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Frontiers in Pharmacology 2024Urothelial carcinoma (UC) is a refractory disease for which achieving satisfactory outcomes remains challenging with current surgical interventions. Antibody-drug...
Urothelial carcinoma (UC) is a refractory disease for which achieving satisfactory outcomes remains challenging with current surgical interventions. Antibody-drug conjugates (ADCs) are a novel class of targeted therapeutics that have demonstrated encouraging results for UC. Although there is a limited number of high-quality randomized control trials (RCTs) examining the use of ADCs in patients with UC, some prospective non-randomized studies of interventions (NRSIs) provide valuable insights and pertinent information. We aim to assess the efficacy and safety of ADCs in patients with UC, particularly those with locally advanced and metastatic diseases. A systematic search was conducted across PubMed, Embase, the Cochrane Library, and Web of Science databases to identify pertinent studies. Outcomes, such as the overall response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), adverse events (AEs), and treatment-related adverse events (TRAEs), were extracted for further analyses. Twelve studies involving 1,311 patients were included in this meta-analysis. In terms of tumor responses, the pooled ORR and DCR were 40% and 74%, respectively. Regarding survival analysis, the pooled median PFS and OS were 5.66 months and 12.63 months, respectively. The pooled 6-month PFS and OS were 47% and 80%, while the pooled 1-year PFS and OS were 22% and 55%, respectively. The most common TRAEs of the ADCs were alopecia (all grades: 45%, grades ≥ III: 0%), decreased appetite (all grades: 34%, grades ≥ III: 3%), dysgeusia (all grades: 40%, grades ≥ III: 0%), fatigue (all grades: 39%, grades ≥ III: 5%), nausea (all grades: 45%, grades ≥ III: 2%), peripheral sensory neuropathy (all grades: 37%, grades ≥ III: 2%), and pruritus (all grades: 32%, grades ≥ III: 1%). The meta-analysis in this study demonstrates that ADCs have promising efficacies and safety for patients with advanced or metastatic UC. https://www.crd.york.ac.uk/prospero/, identifier: CRD42023460232.
PubMed: 38933670
DOI: 10.3389/fphar.2024.1377924 -
Nutrients Jun 2024Taste disorders (TDs) are common among systemically treated cancer patients and negatively impact their nutritional status and quality of life. The novel food approved... (Randomized Controlled Trial)
Randomized Controlled Trial
Taste disorders (TDs) are common among systemically treated cancer patients and negatively impact their nutritional status and quality of life. The novel food approved by the European Commission (EFSA), dried miracle berries (DMB), contains the natural taste-modifying protein miraculin. DMB, also available as a supplement, has emerged as a possible alternative treatment for TDs. The present study aimed to evaluate the efficacy and safety of habitual DMB consumption in malnourished cancer patients undergoing active treatment. An exploratory clinical trial was carried out in which 31 cancer patients were randomized into three arms [standard dose of DMB (150 mg DMB/tablet), high dose of DMB (300 mg DMB/tablet) or placebo (300 mg freeze-dried strawberry)] for three months. Patients consumed a DMB tablet or placebo daily before each main meal (breakfast, lunch, and dinner). Throughout the five main visits, electrochemical taste perception, nutritional status, dietary intake, quality of life and the fatty acid profile of erythrocytes were evaluated. Patients consuming a standard dose of DMB exhibited improved taste acuity over time (% change right/left side: -52.8 ± 38.5/-58.7 ± 69.2%) and salty taste perception (2.29 ± 1.25 vs. high dose: 2.17 ± 1.84 vs. placebo: 1.57 ± 1.51 points, < 0.05). They also had higher energy intake ( = 0.075) and covered better energy expenditure (107 ± 19%). The quality of life evaluated by symptom scales improved in patients receiving the standard dose of DMB (constipation, = 0.048). The levels of arachidonic (13.1 ± 1.8; 14.0 ± 2.8, 12.0 ± 2.0%; = 0.004) and docosahexaenoic (4.4 ± 1.7; 4.1 ± 1.0; 3.9 ± 1.6%; = 0.014) acids in erythrocytes increased over time after DMB intake. The standard dose of DMB increased fat-free mass vs. placebo (47.4 ± 9.3 vs. 44.1 ± 4.7 kg, = 0.007). Importantly, habitual patients with DMB did not experience any adverse events, and metabolic parameters remained stable and within normal ranges. In conclusion, habitual consumption of a standard 150 mg dose of DMB improves electrochemical food perception, nutritional status (energy intake, fat quantity and quality, fat-free mass), and quality of life in malnourished cancer patients receiving antineoplastic treatment. Additionally, DMB consumption appears to be safe, with no changes in major biochemical parameters associated with health status. Clinical trial registered (NCT05486260).
