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European Heart Journal May 2024Low-dose colchicine (0.5 mg daily) is now FDA-approved for secondary prevention in patients with coronary disease and will be increasingly prescribed in clinical... (Review)
Review
Low-dose colchicine (0.5 mg daily) is now FDA-approved for secondary prevention in patients with coronary disease and will be increasingly prescribed in clinical practice. In this State-of-the-Art Review, data were collated from contemporary systemic reviews of case reports, drug registries, and placebo-controlled trials that assessed specific issues of safety related to the continuous use of colchicine in a range of clinical settings to inform physicians, pharmacists, and patients of the absolute risks of continuous use of low-dose colchicine, including among individuals taking statin therapy. Based upon these collective data, it is concluded that aside mild diarrhoea on initiation of colchicine that typically subsides in the vast majority of patients within a week of therapy, continuous use of low-dose colchicine is well tolerated and very safe. It does not affect renal, liver, or cognitive function, has no adverse effects on bleeding, wound healing, fertility, or pregnancy, and does not increase risks of cancer, serious infection, or cause-specific mortality. When appropriately prescribed to patients without significant renal or hepatic impairment, reports of myelosuppression, myotoxicity, and serious drug-drug interactions are rare and no more frequent than placebo, including in patients taking statin therapy. Physicians, pharmacists, and patients can be reassured that in the absence of significant renal or hepatic impairment continuous use of low-dose colchicine can be used safely in patients with atherosclerosis for the purpose of reducing cardiovascular risk.
Topics: Colchicine; Humans; Atherosclerosis; Drug Interactions; Female; Hydroxymethylglutaryl-CoA Reductase Inhibitors
PubMed: 38596868
DOI: 10.1093/eurheartj/ehae208 -
The British Journal of Dermatology Apr 2024Mycosis fungoides (MF) and Sézary syndrome (SS) are chronic malignant diseases that typically necessitate diverse strategies to achieve remission. Systemic interferon...
Real-world study on the use of pegylated interferon alpha-2a for treatment of mycosis fungoides/Sézary syndrome using Time to Next Treatment as a measure of clinical benefit: An EORTC CLTG study.
INTRODUCTION
Mycosis fungoides (MF) and Sézary syndrome (SS) are chronic malignant diseases that typically necessitate diverse strategies to achieve remission. Systemic interferon alpha (IFN-α, subtypes 2a and 2b) has been used for MF/SS since 1984, however its production was recently stopped and so the recombinant pegylated (PEG) form of IFN α-2a remains as single IFN alternative treatment, even though not approved for MF/SS.
OBJECTIVE
To assess effectiveness and safety of PEG IFN α-2a in monotherapy and in combination with other treatments using time to next treatment (TTNT) as a measure of clinical therapeutic benefit in real world setting.
METHODS
We conducted an international and multicenter retrospective study of patients with MF and SS at any stage, treated with PEG IFN α-2a, from July 2012 to February 2022. Patients were included across 11 centers in 10 countries. Primary endpoints were to determine TTNT of PEG IFN α-2a and the adverse events (AE) in MF/SS.
RESULTS
In total 105 patients were included, mean age was 61 (22-86 years); 42 (40%) with disease stage IA-IIA, 63 (60%) with stage IIB-IVB. PEG IFN α-2a was combined with other therapies in 67 (64%) patients, usually with extracorporeal photopheresis (36%) and bexarotene (22%). Fifty-seven percent of stage I-IIA patients achieved ORR, whereas 51% of stage IIB-IVB. Combination therapy showed a TTNT of 10.4 months, while 7 months in monotherapy (p=0.0099). Overall, TTNT was 9.2 months, ORR was 53% (56/105), CR and PR were 13% and 40%, respectively.AE were described in 69% (72) of the patients. Flu-like symptoms (27%), lymphopenia (23%) and elevated liver function (10%) were the most frequently reported. Grade 3-4 adverse events were reported in 23 (21%) patients, which were mostly related to myelosuppression.
LIMITATIONS
retrospective data analysis and unrestricted number of combination therapies.
CONCLUSIONS
PEG IFN α-2a for MF/SS showed ORR of 53%, TTNT of 9.2 months, superiority of combination regimens in comparison to monotherapy and doses of 180 mcg/weekly related to higher ORR.
