Journal of Oncology Pharmacy Practice最新文献

Background: Acute myeloid (AML) and promyelocytic (APL) leukemia patients are at high risk for infection and mortality. While guidance for infection prevention is provided by the National Comprehensive Cancer Network (NCCN) and the American Society of Clinical Oncology (ASCO), each institution may vary in antimicrobial prophylaxis prescribing practices. The discrepancy may be explained by medication intolerance, cost, and low incidence of mold infections in leukemia patients. A recent meta-analysis demonstrated mortality benefits with the use of posaconazole, which was adopted by the NCCN. Despite known risks, it is unclear whether universal mold-active coverage is indicated for all AML and APL patients.

Objective: To assess the incidence of breakthrough infections in AML and APL patients.

Methods: This was a single-center, retrospective chart review of AML and APL patients receiving induction therapy at Baylor St Luke's Medical Center (BSLMC) between January 2019 and October 2021. The primary outcome assessed the incidence of breakthrough infections. Descriptive statistics were used to summarize the data.

Results: A total of 55 patients were included and 54 (98%) had prolonged neutropenia with a median duration of 30 days. Five patients (9.3%) experienced breakthrough infections during induction while 21 individuals (38.9%) during the follow-up period. Aspergillus infections occurred in three patients receiving nonmold coverage compared to none on mold-active agents (p = 1.0) with no statistical difference in mortality.

Conclusion: Despite the majority of patients not receiving mold-active prophylaxis, nonmold-active prophylaxis may be sufficient with consideration of low aspergillosis incidence.

Objective: Pacritinib is a novel kinase inhibitor approved for the treatment of adults with intermediate or high-risk primary or secondary myelofibrosis. Strong and moderate CYP3A4 inhibitors, such as some azole antifungals, are contraindicated or recommended to be avoided in combination with pacritinib, respectively. We aim to report our experience in patients who received pacritinib with concurrent azole antifungal therapy.

Data sources: We queried for patients with hematologic malignancies in the electronic medical record who received concurrent pacritinib and azole antifungal therapy.

Data summary: There were five cases of concurrent pacritinib and azole antifungal therapy in which none of the patients experienced grade 3 or higher non-hematologic toxicities. Some patients required dose modifications and/or interruptions in pacritinib therapy.

Conclusion: This is the first clinical experience describing concurrent pacritinib and azole antifungals. Our experience shows that in the setting where this interaction cannot be avoided, concurrent administration is feasible with close monitoring and possible empiric dose reductions in select patients.

Aim: To present the characteristics of drug hypersensitivity reactions (DHRs) among taxane recipients with non-small cell lung carcinoma (NSCLC), and to describe the results of rapid drug desensitization (RDD).

Methods: A retrospective cross-sectional study included 45 patients who were treated with taxane for NSCLC and were found to be hypersensitive to taxane. All patients were administered the standard 3-bag, 12-step RDD protocol following the development of DHR. RDD success was evaluated separately for each cycle, and successful RDD was defined as the completion of the cycle with application of 12 steps of the desensitization protocol and the absence of early and/or late reactions afterwards.

Results: Among 45 patients hypersensitive to taxane 43 (95.6%) successfully received taxane cycles with desensitization. Failed RDD occurred in only 2 (4.4%) patients. The total number of desensitization cycles was 183, of which 181 (98.9%) were successful. The mean age of patients with successful desensitization was 59.42 ± 10.48 years and 37 (86.0%) of them were male.

Conclusion: RDD is a reliable procedure that enables effective administration and completion of first-line taxane treatments in taxane-sensitive patients.

Introduction: Imatinib is an orally administered tyrosine kinase inhibitor with wide clinical use in different indications from solid tumors to hematologic malignancies. Inclusion body myositis (IBM) is an acquired myopathy of both inflammatory and degenerative nature.