Topics: Humans; Male; Female; Pilot Projects; Neoplasms; Middle Aged; Malnutrition; Dietary Supplements; Quality of Life; Aged; Nutritional Status; Treatment Outcome; Taste Perception; Adult
PubMed: 38931260
DOI: 10.3390/nu16121905 -
Biomedicines May 2024The SARS-CoV-2 virus has spread rapidly despite implementing strategies to reduce its transmission. The disease caused by this virus has been associated with a diverse... (Review)
Review
The SARS-CoV-2 virus has spread rapidly despite implementing strategies to reduce its transmission. The disease caused by this virus has been associated with a diverse range of symptoms, including common neurological manifestations such as dysgeusia, anosmia, and myalgias. Additionally, numerous cases of severe neurological complications associated with this disease have been reported, including encephalitis, stroke, seizures, and Guillain-Barré syndrome, among others. Given the high prevalence of neurological manifestations in this disease, the objective of this review is to analyze the mechanisms by which this virus can affect the nervous system, from its direct invasion to aberrant activation of the immune system and other mechanisms involved in the symptoms, including neuropsychiatric manifestations, to gain a better understanding of the disease and thus facilitate the search for effective therapeutic strategies.
PubMed: 38927354
DOI: 10.3390/biomedicines12061147 -
International Journal of Surgery Case... Jun 2024Vitamin B12 deficiency can manifest through various oral manifestations such as glossitis, glossodynia, recurrent ulcers, cheilitis, dysgeusia, lingual paresthesia,...
INTRODUCTION AND IMPORTANCE
Vitamin B12 deficiency can manifest through various oral manifestations such as glossitis, glossodynia, recurrent ulcers, cheilitis, dysgeusia, lingual paresthesia, burning sensations, and pruritus. These oral signs can serve as early indicators of systemic conditions such pernicious anemia.
CASE PRESENTATION
A 67 year old northern African female presented at the oral surgery service with complaints of a sore mouth and difficulty eating certain types of food. Her medical history revealed hypothyroidism and no history of gastrectomy. She was diagnosed with pernicious anemia in 2014 and is under hydroxocobalamin injection 5000μg/month since then. Dental history indicated extraction of all teeth, and in 2014, the patient was diagnosed with oral lichen planus. There were no contributory oral habits. Intraoral examination revealed a band like erythematous lesion on the palate with two superficial ulcerations, diagnosed as related to her pernicious anemia. The patient was prescribed a mouthwash containing sodium bicarbonate and corticosteroid to reduce inflammation and alleviate pain. A low level laser therapy was also considered to reduce the burning sensations.
CLINICAL DISCUSSION
Pernicious anemia (PA) is an autoimmune disease characterized by the gradual atrophy of the gastric mucosa, predominantly affecting the body and fundus of the stomach, leading to vitamin B12 deficiency. Its insidious onset often masks its presence. Patients have no anemic symptoms. However, they can present with oral manifestations related to vitamin B12 deficiency. Those oral signs can precede hematological symptoms helping in early diagnosis of PA.
CONCLUSION
Dentists and other oral health care providers must be aware of this condition and its oral manifestations. Investigating vitamin B12 levels should be considered in patients presenting with oral ulcers, oral erythema or burning sensations without an apparent origin.
PubMed: 38917702
DOI: 10.1016/j.ijscr.2024.109931 -
Clinical Nutrition ESPEN Jun 2024Among the side effects of chemotherapy, there is dysgeusia, which is an alteration or damage to the taste perception that negatively impacts the biopsychosocial sphere...
BACKGROUND/OBJECTIVE
Among the side effects of chemotherapy, there is dysgeusia, which is an alteration or damage to the taste perception that negatively impacts the biopsychosocial sphere of the patient. Therefore, it is important to recognize and manage it appropriately. The objective of this study is to identify clinical pharmacological strategies to reduce dysgeusia in chemotherapy patients.
METHODS
A systematic literature review was conducted following the PRISMA guidelines between February and May 2023, utilizing PubMed, Embase, Cochrane Library, CINAHL, and the British Nursing Database. Methodological quality and bias risk assessment were performed using the JBI framework, while evidence certainty was evaluated using the Oxford OCEBM methodology.
