Evaluation of pentamidine tolerability and efficacy between CYP2C19 phenotypes.

Intravenous pentamidine is used for prophylaxis against Pneumocystis jirovecii pneumonia, an infection seen in hematopoietic stem cell transplant recipients. Pentamidine is partially metabolized by CYP2C19, which is vulnerable to pharmacogenetic variation. This retrospective study evaluated allogeneic hematopoietic stem cell transplant patients who received intravenous pentamidine as P. jirovecii pneumonia prophylaxis. The primary objective was the association between CYP2C19 phenotype and discontinuation of pentamidine due to drug-related side effects based on univariate logistic regression (N = 81). Ten patients (12.3%) discontinued pentamidine because of side effects. There was no difference in discontinuation between phenotype groups (p = 0.18) or discontinuation due to side effects (p = 0.76). Overall, no association was seen between phenotypes and pentamidine-related side effects (p = 0.475). Drug discontinuation rates and P. jirovecii pneumonia infection rates were low.

Post-Transplant Cyclophosphamide for the Prevention of Graft-vs.-Host Disease in Allogeneic Hematopoietic Cell Transplantation: A Guide to Management for the Advanced Practitioner.

Cyclophosphamide remains a critical component to haploidentical transplant conditioning regimens. Post-transplant cyclophosphamide (PTCy) emerged as an effective component of graft-vs.-host disease (GVHD) prophylaxis in the nonmyeloablative haploidentical bone marrow transplant setting. The relative ease of administration compared with ex vivo manipulations and efficacy in reducing GVHD has led to increasing PTCy use in transplant centers around the world. The role of PTCy has expanded to haploidentical transplantation with myeloablative conditioning regimens and peripheral blood progenitor cells as the donor source. Moreover, encouraging results in GVHD management have been shown with the use of PTCy alone or in combination with other immunosuppressives in the human leukocyte antigen-matched donor setting. The toxicity profile of cyclophosphamide varies extensively depending on dose, duration, overall drug exposure, and, potentially, pharmacogenetics. This review highlights the pharmacology, pharmacokinetics, and toxic effects of cyclophosphamide and offers practical guidance for clinical application in the post-transplant setting. We summarize data on the management of high-dose cyclophosphamide toxicities and provide insights into the pharmacogenetic implications on drug efficacy and safety data.

Prenatal Exposure to Tobacco and Cannabis in Six Race/Ethnicity Groups during the First Three Years after Legalization of Cannabis for Recreational Use in California.

There are known health concerns linked to prenatal tobacco and cannabis exposures. This study aims to objectively determine the level of exposure to tobacco and cannabis in pregnant individuals from six race/ethnicity groups (Black, Hispanic, Asian Indian, Native American, Vietnamese, and White) in the first three years following legalization of recreational marijuana use in 2018 in California. We used a cross-sectional sample of prenatal screening program participants (2018-2020) from southern and central California (N = 925). Exposures were estimated by a lab analysis of cotinine (tobacco) and 11-hydroxy-Δ9-tetrahydrocannabinol (OH-THC, cannabis) in banked serum. Disparities in tobacco exposure were evident, with Black subjects experiencing the highest smoking rate (16%) followed by Native American (10%) and White (8%) subjects, and ≤2% among Hispanic, Asian Indian, and Vietnamese subjects. Environmental tobacco exposure generally showed a similar pattern of exposure to tobacco smoking across race/ethnicity groups. Cannabis detection ranged from 5% among Hispanic subjects to 12% and 13% among White and Black subjects, respectively, and was higher among tobacco users and those exposed to environmental tobacco smoke than those with no cotinine detected. Tobacco and cannabis exposure were generally greatest in younger subjects and those with indices of a lower economic status; however, among Black subjects, cannabis exposure was greatest in older subjects and those with a higher socioeconomic status. Race/ethnicity, age, and socioeconomic factors can inform targeting of high-exposure groups for intervention.

Financial Toxicity Intervention Improves Outcomes in Patients With Hematologic Malignancy.