Case report: We present an 81 years old male with a history of gastrointestinal stromal tumor (GIST) operated 8 years ago and was evaluated for the progressive loss of weight and muscle strength leading to total immobilization in 6 months. He was under imatinib for 8 years despite the remission of GIST. Physical examination disclosed diffuse loss of muscle strength, most prominently involvement of distal upper and proximal lower extremity in an asymmetrical pattern with normal serum creatinine kinase level (CK). Further investigations including bilateral thigh MRI, electromyography (EMG), and PET/CT suggested myositis and degenerative myopathy and ruled out any malignancy. Quadriceps femoris biopsy proved the diagnosis of IBM and no trigger except for imatinib was displayed.

Management and outcome: Clinical improvement in terms of weight loss and muscle weakness was achieved after the discontinuation of imatinib.

Discussion: This is the first case of IBM associated with prolonged use of imatinib not reported in the literature so far. Since imatinib is widely used in different conditions, it is important to be aware of even its rare adverse effects. Poor response of IBM to conventional immunosuppressive agents enhances the value of etiology identification to relieve symptoms in addition to supportive care.

Objective: This study aims to assess outcomes among patients with non-small cell lung cancer (NSCLC) who received treatment with pembrolizumab on a weight-based dose (WBD) or fixed-dose (FD) regimen using a non-inferiority (NI) analysis.

Material and methods: This retrospective cohort study included adult patients with NSCLC weighing under 100 kg who received pembrolizumab between 1 January 2015 and 31 December 2020. Patients were grouped into either WBD or FD cohort based on the initial pembrolizumab dose and dosing regimen. The primary effectiveness outcome was overall survival (OS), analyzed using NI analysis with a lower margin of 10% comparing WBD to FD. Safety outcomes were all-cause emergency room visits or hospitalizations and incidence of selected immune-related adverse events (irAEs) and analyzed using NI analysis with an upper margin of 10%. All patients were followed until the end of health plan membership, death, or 30 June 2022, whichever occurred first.

Results: A total of 1413 patients were evaluated. OS was observed in 36.6% of the FD group, and 37.7% in the WBD group (rate difference: 1%, 90% CI: -6%-8%, NI p-value < 0.01). NI was met in all three safety outcomes: proportion of all-cause emergency room visits (rate difference: 1.1%, NI p-value < 0.01); proportion of hospitalizations (rate difference: 2%, NI p-value < 0.01); and composite incidence of irAEs (rate difference: -2.2%, NI p-value = 0.03).

Conclusion: These findings suggest that WBD of pembrolizumab may be as appropriate as FD for the treatment of lung cancer.

Introduction: Workers can reduce their risk of exposure to hazardous drugs by following safe handling guidelines. Healthcare centers need to dedicate time and resources in order to implement new safety recommendations. The objective was to present the results of a national survey about the safe handling of hazardous drugs in healthcare centers.

Methods: Quebec healthcare centers performed an auto-evaluation to the newly updated safe handling guidelines in 2021. Centers rated each criterion as compliant or non-compliant. The guidelines tailored recommendations according to three categories of hazards: G1, consisting mostly of carcinogenic drugs; G2, other hazardous drugs; and G3, those with reproductive toxicity. The questionnaire prompted participants to document their planned corrective measures for non-compliant criteria.

Results: Most centers participated (28/29, 97%). The overall compliance was 58% (8761/15,216 criteria). The conformity per theme was hygiene and sanitation (1290/1,878, 69%), laundry (221/367, 60%), pharmacy (2658/4,474, 59%), nursing (3436/6,017, 57%), spills and accidental exposure (353/649, 54%), and general measures (803/1,831, 44%). It was higher for recommendations regarding G1s (4226/6,115, 69%) than for G2s (1626/3557, 46%) and G3s (372/916, 41%).

Conclusions: This project successfully used an innovative approach that combined a national auto-evaluation survey, an actionable report, and the involvement of a community of practice. Centers were able to benchmark their implementation of safe handling guidelines, and community of practices may help in sharing the best practices. The design of the questionnaire helped in targeting corrective measures. More work is needed for safe handling practices that relate to G2 and G3 drugs.

Introduction: Treatment of advanced HepatoCellular Carcinoma (HCC) is based on first-line (L1) combination of atezolizumab and high-dose (HD) bevacizumab while second-line (L2) refers one antiangiogenic protein kinase inhibitors (aaPKI). This prolonged antiangiogenic pressure let us to observe an increasing occurrence of Hand-Foot Syndromes (HFS) in patients receiving aaPKI after HD bevacizumab combination. This study reports observations and discussions about the evidence and hypothesis that could be made.

