Incidence of port site complications in relation to timing of bevacizumab infusion.

INTRODUCTION: Bevacizumab is a monoclonal antibody that targets vascular endothelial growth factor, with a serious complication of wound healing complications. The package insert currently does not have recommendations on the management of bevacizumab administration around minor procedures, including port placements. Currently, there are only two trials that have examined the optimal timing of bevacizumab after port placement. METHODS: This is a single-center retrospective trial aiming to evaluate the rate of wound dehiscence and other port site complications depending on the time between port placement and bevacizumab infusion. Eligible patients who have had at least one port place and have received bevacizumab for an oncologic indication were identified in a study period of 1/1/2016-3/31/2021. The primary outcome of this study was the incidence of wound dehiscence in relation to the timing of bevacizumab infusion. RESULTS: A total of 243 patients met the inclusion criteria, and 116 port placements had a port site complication. For wound dehiscence, 6% was observed 0 days from port placement, 10% was observed 1 day from port placement, 0% was observed 2 days from port placement, 0% was observed 3-7 days from port placement, 3% was observed 8-14 days from port placement, and 3% was observed 15-30 days from port placement. CONCLUSIONS: The results of this study show an inverse relationship between the risk of wound dehiscence and port site complication and the timing of bevacizumab infusion to port placement, with an increase in absolute risk of wound dehiscence when bevacizumab is given within 2 days of port placement.

Antibody drug conjugates: Design implications for clinicians.

OBJECTIVE: There are currently 11 antibody-drug conjugates (ADC) that are FDA approved for use in oncologic disease states, with many more in the pipeline. The authors aim to review the pharmacokinetic profiles of the components of ADCs to engage pharmacist practitioners in practical considerations in the care of patients. This article provides an overview on the use of ADCs in the setting of organ dysfunction, drug-drug interactions, and management of on- and off-target adverse effects. DATA SOURCES: A systematic search of the literature on ADCs through September 2023 was conducted. Clinical trials as well as articles on ADC design and functional components, adverse effects, and pharmacokinetics were reviewed. Reviewed literature included prescribing information as well as tertiary sources and primary literature. DATA SUMMARY: A total of 11 ADCs were reviewed for the purpose of this article. A description of the mechanism of action and structure of ADCs is outlined, and a table containing description of each currently FDA-approved ADC is included. Various mechanisms of ADC toxicity are reviewed, including how ADC structure may be implicated. CONCLUSION: It is imperative that pharmacist clinicians understand the design and function of each component of an ADC to continue to assess new approvals for use in oncology patients. Understanding the design of the ADC can help a pharmacy practitioner compare and contrast adverse effect profiles to support their multidisciplinary teams and to engage patients in education and management of their care.

Impact of institutional interventions on the rate of paclitaxel hypersensitivity reactions.

PURPOSE: Paclitaxel is associated with hypersensitivity reactions (HSRs). Intravenous premedication regimens have been devised to decrease the incidence and severity of HSRs. At our institution oral histamine 1 receptor antagonists (H1RA) and histamine 2 receptor antagonists (H2RA) were adopted as standard. Standardizations were implemented for consistent premedication use in all disease states. The purpose of this retrospective study was to compare the incidence and severity of HSRs before and after standardization. METHODS: Patients who received paclitaxel from 20 April 2018 to 8 December 2020 having an HSR were included in analysis. An infusion was flagged for review if a rescue medication was administered after the start of the paclitaxel infusion. The incidences of all HSR prior to and post-standardization were compared. A subgroup analysis of patients receiving paclitaxel for the first and second time was performed. RESULTS: There were 3499infusions in the pre-standardization group and 1159infusions in the post-standardization group. After review, 100 HSRs pre-standardization and 38 HSRs post-standardization were confirmed reactions. The rate of overall HSRs was 2.9% in the pre-standardization group and 3.3% in the post-standardization group (p = 0.48). HSRs, during the first and second doses of paclitaxel, occurred in 10.2% of the pre-standardization and 8.5% of the post-standardization group (p = 0.55). CONCLUSIONS: This retrospective interventional study demonstrated that same-day intravenous dexamethasone, oral H1RA, and oral H2RA are safe premedication regimens for paclitaxel. No change in the severity of reactions was seen. Overall, better adherence to premedication administration was seen post-standardization.

Xerostomia: an immunotherapy-related adverse effect in cancer patients.

PURPOSE: Xerostomia is an underrecognized adverse effect of immunotherapy (IO) that can significantly impact patients' quality of life by leading to poor nutritional status, dental caries, and oral candidiasis. The purpose of this case series was to describe the onset, severity, clinical course, and management of IO-induced xerostomia. METHODS: This was a retrospective case series conducted at an outpatient cancer center. Data collection was conducted via chart review. The severity of dry mouth symptoms was graded using the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. RESULTS: Six patients with advanced solid tumors who received a PD-1 inhibitor or PD-1/CTLA-4 inhibitor combination therapy were evaluated. The median time to onset of xerostomia was 4.5 months overall, though symptoms developed sooner in patients who received IO as subsequent-line therapy (median = 1.9 months). All patients developed other immune-related adverse events (IRAEs) such as hypothyroidism. Five patients (83%) had grade 2 dry mouth symptoms, and similarly, 5 patients eventually required prescription medications such as sialogogues and topical or systemic corticosteroids to alleviate symptoms. Two patients (33%) required interruptions in IO. All 3 patients who received cevimeline noticed improvement in symptoms, and one patient who received prednisone dosed at 1 mg/kg/day tapered over 5 weeks also experienced significant relief. CONCLUSION: While the optimal management of IO-induced xerostomia has not yet been established by national guidelines, increased awareness can prompt faster initiation of supportive care measures that can prevent significant discomfort and poor oral intake. Thoughtful use of over-the-counter topical agents, sialogogues, corticosteroids, and treatment interruptions can help improve tolerability of this adverse effect.