PubMed: 38596857
DOI: 10.1093/bjd/ljae152 -
Clinical Cancer Research : An Official... Jun 2024Initially, prostate cancer responds to hormone therapy, but eventually resistance develops. Beta emitter-based prostate-specific membrane antigen (PSMA)-targeted...
PURPOSE
Initially, prostate cancer responds to hormone therapy, but eventually resistance develops. Beta emitter-based prostate-specific membrane antigen (PSMA)-targeted radionuclide therapy is approved for the treatment of metastatic castration-resistant prostate cancer. Here we introduce a targeted alpha therapy (TAT) consisting of the PSMA antibody pelgifatamab covalently linked to a macropa chelator and labeled with actinium-225 and compare its efficacy and tolerability with other TATs.
EXPERIMENTAL DESIGN
The in vitro characteristics and in vivo biodistribution, antitumor efficacy, and tolerability of 225Ac-macropa-pelgifatamab (225Ac-pelgi) and other TATs were investigated in cell line- and patient-derived prostate cancer xenograft models. The antitumor efficacy of 225Ac-pelgi was also investigated in combination with the androgen receptor inhibitor darolutamide.
RESULTS
Actinium-225-labeling of 225Ac-pelgi was efficient already at room temperature. Potent in vitro cytotoxicity was seen in PSMA-expressing (LNCaP, MDA-PCa-2b, and C4-2) but not in PSMA-negative (PC-3 and DU-145) cell lines. High tumor accumulation was seen for both 225Ac-pelgi and 225Ac-DOTA-pelgi in the MDA-PCa-2b xenograft model. In the C4-2 xenograft model, 225Ac-pelgi showed enhanced antitumor efficacy with a T/Cvolume (treatment/control) ratio of 0.10 compared with 225Ac-DOTA-pelgi, 225Ac-DOTA-J591, and 227Th-HOPO-pelgifatamab (227Th-pelgi; all at 300 kBq/kg) with T/Cvolume ratios of 0.37, 0.39, and 0.33, respectively. 225Ac-pelgi was less myelosuppressive than 227Th-pelgi. 225Ac-pelgi showed dose-dependent treatment efficacy in the patient-derived KuCaP-1 model and strong combination potential with darolutamide in both cell line- (22Rv1) and patient-derived (ST1273) xenograft models.
CONCLUSIONS
These results provide a strong rationale to investigate 225Ac-pelgi in patients with prostate cancer. A clinical phase I study has been initiated (NCT06052306).
Topics: Male; Humans; Animals; Actinium; Mice; Xenograft Model Antitumor Assays; Cell Line, Tumor; Glutamate Carboxypeptidase II; Antigens, Surface; Alpha Particles; Tissue Distribution; Prostatic Neoplasms; Immunoconjugates; Prostatic Neoplasms, Castration-Resistant; Radiopharmaceuticals
PubMed: 38593212
DOI: 10.1158/1078-0432.CCR-23-3746 -
Future Oncology (London, England) Apr 2024Side effects from chemotherapy-induced myelosuppression can negatively affect patients' quality of life (QoL). Neutropenia increases infection risk, and anemia... (Review)
Review
Side effects from chemotherapy-induced myelosuppression can negatively affect patients' quality of life (QoL). Neutropenia increases infection risk, and anemia frequently results in debilitating fatigue. Additionally, the bleeding risk associated with thrombocytopenia can lead to fear and anxiety. However, traditional interventions for myelosuppression fall short of the ideal. Granulocyte colony-stimulating factors reduce the risk of severe neutropenia but commonly lead to bone pain. Erythropoiesis-stimulating agents are not always effective and may cause thromboembolic events, while transfusions to correct anemia/thrombocytopenia are associated with transfusion reactions and volume overload. Trilaciclib, which is approved for reducing myelosuppression in patients with extensive-stage small cell lung cancer, together with several investigational agents in development for managing myelosuppression have the potential to improve QoL for patients on chemotherapy.
