Evaluation of drug interactions in patients treated with antidepressants at a tertiary care cancer center.

OBJECTIVE: We evaluated potential drug interactions in patients treated with antidepressants at a tertiary care cancer center to determine if it affects resource utilization. METHODS: We identified a cohort of patients with continuous care at the study institution by tagging patients who received at least three prescriptions for antidepressants within a continuous 6-month period. Data collected included demographics, cancer type and comorbidities, resource utilization (hospital and emergency room visits), and potential major drug interactions. Descriptive statistics and logistic regression were utilized in the analysis. RESULTS: The study population, which included 297 patients, was 70% female and 71% Caucasian; the mean age was 53 years (SD, 12 years), with a mean follow-up period (duration of therapy) of 403 days. Overall, 145 (49%) of the patients had a drug combination that could result in a potential major drug interaction with antidepressants. There were 118 (40%) patients with a potential major drug interaction that could lead to serotonin syndrome symptoms and 59 (20%) patients with a potential major drug interaction with anticoagulants. Potential major drug interactions were associated with an increased number of hospital and ER visits (odds ratio [OR], 2.37; 95% confidence interval [CI], 1.39-4.03). This finding was consistent for the two subanalysis groups as well, serotonin syndrome-inducing drugs (OR, 2.28; 95% CI, 1.33-3.92) and anticoagulants (OR, 3.66; 95% CI, 1.85-7.22). CONCLUSION: Potential drug interactions are frequent in patients receiving antidepressants in a tertiary care cancer center and are associated with an increase in resource utilization.

Cost-effectiveness analysis of a randomized study comparing radiosurgery with radiosurgery and whole brain radiation therapy in patients with 1 to 3 brain metastases.

BACKGROUND: In this study, we compare 2 treatment options and determine cost-effectiveness and cost-utility. METHODS: We carried out a decision analysis populated with data from patients with brain metastasis in a concurrent trial randomized to either stereotactic radiosurgery (SRS) and observation or SRS and whole brain radiation therapy. Outcomes included actual life years saved (LYS), quality-adjusted life years (QALYs), and incremental cost-effectiveness ratio (ICER). Costs used were from the healthcare perspective and utilities were captured through a time-trade-off method, using 10-year, 5-year, and 1-year time horizons. One-way sensitivity analyses were carried out to determine robustness of the decision analysis model. RESULTS: Compared with SRS and whole brain radiation therapy, SRS and observation not only had a higher average cost ($74,000 vs $119,000, respectively) but also a higher average effectiveness (0.60 LYS vs 1.64 LYS, respectively) with an ICER of $44,231/LYS or $41,783/QALY (with utilities captured using a 10-year horizon). Slightly higher ICER estimates were achieved with utilities captured using the other time horizons ($43,280/QALY and $44,064/QALY, respectively). Sensitivity analysis showed that the following variables had the highest impact on the ICER: probability of no recurrence in recursive-partitioning analysis class 2 after SRS and observation; probability of being alive after SRS and observation in recursive-partitioning analysis class 2 and being treated for recurrence. CONCLUSIONS: Compared with other interventions in the $50,000 to $100,000/QALY cost-effectiveness range, the application of SRS and observation, with subsequent neurosurgical management of recurrences, is shown to be a reasonable treatment modality for brain metastases.

Evaluation of medication compliance in patients on antidepressants at an outpatient tertiary cancer center setting.

OBJECTIVE: The purpose is to evaluate antidepressant compliance in a cancer population at a tertiary cancer center and to determine if there are covariates of importance in predicting the level of compliance in the study population. METHODS: Patients who received at least three prescriptions covering parts of each month for a continuous 6-month period with at least one of the months being in 2006 from a tertiary cancer center were identified as the prevalent population of interest for this retrospective study. Data collected included demographics, cancer and co-morbid diagnoses, and compliance to antidepressant medication using medication possession ratio (MPR) by patient, medication class, and individual agents. Analysis was conducted using descriptive statistics, analysis of variance, and logistic regression (using MPR ≥ 80 as cutoff). RESULTS: The study population included 297 patients with demographics showing 69% female, 71% Caucasian, a mean age of 52.94 (SD: 12.42), and an average 403 days of follow-up. The MPR for the total study population was 0.87 with 78% of the population having an MPR of ≥ 80% and 22% having an MPR of less than 80%. While there was no significant difference in MPR by different pharmaceutical classes, there were significant differences in the MPR by specific agents (p = 0.02), with nortriptyline having the lowest MPR of 0.79 and doxepin, fluoxetine, mirtazapine, and venlafaxine all having MPR over 0.90. There was also a trend toward a difference in MPR between Caucasians versus non-Caucasians, p = 0.055. CONCLUSION: There appears to be relatively good compliance to antidepressant medications in the study population.

