Practical considerations in the management of patients treated with bosutinib for chronic myeloid leukemia.

Bosutinib is a second-generation tyrosine kinase inhibitor indicated for the treatment of patients with newly diagnosed Philadelphia chromosome-positive chronic phase chronic myeloid leukemia (CML), and for patients with Ph + chronic phase, accelerated phase, or blast phase CML resistant or intolerant to prior therapy. As is the case for all TKIs approved for treatment of CML, bosutinib is associated with adverse events (AEs) that require appropriate management to ensure adherence to treatment and optimized outcomes. The aim of this review is to provide physicians with updated practical information for the prevention and management of AEs occurring during treatment with bosutinib, including dosing strategies, based on the latest published evidence and clinical experience. Clinical studies and real-world evidence have shown bosutinib has a generally favorable safety profile, which has remained consistent across lines of therapy and in long-term reports. Adjusting the starting dose and/or modifying the dose during treatment with bosutinib are important strategies to manage AEs and improve tolerability, which are recognized within the label and in treatment guidelines. Dosing adjustment strategies to manage AEs are a recognized management approach for other TKIs in the treatment of CML and are not exclusive to bosutinib. In summary, long-term results from clinical trials and emerging real-world evidence demonstrate bosutinib has a safety profile that can largely be managed with treatment modifications and/or supportive care. Increased experience in managing toxicities and by using a personalized dosing approach may further improve adherence and outcomes with bosutinib.

Management of luspatercept therapy in patients with transfusion-dependent ß-thalassaemia.

Patients with transfusion-dependent ß-thalassaemia require lifelong, regular red blood cell transfusions for survival; however, frequent blood transfusions are associated with an increased risk of iron overload, transfusion-transmitted disease and alloimmunization, as well as reduced quality of life. Luspatercept, an erythroid maturation agent that promotes late-stage erythroid maturation independently of erythropoietin, has demonstrated efficacy in reducing transfusion burden in patients with transfusion-dependent ß-thalassaemia. In this review, we discuss treatment initiation, ongoing evaluation, dose adjustment and management of adverse events in transfusion-dependent patients with ß-thalassaemia receiving luspatercept, and we provide guidance on how to determine whether patients are deriving clinical benefit.

Safety and Effectiveness of an All-Oral, Bedaquiline-Based, Shorter Treatment Regimen for Rifampicin-Resistant Tuberculosis in High Human Immunodeficiency Virus (HIV) Burden Rural South Africa: A Retrospective Cohort Analysis.

BACKGROUND: At the end of 2018, South Africa updated its all-oral regimen, to include bedaquiline (BDQ) and 2 months of linezolid (LZD) for all patients initiating the shorter 9-12 months regimen for rifampicin-resistant tuberculosis (RR-TB). We assessed a group of patients in rural KwaZulu-Natal for safety and effectiveness of this treatment regimen under programmatic conditions. METHODS: We conducted a retrospective cohort analysis on RR-TB patients treated with a standardized all-oral short regimen between 1 July 2018 and 30 April 2019 in 3 facilities in King Cetshwayo District. An electronic register (EDR web) and facility-based clinical charts were used to collect variables, which were entered into an Epi-Info database. RESULTS: Our cohort included 117 patients; 68.4% (95% confidence interval [CI]: 59.3-76.3) tested positive for human immunodeficiency virus (HIV). The median time to culture conversion was 56 days (95% CI: 50-57). Treatment success was achieved in 75.2% (95% CI: 66.5-82.3) of patients. Mortality within the cohort was 12.8% (95% CI: 7.8-20.3). Anemia was the most frequent severe adverse event (AE). The median time to develop severe anemia was 7.1 weeks (interquartile range [IQR] 4.0-12.9) after treatment initiation. LZD was interrupted in 25.2% (95% CI: 17.8-34.5) of participants. CONCLUSIONS: An all-oral shorter regimen, including BDQ and LZD as core drugs for the treatment of RR-TB, shows good outcomes, in a high HIV burden rural setting. AEs are common, especially for LZD, but could be managed in the program setting. Support is needed when introducing new regimens to train staff in the monitoring, management, and reporting of AEs.