PubMed: 38587388
DOI: 10.2217/fon-2023-0513 -
Clinical and Experimental Medicine Apr 2024Letermovir, initially approved for cytomegalovirus (CMV) prophylaxis in hematopoietic stem-cell transplantation, has gained attention for off-label use in... (Review)
Review
Letermovir, initially approved for cytomegalovirus (CMV) prophylaxis in hematopoietic stem-cell transplantation, has gained attention for off-label use in lung-transplant (LTx) recipients. Given the high susceptibility of LTx recipients to CMV infection, this study explores the effectiveness and safety of letermovir prophylaxis. A retrospective analysis of using letermovir for LTx recipients at Tohoku University Hospital (January 2000 to November 2023) was conducted. Case summaries from other Japanese transplant centers and a literature review were included. Six cases at Tohoku University Hospital and one at Kyoto University Hospital were identified. Prophylactic letermovir use showed positive outcomes in managing myelosuppression and preventing CMV replication. The literature review supported the safety of letermovir in high-risk LTx recipients. Despite limited reports, our findings suggest letermovir's potential as prophylaxis for LTx recipients intolerant to valganciclovir. Safety, especially in managing myelosuppression, positions letermovir as a promising option. However, careful consideration is important in judiciously integrating letermovir into the treatment protocol.
Topics: Humans; Acetates; Antiviral Agents; Cytomegalovirus; Cytomegalovirus Infections; Hematopoietic Stem Cell Transplantation; Lung; Off-Label Use; Quinazolines; Retrospective Studies; Transplant Recipients
PubMed: 38578337
DOI: 10.1007/s10238-024-01330-2 -
World Journal of Clinical Cases Mar 2024The prognosis for patients with advanced metastatic cervix cancer (MCC) is poor, and this disease continues to pose a considerable therapeutic challenge. Despite the...
BACKGROUND
The prognosis for patients with advanced metastatic cervix cancer (MCC) is poor, and this disease continues to pose a considerable therapeutic challenge. Despite the administration of first-line regimens consisting of cisplatin, paclitaxel, and bevacizumab, survival rates for patients with metastasis remain poor. The emergence of bispecific antibodies (BsAbs) offers a novel treatment option for patients diagnosed with MCC.
CASE SUMMARY
In this report, we present a patient with MCC who was treated with cadonilimab monotherapy at a dose of 6 mg/kg every two weeks after chemotherapy was proven to be intolerable. The patient exhibited a sustained complete response for a duration of 6 months, demonstrating an optimistic outlook.
CONCLUSION
This case illustrates the considerable efficacy of cadonilimab for treating advanced MCC. Therefore, BsAb therapy is a promising strategy for effectively treating patients with advanced MCC and should be considered as an option when patients are intolerant to standard chemotherapy.
PubMed: 38576806
DOI: 10.12998/wjcc.v12.i8.1510 -
Archives of Gynecology and Obstetrics Jun 2024To investigate the effect and safety of ovarian tissue cryopreservation (OTC) for fertility preservation in female patients with hematological diseases.
PURPOSES
To investigate the effect and safety of ovarian tissue cryopreservation (OTC) for fertility preservation in female patients with hematological diseases.
METHODS
We designed a retrospective study. The clinical data of patients with hematological diseases undergoing OTC admitted to Peking University People's Hospital from April 2017 to January 2023 were analyzed and summarized.