Impact of changes in reimbursement policies and institutional practice algorithm for utilization of erythropoietic-stimulating agents on treatment patterns and costs in anemic lymphoma patients.

PURPOSE: The objective of this study was to assess the impact of a new evidence-based institutional practice algorithm on the patterns and costs of treatment of chemotherapy-induced anemia (CIA) in lymphoma patients prescribed erythropoietic-stimulating agents (ESAs). METHODS: The study design was retrospective, with a historical control group. Patient demographic data, clinical data (including chemotherapy and hemoglobin values), and cost data were extracted from patient medical charts and institutional databases. Descriptive statistics, t tests, and chi-square analyses were conducted to evaluate the study objectives. RESULTS: The study population consisted of 154 patients, 90 patients in the pre-implementation group and 64 in the post-implementation group. Both groups had similar demographic and baseline clinical characteristics. After implementation, there was a significant decrease in the mean hemoglobin level at the time of subsequent ESA dosing from 9.59 to 8.98 g/dL (P < 0.0001). The proportion of patients who received an ESA at a hemoglobin level >10 g/dL decreased significantly from 66% to 17% (P < 0.0001). There was no significant difference in the mean hemoglobin level at week 4 of ESA therapy, which may indicate that patients were not clinically affected by the change in practice. There were also no significant differences in the number of transfusions administered associated with the treatment of CIA in the study population. CONCLUSIONS: The results of the study show an association between implementation of the new institutional practice algorithm for ESA usage in CIA and a change in ESA utilization patterns.

Accuracy of reporting current medications by cancer patients presenting to an emergency center.

BACKGROUND: Due to high coexistence of comorbidity, cancer patients take many medications and are susceptible to negative consequences of polypharmacy. To avoid adverse events during care transitions, patients need to correctly communicate their medications. The emergency center (EC) presents opportunities to assess patients' knowledge of medications and reconcile medication profiles. OBJECTIVE: The purpose was to evaluate the medication knowledge of cancer patients presenting to the EC and to identify factors associated with higher knowledge. DESIGN AND MEASUREMENTS: For the cross-sectional self-administered survey, 254 patients were enrolled and gave name, dose, frequency, route, and indication for medications. Responses were checked for accuracy against outpatient pharmacy dispensing records within or outside M. D. Anderson Cancer Center. Demographic data was obtained from medical records. For each patient, we calculated a patient medication knowledge (PMK-overall) score indicating percentage of correct responses. RESULTS: Median PMK-overall score was 80%. Patients who used a medication aid to fill out the survey were 6.5 times more likely to have a high level of medication knowledge, or PMK-overall score > or = 80%. Predictors of using a medication aid included lower education level, solid tumor, more than five medications, married, and using a medication list at home. CONCLUSIONS: Though our findings may not be generalizable to settings outside the EC, we found cancer patients to have high levels of medication knowledge. Future studies should validate the use of PMK scores to predict medication adherence and other outcomes. Patients should be encouraged to use a medication aid when presenting information to the health care system.

Neurocognition in patients with brain metastases treated with radiosurgery or radiosurgery plus whole-brain irradiation: a randomised controlled trial.

