irradiated tissue, weeks to months after the completion of radiation therapy. The distribution pattern of inflammation typically involves, and remains limited to, the boundaries of prior radiation treatment fields. Several classical chemotherapy drugs have been reported to have the potential for causing radiation recall syndrome. With the increasing availability and expanding use of novel biologic and targeted therapy anticancer drugs, isolated reports of radiation recall syndrome secondary to this class of agents are starting to appear in the literature. We describe a case of everolimus-induced radiation recall pneumonitis in a patient with metastatic renal cell cancer.

Primary clear cell ductal adenocarcinoma of the pancreas: a case report and clinicopathologic literature review.

We present a very rare, interesting case of a carcinoma of the pancreas with predominantly abundant clear cell morphology. According to the WHO classification, primary clear cell carcinoma of the pancreas is classified as a rare "miscellaneous" carcinoma. The tumor was observed in the distal body and tail of the pancreas of a 74-year-old woman. The histopathology of tumor cells showed well-defined cell membranes, clear cytoplasm, and prominent cell boundaries. Immunohistochemical (IHC) staining showed positive reactions to antibodies against vimentin, cytokeratin 7 (CK-7), mucicarmine (MUC-1), periodic acid-Schiff (PAS), periodic acid-Schiff with diastase (PASD), carcinoembryonic antigen (CEA), and Carbohydrate Antigen 19-9 (CA 19-9). On the other hand, IHC staining was negative for alpha-fetoprotein (AFP), cytokeratin 20 (CK-20), HMB45, chromogranin, and synaptophysin. The patient was subsequently diagnosed with a primary solid-type pancreatic clear cell carcinoma with hepatic metastasis. Herein, we report this rare case and include a review of the current literature of this tumor.

Does an elevated serum vitamin B(12) level mask actual vitamin B(12) deficiency in myeloproliferative disorders?

Elevation of the methylmalonic acid level is a sensitive marker of vitamin B(12) deficiency. Our cross-sectional observational study of 33 patients with myeloproliferative disorders found that 9 patients, 27.27% had occult deficiency despite having normal to elevated serum vitamin B(12) levels. Early detection of vitamin B(12) deficiency by using the methylmalonic acid measurement may prevent significant neurologic and hematologic complications in patients with myeloproliferative disorders. In patients with myeloproliferative disorders, normal to high serum vitamin B(12) concentrations have often been reported. The primary objective of this study was to determine whether normal or elevated serum vitamin B(12) levels in myeloproliferative disorders might actually mask the true underlying vitamin B(12) deficiency in some patients. Thirty-three patients (12 men, 21 women; mean age, 70.55 years [range, 37-90 years]) with polycythemia vera (n = 13), essential thrombocythemia (n = 12), chronic myelogenous leukemia (n = 5), and idiopathic myelofibrosis (IMF) (n = 3) were accrued over a period of 1 year, from March 2009 to February 2010. From all of the subjects, serum vitamin B(12) level, methylmalonic acid level, a basic complete blood cell count panel, and liver and renal function tests were obtained. Normal to elevated serum vitamin B(12) levels were recorded in all the patients. However, elevated serum methylmalonic acid levels were found in 9 (27.27%) patients, with a prevalence of 2 patients with polycythemia vera, 23% in polycythemia vera, 4 patients with essential thrombocythemia, 33.3% in essential thrombocythemia, 1 patient with chronic myelogenous leukemia, 20% in chronic myelogenous leukemia, and 2 patients with idiopathic myelofibrosis, 66.7% in IMF. Our data suggest that 27.27% of the total enrolled patients had occult vitamin B(12) deficiency despite normal to elevated vitamin B(12) levels on regular serum vitamin B(12) testing.