Journal of Oncology Pharmacy Practice最新文献

IntroductionBone-modifying agents (BMAs) effectively prevent skeletal-related events (SREs) in bone metastases (BMs). While early BMA use is recommended upon BM diagnosis, its benefits and optimal timing remain unclear. This study investigated whether early BMA initiation after BM diagnosis delays SRE onset by analyzing pooled data from placebo-controlled trials.MethodsRandomized controlled trials in which a BMA or placebo was administered after BM diagnosis were extracted. For each trial's BMA and placebo arms, the waiting period from BM diagnosis to BMA initiation and the effective period from BMA initiation to SRE onset were investigated. The hazard ratio (HR) for the SRE-free period relative to the placebo period was calculated. A waiting period of ≤6 months was defined as the early initiation group, whereas that of >6 months was the delayed initiation group. The HRs were meta-analyzed.ResultsData from 17 studies were analyzed. Early initiation of BMAs showed a trend toward a longer duration of efficacy compared with delayed initiation (+5.5 versus [vs.] + 3.2 months, p = 0.056). However, the pooled HR demonstrated efficacy at both initiation timepoints (0.62 [0.56-0.69] vs. 0.73 [0.60-0.83]).ConclusionsAlthough early initiation of a BMA after BM diagnosis is recommended, its efficacy-specifically whether it prolongs the time to SRE onset-remains unclear.

BackgroundSecond-generation antiandrogens have significantly improved outcomes in patients with prostate cancer; however, their complex pharmacokinetic profiles can result in significant drug-drug interactions (DDIs) in patients with comorbid conditions which require chronic anticoagulation.ObjectiveThis review aims to describe the DDIs between antiandrogens and commonly used anticoagulants, with a focus on understanding the clinical implications of pharmacokinetics and drug metabolism.MethodsA comprehensive literature review of pharmacokinetic data, clinical trials, and prescribing information was performed. Drug metabolism of antiandrogens and anticoagulants was examined, including the effects of CYP450 enzyme and/or P-glycoprotein (P-gp) inhibition and induction on anticoagulant efficacy and safety.ResultsEnzalutamide and apalutamide are strong inducers of CYP3A4, which may reduce exposure to warfarin, apixaban, and rivaroxaban. Apalutamide induces P-gp, and therefore has DDIs with all direct oral anticoagulants (DOACs). Darolutamide and abiraterone exhibit minimal CYP450 induction and inhibition, and do not interact with warfarin or DOACs.ConclusionDrug-drug interactions between antiandrogens and anticoagulants are common and can affect therapeutic efficacy and safety. Clinical decision-making surrounding drug selection requires an interprofessional approach grounded in pharmacokinetic knowledge to ensure safe and effective care in patients with prostate cancer.

IntroductionBreast cancer is the most prevalent neoplasm among women and one of the leading causes of death in developed countries. There are screening programs aimed at reducing the morbidity and mortality associated with breast cancer Breast Self-Examination (BSE) is a primary method which involves examining their breasts and armpits to detect changes, facilitating an early detection of this disease.MethodsA quasi-experimental study was conducted to assess the effect of health education on BSE among adult women through pharmaceutical intervention.ResultsHealth education significantly reduced perceived barriers (p < 0.001), with the most notable improvement in self-efficacy dimension (4.94 ± 3.17 to 8.11 ± 2.64, p < 0.001) after the intervention. Women performing BSE increased significantly from 59.7% to 95.5% (p < 0.001). Quality of life improved by more than 6 points on a 100-point scale (p = 0.001). Women under 40 were more confident in performing BSE correctly (OR = 2.284, 95%CI = 1.364 - 3.823, p < 0.001), better understood the procedure (OR = 2.741, 95%CI = 1.544 - 4.866, p < 0.001), knew better the proper body positions (OR = 1.787, 95%CI = 1.236 - 2.584, p < 0.001) and were more aware of the dates for BSE (OR = 1.399, 95%CI = 1.132 - 1.729, p < 0.001).ConclusionThe lack of knowledge among women about this practice underscores the need to implement and promote more health programs that encourage learning and education about one's own body.

Introduction: Immune checkpoint inhibitors (ICIs), such as pembrolizumab, are integral to cancer therapy but can cause severe immune-related adverse events (irAEs), including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). These rare, life-threatening reactions typically occur early in treatment, with delayed onset being less commonly reported.

Case report: We present a 67-year-old female with triple-negative breast cancer who developed a diffuse, painful rash five months after discontinuing pembrolizumab. Physical exam revealed ∼15% body surface area involvement without mucosal lesions. Biopsy confirmed SJS/TEN overlap. The patient had previously experienced pembrolizumab-induced Grade 2 pneumonitis.

Management & outcome: Initial treatment with high-dose corticosteroids yielded minimal improvement. Intravenous immunoglobulin (IVIG) was added, resulting in clinical stabilization. The patient was discharged after 11 days with a steroid taper and showed gradual symptom improvement at one-month follow-up.

Discussion: This case highlights an exceptionally delayed onset of pembrolizumab-induced SJS/TEN overlap, extending known timelines for irAE manifestation. Prior pneumonitis may have predisposed the patient to subsequent cutaneous toxicity. Despite a SCORTEN score predicting high mortality, aggressive immunosuppressive therapy led to a favorable outcome. This underscores the importance of prolonged vigilance and multidisciplinary management in patients with prior irAEs.