BACKGROUND: It is unclear whether the benefit of adding whole-brain radiation therapy (WBRT) to stereotactic radiosurgery (SRS) for the control of brain-tumours outweighs the potential neurocognitive risks. We proposed that the learning and memory functions of patients who undergo SRS plus WBRT are worse than those of patients who undergo SRS alone. We did a randomised controlled trial to test our prediction. METHODS: Patients with one to three newly diagnosed brain metastases were randomly assigned using a standard permutated block algorithm with random block sizes to SRS plus WBRT or SRS alone from Jan 2, 2001, to Sept 14, 2007. Patients were stratified by recursive partitioning analysis class, number of brain metastases, and radioresistant histology. The randomisation sequence was masked until assignation, at which point both clinicians and patients were made aware of the treatment allocation. The primary endpoint was neurocognitive function: objectively measured as a significant deterioration (5-point drop compared with baseline) in Hopkins Verbal Learning Test-Revised (HVLT-R) total recall at 4 months. An independent data monitoring committee monitored the trial using Bayesian statistical methods. Analysis was by intention-to-treat. This trial is registered at www.ClinicalTrials.gov, number NCT00548756. FINDINGS: After 58 patients were recruited (n=30 in the SRS alone group, n=28 in the SRS plus WBRT group), the trial was stopped by the data monitoring committee according to early stopping rules on the basis that there was a high probability (96%) that patients randomly assigned to receive SRS plus WBRT were significantly more likely to show a decline in learning and memory function (mean posterior probability of decline 52%) at 4 months than patients assigned to receive SRS alone (mean posterior probability of decline 24%). At 4 months there were four deaths (13%) in the group that received SRS alone, and eight deaths (29%) in the group that received SRS plus WBRT. 73% of patients in the SRS plus WBRT group were free from CNS recurrence at 1 year, compared with 27% of patients who received SRS alone (p=0.0003). In the SRS plus WBRT group, one case of grade 3 toxicity (seizures, motor neuropathy, depressed level of consciousness) was attributed to radiation treatment. In the group that received SRS, one case of grade 3 toxicity (aphasia) was attributed to radiation treatment. Two cases of grade 4 toxicity in the group that received SRS alone were diagnosed as radiation necrosis. INTERPRETATION: Patients treated with SRS plus WBRT were at a greater risk of a significant decline in learning and memory function by 4 months compared with the group that received SRS alone. Initial treatment with a combination of SRS and close clinical monitoring is recommended as the preferred treatment strategy to better preserve learning and memory in patients with newly diagnosed brain metastases.

Disparities in outpatient antidepressant prescribing patterns and determinants of resource utilization at a tertiary care cancer center.

Our objective was to assess the prevalence of use of different classes of antidepressants, prescribing patterns, and determinants of exposure to specific types of antidepressants and resource utilization at a comprehensive cancer center from 2001 to 2006. Data were collected from the institution's outpatient pharmacy database and cross-referenced with the institution's electronic medical record system. Data collected included demographic characteristics, cancer diagnosis, comorbidities, prescribing physician and service, type and number of antidepressant prescriptions, and resource utilization. Significant differences in the usage and prescribing patterns of the type of antidepressants were found in the analysis by gender and ethnicity, with women seeing a psychiatrist more often than men (P = 0.001) and Caucasians receiving more selective serotonin reuptake inhibitors (SSRIs) than other ethnic groups (P = 0.002). In terms of resource utilization, men had significantly more hospital admissions (P < 0.0001) and emergency room visits (P = 0.004) than women, whereas non-Caucasian ethnic groups had more emergency room visits (P < 0.0001) and clinic visits (P = 0.001) than Caucasians. Further investigation of men and non-Caucasians in the screening, evaluation, and treatment of depression is necessary to confirm disparities and evaluate their possible causes.

Continued challenges with the use of erythropoiesis-stimulating agents in patients with cancer: perspectives and issues on policy-guided health care.