PURPOSE: Patients with hematologic malignancies are extremely vulnerable to financial toxicity (FT) because of the high costs of treatment and health care utilization. This pilot study identified patients at high risk because of FT and attempted to improve clinical outcomes with comprehensive intervention. METHODS: All patients who presented to the Levine Cancer Institute's Leukemia Clinic between May 26, 2019, and March 10, 2020, were screened for inclusion by standardized two question previsit survey. Patients screening positive were enrolled in the comprehensive intervention that used nurse navigators, clinical pharmacists, and community pro bono financial planners. Primary outcomes were defined as improvement in mental and physical quality of life in all patients and improvement in overall survival in the high-risk disease group. RESULTS: One hundred seven patients completed comprehensive intervention. Patients experiencing FT had increased rates of noncompliance including to prescription (16.8%) and over-the-counter medications (15.9%). The intervention resulted in statistically significantly higher quality of life when measured by using Patient-Reported Outcomes Measurement Information System physical (12.5 ± 2.2 v 13.7 ± 1.8) and mental health scores (11.4 ± 2.2 v 12.4 ± 2.2; all P < .001). In patients with high-risk disease (as determined by using disease-specific scoring systems), risk of death in those receiving the intervention was 0.44 times the risk of death in those without the intervention after adjusting for race, and treatment with stem-cell transplant, oral chemotherapy, or immunotherapy (95% CI, 0.21 to 0.94; P = .034). CONCLUSION: Screening and intervention on FT for patients with hematologic malignancies is associated with increased quality of life and survival.

Pharmacogenomics-guided supportive oncology: A tale of two trials.

Cancer-related symptoms, like depression, nausea, and pain, are common and negatively affect quality of life. Unfortunately, there is large inter-individual variability in response to supportive care medications for these symptoms. Pharmacogenomics may inform prescribing by identification of those genetically at risk for drug related adverse events or therapeutic failure. While such information can be applied to many drugs, there are specific oncology populations that could greatly benefit from pharmacogenomics-guided supportive care management due to high symptom burden, including those receiving palliative medicine and hematopoietic stem cell transplantation. The goal of this paper is to provide an overview of, and lessons learned from, the development of two prospective pharmacogenomics-guided interventional trials ("Supportive Care PGx Trial" and "Transplant PGx Trial") across two different clinical settings at the Levine Cancer Institute: the Department of Supportive Oncology and the Transplant and Cellular Therapy section. Key considerations included the appropriate study design and endpoints (balancing study goals and resources), dissemination and application of individual pharmacogenetics results, technical details about assay development, and overall care coordination to minimize clinic disruption.

In Vitro and In Vivo evaluation of a novel folate-targeted theranostic nanoemulsion of docetaxel for imaging and improved anticancer activity against ovarian cancers.

Ovarian cancer ranks fifth in cancer related deaths for women in USA. The high mortality rate associated with ovarian cancer is due to diagnosis at later stages of disease and the high recurrence rate of 60-80%. Recurrent ovarian cancers are more likely to present as multidrug resistance (MDR) leading to unfavorable response from 2nd and 3rd line chemotherapy. Nanoemulsions (NEs) are emerging as an attractive drug delivery system to overcome MDR challenges. NEs can also minimize exposure of therapeutic cargo to normal tissues potentially reducing side effects. In >80% of ovarian cancers, Folate Receptor-α (FR-α) is expressed at 10- to 100-fold higher levels than on non-pathological tissues. Therefore, folate (FA) is being evaluated as an active targeting moiety for FR-α+ ovarian cancer. To improve therapeutic outcome with reduced toxicity, we developed NMI-500, a FA targeted gadolinium (Gd) annotated NE loaded with docetaxel (DTX). NMI-500 has been developed as theranostic agents as Gd will enable physician to acquire real time pharmacodynamics data on NE + DTX accumulation in target lesions. In present study, characterization for key translational metrics of NMI-500 showed size distribution in range of 120 to 150 nm and zeta potential around -45 mV. Active targeting of FA was evaluated against FR-α+ KB cells and results demonstrated significant improvement in cell association which was surface ligand density dependent. We found that NMI-500 was able to inhibit tumor growth in a spontaneous transgenic ovarian cancer model with improved safety profile and this growth inhibition could be longitudinally followed by MRI. These results indicate NMI-500 warrants advancement to clinical trials.

Sequential use of the androgen synthesis inhibitors ketoconazole and abiraterone acetate in castration-resistant prostate cancer and the predictive value of circulating androgens.

