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Studies have been conducted to identify factors that may predict North American Pharmacist Licensure Examination (NAPLEX) outcomes, but there is no proposed single or combination of predictors that can be implemented reliably in academia. We aimed to develop a NAPLEX outcomes predictive model that could be practical, measurable, and reliable.The study cohort consisted of students who graduated from 2012 to 2016 who had taken NAPLEX and whose first-attempt examination scores were available to the school of pharmacy. Students were considered to have poor performance on NAPLEX if they received an overall score of less than or equal to 82. Linear and logistic regression analysis were utilized to identify independent predictors.Seventy of 433 (16.2%) students were identified as poor performers. Independent factors that were associated with a poor outcome on NAPLEX were: age28 years at graduation, Pharmacy College Admission Test scaled score74, High Risk Drug Knowledge Assessment score90, third-year Pharmacy Curriculum Outcome Assessment scaled score349, and grades of74 in more than three courses. These predictors were utilized to stratify students into four risk groups: Low, Intermediate-1, Intermediate-2, and High. Mean NAPLEX scores for these groups were 106.4, 97.4, 87.1, and 75.1, respectively.The model can be used as a practical tool to identify students who are at risk for poor performance on NAPLEX. Four of the five predictors in the model could be generalizable to other schools of pharmacy.

To examine the available trials evaluating the effect of obesity on the pharmacokinetic parameters of chemotherapy agents.A PubMed search (January 1977-June 2013) was conducted for English-language articles evaluating obesity and its relationship to pharmacokinetic parameters of chemotherapy agents. Search terms included: chemotherapy, obesity, excess weight, overweight, neoplasm, pharmacokinetics, dosing, cancer, body mass index, toxicity, efficacy, body surface area.All articles were critically evaluated, and all pertinent information was included. Studies were included if they addressed obesity and pharmacokinetic parameters.Obesity and cancer are preeminent health care challenges in the 21st century, with obese persons being at an increased risk of cancer. Given this background, it is troubling that limited information is available for dosing chemotherapy agents in obese patients. Pharmacokinetic parameters of other drug classes have been affected by increased weight. It is important to evaluate the effect on chemotherapy agents given their narrow therapeutic window. Dose capping has been used to limit excess toxicity in obese patients at the risk of providing a less-effective regimen. Data suggest an increased dose of carboplatin, cisplatin, ifosfamide, paclitaxel, and vincristine may be needed in obese patients. The literature also suggests that no dosing alteration may be necessary for obese patients receiving topoisomerase I and II inhibitors, 5-fluorouracil, methotrexate, and docetaxel. A dose decrease might be suitable for cyclophosphamide.Some cytotoxic agents used in practice have altered pharmacokinetics in obese patients. Studies prospectively validating dose individualization for obese patients are needed.

BACKGROUND A previous study has shown that shorter bevacizumab infusions (0.5 mg/kg/min) can be safely administered without increasing the risk of infusion-related hypersensitivity reactions (HSRs). However, the risk of proteinuria and hypertension in patients receiving shorter infusions of bevacizumab is undetermined. PATIENTS AND METHODS This was a multicenter, prospective, observational study in patients receiving

Purpose The purpose of this study was to investigate if patients of nonwhite race are less likely to receive insulin therapy for treatment of poorly controlled diabetes than patients of white race. Methods A retrospective review was performed of patients with an A1C >10%. The primary objective was to determine any difference in the initiation of insulin between white and nonwhite patients. Secondary outcomes measured the impact of clinic type and provider specialty on the initiation of insulin therapy. Exclusion criteria included those patients with type 1 diabetes mellitus, those who were previously receiving insulin, and those without an outpatient clinic visit within 14 days of an A1C >10%. Results A total of 277 patients were included. Of these patients, 132 (47.7%) were white, followed by 95 (34.2%) black non-Hispanic patients and 30 (10.8%) Hispanic/Latino patients. No difference was found in receipt of insulin therapy for nonwhite patients as compared to white patients (12.5 vs 21.4, P = .117). Neither clinic type nor provider specialty impacted initiation of insulin therapy. No changes to medication regimen were made at 35% of clinic visits. Conclusions Failure to intensify diabetic medications was common in this outpatient setting. There were no disparities in the receipt of insulin therapy between white and nonwhite patients.