Hematologic adverse events following palbociclib dose reduction in patients with hormone receptor-positive/human epidermal growth factor receptor 2-negative advanced breast cancer: pooled analysis from randomized phase 2 and 3 studies.

BACKGROUND: Palbociclib improves outcomes for women with hormone receptor-positive/human epidermal growth factor receptor 2-negative advanced breast cancer (HR+/HER2- ABC). Dose reductions are recommended for the management of hematologic toxicities. A previous pooled analysis from the PALOMA clinical trials showed that 36.9% of patients required dose reduction, predominantly during the first 6 months of treatment and with decreasing frequency during subsequent 28-day treatment cycles (C). Previous data have shown that palbociclib dose reductions do not affect efficacy. This pooled, post hoc analysis evaluated the frequency of hematologic adverse events (AEs) before and after palbociclib dose reduction in PALOMA-1, PALOMA-2, and PALOMA-3. METHODS: This analysis evaluated the frequency of hematologic AEs 30 days before dose reduction and during each subsequent treatment from C1 to C6 among patients who required palbociclib dose reduction. Data were pooled from 3 randomized studies. PALOMA-1 was a phase 2, open-label study of postmenopausal patients untreated for ABC receiving palbociclib plus letrozole or letrozole alone. PALOMA-2 was a phase 3, double-blind study of postmenopausal patients untreated for ABC receiving palbociclib plus letrozole or placebo plus letrozole. PALOMA-3 was a phase 3, double-blind study of pre/perimenopausal or postmenopausal patients, whose disease progressed on prior endocrine therapy, receiving palbociclib plus fulvestrant or placebo plus fulvestrant. RESULTS: A total of 311 (35.5%) patients with HR+/HER2- ABC required a palbociclib dose reduction (93.6% due to AEs) from 125 to 100 mg. Mean patient age was 59.9 years, and 46.9% of patients had visceral disease. Median time to dose reduction was 70 days. The majority of dose reductions occurred within 3 months of starting palbociclib treatment. Incidences of all-grade and grades 3/4 hematologic AEs were lower following dose reduction. CONCLUSIONS: A decrease in frequency and severity of hematologic AEs, including febrile neutropenia, following palbociclib dose reduction was observed, supporting the recommended use of dose reduction in AE management. TRIAL REGISTRATION: These studies were sponsored by Pfizer. ClinicalTrials.gov: NCT00721409; registration date July 24, 2008. ClinicalTrials.gov: NCT01740427; registration date December 4, 2012. ClinicalTrials.gov: NCT01942135; registration date September 13, 2013.

Management of common adverse events related to first-line dacomitinib use in EGFR mutation-positive non-small-cell lung cancer: a pooled safety analysis.

Aim: This pooled safety analysis was conducted to analyze incidence and management of key dacomitinib-associated adverse drug reactions (ADRs). Patients & methods: Patients with EGFR mutation-positive advanced non-small-cell lung cancer who received first-line dacomitinib at the 45 mg/day recommended starting dose were included. ADRs were identified based on reasonable association with EGFR tyrosine kinase inhibitors. Results: Overall, 251/255 patients (98%) experienced ADRs. The most common were diarrhea, rash, stomatitis, nail disorder and dry skin. Dose interruptions and dose reductions were reported in 47 and 52% of patients, respectively. Fewer grade 3 key ADRs were observed following dose reductions. Conclusion: Dacomitinib was generally tolerable. Most reported ADRs were known to be associated with EGFR tyrosine kinase inhibitors and were managed with standard medical management and dose modifications.

Refining sorafenib therapy: lessons from clinical practice.

