Journal of Oncology Pharmacy Practice最新文献

Purpose: The standard of care for locally advanced, human epidermal growth factor receptor 2 positive (HER2+) breast cancer includes neoadjuvant chemotherapy with docetaxel, carboplatin, trastuzumab, and pertuzumab (TCHP). Many patients do not receive the full course of therapy due to various complications, possibly affecting the potential to achieve a pathologic complete response (pCR). The amount of therapy received is typically measured by relative dose intensity (RDI). This study aimed to evaluate pCR rates in patients receiving optimal and suboptimal RDI TCHP.

Methods: This study was a retrospective chart review of patients treated between 2014 and 2021 at UK HealthCare. Patients included were 18 years of age or older with HER2+ breast cancer and received at least one cycle of neoadjuvant TCHP. The primary objective compared pCR rates in patients receiving ≥ 85% RDI or <85% RDI. Secondary objectives included pCR rates based on clinical stage, age, body mass index, or hormone receptor status; factors leading to discontinuation or delay in treatment; and impact of dose reductions and delays on pCR.

Results: A total of 101 patients were included and divided into two cohorts: 54 patients received ≥ 85% RDI and 47 patients received <85% RDI. Patients who received ≥ 85% total RDI had an approximate increase of 17% in pCR rates (59.3% vs 42.6%, p = 0.11). Additionally, 82% of patients experienced a dose delay or adjustment.

Conclusions: Patients who received ≥ 85% RDI had increased pCR rates compared to patients receiving <85% RDI. A larger patient population is needed to formulate definitive conclusions on the impact of RDI and pCR rates.

Introduction: Breast cancer (BC) is the most diagnosed tumor among women worldwide. The aim of this study was to investigate the incidence and causes of low relative dose intensity (RDI) < 85% for taxane-based chemotherapy regimens used in the treatment of BC in Sultan Qaboos University Hospital (SQUH).

Methods: This was a retrospective study that included 303 BC patients, treated with taxane-based chemotherapy protocols at SQUH. RDI was calculated for each chemotherapy regimen and causes and predictors of low RDI < 85% were identified. Prophylactic and therapeutic supportive measures for certain toxicities were studied.

Results: 50.8% of the patients had neoadjuvant chemotherapy, 38% had adjuvant chemotherapy, and 11.2% of patients were given palliative treatment. AC-T and AC-THP were the most used regimens (40.3% and 17.2%). Mean RDI of used taxane-based chemotherapy regimens was 93.4%. Dose delays, dose reductions, and treatment discontinuation occurred in 36.6%, 14.8%, and 11.5%, respectively. Thirty-eight patients (12.5%) had low RDI < 85% which was reduced to 9.9% after the use of an alternative taxane. Age and chemotherapy intent were significant risk factors. 83.8% received primary granulocyte colony stimulating factor.

Conclusion: An optimal RDI greater than 85% was achieved in most cases. Furthermore, prophylactic and therapeutic supportive measures were widely used.

Introduction: For patients with metastatic head and neck squamous cell cancer (HNSCC), the outcomes of pembrolizumab in combination with a platinum agent and taxane as first-line therapy remain unknown. The purpose of this study is to characterize the impact of substituting the 5-fluorouracil (5-FU) backbone for a taxane in this chemoimmunotherapy regimen on safety/tolerability and survival outcomes.

Methods: This was an IRB-approved, single-center, retrospective, active comparator, new-user design study in adult patients with HNSCC treated between January 2018 and September 2021. The primary objective was to assess safety and tolerability of pembrolizumab in combination with a platinum agent and taxane against an active comparator arm of pembrolizumab in combination with a platinum agent and 5-FU. Safety and tolerability were evaluated by assessing differences in overall toxicities, with further secondary analysis evaluating differences in hematologic toxicities and pre-defined non-hematologic toxicities.

Results: There was no statistical difference demonstrated with the primary endpoint between the cohorts. Reduced toxicity rates were found in the taxane arm for mucositis and creatinine levels. No grade 4 non-hematologic toxicities were reported. Patients receiving 5-FU were more likely to have dose reductions upfront, discontinue treatment due to intolerances and had significantly higher mucositis.

