Journal of Oncology Pharmacy Practice最新文献

Background: Tacrolimus is administered via a continuous or intermittent IV infusion to prevent acute graft versus host disease (aGvHD) in pediatric hematopoietic stem cell transplant (HSCT) recipients. Limited comparison data is available.

Objectives: The primary objective was to compare the proportion of therapeutic tacrolimus trough levels in the first 30 days post-stem cell infusion. Secondary outcomes were prevalence of aGvHD, intra-patient variability (IPV) and safety.

Study design: This was a retrospective cohort study that included pediatric HSCT recipients between March 1, 2015 and October 31,2021 at BC Childrens Hospital. Adverse events were assessed using the Naranjo scoring tool.

Results: Overall, 60 transplants in 59 patients were included; n = 36 intermittent IV and n = 24 continuous IV. Median proportion of blood levels (intermittent and continuous) within 8-12 ug/L was 38% and 56%, respectively (p = 0.04). IPV was 33% and 31% and aGvHD was 39% and 38% in intermittent and continuous respectively. There was a higher proportion of adverse effects in the intermittent group with the exception of hypomagnesemia.

Conclusions: Continuous IV tacrolimus provided a higher proportion of levels within therapeutic range. Neither achieved therapeutic trough levels in more than 56% of transplants. However, there was large intra-patient variability in both groups.

Objective: This article aims to expand on the existing literature regarding the incidence of withdrawal pain following discontinuation of Trk inhibitors and to explore strategies that mitigate this withdrawal pain.

Data source: A retrospective observational study was conducted among patients who were at least 18 years-old or older and had documentation of starting larotrectinib or entrectinib at University of California, San Francisco (UCSF) between November 2018 and November 2022. Data were collected from electronic records and pharmacy databases and a total of 21 patients were identified in this study.

Data summary: Of the 21 patients included in this study, five patients (24%) experienced pain during temporary or permanent discontinuation of Trk inhibitor with the onset of withdrawal pain ranging from a few hours to three days following discontinuation. Various strategies were implemented to manage this pain including restarting of Trk inhibitor, tapering of Trk inhibitor on discontinuation, minimizing dose interruptions and use of prescription pain medications.

Conclusion: This article illustrates the presence of withdrawal pain syndrome in patients stopping a Trk inhibitor treatment and highlight the need for patient education to avoid missing any doses and for development of a guideline for Trk inhibitor discontinuation.

Objective: Chemotherapy medications are usually having high costs, and new targeted drugs can be especially expensive, representing a challenge on healthcare, particularly in low- and middle-income countries. As cytotoxic leftover management is crucial for reducing medication wastage, the aim of this study is to evaluate and optimize leftover management circuit in NIO'S Pharmacy Centralized Chemotherapy Preparation Unit (CCPU) through a Failure Mode, Effects and Criticality Analysis (FMECA), and propose continuous improvement element to enhance the security of the process.

Method: The FMECA were conducted in NIO's CCPU from March to May 2023, then continuous improvement plan was established to enhance the security of the process. The failure modes, their causes, impact, and criticality were assessed through criticality index calculation (CI = severity × frequency × detectability), and the risk concerned safety and effectiveness disruptions in chemotherapy preparation circuit using cytotoxic leftover.

Results: Leftover management circuits were described in flowchart form, where 18 failure modes were detected in four different steps of the process from chemotherapy preparation to disposal. Failure with highest critical index were detected in the case of equipment malfunction, improper storage temperature, and humidity. Continuous improvement recommendations were proposed in a table form.

Conclusion: FMECA analysis applied to NIO's chemotherapy leftover management process allowed us to evaluate, secure, and optimize the circuit, and to propose several actions to implement in a perspective of continuous improvement.

Introduction: Cytochrome P450 (CYP) enzyme inhibitors may increase the toxicity of many chemotherapies. Medication databases classify doxorubicin coadministration with CYP2D6 or CYP3A4 inhibitors as either a major interaction or contraindication. This study assessed the incidence of toxicity secondary to doxorubicin given with or without CYP enzyme inhibitors in breast cancer patients receiving doxorubicin and cyclophosphamide.

Methods: This retrospective study included female breast cancer patients treated with doxorubicin and cyclophosphamide (AC). Patients were divided into three arms: no moderate or strong CYP inhibitor interactions, moderate or strong CYP2D6 inhibitor interactions, or moderate or strong CYP3A4 inhibitor interactions. Primary outcomes included incidence of doxorubicin-associated toxicity, unplanned medical visits, chemotherapy treatment delays, and doxorubicin dose reductions. The secondary endpoint was time to toxicity.

Results: There were 171 patients included (n = 20 patients in the CYP2D6 inhibitor group and n = 15 in the CYP3A4 inhibitor group). Neither CYP inhibitor group showed a difference in incidence of hepatotoxicity, cardiotoxicity, myelotoxicity, moderate/severe nausea, or treatment delays. Compared to the no CYP inhibitor group, the CYP2D6 inhibitor group experienced a higher incidence of unplanned medical visits (45% vs. 19.4%; p = 0.023) and more frequent doxorubicin dose reductions (30% vs. 7.2%; p = 0.006). The CYP3A4 inhibitor group did not differ from the no CYP inhibitor group for these outcomes.