Understanding the best use of sorafenib is essential in order to maximize clinical benefit in hepatocellular carcinoma. Based on Phase III and noninterventional study data, as well as our extensive experience, we discuss dose modification in order to manage adverse events, disease response evaluation and how to maximize treatment benefit. Sorafenib should be initiated at the approved dose (400 mg twice daily) and reduced/interrupted as appropriate in order to manage adverse events. Dose modification should be considered before discontinuation. Appropriate tumor response assessment is critical. Focusing on radiologic response may result in premature sorafenib discontinuation; symptomatic progression should also be considered. If second-line therapies or trials are unavailable, continuing sorafenib beyond radiologic progression may provide a clinical benefit. Our recommendations enable the maximization of treatment duration, and hence clinical benefit, for patients.

Ipilimumab in patients with cancer and the management of dermatologic adverse events.

Ipilimumab is a fully human monoclonal antibody that blocks cytotoxic T-lymphocyte antigen-4 to augment antitumor T-cell responses. Phase III studies have demonstrated survival benefit in both previously treated and treatment-naïve patients with metastatic melanoma. In clinical trials, adverse events (AEs) related to treatment with ipilimumab were mostly grade 1/2 (as per Common Terminology Criteria for AEs, Version 4.02), and mostly reversible with appropriate management. Distinct immune-related AEs that may reflect the mechanism of action of ipilimumab have been identified, and occur commonly in the skin, typically presenting as a maculopapular rash, which can be accompanied by pruritus, pruritus with no skin lesions, alopecia, and vitiligo. Histologic analyses have revealed epidermal spongiosis, and perivascular CD4(+) T-cell infiltrates with some eosinophils in areas of rash. Timely implementation of toxicity-specific treatment guidelines that emphasize vigilance and early intervention allows mitigation of dermatologic AEs. Adherence to guidelines is necessary to maintain quality of life, ensure consistent dosing, and obtain the best possible clinical outcome.

Safety profile of trastuzumab deruxtecan in advanced breast cancer: Expert opinion on adverse event management.

Trastuzumab deruxtecan (T-DXd) is an antibody-drug conjugate that targets human epidermal growth factor receptor 2 (HER2) and has shown promising results in the treatment of advanced/metastatic breast cancer. The objective of this report is to provide guidance on the prophylaxis, monitoring, and management of adverse events (AEs) in patients with breast cancer treated with T-DXd, and to emphasize that proper management of AEs is needed to optimize the effectiveness of T-DXd treatment and reduce the number of discontinuations. The article covers various aspects of T-DXd treatment, including its clinical efficacy, safety profile, and dosing considerations, and provides practical recommendations for managing AEs, such as nausea/vomiting, interstitial lung disease, and hematologic toxicity. Although there are still many knowledge gaps about the cause and incidence of AEs in real-world patients, this document may serve as a valuable resource for clinicians who are involved in the care of breast cancer patients receiving T-DXd treatment.

The Role of Nurses in the Management of Adverse Events in Patients Receiving First-Line Axitinib Plus Immuno-Oncology Agents for Advanced Renal Cell Carcinoma.

OBJECTIVES: The recent approval of first-line tyrosine kinase inhibitor plus immuno-oncology agent combination therapy for the treatment of advanced renal cell carcinoma offers substantially improved response rates and survival compared with the previous standard of care. This expansion of treatment options has also led to a greater range and complexity of potential treatment-related adverse events related to overlapping toxicities. The aim of this article is to discuss the management of common treatment-emergent adverse events (AEs) associated with axitinib plus immuno-oncology therapy, highlight the specific roles of oncology nurses in managing these events, and provide AE management resources to aid oncology nurses in their care of patients with advanced renal cell carcinoma. DATA SOURCES: Author experience, journal articles, and treatment guidelines were used. CONCLUSION: The use of oncology nurses and nurse-led innovations to monitor and assess treatments can have a positive impact on the management of AEs in cancer patients by identifying those who are most at risk, providing regular assessment, appropriate patient education, and supporting the monitoring of patient safety. IMPLICATIONS FOR NURSING PRACTICE: Skilled oncology nurses should be a key part of a team that addresses the supportive care needs and management of AEs that are associated with novel cancer treatments. Early and ongoing communication between the patient and oncology nurses regarding the development of adverse events is a critical component of maximizing treatment outcomes and quality of life.

