Assessment of a Mindfulness Meditation Elective in an Accelerated Doctor of Pharmacy Program.

Objective. The objective of this study was to determine the effect of a live 14-week mindfulness elective course on the well-being of Doctor of Pharmacy (PharmD) students in an accelerated program.Methods. Pharmacy students enrolled in a mindfulness elective participated in weekly class sessions that included an eight-week mindfulness program geared toward emerging adults. Eight weekly reflections were assigned to students and evaluated using the Text iQ text-analysis tool in Qualtrics. Investigators analyzed the sentiment scores assigned by Text iQ to detect differences in the tone of student reflections over time.Results. Twenty-four students were enrolled in this elective, and 22 students submitted complete reflections for evaluation. Mean sentiment scores and the percentage of responses in sentiment score categories (very positive and positive, mixed and neutral, very negative and negative) for these reflections showed significant differences between weeks.Conclusion. The tone of student reflections was more positive after the students learned and incorporated mindfulness practice into their accelerated PharmD curriculum.

Exploring the effects of a smartphone-based meditation app on stress, mindfulness, well-being, and resilience in pharmacy students.

PURPOSE: The purpose of this study was to investigate the effects of the smartphone-based meditation app Ten Percent Happier on stress, mindfulness, well-being, and resilience in pharmacy students. METHODS: Pharmacy students in a professional year of study were recruited to participate. Students were instructed to meditate using the Ten Percent Happier app for at least 5 days a week for 4 weeks. Students could use the app at their discretion for weeks 5 to 12. Baseline, week 4, and week 12 responses were collected from the following instruments: the Perceived Stress Scale, the Five-Facet Mindfulness Questionnaire-15, the Flourishing Scale, and the Brief Resilience Scale. RESULTS: Eighty-nine pharmacy students volunteered for the study. Sixty (67%) enrolled by completing the baseline survey. Of these, 28 (47%) completed the week 4 survey and 22 (37%) completed the week 12 survey. Participants experienced a reduction in perceived stress (P = 0.0005) and increases in resilience (P < 0.0001) and well-being (P = 0.0006). Increases in mindfulness were seen in 4 of the 5 subscales of the Five-Facet Mindfulness Questionnaire-15 (P ≤ 0.05). These benefits were noted at week 4 and maintained at week 12. CONCLUSION: Pharmacy students who practiced mindful meditation through the Ten Percent Happier app for an average of 5 days a week for 4 weeks experienced reduced stress and improved mindfulness, well-being, and resilience. Benefits experienced during the intervention were maintained at the 8-week follow-up, despite app usage decreasing to an average of 4 days a week.

Role of Immune Checkpoint Inhibitors in Small Cell Lung Cancer.

BACKGROUND: Small cell lung cancer (SCLC) accounts for approximately 13% of all lung cancer diagnoses each year. SCLC is characterized by a rapid doubling time, early metastatic spread, and an unfavorable prognosis overall. AREAS OF UNCERTAINTY: Most patients with SCLC will respond to initial treatment; however, the majority will experience a disease recurrence and response to second-line therapies is poor. Immune checkpoint inhibitors may be an option given the success in other diseases. DATA SOURCES: A literature search was conducted using Medline (1946-July week 1, 2017) and Embase (1996-2017 week 28) with the search terms small cell lung cancer combined with nivolumab or ipilimumab or pembrolizumab or atezolizumab or tremelimumab or durvalumab. Five clinical trials, including extended follow-up for 2, that evaluated immune checkpoint inhibitors in limited stage or extensive stage SCLC were included. RESULTS: In 2 phase 2 trials, ipilimumab was added to upfront chemotherapy. In both trials, an improvement in progression-free survival was seen. Toxicity, when combined with a platinum and etoposide, was significant. In a confirmatory phase 3 trial, ipilimumab did not prolong overall survival when added to first-line chemotherapy. Overall, response rates were similar between the placebo and ipilimumab groups. A phase 1/2 trial evaluated nivolumab alone or in combination with ipilimumab in recurrent SCLC. Results revealed that nivolumab monotherapy and the combination of nivolumab and ipilimumab were relatively safe and had antitumor activity. Pembrolizumab has been evaluated in a multicohort, phase 1b trial. Preliminary data showed a durable response in the second-line setting. CONCLUSION: Given the lack of overall survival data and significant toxicity associated with the combination of ipilimumab with first-line chemotherapy, this treatment is not a reasonable option at this time. Nivolumab alone or in combination with ipilimumab is a valid option for recurrent SCLC.