PURPOSE: Patients previously treated with ketoconazole were excluded from phase III trials of abiraterone acetate due to potential overlapping mechanism of action. The purpose of this study was to determine the clinical utility of abiraterone and its impact on circulating androgens following ketoconazole. EXPERIMENTAL DESIGN: Chemotherapy-naïve patients with progressive metastatic castration-resistant prostate cancer (mCRPC) and prior ketoconazole therapy ≥28 days received abiraterone acetate 1,000 mg daily and prednisone 5 mg twice daily. The primary endpoint was the proportion of patients with PSA response, defined as ≥30% PSA decline at 12 weeks. H0 = 0.30 versus H1 = 0.50 (α = 0.05, power = 0.83). Circulating androgen levels were measured using liquid chromatography tandem mass spectrometry. RESULTS: Thirty-nine patients were included in the final analysis. Twenty (51%; 95% confidence interval, 36%-66%) patients had ≥30% PSA decline; the null hypothesis was rejected. Sixteen (41%) had ≥50% PSA decline. Median PFS (progression-free survival) was 16 weeks; median radiographic PFS (rPFS) was 36 weeks. Samples for measurement of baseline androgens were available in 37 patients. The PSA response proportion was 59% in 29 patients with DHEA ≥ limit of quantitation (LOQ), compared with 13% in 8 patients with DHEA < LOQ (P = 0.042). Median PFS was 6 and 16 weeks in DHEA < LOQ and DHEA ≥ LOQ patients, respectively (P = 0.017); median rPFS was 14 and 36 weeks in DHEA < LOQ and DHEA ≥ LOQ patients, respectively (P < 0.001). CONCLUSIONS: Abiraterone demonstrates modest clinical efficacy in mCRPC patients previously treated with ketoconazole. Patients with DHEA ≥ LOQ were more likely to demonstrate PSA responses and longer PFS. Analysis of circulating androgens merits further investigation as a biomarker for response to androgen synthesis inhibitor therapy.

Bridging the gap: a descriptive study of knowledge and skill needs in the first year of oncology nurse practitioner practice.

PURPOSE/OBJECTIVES: To identify the knowledge and skill needs of oncology nurse practitioners (ONPs) as they enter cancer care practice, and to identify necessary educational resources. DESIGN: Cross-sectional, descriptive. SETTING: A national e-mail survey. SAMPLE: 610 self-described ONPs from the Oncology Nursing Society's database. METHODS: The project team developed a 28-item electronic survey. The survey was randomly distributed via e-mail. MAIN RESEARCH VARIABLES: ONPs' feelings of preparedness in the first year of ONP practice. FINDINGS: In the first year of practice, 90% of ONPs rated themselves as prepared or very prepared in obtaining patient history, performing physical examination, and documenting findings. ONPs rated themselves as not at all or somewhat prepared in clinical issues of chemotherapy/biotherapy competency (n = 81, 78%), recognizing and managing oncologic emergencies, (n = 77, 70%), and recognizing and managing drug toxicities (n = 63, 61%). The primary source of oncology education for ONPs new to practice was almost exclusively the collaborating or supervising physician (n = 84, 81%). CONCLUSIONS: Specific knowledge and skills, such as information about chemotherapy, oncologic emergencies, and side effects of therapy, are needed before an ONP enters a cancer care practice. IMPLICATIONS FOR NURSING: Cancer-specific education should be made available to new ONPs as they begin independent practice.

Evolution of an international collaboration: a unique experience across borders.

An international collaboration to support and mentor palliative care nurses was developed between two educational institutions in the New England region of the United States and the Hospice Casa Sperantei in Brasov, Romania. Through teleconferences, onsite visits, research, and shared publications, the collaboration continues to be a dynamic experience for the partners and students. The seven-year relationship has affected the Romanian nursing team by providing professional education and support, as well as validation of clinical practice.

Enhancing end-of-life care with dignity: characterizing hospice nursing in Romania.

AIMS: The purpose of this research was to characterize the nursing actions practiced by Romanian nurses affiliated with Hospices of Hope that promote dignified dying and explore needs to promote a more dignified death. METHODS: A survey method used the International Classification for Nursing Practice dignified dying survey. A convenience sample of 43 hospice nurses responded. Descriptive statistics, t-tests and content analysis were used to analyze the data. RESULTS: Characteristics that promoted dignified dying included the use of a formal, iterative process of assessment, interventions that supported pain and symptom management, and spiritual comfort at the end of life. Participants described family-centered hospice care that integrated Christian orthodox tradition that transformed patients as death approached. CONCLUSION: Dignity for terminally ill Romanian will be enhanced as the nurses implement these interventions. Awareness of cultural and spiritual differences concerning end of life will facilitate dialogue among nurse scientists.