Publications by authors named "Laadem A"
Purpose: To evaluate DS-6157a, an antibody-drug conjugate targeting G protein-coupled receptor 20 (GPR20), in gastrointestinal stromal tumors (GIST).
Patients And Methods: In this phase I multicenter, open-label, multiple-dose study, patients with previously treated advanced GIST received intravenous DS-6157a on Day 1 of 21-day cycles, with a starting dose of 1.6 mg/kg.
Article Synopsis
- Racial disparities in cancer outcomes are well-documented, with Black patients facing the highest death rates, but limited research exists on myelodysplastic syndromes (MDS) specifically.
- This study analyzed demographic, clinical, socioeconomic factors, and survival outcomes between Black and White MDS patients using data from 37,562 cases diagnosed between 2001 and 2013.
- Results showed that Black patients had longer overall survival compared to White patients, although this varies by specific MDS subtype and should be interpreted carefully.
Article Synopsis
- β-Thalassemia is a genetic blood disorder that causes issues with hemoglobin production, leading to the need for regular blood transfusions and potential complications like iron overload.
- Luspatercept is the first approved therapy in the U.S. that helps improve anemia in adult patients with β-thalassemia who rely on these transfusions, showing effective dosage and reduced transfusion needs.
- Studies indicate that luspatercept has a favorable safety profile and its administration is based on body weight, making it a promising alternative therapy for managing β-thalassemia.
Article Synopsis
- Luspatercept is a fusion protein that helps improve late-stage red blood cell development and has been studied in 260 patients with anemia from myelodysplastic syndromes.
- The drug has predictable pharmacokinetics and its dosage varies from 0.125 to 1.75 mg/kg, with body weight being the main factor for determining the correct dose.
- The findings indicate that higher serum levels of luspatercept improve the chances of patients achieving transfusion independence and experiencing fewer severe side effects, supporting a dose range of 1.0 to 1.75 mg/kg for effective long-term treatment.
Background: Patients with transfusion-dependent β-thalassemia need regular red-cell transfusions. Luspatercept, a recombinant fusion protein that binds to select transforming growth factor β superfamily ligands, may enhance erythroid maturation and reduce the transfusion burden (the total number of red-cell units transfused) in such patients.
Methods: In this randomized, double-blind, phase 3 trial, we assigned, in a 2:1 ratio, adults with transfusion-dependent β-thalassemia to receive best supportive care plus luspatercept (at a dose of 1.
Background: Patients with anemia and lower-risk myelodysplastic syndromes in whom erythropoiesis-stimulating agent therapy is not effective generally become dependent on red-cell transfusions. Luspatercept, a recombinant fusion protein that binds transforming growth factor β superfamily ligands to reduce SMAD2 and SMAD3 signaling, showed promising results in a phase 2 study.
Methods: In a double-blind, placebo-controlled, phase 3 trial, we randomly assigned patients with very-low-risk, low-risk, or intermediate-risk myelodysplastic syndromes (defined according to the Revised International Prognostic Scoring System) with ring sideroblasts who had been receiving regular red-cell transfusions to receive either luspatercept (at a dose of 1.
β-thalassemia is a hereditary disorder with limited approved treatment options; patients experience anemia and its complications, including iron overload. The study aim was to determine whether luspatercept could improve anemia and disease complications in patients with β-thalassemia. This open-label, nonrandomized, uncontrolled study consisted of a 24-week dose-finding and expansion stage (initial stage) and a 5-year extension stage, currently ongoing.
View Article and Find Full Text PDFβ-Thalassemia, a hereditary blood disorder caused by reduced or absent synthesis of the β-globin chain of hemoglobin, is characterized by ineffective erythropoiesis, and can manifest as nontransfusion-dependent thalassemia (NTDT) or transfusion-dependent thalassemia (TDT). Many patients with NTDT develop a wide range of serious complications that affect survival and quality of life (QoL). Patient-reported outcomes (PRO), including health-related QoL (HRQoL), are important tools for determining patient health impairment and selecting appropriate treatment.