Beyond monotherapy: An era ushering in combinations of PARP inhibitors with immune checkpoint inhibitors for solid tumors.

The introduction of PARP inhibitors (PARPis) and immune checkpoint inhibitors (ICIs) has marked a significant shift in the treatment landscape for solid tumors. Emerging preclinical evidence and initial clinical trials have indicated that the synergistic application of PARPis and ICIs may enhance treatment efficacy and potentially improve long-term patient outcomes. Nonetheless, how to identify specific tumor types and molecular subgroups most likely to benefit from this combination remains an area of ongoing research. This review thoroughly examines current studies on the co-administration of PARPis and ICIs across various solid tumors. It explores the underlying mechanisms of action, evaluates clinical efficacy, identifies potential responder populations, and delineates common adverse events alongside strategic management approaches. The aim is to offer a detailed understanding of this combination therapy, potentially guiding future therapeutic strategies for solid tumors.

Pembrolizumab-induced nephrotoxicity in a patient with breast cancer.

The introduction of immunotherapy has revolutionized the treatment and improved outcomes of multiple types of cancer. Although breast cancer is a less immune-responsive tumor type, the incorporation of pembrolizumab into chemotherapy regimens in the neoadjuvant and first-line metastatic setting for the triple-negative disease has improved outcomes. However, the use of this type of treatment is associated with a spectrum of adverse events. Although rarely affected, kidneys can be a target for immunotherapy, leading to irreversible injury if not recognized and addressed early. A 52-year-old woman presented with clinical stage II right breast cancer diagnosed at an outside facility. Neoadjuvant docetaxel/carboplatin/pembrolizumab every 3 weeks was started. Given the partial response on MRI after the 4th cycle, treatment was switched to doxorubicin/cyclophosphamide. However, pembrolizumab was held in cycle 2 due to the rash and then resumed in cycle 3 after the resolution of symptoms. Elevated creatinine was noted 3 weeks after the last dose of pembrolizumab without improvement despite adequate fluid resuscitation. Diagnostic workup was unremarkable except for pyuria and minimal albuminuria on urinalysis. In the absence of other risk factors and the temporal relationship between pembrolizumab administration and the onset of acute kidney injury (AKI), immune-related nephrotoxicity was the underlying diagnosis. After initiation of corticosteroids, creatinine decreased back to baseline without the need for kidney biopsy. An addendum to the original pathology report from the outside facility surfaced 5 months after starting treatment, revealing that the second breast lesion had a Fluorescence in situ hybridization (FISH) test performed that was positive. Given this fact, therapy was changed to two cycles of neoadjuvant paclitaxel/carboplatin/trastuzumab/pertuzumab, with approximately 8 weeks between the last pembrolizumab dose and the first dose of trastuzumab. Thereafter, she underwent a right breast mastectomy which showed residual invasive carcinoma with negative margins and lymph nodes. She completed 1 year of trastuzumab. Immune-related AKI is a rare, but potentially serious complication associated with an increase in mortality. Further research is needed in the development and early detection. There is promising research in the development of noninvasive biomarkers which has the added benefit of identifying patients who can be re-challenged with immunotherapy.

Chronic Lymphocytic Leukemia: Management of Adverse Events in the Era of Targeted Agents.

The treatment landscape for CLL has undergone a profound transformation with the advent of targeted agents (TAs) like Bruton's Tyrosine Kinase inhibitors (BTKis) and BCL-2 inhibitors (BCL-2is). These agents target crucial cellular pathways in CLL, offering superior efficacy over traditional chemo-immunotherapy, which has led to improved progression-free and overall survival rates. This advancement promises enhanced disease control and potentially normal life expectancy for many patients. However, the journey is not without challenges, as these TAs are associated with a range of adverse events (AEs) that can impact treatment efficacy and patient quality of life. This review focuses on detailing the various AEs related to TA management in CLL, evaluating their frequency and clinical impact. The aim is to present a comprehensive guide to the effective management of these AEs, ensuring optimal tolerability and efficacy of TAs. By reviewing the existing literature and consolidating findings, we provide insights into AE management, which is crucial for maximizing patient outcomes in CLL therapy.