Exemestane induced cholestatic liver injury - A case report.

PURPOSE: Exemestane, a steroidal aromatase inhibitor, is an important therapeutic option in the treatment of post-menopausal hormone receptor positive breast cancer. Adverse effects include hot flashes and bone loss, but rarely is hepatotoxicity reported. We report a case of exemestane induced cholestatic liver injury following exemestane initiation. CASE REPORT: A now 77-year-old Caucasian female with primary biliary cirrhosis (PBC), and metastatic hormone receptor positive breast cancer originally diagnosed in 2000 who developed symptoms of pruritus, diarrhea, grade 2 transaminitis, and grade 1 hyperbilirubinemia three weeks after exemestane initiation.Management and outcome: Due to the patient's signs and symptoms, exemestane was discontinued and the patient was continued on cholestyramine until resolution of her laboratory abnormalities. Approximately a week after discontinuation, the patient was started and maintained on anastrozole without recurrence of her symptoms. DISCUSSION: Hepatotoxicity with aromatase inhibitors have rarely been reported in clinical trials and to date, instances of exemestane induced hepatotoxicity has only been reported in two case reports. The patient's history of primary biliary cirrhosis may be an important risk factor for the development of hepatotoxicity from exemestane.

A Retrospective Analysis of Metronomic Cyclophosphamide, Methotrexate, and Fluorouracil (CMF) Versus Docetaxel and Cyclophosphamide (TC) as Adjuvant Treatment in Early Stage, Hormone Receptor Positive, HER2 Negative Breast Cancer.

BACKGROUND: Anthracycline and taxane-based doublets have largely replaced cyclophosphamide, methotrexate, and fluorouracil (CMF) as preferred regimens in the adjuvant treatment of breast cancer. Metronomic CMF is associated with improved tolerability over anthracycline or taxane-based regimens. Previously, there have been no direct comparisons between taxane-based regimens and CMF. MATERIALS AND METHODS: We performed a retrospective review of 98 breast cancer patients treated at the Seattle Cancer Care Alliance from February 2015 through December 2018 that received either metronomic CMF or docetaxel and cyclophosphamide (TC) as adjuvant therapy for early-stage, hormone receptor-positive/human epidermal growth factor receptor-2 negative (HR+/HER2-) breast cancer. The primary outcome assessed was disease-free survival (DFS). Secondary outcomes included overall survival (OS), dose intensity, and adverse effects. RESULTS: With an average follow-up of 35.9 and 28.2 months for CMF and TC, respectively, there was no significant difference in DFS or OS between the chemotherapy regimens. DFS at 3 years was 96.7% vs. 94.3% and OS 96.7% vs. 100% for CMF and TC, respectively. There were more dose delays in the CMF group, but on average, patients receiving either regimen achieved a dose intensity ≥85%. There was a trend towards increased hospitalization or emergency department utilization (23.1% vs. 10.6%) and Grade 4 toxicities (9.6% vs. 4.3%) with TC vs. CMF. CONCLUSION: Metronomic CMF offers equivalent survival outcomes to TC and remains a viable option in the adjuvant treatment of HR+/HER2- breast cancer. There was a trend towards increased Grade 4 toxicities and hospitalizations with TC, suggesting that metronomic CMF may offer a more tolerable treatment option while maintaining excellent disease outcomes.

Establishing clinical pharmacist telehealth services during the COVID-19 pandemic.

PURPOSE: After community transmission of the novel virus that causes coronavirus disease 2019 (COVID-19) was detected in the State of Washington in February 2020, innovative measures, such as telehealth appointments, were needed to safely continue to provide optimal pharmaceutical care for patients with chronic conditions and cancer. SUMMARY: Prior to the COVID-19 pandemic, federal regulations limited the scope of telehealth pharmacist services. However, enactment of the Coronavirus Preparedness and Response Supplemental Appropriations Act, followed by guidance by the Centers for Medicare and Medicaid Services and the Department of Health and Human Services, allowed currently credentialed providers (including pharmacists) to continue to provide patient care services via telehealth with fewer restrictions. Our health system has numerous credentialed pharmacists across multiple ambulatory care clinics. In this article, we highlight our process of expediting the implementation of telehealth services. This process included obtaining authorization for the credentialed pharmacists to provide telehealth services, completion of training modules, implementation of new technology platforms, development of new workflows, and utilization of resources for providers and patients to facilitate successful completion of telehealth visits. We also highlight the consent and documentation components crucially important to the telehealth visit and share some of our successes, as well as identified limitations, in providing pharmacist services via telehealth. CONCLUSION: In the setting of the COVID-19 pandemic, our institution was able to swiftly implement clinical pharmacist telehealth services for many patients, offering a safe and effective way to continue providing a high level of care. This article discusses our experience with and potential limitations of telehealth to assist other pharmacists seeking to implement and/or expand their telehealth services.