Profile of ramucirumab in the treatment of metastatic non-small-cell lung cancer.

The interaction between vascular endothelial growth factor and its receptor is an important therapeutic target due to the importance of this pathway in carcinogenesis. In particular, this pathway promotes and regulates angiogenesis as well as increases endothelial cell proliferation, permeability, and survival. Ramucirumab is a fully human monoclonal antibody that specifically targets the vascular endothelial growth factor receptor-2, the key receptor implicated in angiogenesis. Currently, ramucirumab is approved for the second-line treatment of metastatic non-small-cell lung cancer (NSCLC) in combination with docetaxel. In a Phase III clinical trial, ramucirumab was shown to improve the overall survival in patients with disease progression, despite platinum-based chemotherapy for advanced NSCLC. This review describes the pharmacology, pharmacokinetics and dynamics, adverse event profile, and the clinical activity of ramucirumab observed in Phase II and III trials in NSCLC.

Ceritinib: a new tyrosine kinase inhibitor for non-small-cell lung cancer.

OBJECTIVE: To review ceritinib for the treatment of anaplastic lymphoma kinase (ALK)-positive metastatic non-small-cell lung cancer (NSCLC). DATA SOURCES: Literature searches were conducted in PubMed, EMBASE (1974 to July week 5, 2014), and Google Scholar using the terms ceritinib, LDK378, and non-small-cell lung cancer. STUDY SELECTION AND DATA EXTRACTION: One phase 1 trial and 2 abstracts were identified. DATA SYNTHESIS: Ceritinib is approved for the treatment of ALK-positive metastatic NSCLC in patients who are intolerant to or have progressed despite therapy with crizotinib. In the phase 1 clinical trial, the maximum tolerated dose was determined to be 750 mg once daily. The overall response rate (ORR) was 58% (95% CI = 48-67) in patients who received ≥400 mg daily (n = 114). In this group, the ORR was 56% (95% CI = 41-67) and 62% (95% CI = 44-78) among crizotinib-exposed and -naïve patients, respectively. The ORR was 59% (95% CI = 47-70) in patients who received 750 mg daily (n = 78). The ORR was 56% (95% CI = 41-70) in crizotinib-treated patients and 64% (95% CI = 44-81) in crizotinib-naïve patients, respectively, in this subset. The median duration of response was 8.2 months. Median progression-free survival was 7.0 months. The most common adverse reactions included diarrhea, nausea, vomiting, abdominal pain, anorexia, constipation, fatigue, and elevated transaminases. CONCLUSIONS: Ceritinib has activity in crizotinib-resistant and crizotinib-naïve patients and appears to be a viable alternative for ALK-positive NSCLC. Long-term data are needed to further define the role of ceritinib in the treatment of NSCLC.

Ado-trastuzumab emtansine for the treatment of human epidermal growth factor receptor 2-positive metastatic breast cancer.