Practical guidelines for the management of adverse events of the T cell engager bispecific tebentafusp.

Tebentafusp is a new T cell receptor bispecific fusion protein and the first approved treatment option for human leucocyte antigen-A*02:01 (HLA-A*02:01) metastatic uveal melanoma, with a proven benefit in overall survival versus the investigator's choice. As a first-in-class therapeutic option, this Immune mobilising monoclonal T cell receptor Against Cancer (ImmTAC) is associated with a new adverse event (AE) profile. Based on clinical experience, a national expert group discussed recommendations for tebentafusp treatment, focusing on AE management. Further topics included prerequisites for initiating tebentafusp treatment, appropriate treatment setting, and patient selection criteria. To provide guidance for treating physicians, the resulting recommendations are summarised including a model standard operating procedure for AE management. Patients in good clinical condition and with a low tumour burden are good candidates for tebentafusp treatment, particularly if treated as early as possible after the diagnosis of metastatic disease. The safety profile of tebentafusp is manageable and includes two major pathologies: cytokine release syndrome (CRS) and skin-related events. Postdose monitoring should thus focus on pyrexia and hypotension as the first symptoms of cytokine release. To minimise the risk of hypotension associated with CRS, patients should receive intravenous fluids before starting treatment. The monitoring of liver values is crucial, as patients may experience an increase in transaminases, which can even manifest as tumour lysis syndrome.

Olaparib tolerability and common adverse-event management in patients with metastatic castration-resistant prostate cancer: Further analyses from the PROfound study.

BACKGROUND: Based on PROfound, olaparib is approved for patients with metastatic castration-resistant prostate cancer following disease progression on at least enzalutamide or abiraterone and who carry relevant alterations in DNA repair genes. To facilitate continued olaparib treatment as long as the patient derives benefit, we describe further safety assessments from PROfound focusing on the four most common adverse events (AEs) and events of special interest. METHODS: Patients were randomized (2:1) to olaparib tablets (300 mg bid) or control (enzalutamide or abiraterone) until disease progression or unacceptable toxicity. Safety was assessed through AE reporting and laboratory assessments. Safety data were also collected from all patients in the control group who experienced radiographic disease progression and subsequently crossed over to olaparib treatment. RESULTS: 256 patients received olaparib and 130 control. Incidence rates for the four most commonly occurring AEs in the olaparib group (all-causality) were anaemia 50%, nausea 43%, fatigue/asthenia 42% and decreased appetite 31%. All were mostly Grade 1 and 2 and all peaked within the first 2 months of treatment as the events were managed where appropriate, primarily with dose interruptions or dose reductions. The extent of bone metastases at baseline or prior taxane use was not associated with the rate of anaemia. Pneumonitis was reported in 2% and 1.5% of patients in the olaparib and control groups, respectively, and one patient (0.4%) in the olaparib group experienced an event of MDS/AML after a 30-day follow-up period. Venous thromboembolic events occurred in 8% of olaparib and 3% of control patients. CONCLUSIONS: The four most common AEs observed in PROfound were generally manageable without the need for treatment discontinuation, allowing patients to remain on treatment for as long as they were deriving clinical benefit. CLINICALTRIALS: gov registration number: NCT02987543.

Management of adverse events associated with cabozantinib plus nivolumab in renal cell carcinoma: A review.