Objective. To examine the relationship between the Pharmacy Curriculum Outcomes Assessment (PCOA) and the North American Pharmacist Licensure Examination (NAPLEX) using a large, multi-institutional sample of student scores. Methods. A matched dataset was obtained from the National Association of Boards of Pharmacy (NABP) consisting of examination scores for the 1,460 students who completed both the PCOA and the NAPLEX between 2012 and 2015 at six schools/colleges of pharmacy (S/COPs). Bivariate correlations were estimated for total and content area scores on both examinations. Students’ total NAPLEX scores were predicted using linear regression models containing total and content area scores on PCOA and dummy variables for S/COP and year. Results. Students’ PCOA total score and NAPLEX total score were significantly and moderately correlated (r=0.54). All correlations between PCOA and NAPLEX total and content area scores were significant. and ranged from r=0.22 to 0.56. Regression results showed pharmaceutical and clinical sciences PCOA content scores were significant predictors of NAPLEX total score while basic biomedical sciences and social/behavioral/administrative sciences were not. The PCOA total and content scores accounted for 30%-33% of the variance in total NAPLEX score. Conclusion. Student PCOA and NAPLEX total and content area scores were significantly correlated, which is consistent with the findings of previous research. The somewhat modest proportion of variance in NAPLEX scores accounted for by PCOA scores illustrates the need for use of additional performance measures when evaluating student preparedness for the NAPLEX. This study provides important baseline data that can be used by S/COPs for comparison with their own student data as well as by researchers seeking to conduct additional analyses following recent changes in the PCOA and NAPLEX blueprints.

Purpose: Clinicians typically cap an obese patient’s chemotherapy regimen as a result of concern for excessive toxicity, without adequate clinical evidence. The purpose of this study was to evaluate the incidence of grade 3 or 4 myelosuppression in obese patients versus nonobese patients with capped dosing on the basis of body surface area (BSA). Methods: A retrospective chart review was conducted comparing obese patients (body mass index [BMI] 30 kg/m 2 ) with capped dosing who received capped chemotherapy doses at a BSA of 2.2 m 2 with nonobese (BMI 25 kg/m 2 ) patients with lung, colorectal, or hormone-refractory prostate cancer. Results: Forty-one obese patients with capped dosing and 244 nonobese patients were included. The obese patient group received on average significantly more cycles of chemotherapy (6 v 4 cycles) compared with the nonobese group. The overall incidence of any chemotherapy-related toxicity was 34% in the obese patient group, compared with 42% in the nonobese patient group (P .356). The incidence of grade 3 or 4 myelosuppression was lower, but not statistically significant, in obese patients with capped dosing compared with the nonobese patient group (22% v 27%; P .493). Conclusions: Overall, obese patients with capped dosing experienced a lower incidence of severe myelosuppression and tolerated more cycles of chemotherapy compared with nonobese patients. The better tolerability of chemotherapy in obese patients with capped dosing suggests that there is room to increase the dose in obese patients above the nationally recognized BSA cap of 2.0 m 2 , especially in early-stage lung or colon cancers in which the intention of treatment is curative.