PURPOSE: An update on completed and ongoing clinical trials of ado-trastuzumab emtansine for the treatment of metastatic breast cancer (MBC) is presented. SUMMARY: Ado-trastuzumab emtansine (Kadcyla, Genentech), the first U.S.-approved antibody-drug conjugate for MBC, is indicated for use as a single-agent therapy in patients with human epidermal growth factor receptor 2 (HER2)-positive MBC who have received prior treatment with unconjugated trastuzumab and a taxane-based regimen. The standard dosage of ado-trastuzumab is 3.6 mg/kg i.v. every three weeks. In completed Phase II or III clinical trials, ado-trastuzumab was found to confer significant survival and quality-of-life benefits. The largest of those trials (the EMILIA study, n = 991) showed that ado-trastuzumab was superior to a regimen of lapatinib plus capecitabine in terms of progression-free survival (9.6 months versus 6.4 months, p < 0.001) and overall survival (30.9 months versus 25.1 months, p < 0.001); it also had a more favorable tolerability profile, with lower rates of treatment-limiting adverse effects. The most common adverse effects of ado-trastuzumab are thrombocytopenia (reported in about 12% of clinical trial participants overall) and increased transaminase levels. Two ongoing Phase III trials-the TH3RESA study (slated for completion in June 2015) and the MARIANNE study (estimated completion in 2016)-may help determine the optimal role of ado-trastuzumab relative to other HER2-targeted agents and its potential use as a front-line therapy for both heavily pretreated and treatment-naive patients with MBC. CONCLUSION: With a novel targeted mechanism of action, ado-trastuzumab is an effective treatment option for HER2-positive MBC in previously treated patient populations.

Vandetanib for the treatment of medullary thyroid carcinoma.

OBJECTIVE: To review the place in therapy of vandetanib for medullary thyroid carcinoma (MTC). DATA SOURCES: Literature searches were performed in Ovid MEDLINE, EMBASE, and Google Scholar using the search terms ZD6474 OR vandetanib OR Caprelsa combined with medullary thyroid carcinoma. STUDY SELECTION AND DATA EXTRACTION: Two phase 2 trials and 1 phase 3 trial were identified. DATA SYNTHESIS: Vandetanib is approved for the treatment of unresectable, locally advanced or metastatic MTC in patients with symptomatic or progressive disease. In the phase 3 randomized, double-blind, placebo-controlled trial, vandetanib 300 mg daily (n = 231) was compared with placebo (n = 100). Vandetanib-treated patients experienced a significant improvement in progression-free survival (PFS; hazard ratio [HR] = 0.46; 95% CI = 0.31-0.69; P < .001). No difference in overall survival (OS) was seen at the time of publication. Most adverse effects were grade 1 or 2 and managed by dose interruptions or reductions. The most common grade 3/4 adverse effects were diarrhea, hypertension, QT prolongation, fatigue, and rash. Because of the potential for QT prolongation, torsades de pointes, and sudden death, vandetanib is restricted via a Risk Evaluations and Mitigation Strategy program. CONCLUSIONS: Vandetanib prolongs PFS but has not been shown to improve OS. Vandetanib can be considered for patients with unresectable locoregional disease. It is a first-line option for patients with unresectable symptomatic distant metastases as well as an option for advanced disseminated symptomatic metastatic disease. Vandetanib is expected to be an important addition to the formulary of health plans that provide prescription drug benefits.

Dosing of enoxaparin for venous thromboembolism prophylaxis in obese patients.

OBJECTIVE: To evaluate the appropriate dosing of enoxaparin as a venous thromboembolism (VTE) prophylaxis in hospitalized obese patients. DATA SOURCES: Literature articles were accessed through MEDLINE (1946 to August week 1, 2013) and EMBASE (1980 to 2013 week 33) searches using the terms enoxaparin, obesity, and thromboprophylaxis. STUDY SELECTION AND DATA EXTRACTION: All articles that involved human subjects and were published in the English language, evaluating the appropriate dose of enoxaparin for VTE prophylaxis in hospitalized, obese patients were included. DATA SYNTHESIS: Appropriate enoxaparin dosing for thromboprophylaxis in adult patients is 40 mg subcutaneously daily or 30 mg subcutaneously twice daily. Although obesity is considered one of the risk factors for thromboembolism, morbidly obese patients were excluded from most clinical trials; therefore, the appropriate enoxaparin preventive dose is not clear in this population. In recent years, the appropriate dose of enoxaparin for VTE prophylaxis in obese patients has been evaluated in 3 clinical studies. All studies enrolled patients with various risk factors for thromboembolism and evaluated different enoxaparin dosing regimens. End point analyses were all based on anti-Xa levels. CONCLUSIONS: Due to a lack of well-designed prospective, randomized control studies, varying doses of enoxaparin are used for VTE prophylaxis in hospitalized, obese patients. All doses studied were monitored using anti-Xa levels. Patient follow-up was of short duration in all studies and did not show long-term effectiveness of enoxaparin. Prospective, randomized controlled studies are warranted to show efficacy and safety of one dosage regimen over another.