Tyrosine kinase inhibitors have been successfully developed in combination with immune checkpoint inhibitors to treat advanced renal cell carcinoma (RCC), further advancing treatment. While safety profiles are generally manageable with combination regimens, overlapping adverse events (AEs) and immune-related AEs can make treatment more complex. The CheckMate 9ER study evaluated the tyrosine kinase inhibitor cabozantinib in combination with the anti-programmed cell death protein-1 antibody nivolumab in patients with previously untreated advanced RCC. Cabozantinib + nivolumab demonstrated superiority over sunitinib for progression-free survival, overall survival, and objective response rate. These outcomes supported the approval of cabozantinib + nivolumab as a first-line therapy for advanced RCC. The safety profile was manageable with prophylaxis, supportive care, dose holds and reductions for cabozantinib, and dose holds and immunosuppressive therapy for nivolumab. This review discusses the safety results of CheckMate 9ER and provides guidance on managing some of the more clinically relevant AEs with a focus on overlapping AEs, including diarrhea, elevated amylase/lipase, hepatotoxicity, dermatologic reactions, fatigue, endocrine disorders, and nephrotoxicity. We discuss AE management strategies (prophylaxis, supportive care, dose modification, and immunosuppressive therapy), and provide recommendations for identifying the causative agent of overlapping AEs and for consulting specialists about organ-specific immune-related AEs. Optimizing AE management can maintain tolerability and should be a priority with cabozantinib + nivolumab treatment.

Practical considerations in the management of inhaled prostacyclin therapy for pulmonary hypertension associated with interstitial lung disease (WHO group 3).

Pulmonary hypertension (PH), as a consequence of lung disease or hypoxia, has been classified as Group 3 PH by the World Symposium on Pulmonary Hypertension. The most common lung diseases associated with Group 3 PH are chronic obstructive pulmonary disease (COPD) and interstitial lung disease (ILD). PH in ILD (PH-ILD) is associated with reduced exercise capacity, greater supplemental oxygen needs, decreased quality of life, and earlier death compared to ILD alone. Several agents have been evaluated in clinical trials for the treatment of Group 3 PH, but only one treatment has been recently approved by the FDA as conclusively demonstrating efficacy for the treatment of pulmonary hypertension in this group. In the INCREASE study, treprostinil inhalation solution (Tyvaso) demonstrated significant clinical benefit for patients with PH-ILD. The inhaled route of administration may be associated with cough, throat irritation, pharyngolaryngeal pain and risk of bronchospasm and are important considerations upon initiation of therapy. Here we provide a practical review of inhaled prostacyclin therapy and suggestions for healthcare professionals to optimize the management and outcomes for the treatment of WHO Group 3, PH-ILD patients. Recommendations include up-to-date practical considerations pertaining to the entire care team and encompass patient education and communication, monitoring, titration methods and mitigation of side effects.

Immunotherapy-related gastritis: Two case reports and literature review.

Immunotherapy is increasingly defining a role in a wide variety of tumours such that as use becomes more ubiquitous, so too will the complications. A relatively rare complication of immunotherapy use is immune-related gastritis. In this case series, we present two cases of immunotherapy-related gastritis from our institution and undertake a comprehensive review and analysis of the literature around this less common adverse event.

A prospective phase II study of multimodal prophylactic treatment for afatinib-induced adverse events in advanced non-small cell lung cancer (Niigata Lung Cancer Treatment Group 1401).

BACKGROUND: Afatinib has shown clinical benefits in patients with non-small cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) mutations. Many patients treated with afatinib experience skin or gastrointestinal toxicity. However, an effective management strategy has not been established. This prospective study was conducted to evaluate the efficacy of multimodal prophylactic treatment for afatinib-induced toxicity. METHODS: This single-arm prospective study was conducted to evaluate the efficacy of multimodal prophylactic treatment for afatinib-induced toxicity in patients with EGFR mutation positive advanced NSCLC who planned to receive a 40 mg dose of afatinib. Eligible patients were treated with oral loperamide (2 mg twice per day), prophylactic minocycline (100 mg once per day), topical medium-class steroids, and gargling with sodium azulene. The primary endpoint was the ability of prophylactic loperamide to prevent severe or intolerable diarrhea during the 4 weeks after the initial administration of afatinib. The incidence, severity and time to occurrence of diarrhea, rash, oral mucositis and paronychia were evaluated based on a daily patient questionnaire. RESULTS: Forty-six patients were enrolled. The primary endpoint analysis was performed in 35 patients as the per-protocol (PP) population. The 4-week successful prophylaxis rate for severe or intolerable diarrhea was 82.9% (90% confidence interval: 70.1-91.9%). In the total population, the incidences of grade 3 or higher rash, oral mucositis and paronychia within 4 weeks were 4%, 2% and 4%, respectively. CONCLUSIONS: Prophylactic loperamide administration was not effective in preventing severe or intolerable diarrhea during afatinib treatment. Adequate dose reduction will be a better approach to manage afatinib-induced diarrhea. Multimodal prevention using minocycline, topical steroids and gargling with sodium azulene may be helpful to maintain compliance with afatinib treatment (UMIN000016167).