Conclusions: This study helps to characterize the safety profile and activity of pembrolizumab in combination with a platinum agent and taxane derivative in HNSCC patients. Within our study, substitution of 5-FU with a taxane did not show an increased risk of toxicities, worsened survival, or decreased odds of achieving a response. Mucositis and elevated creatinine rates were significantly reduced within the taxane arm.

Background: Immune checkpoint inhibitors (ICIs) are associated with potentially severe immune-related adverse events (irAEs). Emerging clinical practice reports have suggested higher incidence of irAEs in real-world settings than initially observed in phase III clinical trials. Objectives were to determine the incidence of irAEs associated with ICIs in a clinical population, the Veterans Health Administration, characterize their time to onset, and explore potential risk factors.

Methods: This retrospective observational study included patients from eight Midwest VA medical centers who initiated an ICI between January 1, 2014, and June 30, 2022. Courses of incident prednisone therapy lasting at least seven days at a dose ≥ 20 mg/day were used to identify irAEs, within two years following ICI initiation. A multivariate Cox proportional hazards regression model was used to explore potential irAE risk factors.

Results: Of 1314 patients, the incidence of irAEs was 19.8%, with most (86.5%) occurring within one year of ICI initiation. Monthly incidence rates peaked three months following ICI initiation at 3.0% and decreased thereafter. Female gender (hazard ratio [HR] = 2.01, 95% confidence interval [CI]: 1.01-4.00) and combination therapy with ipilimumab and nivolumab (HR = 2.46, 95% CI: 1.44-4.21) were significantly associated with irAE incidence.

Conclusions: These findings are consistent with recent studies in clinical populations that demonstrate higher irAE incidence rates than originally reported in clinical trials. Our findings may enhance prompt recognition and treatment of irAEs for VA patients.

There is a need to develop more effective salvage therapies for patients with relapsed melanoma of the skin. Research has shown that chemotherapy-induced cancer cell death may increase immunogenic antigen exposure, or upregulation of co-inhibitory ligands such as PD-L1, thereby augmenting immune checkpoint inhibitor (ICI) efficacy. In addition, chemotherapy preconditioning may lead to depletion of Tregs, known to suppress immune anti-melanoma responses. As a result, regimens including both chemotherapy and ICI constructs are currently successfully employed in the 1^st line therapy of many solid tumors. We report a series of three patients with metastatic melanoma, refractory to ICI treatment, who responded to salvage therapy with temozolomide (TMZ) in combination with PD-1 inhibitors, with or without CTLA-4 inhibitors. The responses were durable, each lasting more than 12 months. In two patients, complete responses are ongoing at 13 and 15 months, respectively. Randomized clinical trials with TMZ plus ICIs for patients with relapsed or refractory malignant melanoma seem warranted.

Introduction: Pomalidomide is used for treating multiple myeloma in patients who have relapsed after prior treatment with lenalidomide and a proteasome inhibitor. Common side effects include mild cytopenias, and deep vein thrombosis. While papulo-erythematous rash has been described, hair effects are rare with this class of agents.

Case report: We describe a 56-year-old man who was diagnosed with multiple myeloma type IgD lambda six years prior. He responded very well to initial treatment with bortezomib-lenalidomide-dexamethasone. After two years, he had a recurrence that was treated with daratumumab-pomalidomide-dexamethasone, and he entered a stringent complete response (CR) within six months. Daratumumab was discontinued after twelve months, and he subsequently remained on maintenance therapy with pomalidomide. Three months into the maintenance regimen, he noticed a change in hair texture to curly, which continued to progress. Causality assessment linked this change to pomalidomide use via the Naranjo nomogram questionnaire, by scoring 5.

Management and outcome: Pomalidomide maintenance therapy was continued without any dose alterations given the excellent clinical outcome. A year later, multiple myeloma remains in stringent complete response. The patient remains with a curly hair phenotype, having fully embraced his new physical appearance.