RESULTS
Out of 1225 consulted records, 12 articles were included. The results underscore the efficacy of diverse pharmacological interventions in mitigating dysgeusia among chemotherapy patients. These include zinc supplementation with a daily dosage ranging between 50 and 220 mg (p ≤ 0.005), lactoferrin at 250 mg thrice daily (p < 0.001), delta-9-tetrahydrocannabinol at 2 mg per day (p < 0.05), and cannabidiol at 150 mg per day (p = 0.04). All studies analysed showed a low risk of bias. The zinc and Delta-9-Tetrahydrocannabinoid treatment proved particularly promising, compared to the other treatments considered, where sample sizes were smaller and the placebo effect was not always clear.
CONCLUSION
Among the various pharmacological strategies identified, those that appear most promising concern the integration of zinc and Delta-9-Tetrahydrocannabinoid. Future studies should further explore the treatments identified in this review to expand the evidence base in this relatively underexplored field.
PubMed: 38900642
DOI: 10.1016/j.clnesp.2024.05.026 -
American Journal of Clinical Dermatology Jun 2024Hedgehog pathway inhibitors (HHIs) have broadened the treatment options available for patients with advanced basal cell carcinoma (BCC) for whom traditional therapeutic... (Review)
Review
Hedgehog pathway inhibitors (HHIs) have broadened the treatment options available for patients with advanced basal cell carcinoma (BCC) for whom traditional therapeutic approaches are not feasible or effective. Sonidegib and vismodegib are oral HHIs that were approved for treatment of patients with advanced BCC after demonstrating promising efficacy in the pivotal Phase II BOLT (NCT01327053) and ERIVANCE (NCT00833417) trials, respectively. However, the incidence and types of treatment-emergent adverse events (AEs) observed with these agents may limit continuous use of HHIs and ultimately impact clinical outcomes. In this review, we summarize the safety and tolerability profiles of sonidegib and vismodegib and discuss potential management strategies for HHI class-effect AEs, including muscle spasms, creatine phosphokinase increase, alopecia, and dysgeusia. These AEs primarily occur early in treatment and can lead to treatment discontinuation. Differences in the pharmacokinetic profiles of sonidegib and vismodegib may contribute to the variability noted in times to onset and resolution of these and other AEs. Evidence suggests that protocol modifications, such as treatment interruptions and dose reductions, are effective ways to manage AEs while maintaining disease control. Nonpharmacologic and pharmacologic interventions may also be considered as part of an AE management strategy. Overall, healthcare providers and patients with advanced BCC should be aware of the HHI class-effect AEs and plan effective management strategies to avoid treatment discontinuation and optimize therapeutic response.
PubMed: 38896403
DOI: 10.1007/s40257-024-00870-3 -
Cancers May 2024Proton therapy has emerged as a crucial tool in the treatment of head and neck and skull-base cancers, offering advantages over photon therapy in terms of decreasing... (Review)
Review
Proton therapy has emerged as a crucial tool in the treatment of head and neck and skull-base cancers, offering advantages over photon therapy in terms of decreasing integral dose and reducing acute and late toxicities, such as dysgeusia, feeding tube dependence, xerostomia, secondary malignancies, and neurocognitive dysfunction. Despite its benefits in dose distribution and biological effectiveness, the application of proton therapy is challenged by uncertainties in its relative biological effectiveness (RBE). Overcoming the challenges related to RBE is key to fully realizing proton therapy's potential, which extends beyond its physical dosimetric properties when compared with photon-based therapies. In this paper, we discuss the clinical significance of RBE within treatment volumes and adjacent serial organs at risk in the management of head and neck and skull-base tumors. We review proton RBE uncertainties and its modeling and explore clinical outcomes. Additionally, we highlight technological advancements and innovations in plan optimization and treatment delivery, including linear energy transfer/RBE optimizations and the development of spot-scanning proton arc therapy. These advancements show promise in harnessing the full capabilities of proton therapy from an academic standpoint, further technological innovations and clinical outcome studies, however, are needed for their integration into routine clinical practice.
PubMed: 38893068
DOI: 10.3390/cancers16111947 -
Targeted Oncology Jun 2024The approved dose of Selinexor, 60 mg twice-weekly, is associated with several clinically relevant toxicities. Preclinical studies show that a sustained-release...