Erythropoiesis-stimulating agents (ESAs) are approved as an alternative to blood transfusions for treating anemia secondary to chemotherapy in patients with cancer. Recently, ESAs have been a source of controversy and confusion in the oncology community. This began when two European trials-the Breast Cancer Erythropoietin Survival Trial (BEST) and the Advanced Head-and-Neck Cancer Treated with Radiotherapy (ENHANCE) Study-raised safety concerns about decreased overall survival and increased venous thromboembolic events. In 2004, the United States Food and Drug Administration (FDA) convened its Oncologic Drugs Advisory Committee (ODAC) to review the data and reassess the risks and benefits of ESAs in patients with cancer. On May 10, 2007, ODAC reconvened when five trials (BEST, ENHANCE, AMG-20010103, AMG-20000161, and EPO-CAN-20) showed decreased overall survival. The briefing document noted that studies demonstrating detrimental effects on survival and/or tumor outcomes used an unapproved treatment regimen designed to maintain hemoglobin levels above 12 g/dl. On May 14, 2007, just days after the ODAC reconvened, the Centers for Medicare and Medicaid Services (CMS) released a proposed decision memo for a national coverage determination (NCD) imposing restrictions on ESAs. For health care providers, aspects of the proposed NCD were markedly inconsistent with FDA-approved ESA use and generally were considered ambiguous and unclear. Over objections of several professional associations and members of Congress, on July 30, 2007, CMS posted the final NCD and declared it effective immediately. When compared with FDA-approved labeling and professional society guidelines, the NCD revealed differences in ESA initiation, dosage escalation, dosage reduction, and definition of response. These discrepancies have generated confusion among health care providers, who are struggling over whether they can feasibly provide a dual system of care-one for Medicare patients and another for non-Medicare patients-that is evidence based. With this supplement, we hope to educate health care providers on the issues and challenges associated with policy-guided health care when discrepancies exist between the policy and evidence-based practice; offer guidance on implementing the NCD; and highlight the important role of pharmacists in the process.

Prescribing patterns and purchasing costs of long-acting opioids over nine years at an academic oncology hospital.

PURPOSE: The prescribing patterns and purchasing costs of long-acting opioids over nine years at an academic oncology hospital were studied. METHODS: Data were collected for doses of transdermal fentanyl, methadone (all routes of administration), and oral sustained-release morphine and oxycodone dispensed for individual inpatient use for the month of October for each year between 1996 and 2004. The dates included in the retrieval were selected to document long-acting opioid use before and after the establishment of the palliative care and rehabilitation medicine department. For each opioid the number of milligrams dispensed daily per patient was determined and converted into a morphine-equivalent daily dose (MEDD). The average wholesale price per dosing unit of each drug during each period studied was obtained from internal databases. Costs were calculated by multiplying the number of units dispensed by the average wholesale price per unit and then normalized to 1996 U.S. dollars. The mean aggregate cost for a single MEDD in a month was determined by multiplying the mean cost per MEDD for each agent by that agent's percent contribution to the total MEDDs dispensed in that month. RESULTS: Long-acting opioid and methadone usage increased from 1996 to 2004. Between 1996 and 2004, the mean cost of a single MEDD dropped from $0.0738 to $0.0330. During the study period, the median daily cost to treat one patient dropped from $5.96 to $2.80. CONCLUSION: Long-acting opioid use increased and cost per MEDD decreased at an academic oncology hospital between 1996 and 2004. The decreased cost of purchasing opioids was attributed to the increased proportional use of methadone.

Prospective study of incidence and severity of epiphora and canalicular stenosis in patients with metastatic breast cancer receiving docetaxel.

PURPOSE: To determine the incidence and severity of epiphora and canalicular stenosis in patients receiving docetaxel weekly or every 3 weeks. PATIENTS AND METHODS: In this prospective trial, each patient underwent an ophthalmologic examination and probing and irrigation of the lacrimal drainage apparatus at baseline and every 4 to 6 weeks after initiation of docetaxel. During each visit, epiphora and canalicular stenosis were graded. Patients with epiphora were treated with tobramycin and dexamethasone drops. If epiphora worsened or if findings on probing and irrigation suggested further canalicular narrowing, silicone intubation was offered. RESULTS: Twenty-eight patients received docetaxel weekly, and 28 patients received docetaxel every 3 weeks. Eighteen patients (64%) who received weekly docetaxel developed epiphora. Epiphora was mild in seven patients, moderate in five, and severe in six. Nine patients had resolution of epiphora with tobramycin and dexamethasone administration. Nine patients had worsened canalicular stenosis; six underwent surgery. The median cumulative docetaxel dose was 496.5 mg at onset of epiphora and 889.5 mg at surgery. Eleven patients (39%) who received docetaxel every 3 weeks developed epiphora. The median cumulative docetaxel dose at onset of epiphora in this group was 420 mg. Epiphora was mild in nine patients, moderate in one, and severe in one. Nine patients had resolution of epiphora with tobramycin and dexamethasone administration. Two patients underwent surgery. CONCLUSION: Epiphora occurred in 64% of patients in the weekly group and in 39% of patients in the every-3-weeks group. Moderate or severe canalicular stenosis was seen in about one-third of patients in the weekly group and in none of the patients in the every-3-weeks group.