This study was conducted to evaluate the effect of inadequate empiric antimicrobial therapy (IEAT) on mortality of patients with Escherichia coli or Klebsiella species bacteremia. Patients with E coli or Klebsiella species bacteremia were retrospectively analyzed to determine the effect of IEAT on 14-day mortality. IEAT of bacteremia was defined as administration of an antimicrobial agent to which the microorganism responsible for the bacteremia was resistant. IEAT was significantly associated with central venous catheter placement, Klebsiella species, and antimicrobial resistance among the 135 patients with E coli or Klebsiella species bacteremia (110 adequate, 25 inadequate). IEAT significantly increased 14-day mortality (32% vs 19%; P = .019). The increased 14-day mortality associated with IEAT was consistent among patients infected with E coli (33% vs 11%) or Klebsiella species (31% vs 15%). Independent risk factors for 14-day mortality in the multivariate analysis included Acute Physiology and Chronic Health Evaluation II (APACHE II) score (odds ratio [OR] 1.16; 95% confidence interval [CI] = 1.07-1.27), IEAT (OR 9.4; 95% CI = 1.36-65.14), and initial imipenem therapy (OR 20.66; 95% CI = 1.48-287.74). Of the 6 patients receiving empiric imipenem/cilastatin, 3 had APACHE II scores ≥ 30 (all 3 of these patients died). The 14-day mortality rate was similar for patients who received IEAT, regardless of whether their therapy was changed (32%) or not (33%). Based on these results and previous studies, greater efforts should be made to identify patients at risk for resistant pathogens before initiating antimicrobial therapy.

The use of thalidomide is limited by adverse effects of sedation, constipation, neuropathy and thromboembolism. In order to discover more potent and less toxic immunomodulators than thalidomide, its chemical structure was modified and lenalidomide was formed. Lenalidomide is approved by the US FDA for the treatment of patients with low-risk myelodysplastic syndrome (MDS) with deletion 5q cytogenetic abnormality. Two studies and a case report have evaluated lenalidomide in these MDS patients and showed significantly higher cytogenetic responses and durable red blood cell transfusion independence. Lenalidomide should be the drug of choice for patients with low and intermediate-1 risk MDS (based on the International Prognostic Scoring System) with chromosome 5q31 deletion with or without other karyotype abnormalities. Lenalidomide, in combination with dexamethasone, has been compared with dexamethasone alone in patients with relapsed or refractory multiple myeloma (MM) in two studies (MM-009 in North America and MM-010 in Europe, Israel and Australia). In these two phase III trials, lenalidomide demonstrated impressive (58-59%) response rates with dexamethasone. Lenalidomide has also been shown to overcome thalidomide resistance in MM patients. Therefore, the lenalidomide plus dexamethasone regimen provides another treatment option, in addition to first line MM treatment regimens of bortezomib, thalidomide or high-dose dexamethasone, for the treatment of relapsed or refractory MM. Lenalidomide does not produce significant sedation, constipation or neuropathy, but does lead to significant myelosuppression, unlike thalidomide. The prescribing information has a black box warning for risk of myelosuppression, deep vein thrombosis/pulmonary embolism and teratogenicity. Administration of lenalidomide is recommended at a starting dose of 10 mg/day orally for deletion 5q in MDS patients. Significant risk of myelosuppression may lead to dose reduction in the majority of these patients. Clinical trials of relapsed and refractory MM have shown that lenalidomide is clinically efficacious at a dosage of 25 mg/day when administered in combination with dexamethasone. Lenalidomide should be continued until disease progression in both MDS and MM patients.

Background: The Veterans Affairs North Texas Health Care System in Dallas, TX, provides a unique opportunity for clinical pharmacists to work as providers. Even though clinical pharmacists are actively involved in patient care, many of their efforts remain undocumented, resulting in an underestimation of the importance of their services and missed opportunities for improvements and new directions. Objective: To document and evaluate the services of a hematology/oncology clinical pharmacy in the outpatient setting. Methods: Pendragon Forms 3.2 software was used to design the documentation template. The template was designed to collect diagnoses, supportive care issues, drug-specific interventions, and prescriptions written. This template was uploaded to the personal digital assistant (PDA) for documentation. Patient-specific information was documented in a password-protected PDA. Data collected from November 1, 2002, to October 31, 2003, were retrospectively analyzed. Results: Clinical pharmacists were involved in 423 patient visits for chemotherapy follow-up or disease management. Cancer diagnoses included colorectal (n = 99), multiple myeloma (59), non–small cell lung (56), chronic lymphocytic leukemia (44), myelodysplastic syndromes (22), and chronic myelogenous leukemia (19). During the 423 patient visits, 342 supportive care issues were addressed including anemia (34%), pain management (22%), constipation/diarrhea (15%), and nausea/vomiting (8%). Major drug-specific interventions included drug addition (41%), discontinuation (23%), and adjustment (21%). Four hundred forty-five prescriptions were filled, of which 181 were new and 150 were refilled. Conclusions: This is the first study, as of July 25, 2006, to document considerable contribution of an outpatient clinical pharmacist in direct cancer patient care. Although the disease management and supportive care issues addressed here may differ based on institution and patient population, the results of our study show that clinical pharmacists have ever-growing roles in the management of these patients.