BACKGROUND
The approved dose of Selinexor, 60 mg twice-weekly, is associated with several clinically relevant toxicities. Preclinical studies show that a sustained-release formulation of selinexor results in a lower toxicity profile.
OBJECTIVE
The phase 1b METSSAR trial assessed the safety and tolerability of an alternative dosing schedule of selinexor (to mimic the sustained-release formulation) in advanced soft tissue sarcoma (STS) patients.
PATIENTS AND METHODS
Selinexor was administered in a split-dose schedule (40 mg, 20 mg, 20 mg in the morning, afternoon, and evening, respectively) on days 1, 8, 15, and 22 of a 28-day cycle, until unacceptable toxicity or disease progression. The primary endpoint was the rate of grade ≥ 3 treatment-related adverse events (TRAEs). Secondary objectives were EORTC QLQ-C30 quality of life (QoL) assessment, and preliminary efficacy.
RESULTS
Twenty patients with 12 STS subtypes were enrolled and received a median of four cycles of treatment. There were no grade ≥ 3 TRAEs. Dysgeusia, nausea, fatigue, and thrombocytopenia were the most common grade ≤ 2 TRAEs. No treatments were discontinued due to TRAE, but four patients (20%) required dose reduction. Median change in global health status (GHS) score from baseline to cycle 2 (by QLQ-C30 v3.0) was - 8.33, and only 39% of patients reported a clinically meaningful decline in GHS score (≥ 10 points). Median symptom scale scores on treatment were increased for fatigue (+12.35), nausea/vomiting (+18.52), and anorexia (+16.67), but reduced for pain (- 3.70). The median progression-free survival (PFS) was 4.0 months (95% confidence interval 1.9-7.5).
CONCLUSIONS
Split-dose once-weekly selinexor was reasonably well tolerated in this heterogeneous group of advanced STS patients with a better, or at least similar, clinician- and patient-reported toxicity profile compared to the standard dosing regimen. Further clinical evaluation is warranted, as better dose delivery can lead to improved antitumor efficacy.
PubMed: 38890222
DOI: 10.1007/s11523-024-01076-7 -
Photobiomodulation, Photomedicine, and... Jun 2024
Randomized Controlled Trial
Topics: Humans; COVID-19; Dysgeusia; Single-Blind Method; Low-Level Light Therapy; Male; Female; Middle Aged; SARS-CoV-2; Aged
PubMed: 38888186
DOI: 10.1089/pho.2024.0045 -
Clinical Cancer Research : An Official... Jun 2024On November 15, 2023, the U.S. Food and Drug Administration (FDA) granted traditional approval to repotrectinib (Augtyro®, Bristol Myers Squibb Corporation), for the...
On November 15, 2023, the U.S. Food and Drug Administration (FDA) granted traditional approval to repotrectinib (Augtyro®, Bristol Myers Squibb Corporation), for the treatment of adult patients with locally advanced or metastatic ROS1-positive non-small cell lung cancer (NSCLC). The approval was based on TRIDENT-1, a single arm trial with multiple cohorts of patients with ROS1 fusion-positive (hereafter "ROS1-positive") NSCLC, (NCT03093116), who were either treatment naïve or had received prior ROS1 TKI and/or platinum-based chemotherapy. The primary efficacy outcome measure is objective response rate (ORR) assessed by blinded independent central review (BICR) using response evaluation criteria in solid tumors (RECIST) version 1.1. ORR was assessed in 71 patients who were ROS1 TKI naïve and 56 patients who had received a prior ROS1 TKI. Among 71 patients who were ROS1 TKI naïve, the ORR was 79% (95% CI 68, 88); median duration of response was 34.1 months (95% CI 26, NE). In patients who had received a prior ROS1 TKI and no prior chemotherapy, the ORR was 38% (95% CI 25, 52). The median duration of response was 14.8 months (95% CI 7.6, NE) BICR-assessed responses were observed in CNS metastases in patients in both cohorts, and in patients who developed resistance mutations following prior TKI therapy. The most common (> 20%) adverse reactions were dizziness, dysgeusia, peripheral neuropathy, constipation, dyspnea, ataxia, fatigue, cognitive disorders, and muscular weakness. A unique feature of this ROS1 TKI approval is the inclusion of robust evidence of efficacy in patients with ROS1-positive NSCLC who had progressed on prior ROS1 TKIs.
PubMed: 38875108
DOI: 10.1158/1078-0432.CCR-24-0949