Clinical-use-associated decrease in susceptibility of vancomycin-resistant Enterococcus faecium to linezolid: a comparison with quinupristin-dalfopristin.

The susceptibility of 135 vancomycin-resistant Enterococcus faecium bacteremic isolates to linezolid and quinupristin-dalfopristin was determined. All were susceptible to linezolid, while 88% were susceptible to quinupristin-dalfopristin prior to the clinical use of the drugs at our hospital. More than 6 months after their clinical use, a decrease in susceptibility was noted for only linezolid at 83%. This was related in part to a single G2576U gene mutation in domain V of the 23S rRNA gene.

Impact of surveillance for vancomycin-resistant enterococci on controlling a bloodstream outbreak among patients with hematologic malignancy.

OBJECTIVE: To determine the impact of stool surveillance cultures of critically ill patients on controlling vancomycin-resistant enterococci (VRE) outbreak bacteremia. DESIGN: Stool surveillance cultures were performed on patients who had hematologic malignancy or were critically ill at the time of hospital admission to identify those colonized with VRE. Hence, contact isolation was initiated. SETTING: A tertiary-care cancer center with a high prevalence of VRE. PARTICIPANTS: All patients with hematologic malignancy who were admitted to the hospital as well as all of those admitted to the intensive care unit were eligible. RESULTS: Active stool surveillance cultures performed between 1997 and 2001 decreased the incidence density of VRE bacteremias eightfold while vancomycin use remained constant. In fiscal year (FY) 1997 and FY 1998, there were five and three VRE outbreak bacteremias, respectively. The outbreak clones were responsible for infection in 69% of those patients with VRE bacteremia. However, the stool surveillance program resulted in the complete control of VRE bacteremia by FY 1999 until the end of the study. CONCLUSION: Despite the steady use of vancomycin, the active surveillance program among high-risk patients with hematologic malignancy and those who were critically ill resulted in the complete control of VRE outbreak bacteremia at our institution.

Blockage of the lacrimal drainage apparatus as a side effect of docetaxel therapy.

BACKGROUND: The current study was conducted to report the severity and management of canalicular and nasolacrimal duct stenosis as a side effect of docetaxel therapy and to report the outcomes of surgical intervention for this condition. METHODS: The records of 148 patients with epiphora associated with docetaxel therapy who were evaluated at the Ophthalmology Service at The University of Texas M. D. Anderson Cancer Center were reviewed. The frequency of docetaxel administration, the dose intensity, the cumulative dose of docetaxel, and any concomitant chemotherapeutic agents were recorded. Each patient underwent an ophthalmologic examination and in-office probing and irrigation. The patients either were treated with topical steroids or offered a surgical procedure for canalicular stenosis- (silicone intubation, dacryocystorhinostomy [DCR] with the placement of silicone tubes, or DCR with the placement of Pyrex glass tubes), depending on the severity of the canalicular stenosis. RESULTS: Docetaxel was given weekly in 71 patients, every 2 weeks in 5 patients, and every 3 weeks in 72 patients. Thirty patients (59 eyes) who received weekly docetaxel underwent surgery to correct epiphora. Twenty-three patients (39 eyes) were treated with temporary silicone tube placement, 9 patients (13 eyes) were treated with DCR with temporary silicone tube placement, and 4 patients (7 eyes) were treated with DCR with permanent Pyrex glass tube placement. Twenty-nine of the 30 patients who underwent surgery reported improvement or total resolution of epiphora after the procedure. Ten additional patients (20 eyes) who received weekly docetaxel had complete closure of their canaliculi but elected not to undergo surgery. Of special note were two patients who received weekly docetaxel in the neoadjuvant setting and developed complete closure of the canaliculi. Of the patients who received docetaxel every 2 or 3 weeks, only 3 required a surgical intervention to correct epiphora; none required Pyrex glass tube placement. CONCLUSIONS: Canalicular and nasolacrimal duct obstruction is a common side effect of weekly docetaxel therapy and can occur even when this drug is used in the neoadjuvant setting. The results of the current study indicate that early temporary silicone intubation in symptomatic patients receiving weekly docetaxel can prevent further closure of the lacrimal drainage apparatus and obviate more involved surgical interventions and permanent Pyrex glass tube placement. Cancer 2003;98:504-7.