Conclusions: CYP inhibitors, particularly CYP2D6 inhibitors, may affect doxorubicin tolerability, as seen in this study by an increased incidence of unplanned medical visits and doxorubicin dose reductions.

Background and objectives: Arthralgia, myalgia, and neuropathic pain are the most common side effects observed due to paclitaxel chemotherapy. The aim of this study was to investigate the prophylactic role, maintenance, remission, and re-occurrence of arthralgia, myalgia, and neuropathic pain post-gabapentin therapy.

Methodology: This study was conducted in the Department of Oncology, Dhiraj Hospital, Vadodara with a sample of 51 patients. Newly detected cancer patients who observed arthralgia, myalgia, and neuropathic pain due to paclitaxel were taken and a baseline pain assessment was done using the Common Terminology Criteria for Adverse Events (CTCAE) and painDETECT questionnaire. Gabapentin was given in the first cycle after symptoms appeared and prophylactic treatment was given in the subsequent three cycles and evaluation of pain was done post-gabapentin therapy to assess the symptomatic as well as prophylactic effect.

Results: At baseline, neuropathic pain score was 22.7 ± 3.6 which reduced to 0.01 ± 0.14 on subsequent follow-ups. Grade 2 arthralgia, myalgia, and neuropathic pain were more observed at baseline which reduces to Grade 0 in the third cycle. The difference in baseline and post-gabapentin therapy was statistically analyzed by conducting t-test which showed p-value <0.00001 and t-value was less than -2 which indicated a statistically significant result.

Conclusion: This study shows that gabapentin reduces neuropathic pain. Prophylactic usage of gabapentin was highly effective at bringing about quick pain relief when compared to symptomatic treatment. In further follow-ups, it was noted that gabapentin maintained the impact throughout the cycles.

Introduction: Oxaliplatin is an anticancer drug used primarily for cancers of the gastrointestinal tract, and oxaliplatin hypersensitivity reaction is a rare but serious side effect. This study aimed to identify the clinical characteristics and risk factors for oxaliplatin hypersensitivity reactions in patients with colorectal cancer.

Methods: This retrospective study included 280 patients who developed oxaliplatin hypersensitivity reactions and 476 patients who did not.

Results: Logistic regression analysis indicated that a history of allergy (odds ratio (OR) = 2.232, 95% confidence interval (CI) (1.209, 4.119), P = .010), previous oxaliplatin exposure (OR = 8.081, 95% CI (3.024, 21.593), P < .001), and chemotherapy regimen (OR = 2.148, 95% CI (1.411, 3.271), P < .001) were risk factors for oxaliplatin hypersensitivity reactions. These reactions averaged 7.29 ± 2.78 (median 7, 1-16) cycles, with a mean cumulative dose of 589.53 ± 274.43 mg. Grade 2 oxaliplatin hypersensitivity reactions were the most common, occurring in 197 patients (70.4%), followed by grade 3 reactions in 68 patients (24.3%), and grade 4 reactions in 9 patients (3.2%). The most common symptom of oxaliplatin hypersensitivity reactions was itching (211 patients, 75.4%), followed by facial flushing (133 patients, 47.5%), and chest discomfort (77 patients, 27.5%).

Conclusions: We identified a history of allergy to previous oxaliplatin exposure and chemotherapy regimens as risk factors for oxaliplatin hypersensitivity reactions. Healthcare providers should be aware of the risk factors for oxaliplatin hypersensitivity reactions and carefully monitor patients receiving oxaliplatin.

Objective: Renal cell carcinoma (RCC) is the most common kidney cancer, with clear cell RCC being the predominant subtype. However, non-clear cell RCC constitutes a significant proportion of cases, presenting distinct challenges in treatment due to its varied histological subtypes. Despite recent advancements, the optimal therapeutic approach for non-clear cell RCC remains uncertain due to limited high-quality evidence. This systematic review aims to evaluate the efficacy of systemic therapies in nccRCC subgroups.

Data source: A comprehensive literature search identified studies from 2010 to 2024, using PubMed and Clinicaltrials.gov databases focusing on clinical trials and treatment outcomes.

Data summary: Results highlight the evolving therapeutic landscape, with targeted agents and immunotherapy demonstrating promising anti-tumor effects. Notably, tyrosine kinase inhibitors (TKIs) such as sunitinib and mTOR inhibitors like temsirolimus have shown efficacy across different subtypes. Combination therapies, including immunotherapy-based regimens, have also shown favorable outcomes. immune checkpoint inhibitors such as nivolumab and pembrolizumab demonstrated encouraging antitumor activity. Furthermore, specific targeting of signaling pathways, such as the c-MET pathway, has demonstrated efficacy in certain PapillaryRCC.