Discussion/conclusion: We report herein a unique hair texture alteration linked with pomalidomide use, not previously documented in literature. The observed hair texture change, from straight to curly, requires further investigation. Future studies may offer more insights into the mechanisms underlying this rare, yet intriguing side effect.

Introduction: The general-purpose rating scales used by clinical pharmacists to rate their activities have not been extensively studied in specialist care units. This study aims to describe drug-related problems (DRPs) and pharmacist interventions (PIs) in a French hematopoietic cell therapy (HCT) unit and to evaluate the PIs' likely clinical, economic, and organizational impacts.

Methods: We retrospectively assessed all DRPs reported and all PIs issued between December 2018 and December 2021. The Act-IP scale was used to rate DRPs and PIs, and the ClEO scale was used to rate each PI's clinical, economic and organizational impacts. Fisher's exact test was used to assess the relationships between PIs and DRPs and between the three dimensions of the ClEO scale.

Results: The DRPs were most frequently related to drug-drug interactions (16.5%), physicochemical incompatibilities (15.5%), and drug monitoring problems (14.9%). 62.8% of the PIs had at least a moderate clinical impact. PIs that recommended drug monitoring were most frequent (26.8%), and most of these (75%) were likely to have prevented incidents that would have required patient monitoring or treatment.

Conclusions: The results of this study showed that after a slight adaptation, the Act-IP scale can be used to map clinical pharmacy activity in an HCT unit. More than 60% of the DRPs/PIs were likely to have had a positive impact on the patient's clinical outcome. All the PIs were rated with a positive organizational impact and PIs likely to lead to cost savings were balanced by those likely to increase costs.

Introduction: Several meta-analyses (MAs) of the efficacy and safety of daratumumab in refractory/relapsed multiple myeloma (RRMM) exist. They include different types of populations, Daratumumab regimens, and outcomes. Moreover, there is a wide variation in methodological quality and risk of bias.

Objective: This study aimed to conduct a systematic review of MAs to summarize the literature on the efficacy and safety profile of daratumumab use in RRMM, and also provide an assessment of the quality and risk of bias of the MAs if sufficient data is available.

Methods: The literature databases Pubmed, Embase, Web of Science, and Cochrane were searched since inception. The quality of methodology was assessed by the AMSTAR-2 tool, and the risk of bias was assessed by the ROBIS tool.

Results: Eight MAs were included in the SR. Most studies reported ORR and CR improvement by adding daratumumab to the chemotherapy regimen. Five MAs reported improvement in PFS in daratumumab-based regimens compared to non- daratumumab-based regimens. Only two MAs reported molecular response, favoring daratumumab. Dara was associated with adverse drug events (ADEs), including pneumonia and diarrhea. Conflicting evidence regarding hematological ADEs association with daratumumab exists. The overall quality of the studies is poor, but the MAs had a low risk of bias overall.

Conclusion: Despite including low-quality MAs, this SR provides a summary that simplifies clinicians' access to efficacy and safety outcomes of daratumumab in RRMM patients. Future studies are required to reduce the uncertainty and produce higher-quality Mas, particularly regarding daratumumab's safety.

Introduction: This report describes a rare occurrence of corneal epithelial keratopathy associated with ribociclib, a cyclin-dependent kinase 4/6 (CDK4/6) inhibitor widely used in breast cancer treatment.

Case report: An 83-year-old female with a recent breast cancer diagnosis presented with blurred vision during the third cycle of ribociclib treatment. Ocular examination revealed corneal epitheliopathy and fluorescein staining findings. Detailed assessments and comparisons were made with existing literature, identifying a few reported cases of vortex keratopathy linked to ribociclib. To the best of our knowledge, this is the first reported case of epitheliopathy.

Management and outcome: Since it decreased visual acuity, ribociclib treatment was discontinued in consultation with oncology. There was no regression in epithelopathy findings and visual acuity did not improve during follow-up visits.

Discussion: This report underscores the uncommon association between ribociclib and corneal epithelial keratopathy, emphasizing the need for comprehensive monitoring and collaboration between oncologists and ophthalmologists.