Reversible ageusia associated with romidepsin therapy.

PURPOSE: The case of a patient who reported the complete loss of his sense of taste after about 3.5 months of romidepsin therapy is presented. SUMMARY: A man with a 12-year history of treatment-refractory cutaneous T-cell lymphoma (CTCL) developed taste disturbances progressing to ageusia (the absence of taste perception) while receiving romidepsin therapy. He reported a metallic taste during the first round of romidepsin therapy (14 mg/m² given as a four-hour infusion on days 1, 8, and 15 of each four-week cycle); during the ninth infusion, he reported the complete loss of taste sensations. The patient chose to continue romidepsin therapy because of a favorable overall response but requested a reduced frequency of infusions due to unabated ageusia. After implementation of a revised administration schedule (infusions only on days 1 and 8 of each cycle), the man gradually regained his sense of taste, with complete reversal of ageusia once romidepsin use was discontinued after two more cycles. The application of the algorithm of Naranjo et al. to this case yielded a score of 6, indicating a probable association between the taste disturbances and romidepsin use. A literature search identified no other reports of romidepsin-associated ageusia. CONCLUSION: A 67-year-old man reported ageusia during the third cycle of romidepsin therapy for CTCL. Taste sensation began to slowly recover following a reduction in the frequency of romidepsin administration, but therapy was ultimately discontinued partly due to the impact of this adverse reaction on the patient's quality of life.

The role of denosumab for prevention of skeletal-related complications in multiple myeloma.

OBJECTIVE: To evaluate the use of denosumab for the prevention of skeletal-related events (SREs) in patients with osteolytic lesions associated with multiple myeloma (MM). DATA SOURCES: MEDLINE/Ovid (1946-April week 3, 2013), EMBASE (1980-2013 week 16), abstracts of the American Society of Clinical Oncology (1983-April 22, 2013), American Society of Hematology (2004-April 22, 2013), European Hematology Association (1994-April 22, 2013), and the European Society for Medical Oncology (1990-April 22, 2013) were searched using the terms denosumab and multiple myeloma. STUDY SELECTION AND DATA EXTRACTION: Clinical trials comparing the efficacy of denosumab with that of bisphosphonates in preventing or delaying SREs in patients with MM were included. Trials solely evaluating bone turnover markers were excluded. One Phase 2 trial, 1 Phase 3 trial, and 1 post hoc Phase 3 analysis were included. DATA SYNTHESIS: A Phase 2 trial compared denosumab to bisphosphonate continuation in patients with elevated urinary N-telopeptide levels (uNTX) despite bisphosphonate therapy. Denosumab patients experienced fewer SREs; however, this was not statistically significant. A Phase 3 trial compared denosumab to zoledronic acid in patients with at least 1 osteolytic lesion. Denosumab delayed the time to a first SRE by 16% (median 20.6 vs 16.3 months; p = 0.0007 for noninferiority). Superiority of denosumab was not reached. A post hoc analysis revealed less favorable survival in MM patients treated with denosumab (HR 2.26; 95% CI 1.13-4.50). The incidence of overall adverse effects was similar between each group in both studies. CONCLUSIONS: Denosumab may be an alternative for the prevention of SREs in patients with MM with deteriorating renal function. Because of the high cost of the drug, low percentage of MM patients in the available studies, and the potential for their decreased survival, use of denosumab should be limited.

Single-agent, broad-spectrum fluoroquinolones for the outpatient treatment of low-risk febrile neutropenia.