Pemetrexed is a newly approved antifolate agent for the treatment of malignant pleural mesothelioma (MPM) and metastatic non-small cell lung cancer (NSCLC). We performed a PubMed/MEDLINE database search to identify relevant literature from January 1966-April 2005. Bibliographies from identified references were searched as well, as were abstracts from the 2004 and 2005 proceedings of the American Society of Clinical Oncology. We discuss the pharmacology of pemetrexed, describing its mechanism of action and comparing it with methotrexate. The pharmacokinetics and pharmacodynamics of pemetrexed are described to provide a better understanding of the properties of this drug. Therapeutic uses are assessed, beginning with the approved indications of MPM and NSCLC. However, pemetrexed has been studied in numerous phase II trials for other types of solid malignancies, and completed trials are reviewed. Data on adverse effects and drug interactions are also provided. Finally, dosing and administration are reviewed, including appropriate premedication. Premedication, including administration of steroids and vitamin supplements, has been shown to decrease the frequency and severity of pemetrexed toxicities. Pemetrexed should be used as a standard of care for unresectable MPM and recurrent metastatic NSCLC.

Purpose. The use trends of i.v. immune globulin (IGIV) and the frequency of acute renal failure (ARF) and thrombosis at one institution were studied. Methods. A retrospective chart review on the indications and dosages of IGIV was conducted with inpatients and outpatients at a Veterans Affairs medical center between May 1, 1998, and June 30, 2003. Patients under 18 years of age were excluded from the study. Patient data were obtained through the center’s computerized patient record system and included patient demographics, comorbidities, frequency of ARF, concomitant therapies, and IGIV therapy courses. ARF was defined as an increase in serum creatinine of ≥0.5 mg/dL within 10 days from the initiation of IGIV therapy. Results. Forty-six patients were identified as receiving at least one cycle of IGIV therapy between May 1, 1998, and June 30, 2003. The three main indications for IGIV therapy were hypogammaglobulinemia, idiopathic thrombocytopenic purpura (ITP), and chronic inflammatory demyelinating polyneuropathy (CIDP). No new cases of thrombosis were found. Six patients (13%) developed ARF after IGIV administration, but none required dialysis. A greater percentage of patients with ARF were 65 years or older, had chronic renal insufficiency or diabetes mellitus, and used nephrotoxic agents, compared with patients who did not develop ARF. No association was observed between ARF and underlying primary disease. Conclusion. A retrospective review of 46 courses of IGIV therapy showed that the therapy was most often used for hematologic, neurologic, and immunologic indications, and the most common diagnoses for which it was used were hypogammaglobulinemia, ITP, and CIDP. ARF developed in 13% of patients, but no case of thrombosis was reported.