Conclusion: While combination therapies, including immunotherapies, have shown positive outcomes, immune checkpoint inhibitors like nivolumab and pembrolizumab have demonstrated encouraging antitumor activity. Additionally, targeting the c-MET pathway has proven effective in certain papillary RCC. Further research is warranted to establish optimal treatment strategies and improve outcomes for patients with non-clear cell RCC. Systemic therapy for non-clear cell RCC is complex and evolving. Further research is needed to delineate optimal treatment strategies for different histological subtypes and improve patient outcomes.

Introduction: Trastuzumab improved the prognosis of patients with human epidermal growth factor receptor 2 (HER2)+ breast cancer (BC). Here, we present a patient who developed acute vision loss due to optic atrophy in both eyes after trastuzumab.

Case report: A 60-year-old female patient was diagnosed with locally advanced HER2+ BC in January 2021. After four cycles of neoadjuvant anthracycline-based chemotherapy followed by four cycles of docetaxel, trastuzumab, and pertuzumab combined treatment, the patient underwent a right modified radical mastectomy. Three days after the end of the second cycle of adjuvant trastuzumab, she presented with acute vision loss. The patient's visual acuity was 90% in the right eye and 60% in the left eye. The left eye had optic nerve edema and spindle hemorrhages. First, on suspicion of optic neuritis, the patient was given a 1 gram/day pulse steroid for three days. However, optic neuritis was not considered during the follow-up. Metastasis was considered at the exit of the left optic nerve. Trastuzumab was started by making a mutual decision with the patient. Six days after the sixth dose of adjuvant trastuzumab, she presented with almost complete vision loss.

Management and outcome: The patient was diagnosed with optic neuritis, and a pulse steroid was administered. Trastuzumab was permanently discontinued. However, the patient's visual acuity in both eyes remained at 5-10%.

Discussion: Vision loss due to optic neuritis is a devastating side effect. Understanding that trastuzumab-induced optic neuritis may develop will help clinicians detect side effects early and manage them more effectively.

Introduction: Bisphosphonates (P-C-Ps) also called diphosphonates are the structural analogs of naturally occurring pyrophosphates. Bisphosphonates are traditionally used and shown to provide long-term success in the treatment and prevention of osteoporosis and other bone loss pathologies. Furthermore, bisphosphonates are gaining popularity in the present era of cancer therapeutics and prevention. The usage of bisphosphonates as adjuvant or neoadjuvant therapy, either as a single agent or combined with other chemotherapy, has been studied in different solid tumors. This review aims to present the various roles of bisphosphonates in solid tumors.

Data sources: Articles in MEDLINE/PubMed and the National Institutes of Health Clinical Trials Registry (http://www. Clinicaltrials.gov) between 1 January 2011 and 1 February 2022 were extracted using MeSH terms "bisphosphonates/diphosphosphonates and mechanism," "bisphosphonates and breast cancer," "bisphosphonates and prostate cancer," "bisphosphonates and lung cancer," "bisphosphonates and cancer risk," and "bisphosphonates and adverse events." Manual searches of some major oncology journals were also conducted.

Discussion: This review article focuses on the antitumor activity of bisphosphonates, safety profile, and the role of bisphosphonates as preventive, neoadjuvant, and adjuvant chemotherapy. A significant improvement in overall survival and cancer-specific survival and recurrence-free survival with the usage of bisphosphonates is noted in breast cancer patients, particularly in post-menopausal women. Though great progress has been achieved in over 20 years, further research is needed to identify the subgroup of patients that are most likely to benefit from adjuvant bisphosphonate therapy and to determine regimens with greater efficacy and better safety profile.

Introduction: Chemotherapy-induced thrombocytopenia (CIT) is a significant challenge in cancer treatment, often leading to dose reductions and reduced number of cycles. The limited effectiveness of platelet transfusions in managing CIT highlights the need for alternative treatments. Thrombopoietin receptor agonists (TPO-RA), including romiplostim, eltrombopag and avatrombopag, have shown potential in increasing platelet counts in CIT patients, necessitating a comprehensive analysis of their efficacy.

Methods: This meta-analysis followed the Preferred Reporting Items for Systemic Reviews and Meta-analysis guidelines, searching Ovid databases up to 5 October 2023. The primary metric of interest was platelet count changes post-TPO-RA administration in CIT patients.

Results: From the initial 867 studies obtained, 7 studies were selected based on the inclusion criteria. The analysis included 348 patients. A significant association was found between TPO-RA administration and platelet count increase, with a combined-effect increase of 69.52 ± 2.24 × 10⁹/l. Subgroup analysis based on Romiplostim use suggested an increase of approximately 70.11 ± 39.07 × 10⁹/l, while non-Romiplostim TPO-RAs showcased an increase of about 68.09 ± 82.58 × 10⁹/l.

Conclusions: The meta-analysis demonstrates the effectiveness of TPO-RAs in managing CIT. Further research comparing platelet increases across standardised TPO-RA regimens is recommended to refine treatment strategies. This analysis provides valuable insights for clinicians in tailoring CIT treatment using TPO-RAs.