Explore the vast range of titles available.

Summary Purpose Preclinical data showed that trientine, a copper-lowering agent, re-sensitized cancer cells to carboplatin through enhanced human copper transporter 1 (hCtr1) -mediated platinum uptake. Experimental Design We studied carboplatin and trientine in patients ( n  = 55; 45 who had failed platinum) with advanced malignancies (Phase I, modified 3 + 3 design). Results The most common cancers were head and neck ( n  = 13), non-small cell lung ( n  = 10) and epithelial ovarian ( n  = 8). The median number of prior regimens was four. No dose-limiting toxicity or treatment-related deaths were observed at doses up to carboplatin AUC 6 given with trientine. Eight patients achieved stable disease (SD) ≥ 6 months (six platinum failures) and one patient with platinum-resistant ovarian cancer, partial response (PR) (total SD ≥ 6 months/PR = 9, 16.4 %). The mean nadir serum copper level in the nine patients with SD ≥ 6 months/PR was 0.55 μg/mL (95 % CI, 0.34–0.75) versus 1.22 μg/mL (95 % CI, 1.02–1.42) ( p  < 0.001) in 38 tested patients with progression. In patients who maintained their ceruloplasmin (major copper-carrying protein) levels at 5–15 mg/dL ( n  = 9), the median progression-free and overall survivals were 9.2 and 15.2 months versus 1.9 ( p  = 0.001) and 5.7 months ( p  = 0.033) in patients who did not ( n  = 38), respectively. Conclusions The combination of a copper-lowering agent with carboplatin was well tolerated and associated with antitumor activity, especially in patients in whom copper and/or ceruloplasmin levels were lowered. Further investigation of this strategy for reversing platinum resistance is warranted.

Penicillamine(D-Penicillamine) and trientine are first-line therapies for Wilson's Disease (WD), yet real-world data on their adverse events (AEs) remain scarce. We analyzed the FDA Adverse Event Reporting System (FAERS) to comprehensively assess the safety of penicillamine and trientine in WD treatment. AEs for penicillamine and trientine (2004Q1-2024Q4) were analyzed using Proportional Reporting Ratio (PRR), Reporting Odds Ratio (ROR), and Bayesian Confidence Propagation Neural Network (BCPNN). We found 1,452 and 760 AEs related to penicillamine and trientine, respectively. In all adverse event (AE) reports, the ratio of females to males was approximately 1.3, with the highest proportion of AE reports in the 21-30 age group, and the largest number of AE reports coming from the United States. Signal detection showed that the most commonly reported AEs for penicillamine and trientine were drug hypersensitivity and tremor, respectively, with the highest proportions in the SOC categories of immune system disorders and gastrointestinal disorders. The main AEs for both drugs involved condition aggravated, and identified potential safety signals requiring further validation for the two drugs, such as decreased bone density and brain atrophy for penicillamine, and memory impairment, oesophageal ulcer and starvation for trientine. In addition, we found that women were more likely to experience drug hypersensitivity in penicillamine adverse event reports, while men were more likely to experience cutis laxa. This study reveals the characteristics of AEs and potential associated risks in the clinical application of penicillamine and trientine, emphasizing individualized medication and vigilant monitoring strategies to provide guidance for safe medication use.

Objectives Wilson disease (WD) is a rare genetic disease affecting copper metabolism and the biliary tract’s copper excretion. Lifelong medication is necessary to prevent liver failure, neurological complications, and death. Although D-penicillamine (DPA), trientine, and zinc are used to treat WD, there is limited research on the long-term outcomes of these drugs, especially in children. This study aimed to evaluate the efficacy and safety of DPA, trientine, and zinc in patients diagnosed with WD during childhood. Methods Ninety out of 92 patients were included in the analysis, excluding two patients who underwent liver transplantation without drug treatment due to an acute liver failure diagnosis. Treatment outcomes and reasons for discontinuation of therapy in 148 treatment blocks (37 DPA, 50 trientine, and 61 zinc) were analyzed using Kaplan–Meier analysis. Results The median age at diagnosis was 8.3 years. There was a statistically significant difference in drug changes due to treatment ineffectiveness among the three drugs: trientine (22/50, 44%), zinc (15/61, 25%), and DPA (2/37, 5%) (all p  < 0.05). Regarding drug changes due to adverse effects, the rate was the highest for DPA, followed by zinc and trientine. There were significant differences between DPA and zinc, zinc and trientine (all p  < 0.05), but no significant difference was observed between DPA and zinc ( p  = 0.22). Conclusions In pediatric WD, DPA, zinc, and trientine have therapeutic effects in that order. However, DPA and zinc are associated with more adverse effects compared to trientine.

Background Wilson disease requires lifelong therapy, currently given daily in multiple divided dosages. Aim To prospectively evaluate once-daily trientine as therapy for Wilson disease. Methods Study group: eight patients (seven males) aged 22–71 years with stable Wilson disease treated from 4 to 50 years. Patients were monitored for 3 months then for 12 months on a single daily dose of trientine (15 mg/kg). Results All patients remained clinically well. ALT and AST fluctuated in some, but none required treatment stoppages or side effects. Liver synthetic function was unchanged. Mean 24-h urine copper and zinc excretions at end of treatment were 313.4 ± 191.7 and 2,214 ± 1,346 μg, respectively. Conclusions Once-daily trientine should be explored further for possible maintenance therapy for WD. Single daily dose may improve adherence to therapy. Larger trials and longer-term follow-up will establish the safety and treatment efficacy of this once-daily treatment regimen for WD (registration: NCT01472874).