Objective: To provide a comprehensive review of the clinical pharmacology and toxicology of gefitinib, with particular attention to its use in early clinical trials. Data source: A PubMed search was conducted using the terms ZD1839, gefitinib, and epidermal growth factor receptor (EGFR). All data from this search were reviewed and other relevant papers identified. The abstracts from the annual meetings of the American Society of Clinical Oncology were also reviewed. Data extraction: The aim of the review was to be comprehensive and descriptive. The authors reviewed studies and case reports containing information deemed to be of interest. Conclusions: EGFR is expressed, overex-pressed, or disregulated in a variety of human solid tumors, resulting in an enhancement of tumor growth. Gefitinib is a selective reversible inhibitor of EGFR that has shown activity in several tumor types. As an oral agent, it is extensively metabolized in the liver through the cytochrome P450 enzyme system, particularly the isoenzyme CYP3A4. In the phase II, IDEAL 1 and 2 trials, gefitinib has shown a response rate of 8.8% -18.4% in refractory lung cancer. Clinical trials in various other nonlung cancer patients include studies of gefitinib as a monotherapy or in combination with various chemotherapy, radiation, and/or hormone therapy regimens. Skin and gastrointestinal toxi-cities are the most frequent adverse events of gefitinib. Recently, interstitial pneumonia has emerged as one of the serious adverse effects among gefitinib patients. In summary, the role of gefitinib in combination or as a monotherapy for a variety of cancers is still evolving.

Vemurafenib is the first molecularly targeted therapy to be licensed in the US and Europe for treatment of advanced melanoma. Its mechanism of action involves selective inhibition of the mutated BRAF V600E kinase that leads to reduced signalling through the aberrant mitogen-activated protein kinase (MAPK) pathway. Its efficacy is restricted to melanomas carrying the BRAF V600E mutation, which is seen in approximately 50% of all melanomas. In a randomized phase III trial, it was superior to dacarbazine in first-line treatment of advanced melanoma, with an overall response rate (ORR) of 48% (95% CI 42, 45), an estimated 6-month progression-free survival (PFS) of 5.3 versus 1.6 months (hazard ratio [HR] 0.26; 95% CI 0.20, 0.33; p < 0.001) and a statistically superior 12-month overall survival (OS) rate of 55% versus 43% (HR 0.62 [95% CI 0.49, 0.77]). Vemurafenib is generally well tolerated, but its use can be associated with development of cutaneous neoplasms such as squamous cell carcinoma (SCC) and keratoacanthoma (KA). These lesions can be excised safely without the need for withholding the drug or reducing its dose. Mechanisms of resistance to vemurafenib do not involve development of secondary mutations in the BRAF kinase domain, but may be related to BRAF V600E over-amplification, bypassing mechanisms via upregulation and overexpression of other components in the MAPK signalling cascade or activation of alternative pathways with potential to enhance cell growth, proliferation and survival. Clinical trials to test the efficacy of vemurafenib in combination with immunomodulatory agents, such as ipilimumab, and MAPK kinase (MEK) inhibitors, such as GDC-0973, in the treatment of advanced melanoma are currently underway. Also under investigation is the use of vemurafenib in other solid tumours with BRAF mutations, such as papillary thyroid cancer.

Treatment options for renal cell carcinoma (RCC) have multiplied in the past 5 years. Pazopanib is the third tyrosine kinase inhibitor (TKI) and the sixth targeted therapy that has received US FDA approval for the treatment of advanced or metastatic RCC. The primary mechanism of action of pazopanib in RCC is through its antiangiogenic properties via inhibition of the intracellular tyrosine kinase of vascular endothelial growth factor receptor and platelet-derived growth factor receptor. A placebo-controlled phase III study demonstrated that pazopanib significantly improved response rates and progression-free survival (PFS) in both treatment-naive and cytokine-pretreated patients. Among treatment-naive patients, the response rate was 32% and PFS was 11.1 months. In cytokine-pretreated patients, the response rate and PFS were 29% and 7.4 months, respectively. Common adverse effects of pazopanib include diarrhoea, hypertension and elevation of liver enzymes. Overall, the adverse effect profile of pazopanib is similar to that of other TKIs used for the treatment of RCC, but variation in the incidence and severity may exist. Pazopanib has an increased propensity to cause hepatotoxicity, which may be fatal in rare cases. Hepatic function must be monitored closely with dose interruption and/or reduction if elevation of hepatic function tests occurs. Pazopanib is administered on an empty stomach at a dose of 800 mg daily until disease progression, but dose reduction may be required in patients with baseline elevation of hepatic function tests, particularly total bilirubin. The minimum dose recommended for baseline hepatic dysfunction or toxicity is 200 mg daily. The potential for drug interactions exists for pazopanib. It is a substrate of cytochrome P450 (CYP) 3A4, P-glycoprotein and breast cancer resistance protein, and it weakly inhibits CYP3A4, CYP2C8 and CYP2D6, and potently inhibits UGT1A1 and OATP1B1. Currently, no study has directly compared pazopanib with other first- or second-line therapies in RCC. However, published clinical trials of pazopanib show similar efficacy outcomes to those of other targeted therapies. Therefore, pazopanib may be considered a first-line treatment option among other therapies including sunitinib, temsirolimus, and bevacizumab plus interferon-α. After failure of cytokine therapy, pazopanib is a treatment option as well as sorafenib or bevacizumab. No study has evaluated pazopanib treatment after failure of another targeted therapy. Future studies will further clarify the comparative efficacy of pazopanib with other agents as well as optimal sequencing with other agents. If similar efficacy is seen among the TKIs, it is likely that varying incidences of adverse effects may be analysed to tailor therapy according to the patient's individual co-morbidities and preferences.