Clinical experience with minocycline and rifampin-impregnated central venous catheters in bone marrow transplantation recipients: efficacy and low risk of developing staphylococcal resistance.

In this retrospective evaluation of the 4-year clinical use of minocycline and rifampin-impregnated catheters in bone marrow transplantation (BMT) patients, we report low risk of development of staphylococcal resistance to the antibiotics coating the catheters and efficacy in preventing primary staphylococcal bloodstream infections.

Canalicular stenosis secondary to weekly versus every-3-weeks docetaxel in patients with metastatic breast cancer.

PURPOSE: To compare the frequency of canalicular stenosis as a side effect of weekly versus every-3-weeks docetaxel in patients with metastatic breast cancer. DESIGN: Retrospective nonrandomized comparative trial. PATIENTS AND METHODS: Eighteen patients enrolled in a phase II study of weekly docetaxel plus trastuzumab and 18 patients enrolled in a phase II study of every-3-weeks docetaxel plus doxorubicin were evaluated. Each patient underwent a comprehensive ophthalmologic examination, probing and irrigation of the nasolacrimal duct, and, in some instances, a nuclear lacrimal scan. MAIN OUTCOME MEASURES: If epiphora (excessive tearing) was reported by the patient, its time of onset was documented. In patients with epiphora, presence or absence of canalicular stenosis was evaluated on the basis of the findings on probing and irrigation. The duration of treatment with docetaxel, the dose frequency, and the cumulative dose of docetaxel were recorded in each case. RESULTS: Fourteen patients (77%) receiving weekly docetaxel plus trastuzumab had epiphora. Nine of these patients had significant anatomic narrowing of the canaliculi. Bicanalicular silicone intubation or dacryocystorhinostomy was recommended in all nine patients. Eight patients underwent surgery and experienced complete or near complete resolution of epiphora. Although two patients (11%) receiving every-3-weeks docetaxel plus doxorubicin reported transient symptoms of epiphora, neither patient was found to have narrowing of the canaliculi, and the epiphora was not severe enough to justify surgical intervention. The mean duration of docetaxel therapy for the patients in this study was 19 weeks. The mean cumulative dose of docetaxel was higher in patients with canalicular stenosis than in patients without this side effect. CONCLUSIONS: Canalicular stenosis was more common in patients receiving weekly docetaxel than in those receiving every-3-weeks docetaxel for metastatic breast cancer. Bicanalicular silicone intubation early in the course of weekly docetaxel therapy should be considered, because this intervention can prevent complete closure of the canaliculi. Once complete or near complete stenosis of the canaliculi occurs, placement of a permanent Pyrex glass tube may become necessary to overcome the blockage of tear outflow.

Pharmacoeconomics in oncology.

Healthcare costs in the USA continue to rise faster than the consumer price index. Nothing demonstrates this more vividly than the double-digit increases posted for the cost of the drug treatment of the oncology patient. A factor that will compound this cost is the expansion in the oncology patient population that will occur as the population ages. Pharmacoeconomics is a discipline that evaluates the relationship between clinical, economic and humanistic outcomes to determine the products and services that maximize the value for each dollar spent. Research in this area is evolving to meet the needs of the individual patient and decision-makers within a payer group, healthcare system, or society. Healthcare interests in countries in Europe, Canada and Australia have already adopted analytical tools and incorporated them into guidelines for drug use. The USA is also moving in this direction now that the Food and Drug Administration is considering requiring studies in pharmacoeconomics in addition to the standard studies of the safety and efficacy of drugs. The importance of this approach to oncology will be seen as policy-makers apply research findings to practice decisions.