View Article and Find Full Text PDFThis study demonstrates the quantitative characteristics of the first patient-reported outcome (PRO) tool developed for patients with nontransfusion-dependent β-thalassemia (NTDT), the NTDT-PRO . A multicenter validation study was performed over 24 weeks, involving 48 patients from Italy, Lebanon, Greece, and Thailand. Most patients were female (68.
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- β-thalassemia is a genetic blood disorder characterized by inadequate production of hemoglobin, leading to chronic anemia and potential dependence on blood transfusions.
- Sotatercept, a treatment aimed at improving red blood cell production by blocking factors that hinder erythropoiesis, was tested in a phase II study involving 46 patients across several countries, with varying doses used over a period of up to 22 months.
- The results showed that Sotatercept was well tolerated, with significant improvements in hemoglobin levels for non-transfusion-dependent patients and a notable reduction in transfusion needs for transfusion-dependent patients.
Article Synopsis
- Myelodysplastic syndromes lead to anaemia due to ineffective production of red blood cells, and sotatercept is being studied as a treatment option that targets negative regulators of this process.
- A phase 2 trial included patients with lower-risk myelodysplastic syndromes who were anemic and either could not use or did not respond to existing treatments; various doses of sotatercept were tested to find a safe and effective level.
- Out of 74 enrolled patients, 49% achieved significant hematological improvement, indicating that sotatercept shows promise as a treatment for this type of anaemia.
Background: Myelodysplastic syndromes are characterised by ineffective erythropoiesis. Luspatercept (ACE-536) is a novel fusion protein that blocks transforming growth factor beta (TGF β) superfamily inhibitors of erythropoiesis, giving rise to a promising new investigative therapy. We aimed to assess the safety and efficacy of luspatercept in patients with anaemia due to lower-risk myelodysplastic syndromes.
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- Sotatercept is being tested as a new treatment for chemotherapy-induced anemia (CIA) in patients with metastatic cancer, based on results from two phase 2 studies.
- In the studies, patients received different doses of sotatercept or a placebo, with the main goal being to see if their hemoglobin levels increased by at least 1 g/dL.
- Both studies were cut short due to slow enrollment, but results showed that higher doses of sotatercept led to significantly more patients experiencing an increase in hemoglobin, with a low incidence of adverse events related to treatment.
Article Synopsis
- Diamond-Blackfan Anemia (DBA) is a disorder that results in low red blood cell counts due to bone marrow failure, often linked to mutations in ribosomal protein genes.
- Current treatments like corticosteroid therapy and bone marrow transplants come with significant risks, highlighting the need for new therapies.
- The study found that RAP-011 (sotatercept) can restore hemoglobin levels in zebrafish models of DBA by enhancing erythropoiesis through a unique mechanism, suggesting its potential as a treatment for DBA patients.
Article Synopsis
- This phase IIa study assessed the safety and tolerability of sotatercept in patients with newly diagnosed and relapsed multiple myeloma, comparing it to a placebo.
- Patients were given either sotatercept or placebo alongside a standard treatment called MPT for a total of four cycles.
- The results indicated that while sotatercept was generally well-tolerated, 58% of those treated experienced severe adverse events, but it also showed promising effects on bone metabolism and increased hemoglobin levels.
Article Synopsis
- Sotatercept is a new protein treatment designed to trap activin receptor type IIA (ActRIIA) ligands, originally created to help with bone health but found to enhance red blood cell production (erythropoiesis).
- In a study involving 31 healthy postmenopausal women, sotatercept was administered in various doses every 28 days and was found to be generally safe, causing significant increases in hemoglobin and red blood cell counts for up to 4 months.
- The results indicated a dose-dependent effect, with potential uses being explored for treating anemia and enhancing bone mineral density in other clinical settings.
Activin receptor antagonists for cancer-related anemia and bone disease.
Expert Opin Investig Drugs
January 2013
Article Synopsis
- Antagonists of activin receptor signaling show promise for treating cancer-related conditions like anemia and bone diseases associated with cancers such as multiple myeloma and solid tumors.
- The review discusses how dysregulation in activin receptor pathways is linked to anemia, osteolysis, and metastatic bone disease, and highlights the development of activin receptor antagonists in a clinical setting.