The purpose of this study was to evaluate the incidence of acute renal failure (ARF) in patients with mild to moderate renal dysfunction, receiving renally adjusted zoledronic acid (ZA) and compare it to patients with normal baseline renal function, receiving standard-dose ZA.This was a retrospective study of patients receiving ZA for the treatment of bone metastasis due to cancer. Patients were divided into two groups: (1) normal group with baseline creatinine clearance (CrCl) of greater than 60 mL/min and standard ZA dose; (2) impaired group with baseline CrCl of 30-60 mL/min and renally adjusted ZA dose. Primary endpoint of ARF was defined as an increase in serum creatinine (SCr) of 0.5 mg/dL or 1.0 mg/dL from a baseline SCr of1.4 mg/dL or ≥ 1.4 mg/dL, respectively.In total, 1,472 evaluable doses of ZA were given to 220 patients. Of these, 184 patients were in the normal group and 36 patients in the impaired group. There were 38 patients (20.7%) who developed ARF in the normal group versus 7 patients (19.4%) in the impaired group. There was no difference in the mean time to the incidence of ARF at 6.1 months in both groups. Incidence of ARF based on CrCl (≥ 25% decline in CrCl) was similar between groups (39.1% vs. 41.7%; p = 0.78).The incidence of ARF is similar between patients in the normal group and impaired group when the ZA dose is renally adjusted.

Objective: To review the serious and common toxicities of bevacizumab and describe their incidence, risk factors, presentation, pathophysiology, and management. Data Sources: Literature for this review article was collected from PubMed, MEDLINE, and the proceedings of the American Society of Clinical Oncology (2000–November 2008). The key terms used in the search were: bevacizumab, vascular endothelial growth factor, angiogenesis inhibitors, toxicity, toxicity management, and adverse event. Study Selection And Data Extraction: Review articles, preclinical studies, and all published Phase 1–3 clinical trials were reviewed. The references listed in identified articles were examined for additional publications. Data Synthesis: The biomedical literature from 2000 to 2008 confirms that bevacizumab carries serious and potentially life-threatening toxicity risks and emphasizes the importance of early recognition, continuous monitoring, and prompt management of these toxicities. Such toxicities include hemorrhage/bleeding, wound healing complications, gastrointestinal perforation, arterial thromboembolism, congestive heart failure, hypertension, proteinuria/nephrotic syndrome, infusion-related hypersensitivity reactions, and reversible posterior leukoencephalopathy syndrome. Patients at the highest risk for these toxicities are individuals with a history of hypertension, thromboembolism, bleeding, cardiovascular disease, or preexisting proteinuria, as these conditions may be exacerbated by bevacizumab use. Additionally, particular tumor types correlate with risk for individual toxicities; for example, patients with squamous non–small-cell lung cancer or rectal cancer have a higher risk of bleeding, those with renal cell carcinoma have a higher proteinuria risk, and patients with colorectal cancer have a higher risk of gastrointestinal perforation. Further investigation is warranted to develop effective management strategies for these toxicities. Conclusions: As bevacizumab is becoming widely used in general oncology practice, it is important to understand the toxicities that can arise and to develop practice guidelines for their management.