OBJECTIVE: To evaluate the use of oral, single-agent, broad-spectrum fluoroquinolones in the treatment of low-risk febrile neutropenia (FN). DATA SOURCES: MEDLINE via Ovid (1948 to May, week 3, 2011) and EMBASE (1980 to 2011, week 21) were searched using the terms febrile neutropenia, fluoroquinolone, quinolone derivative, levofloxacin, moxifloxacin, and neoplasm. References of selected articles, review articles, and treatment guidelines were reviewed. STUDY SELECTION AND DATA EXTRACTION: Trials evaluating the efficacy of oral, single-agent, broad-spectrum fluoroquinolones in the treatment of chemotherapy-induced FN were included if the majority of patients in the study had low-risk FN. Trials involving pediatric patients, non-Food and Drug Administration-approved fluoroquinolones, or monotherapy with ciprofloxacin or ofloxacin were excluded. Data extracted included study design, patient demographics, antiinfective regimens, and treatment outcomes. DATA SYNTHESIS: Four clinical trials were included. One trial compared levofloxacin with piperacillin/tazobactam with a success rate (afebrile at 72 hours) of 76.5% in the levofloxacin group compared with 88.3% in the piperacillin/tazobactam group. This trial was not limited to low-risk patients. The remaining 3 trials investigated moxifloxacin monotherapy in low-risk patients. Two of these were noncontrolled trials with success rates (afebrile at 5 days) of 91% and 95%. The final trial randomized patients to moxifloxacin or ceftriaxone and had success rates (hospital discharge at 48 hours) of 79.2% and 73.9%, respectively. In all 4 trials, treatment of FN with levofloxacin or moxifloxacin was deemed to be safe and effective. Although all studies had positive results, they were limited by small sample sizes and the absence of universal use of control comparisons. CONCLUSIONS: Use of oral, single-agent, broad-spectrum fluoroquinolones for outpatient treatment of FN in low-risk patients has shown promising results. At this time, this type of therapy should be limited to low-risk patients. Future clinical trials should include larger sample sizes and a comparison with existing first-line oral therapy-oral ciprofloxacin plus amoxicillin/clavulanate.

Efficacy and safety of modafinil in the treatment of cancer-related fatigue.

OBJECTIVE: To review the efficacy and safety of modafinil in the treatment of cancer-related fatigue (CRF). DATA SOUCES: Literature was accessed via MEDLINE (1950-week 3, November 2008), International Pharmaceutical Abstracts, and Google Scholar using the terms modafinil, cancer, and fatigue. Reference citations from articles identified were reviewed. STUDY SELECTION AND DATA EXTRACTION: All English-language publications identified were analyzed for significance. Studies relevant to the objective were used, including 2 prospective open-label studies, one randomized double-blind, dose-controlled trial with an open-label extension, and one Phase 3 randomized, placebo-controlled, double-blind trial. DATA SYNTHESIS: Fatigue is a nearly universal adverse effect of cancer and its treatment that is unrelated to physical exertion, is not relieved by sleep or rest, and negatively affects quality of life. Modafinil is a central nervous system stimulant with minimal toxicity and a low propensity for abuse. Clinical data demonstrate that modafinil significantly reduces fatigue in patients who have received cancer treatment or are currently undergoing chemotherapy. Additional benefits include improvement in cognitive function, mood, general activity, walking ability, normal work ability, relations with other people, and enjoyment of life. Limitations of the available data include open-label design in 3 of the 4 studies; the absence of numerical results of fatigue assessments in the abstract of 1 trial, preventing the determination of clinical significance; and the full inclusion/exclusion criteria, which were not included in the published abstracts. These limitations leave readers without a clear picture of the study populations. Finally, different patient populations at different points in treatment with varying durations of therapy were used, which makes extrapolation of data to the general population challenging. CONCLUSIONS: Further randomized placebo-controlled trials are necessary to amass evidence for the effective and safe use of modafinil for CRF; however, if traditional therapies have failed or are intolerable, modafinil can be considered a treatment option.