- Sotatercept, a novel receptor fusion protein, has demonstrated positive effects in increasing red blood cells and inhibiting tumor growth in both preclinical and early clinical studies, indicating its potential as a first-in-class therapy for cancer-related anemia and bone diseases.
Article Synopsis
- Rasburicase is effective in managing plasma uric acid levels in adults with hematologic malignancies, showing a higher response rate (87%) compared to allopurinol alone (66%) and rasburicase plus allopurinol (78%).
- The study involved 275 patients categorized into three treatment groups: rasburicase alone, rasburicase followed by allopurinol, and allopurinol alone, with primary focus on maintaining plasma uric acid levels at or below 7.5 mg/dL.
- Rasburicase not only showed better efficacy but also provided faster control over uric acid levels compared to allopurinol, achieving results in just 4 hours for hyperuricemic
Article Synopsis
- - Our study evaluated the effectiveness of high-dose chemotherapy (HD-CT) compared to conventional chemotherapy (CT) for patients with metastatic breast cancer, involving 61 patients from 1992 to 1996.
- - Results showed that patients receiving HD-CT had a median time to progression (TTP) of 12 months, significantly better than the 6 months for the standard CT group, with lower relapse rates at both 2 and 5 years.
- - The median overall survival (OS) was also longer for HD-CT patients, with 44.1 months compared to 19.3 months for standard CT, suggesting HD-CT may improve patient outcomes, but more research is required to confirm its long
Purpose: To determine maximum tolerated dose, safety and efficacy of weekly 24 h infusional 5-fluorouracil (5-FU) combined alternately with oxaliplatin and irinotecan.
Patients And Methods: Advanced colorectal carcinoma patients in first- or second-line chemotherapy received increasing doses of 5-FU (weekly 24 h continuous intravenous infusion without leucovorin) on days 1, 8, 15 and 22, irinotecan days 1 and 15; and oxaliplatin days 8 and 22, every 35 days.
Results: Thirty-four patients received 175 cycles.
Purpose: A phase II-III randomised study to compare safety and efficacy of an oxaliplatin/cyclophosphamide (OXAC) combination, vs. the reference combination of cisplatin/cyclophosphamide (CPC), in untreated advanced ovarian cancer patients.
Patients And Methods: 182 patients were enrolled, of whom 177 were treated: 86 with OXAC (130 mg/m2 oxaliplatin two-hour intravenous (i.
Around 3,000 cisplatin analogues have been synthetised over the past 30 years but only half a dozen are presently in clinical development, while only two (cisplatin and carboplatin) have been available prior to the recent European registration of oxaliplatin. Oxaliplatin is a new platinum salt belonging to the DACH (diaminocyclohexane) platinum family, and is the only such cisplatin analogue that has entered clinical development and achieved approval for marketing. During its development, oxaliplatin has aroused lively interest due, firstly, to its in vitro and in vivo antitumoral activity, especially in cisplatin-resistant models and cell lines expressing resistance genes, and, secondly, to its good clinical tolerance, the absence of renal or auditory toxicity being combined with a low hematotoxicity.
View Article and Find Full Text PDFTo determine the feasibility of the paclitaxel, oxaliplatin, cisplatin combination in advanced ovarian cancer (AOC), 15 patients with AOC (8 chemonaive, and 7 second-line, disease-free interval > or = 12 months) received paclitaxel 135 mg/m2 at day 1, with oxaliplatin 100 mg/m2 and cisplatin 75 mg/m2 at day 2, every 3 weeks for 6 cycles. Pretreated patients received prophylactic granulocyte colony-stimulating factor (5 microg/kg/d, days 6-13). Seventy cycles were administered; median 5 (range: 2-6 cycles) in chemonaive, and 4 (range: 2-6) in pretreated patients.
View Article and Find Full Text PDFThe first studies on intensive chemotherapy for metastatic breast cancer conducted in the 80s were disappointing. Despite good response rates, the duration of remission was short and long-term survivals exceptional. Nevertheless, these phase I and II trials helped to develop a better understanding of the potential indications of this new therapeutic approach and apprehend its technical aspects.
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