Treatment of metastatic colorectal disease has evolved over the last decade. Two epidermal growth factor receptor (EGFR) monoclonal antibodies--cetuximab and panitumumab--have been developed in an effort to provide yet another therapeutic option. The EGFR is a transmembrane glycoprotein, expressed constitutively throughout the body and found on many epithelial tissues. The monoclonal antibodies bind to and inhibit the activation of the receptor in the body. This inhibition prevents tumor cell growth, angiogenesis, invasion, and metastasis, and induces apoptosis. Cetuximab and panitumumab exhibit nonlinear pharmacokinetics. Both monoclonal antibodies are approved for the treatment of refractory metastatic colorectal cancer. Cetuximab in combination with irinotecan has significantly better response rates and progression-free survival compared with those of cetuximab or irinotecan alone. Cetuximab and panitumumab as monotherapy have shown significantly better response rates and progression-free survival compared with best supportive care in patients refractory to irinotecan and oxaliplatin. In the Cetuximab Combined with Irinotecan in First Line Therapy for Metastatic Colorectal Cancer (CRYSTAL) trial, treatment-naive patients received cetuximab in combination with the chemotherapy regimen infusional leucovorin, fluorouracil, and irinotecan (FOLFIRI) or FOLFIRI alone; the difference in progression-free survival was statistically significant but suggested only a modest benefit over FOLFIRI alone (8.9 vs 8 mo, p=0.036). Results of a preplanned analysis of the first 231 events in the Panitumumab Advanced Colorectal Cancer Evaluation (PACCE) trial favored the control group (chemotherapy regimen with folinic acid [leucovorin], fluorouracil, and oxaliplatin [FOLFOX] plus bevacizumab) instead of the control group plus panitumumab. For clinical consideration, many trials have shown that the intensity or absence of EGFR expression is not a clinically significant predictor of outcomes. Development and intensity of a rash are suggested to be a positive predictor of outcomes in patients. The most common adverse events of EGFR monoclonal antibody therapy are rash, diarrhea, and hypomagnesemia. Other serious but not common adverse events include hypersensitivity reactions and pulmonary toxicity. The availability of EGFR monoclonal antibodies has provided another weapon in the arsenal to treat refractory metastatic colorectal cancer. They have shown safety and efficacy in combination with other chemotherapy regimens and as monotherapy; however, their use as metastatic colorectal cancer therapy needs to be further explored.

Background: Even though all immunoglobulin intravenous (IGIV) end products have high IgG concentrations, variations in manufacturing processes lead to unique product characteristics. Objective: Solvent/detergent-treated IGIV (IGIV-S/D) liquid 10% (Gammagard® or Kiovig® liquid) is one of the newer products, and this article will discuss and compare its efficacy, safety, tolerability and effect on patient care. Methods: The search terms ‘immunoglobulin,’ ‘IGIV,’ ‘IVIG,’ and ‘liquid’ were entered into PubMed/Medline and Google for the literature search in preparation of this manuscript. Additional references were screened from researched literature. Results/conclusion: Gammagard liquid 10% has shown significant activity in primary immunodeficiency and immune thrombocytopenic purpura. It is a sugar- and sodium-free product with improved safety, tolerability and convenience. Overall, Gammagard liquid is a valuable addition to available therapies that has utility in life-threatening and complicated diseases, an...

