Management of adverse events related to first-generation tyrosine receptor kinase inhibitors in adults: a narrative review.

OBJECTIVE: The aim of this article is to conduct a literature review on first-generation TRK inhibitors (TRKi), namely entrectinib and larotrectinib, to describe the most common adverse events (AEs) and their management in adults. METHODS: A search strategy was conducted in MEDLINE, EMBASE, and Google Scholar using a list of predetermined keywords. Peer-reviewed articles written in English and published through June 2021 were included. Articles covered included randomized clinical trials and expert recommendations, as well as patent and other types of reviews. RESULTS: The discussed AEs include weight gain and withdrawal pain, as well as neuromuscular, central nervous system (dysesthesias and peripheral sensory neuropathies, dizziness and ataxia, and dysgeusia), gastrointestinal (nausea, vomiting, and diarrhea), and respiratory symptoms. Additionally, several AEs encountered with entrectinib specifically (cognitive and vision disorders, congestive heart failure, QTc elongation, and skeletal fractures) are discussed. First, an overall mechanism of action explaining these AEs is presented. Then, for each AE, incidence and severity are stated and followed by practical management recommendations. While nearly all AEs were reversible upon TRKi suspension, the proposed managements are mainly constituted of pharmacological and non-pharmacological interventions. CONCLUSION: With the estimated growth of gene sequencing in the coming years, it is foreseeable that TRKi will take a larger position in the oncologic therapeutic arsenal. Therefore, adequate management of AEs associated with TRKi in adults should be a prime focus.

Adjuvant treatment for endometrial cancer: literature review and recommendations by the Comité de l'évolution des pratiques en oncologie (CEPO).

OBJECTIVE: Despite the very good prognosis of endometrial cancer, a number of patients with localized disease relapse following surgery. Therefore, various adjuvant therapeutic approaches have been studied. The objective of this review is to evaluate the efficacy and safety of neoadjuvant and adjuvant therapies in patients with resectable endometrial cancer and to develop evidence-based recommendations. METHODS: A review of the scientific literature published between January 1990 and June 2012 was performed. The search was limited to published phase III clinical trials and meta-analyses evaluating the efficacy of neoadjuvant or adjuvant therapies in patients with endometrial carcinoma or carcinosarcoma. A total of 23 studies and five meta-analyses were identified. RESULTS: The selected literature showed that in patients with a low risk of recurrence, post-surgical observation is safe and recommended in most cases. There are several therapeutic modalities available for treatment of endometrial cancers with higher risk of recurrence, including vaginal brachytherapy, external beam radiotherapy, chemotherapy, or a combination of these. CONCLUSIONS: Considering the evidence available to date, the CEPO recommends the following: (1)post-surgical observation for most patients with a low recurrence risk; (2)adjuvant vaginal brachytherapy for patients with an intermediate recurrence risk; (3)adjuvant pelvic radiotherapy with or without vaginal brachytherapy for patients with a high recurrence risk; addition of adjuvant chemotherapy may be considered as an option for selected patients (excellent functional status, no significant co-morbidities, poor prognostic factors); (4)adjuvant chemotherapy and pelvic radiotherapy with or without brachytherapy and para-aortic irradiation for patients with advanced disease;

Patient and work flow and costs associated with staff time and facility usage at a comprehensive cancer centre in Quebec, Canada--a time and motion study.

BACKGROUND: Mapping patient and work flow and cost analysis studies can help determine the most efficient and cost effective way of providing health services while still maintaining the best standards of care. This study used both time and motion methodology and hospital data to assess the contribution of staff time and facility usage to the overall cost of cancer care during patient visits to a comprehensive cancer centre in Quebec, using metastatic colorectal cancer as a model. METHODS: A workflow diagram was created mapping direct and indirect steps involved during a patient's physician or treatment (FOLFOX/bevacizumab or XELOX/bevacizumab) visit. Staff were timed as they performed each task and this data together with compensation amounts were used to calculate personnel costs. Mean work times and 95% confidence intervals (CI) were calculated. Operation and maintenance (O&M) costs for the Centre were calculated using information from hospital databases. All costs were presented in constant Canadian dollars for the 2010-2011 fiscal year period. RESULTS: For physician visits, direct and indirect personnel costs were $9.25 (95%CI:$7.00-$11.51) and O&M costs were $60.21, for a total of $69.46 (95%CI:$67.21-$71.72). For treatment visits, personnel and O&M costs were $71.91 (95%CI:$45.53-$98.29) and $62.00 respectively for a total of $133.91 (95%CI:$107.53-$160.29). When calculated for treatment alone, the total cost was $136.06 (95%CI:$109.16-$162.95) for FOLFOX/bevacizumab and $119.94 (95%CI:$96.89-$142.99) for XELOX/bevacizumab. The highest cumulative personnel costs were for the pharmacists and nurses ($38.87 and $34.82 respectively). Regarding patient flow, total time in between steps was 77.6 and 49.5 minutes for a physician or treatment visit respectively. CONCLUSIONS: This study from a health care provider's perspective, demonstrated that in the context of increasingly expensive therapies, costs associated with staff time and facility usage do not contribute greatly to the overall cost of treating cancer at this cancer centre. It also illustrated the need for improvements in patient and work flow to reduce wait times in the clinic.

Changes in pattern of use, clinical characteristics and persistence rate of hormone replacement therapy among postmenopausal women after the WHI publication.

UNLABELLED: The WHI was stopped prematurely because of an increased risk of breast cancer, stroke and cardiovascular diseases (CVD) in the hormone replacement therapy (HRT) arm of the trial. Changes in the use of HRT are expected. OBJECTIVE: To assess the impact of the Women's Health Initiative (WHI) publication on the rate of HRT prescription, and the clinical characteristics and persistence rate of new users and its determinants. METHODS: From the RAMQ databases, the total numbers of HRT prescriptions, and of new HRT's users were calculated between 2 January 1998 and 31 May 2003. To assess the clinical characteristics of women, two retrospective cohorts of new HRT's users were constructed before (pre-WHI) and after (post-WHI) the WHI study publication. The persistence rate after 1 year of follow-up was estimated using a Kaplan-Meier analysis. Cox regression models were used to estimate the rate ratio of HRT cessation. RESULTS: The total numbers of HRT users and of new users declined respectively by 28% and 50% in post-WHI. The standard dosage of HRT was significantly less used, while the proportion of women with risk factors of CVD or at very high risk of coronary artery disease (CAD) did not change. The rate of persistence in the pre-WHI cohort was 59% compared to 45% in the post-WHI (p < 0.0001), and women with risk factors of CVD or at very high risk of CAD were less likely to cease their HRT. CONCLUSION: One year after publication, significant changes had already occurred in the trends of use, women's characteristics and estrogen dosage. No change in the proportion of new users with CVD risk factors or at very high risk of CAD was seen.