ObjectiveHematopoietic stem cell transplant (HSCT) is the only curative option for genetic, immunological, and hematological disorders such as leukemia, lymphoma, and bone marrow failure syndromes. Graft-versus-host disease (GVHD) remains the most frequent post-transplant complication and is commonly managed with cyclosporine. However, recipients of HSCT are at high risk of life-threatening infections despite prophylaxis, and azole antifungals can alter cyclosporine concentrations, predisposing patients to toxicities. This study is the first from Pakistan to evaluate the effect of azole antifungals on cyclosporine levels and associated toxicities.Material and methodsA retrospective analysis was performed on 150 HLA-matched HSCT recipients at the National Institute of Blood Disease and Bone Marrow Transplantation (NIBD and BMT) who received cyclosporine with either fluconazole or voriconazole between October 2018 and December 2022. Cyclosporine levels and toxicities were assessed on day +14. Primary outcomes included cyclosporine-related adverse effects (hypertension, nephrotoxicity, hepatotoxicity, neurotoxicity, electrolyte imbalance), while the secondary objective was to correlate toxicities with cyclosporine drug concentrations in the presence of triazole antifungals.ResultsThe study included 97 males (64.4%) and 53 females (35.3%), with a median age of 11 years (range: 6-20). Beta-thalassemia major was the most common indication (n = 71, 47%). According to NCI-CTCAE criteria, the most frequent Grade 2 toxicity was hypokalemia (20%), and hepatotoxicity (16%) was the most common Grade 3 event. No Grade 4 toxicities were observed. Supratherapeutic cyclosporine levels occurred with both fluconazole and voriconazole.ConclusionWhile dose adjustment is standard with voriconazole, our findings suggest the need for similar consideration with fluconazole. Larger studies are required to confirm this observation.

IntroductionTaxane-induced peripheral neuropathy (TIPN) is a common toxicity among patients with breast cancer (BC). Numerous pairwise comparisons have been performed to evaluate neuropathy associated with different taxane agents (docetaxel, paclitaxel, cabazitaxel, nab-paclitaxel, liposomal paclitaxel, and paclitaxel injection concentrate for nanodispersion [PICN]). This network meta-analysis aimed to study the comparative incidence of TIPN associated with taxane agents in females with BC.MethodsA comprehensive data search was performed in PubMed, Web of Science, and Scopus up to August 2024. The studies that compare neuropathy in taxane agents were systematically reviewed. A network meta-analysis was carried out based on a Bayesian framework to evaluate the incidence of peripheral neuropathy in taxanes compared to paclitaxel, as reference comparator. The Surface Under the Cumulative Ranking Curve (SUCRA) was used to rank taxanes based on their neuropathy.ResultsA total of 27 studies with 12101 patients were included. When compared with paclitaxel, nab-paclitaxel was associated with a significantly higher incidence of peripheral neuropathy (OR: 1.74, CrI: 1.22-2.48). Docetaxel (OR: 0.626, CrI: 0.441-0.881) and cabazitaxel (OR: 0.158, CrI: 0.0664-0.375) demonstrated a significantly lower incidence of peripheral neuropathy compared to paclitaxel. Liposomal paclitaxel and PICN lack significant difference compared to paclitaxel. Our analysis provided the order for peripheral neuropathy (from lowest to highest) as follows: cabazitaxel, docetaxel, liposomal paclitaxel, paclitaxel, PICN, nab-paclitaxel.ConclusionsNab-paclitaxel is associated with a significantly higher incidence of peripheral neuropathy compared to paclitaxel in females with BC. Docetaxel and cabazitaxel are linked with less peripheral neuropathy compared with paclitaxel in this population. No significant differences were observed in liposomal paclitaxel and PICN compared to paclitaxel.

Introduction: Transitioning historically inpatient chemotherapy regimens to outpatient administration can reduce hospital stays, resource use, and healthcare expenditures while improving patient quality of life. However, agents like ifosfamide, commonly used in sarcoma, often necessitate inpatient administration for close monitoring of adverse effects. The Fred Hutchinson Cancer Center (FHCC) sarcoma group has developed criteria for outpatient ifosfamide administration after one successful inpatient administration. Nevertheless, there remains a paucity of literature characterizing the safety profile of outpatient ifosfamide administration.

Methods: This was a single-center, retrospective, observational study that included adults 18 years and older with a diagnosis of sarcoma receiving an ifosfamide-based regimen in the outpatient setting at FHCC between March 2021 and September 2024. The primary outcome was a composite proportion of grade 3 or higher ifosfamide-related neurotoxicity, hemorrhagic cystitis, febrile neutropenia, and uncontrolled nausea or vomiting. Secondary outcomes included days of hospitalization saved with outpatient administration.

Results: A total of 12 patients met the inclusion criteria. The most common outpatient treatment regimen was AIM (42%) followed by IE (25%) and VDC-IE (25%). Out of a total of 53 outpatient cycles, 15 cycles (28.3%) across 4 patients (33.3%) had at least 1 grade 3 or higher adverse effect of interest included in the primary outcome. A total of 257 hospitalization days were saved with outpatient administration, resulting in an estimated cost savings of $987,651.

Conclusion: Overall, among sarcoma patients meeting the FHCC outpatient ifosfamide criteria, administration of ifosfamide in the outpatient setting is safe with considerable cost savings to the institution.