Purpose. A number of immunoglobulin intravenous (IGIV) products have been approved by the Food and Drug Administration (FDA) and are available commercially. Factors that need to be taken into consideration when selecting an appropriate IGIV product are discussed. Summary. Pathogen safety is of particular concern in IGIV products. Manufacturers of IGIV products have introduced different steps to ensure pathogen inactivation and clearance. Physical viral inactivation methods include heat and pasteurization. Chemical viral inactivation methods include acidic treatment, solvent/detergent, and caprylate. Viral removal is accomplished via precipitation, chromatography, or nanofiltration. Pathogen inactivation processes may inadvertently affect IGIV product characteristics, including composition, concentration, purity, and yield, which may, in turn, affect tolerability, efficacy, and convenience of usage. Tolerability of IGIV products is dependent on factors such as volume load, osmolarity, IgA content, and stabilizing agent. For example, sucrose, used as a stabilizing agent in some IGIV products, has been associated with an increased risk of IGIV-induced acute renal failure. The qualities of IGIV products that contribute to convenience of usage for patients and healthcare professionals include liquid formulation, longer shelf life, multiple package sizes, and shorter infusion time. Cost effectiveness of therapy is another important consideration in IGIV product selection. Contributing factors to cost effectiveness include acquisition cost, reimbursement, product preparation, storage, shelf life, and adverse event management. Conclusion. The various IGIV products differ in terms of production process, tolerability, and convenience. Pharmacists should be cognizant of these differences when ordering IGIV therapy for their patients. Additionally, overall cost-effectiveness of therapy should be an important consideration.

Abstract 4444 Background: In patients with chronic unexplained neutrophilic leukocytoses (UNL), underlying Chronic Myeloid Leukemia (CML) is a concern. In these patients, peripheral blood BCR-ABL mutation analyses using fluorescent in situ hybridization (FISH) is often performed to investigate for CML. Diagnostic yield of this test, in patients presenting UNL and especially in those with mild leukocytoses is uncertain. Objective: To establish the overall incidence BCR-ABL mutation in patients with UNL using peripheral blood FISH analyses. To determine the incidence within subgroups based on severity of leukocytoses. To explore the association between a positive test and the presenting clinical and laboratory features. Patients and Methods: We performed a retrospective chart review (2000–2010) of adult patients referred to the hematology service at the Dallas Veterans Administration Medical Center for evaluation of UNL. All patients had undergone, peripheral blood BCR-ABL mutation analyses by FISH. Neutrophilic leukocytoses were defined as a white blood count (WBC) above 11 × 109/L along with an absolute neutrophil count (ANC) greater than 7 × 109/L. It was considered unexplained, if it persisted on repeat testing and the referring physician deemed its etiology as uncertain. The primary end point was incidence of BCR-ABL positivity in patients with UNL. Incidence of BCR-ABL positivity within subgroups based on degree of WBC elevation defined as mild (11–20 × 109/L), moderate (>20–50 × 109) or severe (>50 × 109) was also calculated. Univariate and multivariate regression analyses of various laboratory and clinical features was performed to identify any confounding variables. Results: The median time from discovery of leukocytoses to the performing the test was 1545 days (n=285). 26 (9.1%) patients were found to be positive for BCR-ABL (n= 286). Majority had mild leukocytoses (n=202). The incidence increased with the severity of leukocytoses. Mild = 4/202 (2%), moderate = 9/62 (14.5%), severe = 13/22 (59.1%). On univariate analyses, a positive test was associated with presence of an elevated LDH (OR=107 CI 14.17–809.99), myeloid left shift (OR=107 CI 14.17–809.99) and hepatosplenomegaly (OR 3.87 CI 1.57–9.54). On multivariate regression, the presence of a myeloid left shift was strongly associated with a positive test (OR=67.20 CI 8.36–540.36). Myeloid left shift was seen in 3/4 (75%) of patients with a mild leukocytoses and positive test for BCR-ABL, Conclusion: In patients with UNL, peripheral blood FISH for BCR-ABL mutation should be restricted to those with moderate to severe leukocytoses. Incidence of BCR-ABL is especially low (2%) in patients with mild leukocytoses ( Disclosures: No relevant conflicts of interest to declare.

e15052 Background: In AIPC, the combination of docetaxel and prednisone has been shown to increase overall survival and progression free survival. Ketoconazole is considered in patients with AIPC t...

e15114 Background: The area under the curve (AUC) of K has been shown to be decreased by 83.4% and 95% when administered concurrently with omeprazole and ranitidine, respectively. No published stud...