Immunotherapy Induced Myasthenic-Like Syndrome in a Metastatic Melanoma Patient With Amyotrophic Lateral Sclerosis.

Immunotherapy agents such as ipilimumab and nivolumab are immensely effective in the treatment of various malignancies. Despite this, neurologic immune-related sequelae (NIRS) have been observed. Prompt diagnosis and treatment is critical to improve patient outcomes. We present a case of a 63-year-old man with stage IV metastatic melanoma beginning treatment with ipilimumab and nivolumab. Gathered history from the patient showed that he had a 3-year presentation of bradykinesia, shuffling gait, and muscle cramping. After one dose, the patient began to have progressively worsening generalized weakness; after receiving the immunotherapy, there was a rapid decline in his health. In addition to weakness, the patient developed diplopia, impaired single breath count, lingual and upper/lower extremity fasciculations, and brisk reflexes. While the lumbar puncture and myasthenia panel were non-diagnostic, the electromyography (EMG) revealed axonal neuropathy and diffuse denervation/reinnervation changes. Furthermore, a magnetic resonance imaging (MRI) displayed fatty replacement of the tongue with a bright tongue sign. These results pointed to the diagnosis of amyotrophic lateral sclerosis (ALS) superimposed onto myasthenic-like syndrome. The patient was started on various treatments; however, unfortunately he died due to acute hypoxic respiratory failure. This case highlights important considerations that must be taken when using immunotherapy, especially in patients with pre-existing neurological deficits. Furthermore, it shows the importance of early diagnosis as treatment can potentially cure adverse sequelae.

Value of clinical trial narrative data to estimate the costs of adverse event management: a feasibility study.

Aims: The objective of this feasibility study was to determine the extent to which data from randomized controlled trials (RCTs) may serve as a useful source for collecting health care resource use (HCRU) for the purposes of estimating costs of managing adverse events (AEs), specifically, grade 3-4 nausea and thrombocytopenia, which may be experienced during chemotherapy treatment.Materials and Methods: The feasibility study was conducted in four steps: (1) HCRU data were extracted from patient narratives in four phase 3 RCTs in non-small cell lung cancer; (2) missing HCRU data were imputed; (3) unit costs were applied to the resulting HCRU data set and costs of managing AEs were estimated; and (4) the overall utility of using RCT data as a source for estimating costs of AEs was evaluated.Results: 33 nausea and 68 thrombocytopenia AEs met eligibility criteria and were evaluated in this study. Medication usage was recorded as a treatment in 76% of nausea AEs, although only 14% of the instances of medication usage included the minimum data elements required for costing. Platelet transfusions were provided in 24% of thrombocytopenia AEs; however, in only one instance were the minimum data elements recorded. Of nausea and thrombocytopenia AEs, 18% and 72%, respectively, required no missing data assumptions or imputation.Limitations: Only two AEs were considered, and they may not be representative of all AEs in terms of suitability for use in estimating HCRU and costs of managing AEs. Not all grade 3-4 AEs met the criteria for requiring a patient narrative. HCRU data in the narratives were incomplete.Conclusions: The usefulness of RCTs for estimating the costs of AEs may be improved by using a standardized form to collect HCRU data for key AEs, including an appropriate level of detail required to estimate costs of managing the AEs.