Background and Aims Current guidelines favor the use of chelating agents (d-penicillamine, trientine) in first line therapy of symptomatic Wilson disease patients. Development of chelator induced immunological adverse events are a concern especially under d-penicillamine therapy. This study assessed the prevalence of co-existing or therapy-related immune-mediated diseases in Wilson disease patients, and evaluated the role of antinuclear antibodies in therapy monitoring. Methods We retrospectively analyzed 235 Wilson disease patients. Medical regimens were classified and analyzed in relation to adverse events and antinuclear antibody courses. Results Coexisting immune-mediated diseases were evident in 19/235 (8.1 %) patients, of which 13/235 (5.5 %) had pre-existing autoimmune diseases. Six patients (2.6 %) developed an autoimmune disease under therapy, all of them under long-term d-penicillamine treatment. Data relating to antinuclear antibody courses during treatment and adverse events were available for patients treated with d-penicillamine ( n  = 91), trientine ( n  = 58), and zinc salts ( n  = 58). No significant increase in antinuclear antibody titers in patients treated with d-penicillamine (16/91; 17.6 %), trientine (12/58; 20.7 %), and zinc (7/58; 12.1 %) were found. Conclusion Under long-term d-penicillamine therapy a minority of patients developed immune-mediated disease. Elevations in antinuclear antibodies were found frequently, but no correlations were evident between increases in antinuclear antibodies and the development of immune-mediated diseases or medical regimes. Thus, the value of antinuclear antibodies for monitoring adverse events under chelator therapy seems to be limited.

Background Wilson disease (WD) is an autosomal recessive disorder of human copper metabolism characterized by copper accumulation in the liver due to impaired excretion of copper into the bile. Brain accumulation of copper may cause neuropsychiatric symptoms. Trientine (triethylenetetramine dihydrochloride) is a copper-chelating agent used to treat patients with WD. Trientine has been considered an option for initial treatment and maintentance therapy of WD due to its safety profile. Case presentation A 40 year old female with a recent diagnosis of WD was started on treatment with trientine for her WD. Within one month she developed profound bloody diarrhea unresponsive to medical treatment. Trientine was discontinued and a colonoscopy with biopsy showed moderately active ileitis and moderate to severe pancolitis, consistent with a drug induced mucosal injury. The colitis improved immediately upon withdrawal of trientine, and recurred when medication was rechallenged because of worsened WD symptoms. After second compulsory discontinuation of trientine, she remained on zinc therapy for her WD and her colitis resolved by time. Conclusion Drug induced colitis is a very rare side effect of trientine. Although trientine therapy is well tolerated and less side effects are reported with this medication than penicillamine, colitis can occur during trientine treatment. Zinc therapy may be an effective alternative for treatment of WD in patients experiencing side effects from chelation therapy.

The mother (H10690/E1064K) presented with late-onset neurological symptoms, whereas her son (E1064K/ E1064K) presented with early-onset, rapidly progressing acute liver failure requiring orthotopic liver transplantation.

Penicillamine(D-Penicillamine) and trientine are first-line therapies for Wilson's Disease (WD), yet real-world data on their adverse events (AEs) remain scarce. We analyzed the FDA Adverse Event Reporting System (FAERS) to comprehensively assess the safety of penicillamine and trientine in WD treatment. AEs for penicillamine and trientine (2004Q1-2024Q4) were analyzed using Proportional Reporting Ratio (PRR), Reporting Odds Ratio (ROR), and Bayesian Confidence Propagation Neural Network (BCPNN). We found 1,452 and 760 AEs related to penicillamine and trientine, respectively. In all adverse event (AE) reports, the ratio of females to males was approximately 1.3, with the highest proportion of AE reports in the 21-30 age group, and the largest number of AE reports coming from the United States. Signal detection showed that the most commonly reported AEs for penicillamine and trientine were drug hypersensitivity and tremor, respectively, with the highest proportions in the SOC categories of immune system disorders and gastrointestinal disorders. The main AEs for both drugs involved condition aggravated, and identified potential safety signals requiring further validation for the two drugs, such as decreased bone density and brain atrophy for penicillamine, and memory impairment, oesophageal ulcer and starvation for trientine. In addition, we found that women were more likely to experience drug hypersensitivity in penicillamine adverse event reports, while men were more likely to experience cutis laxa. This study reveals the characteristics of AEs and potential associated risks in the clinical application of penicillamine and trientine, emphasizing individualized medication and vigilant monitoring strategies to provide guidance for safe medication use.

Progressive hepatolenticular degeneration, or Wilson's disease, is a genetic disorder of copper metabolism. Knowledge of the clinical presentations and treatment of the disease are important both to the generalist and to specialists in gastroenterology and hepatology, neurology, psychiatry, and paediatrics. Wilson's disease invariably results in severe disability and death if untreated. The diagnosis is easily overlooked but if discovered early, effective treatments are available that will prevent or reverse many manifestations of this disorder. Studies have identified the role of copper in disease pathogenesis and clinical, biochemical, and genetic markers that can be useful in diagnosis. There are several chelating agents and zinc salts for medical therapy. Liver transplantation corrects the underlying pathophysiology and can be lifesaving. The discovery of the Wilson's disease gene has opened up a new molecular diagnostic approach, and could form the basis of future gene therapy.