Methods: Patients who received the L1 combination from September 1^st 2020 to December 31^st 2022 to identify L2 aaPKI. Demographic, biological, oncological data and occurrence of HFS were collected. In addition were collected the number of L1 combination cycles, type of aaPKI, and delay between last L1 cycle and L2 initiation. This study had a purely exploratory purpose, so no statistical analysis was planned.

Results: 17 patients received an aaPKI after the L1 HD bevacizumab combination with a median time of 26 days from last L1 cycle to L2 start. Five patients experienced HFS including grade 3 (n = 2) with sorafenib and cabozantinib. The HFS occurred with a median delay of 23 days (IQR: 21-28) from aaPKI start. Three patients experienced aaPKI-related dose-limiting toxicity.

Conclusions: Proportion of patients experienced HFS in our cohort did not differ from pivotal trials data and the sample size do not allow to conclude. Hypotheses include timing of aaPKI start in HCC treatment, vascular toxicity at aaPKI start after HD bevacizumab discontinuation instead combination, patient-related outcome for a better understanding of these aaPKI-related HFS post HD bevacizumab.

Introduction: Pembrolizumab is a humanized monoclonal antibody IgG4 programmed cell death protein 1 antagonist, and its use in oncology has been increasing in recent years, providing durable and favorable responses and tolerable toxicity profiles in various types of cancer. We describe a case of pembrolizumab related perforated appendicitis in a patient with stage 3C malignant melanoma (MM).

Case report: A 70-year-old male patient who had no known disease was diagnosed with MM as a result of the excision of the mass on his right shoulder. The disease stage was stage 3C (pT4aN1bM0). Subsequently, adjuvant pembrolizumab treatment was started. A few days after the fourth maintenance course, he presented to the emergency department complaining of abdominal pain, nausea and vomiting. Emergency abdominal tomography showed a significant increase in the diameter of the appendix vermiformis, peritoneal thickening and appendiceal wall defects that could be significant in terms of perforation.

Management and outcome: The mentioned finding and given the clinical presentation, was attributed to a perporating of the appendix, so the patient was hospitalized in the Department of Surgery and the patient underwent emergency appendectomy. Histological findings were consistent with appendicitis. After a day in the hospital, the abdominal pain subsided, C-reactive protein tended to decrease and the patient was discharged.

Discussion: In patients who develop acute abdominal pain with or without diarrhea during immunotherapy, urgent imaging, endoscopic and clinical evaluation should be performed, and bowel perforation, although rare, should be considered as a potential complication of any immunotherapy.

Introduction: Adherence to imatinib in chronic myeloid leukemia (CML) patients is estimated to be as low as 70% despite its clinical benefit, and our understanding of the impact of nonadherence in this population is limited. This study presents a novel application of the Alternating Conditional Estimation (ACE) algorithm in newly diagnosed CML patients to map the full dose-response curve (DRC) and determine how the strength of this curve varies over time.

Methods: We applied the ACE algorithm alongside a backward elimination procedure to detect the presence of time dependence and nonlinearity in the relationship between imatinib adherence and time-to-remission. An extended Cox model allowing for the flexible modeling of identified effects via unpenalized B-splines was subsequently fit and assessed.

Results: The substantial improvement in model fit associated with the extended Cox approach suggests that traditional Cox proportional hazards model assumptions do not hold in this setting. Results indicate that the DRC for imatinib is non-linearly increasing, with an attenuated effect above a 74% adherence rate. The strength of this effect on remission varied over time and was strongest in the initial months of treatment, reaching a peak around 90 days post-initiation (log hazard ratio: 2.12, 95% confidence interval: 1.47 to 2.66).

Conclusion: Most patients that achieved remission did so by 4 months (120 days) with consistently high adherence, suggesting that this could be a critical time and duration for realizing treatment benefit and patient monitoring. Findings regarding the relationship between adherence and remission can additionally help guide the design of future studies.