RESULTS
A total of 24 patients were included in the study, including 19 patients with malignant hematological diseases and 5 patients with non-malignant hematological diseases. The former included 14 patients with acute leukemia, 1 patient with chronic leukemia, and 4 patients with myelodysplastic syndrome, while the latter 5 patients were aplastic anemia (AA). 16 patients had received chemotherapy before OTC. The average age of 24 patients was 22.80 ± 6.81 years. The average anti-Mullerian hormone (AMH) was 1.97 ± 2.12 ng/mL, and the average follicle-stimulating hormone (FSH) was 7.01 ± 4.24 IU/L in examination before OTC. FSH was greater than 10.0 IU/L in 4 cases. The pre-OTC laboratory tests showed that the average white blood cell (WBC) count was (3.33 ± 1.35) × 10/L, the average hemoglobin was 91.42 ± 22.84 g/L, and the average platelet was (147.38 ± 114.46) × 10/L. After injection of recombinant human granulocyte colony-stimulating factor (rhG-CSF), blood transfusion, and iron supplementation in pre-OTC treatment, the average WBC count was (4.91 ± 3.07) × 10/L, the average hemoglobin was 98.67 ± 15.43 g/L, and the average platelet was (156.38 ± 103.22) × 10/L. Of the 24 patients, 22 underwent laparoscopic bilateral partial oophorectomy and oophoroplasty, and 2 underwent laparoscopic unilateral oophorectomy. The average duration of OTC was 59.54 ± 17.58 min, and the average blood loss was 32.1 ± 41.6 mL. The maximum blood loss was 200 mL. There was no significant difference in WBC count and hemoglobin concentration after OTC compared to pre-OTC period. Only the platelet count after OTC surgery was significantly different from that before surgery ([134.54 ± 80.84 vs. 156.38 ± 103.22] × 10/L, p < 0.05). None of the 24 patients had serious complications after OTC. 2 patients had mild infection symptoms, but both recovered well. 23 patients underwent hematopoietic stem cell transplantation (HSCT) after OTC. The median and interquartile range from OTC to the pretreatment of HSCT was 33 (57) days, and the median and interquartile range from OTC to HSCT was 41 (57) days. Seven of them began pretreatment of HSCT within 20 days and began HSCT within 30 days after OTC. All patients were followed up. Of the 23 patients who underwent HSCT after surgery, 22 presented with amenorrhea and 1 with scanty menstrual episodes. Seven patients underwent hormone replacement therapy (HRT) after HSCT. A patient with AA underwent ovarian tissue transplantation (OTT) 3 years after HSCT and resumed regular menstruation 6 months after OTT.
CONCLUSIONS
Ovarian tissue cryopreservation has a promising future in fertility protection in patients with hematological diseases. However, patients with hematological malignancies often have received gonadotoxic therapy before OTC, which may be accompanied by myelosuppression while patients with non-malignant hematological diseases often present with severe hemocytopenia. So perioperative complete blood count of patients should be paid attention to. There was no significant difference in the WBC count and hemoglobin concentration in patients with hematological diseases before and after OTC surgery, and the platelet count decreased slightly within the normal range. Infection is the most common post-OTC complication, and HSCT pretreatment can be accepted as early as the 10th day after OTC. OTC has no adverse effects on patients with hematological diseases and does not delay HSCT treatment. For young patients with hematological diseases, OTC is an effective method of fertility preservation.
Topics: Humans; Female; Fertility Preservation; Retrospective Studies; Cryopreservation; Adult; Ovary; Young Adult; Adolescent; Hematologic Diseases; Anti-Mullerian Hormone; Follicle Stimulating Hormone; Myelodysplastic Syndromes
PubMed: 38575798
DOI: 10.1007/s00404-024-07484-4 -
[Rinsho Ketsueki] the Japanese Journal... 2024Acute myelogenous leukemia (AML) has a poor prognosis in patients who are ineligible for intensive chemotherapy. The combination of azacitidine and venetoclax has been...
Acute myelogenous leukemia (AML) has a poor prognosis in patients who are ineligible for intensive chemotherapy. The combination of azacitidine and venetoclax has been shown to have high overall efficiency and remission rates, even in patients ineligible for aggressive chemotherapy. However, myelosuppression is often prolonged after treatment, and infection can also occur. Severe myelosuppression is often addressed by dose titration, but specific dose titration methods have not been clarified. We used the standard induction therapy with azacitidine plus venetoclax, and if blasts decreased to 20% or less, switched to 7+7 therapy to shorten venetoclax to 7 days starting from the next cycle. In the 19 patients we treated (median age 80 years), response rate above MLFS was 100%, CR 57.9%, CRc (CR+CRi) 78.8%, median OS 693 days, median PFS 458 days, and median OS was not reached in previously untreated patients. This indicates that 7+7 is a highly effective and well-tolerated treatment.
Topics: Humans; Aged, 80 and over; Azacitidine; Antineoplastic Combined Chemotherapy Protocols; Bridged Bicyclo Compounds, Heterocyclic; Sulfonamides; Leukemia, Myeloid, Acute
PubMed: 38569855
DOI: 10.11406/rinketsu.65.135 -
Life (Basel, Switzerland) Feb 2024Doxorubicin (DOX) is a prevalent anticancer agent; however, it is unfortunately characterized by high cardiotoxicity, myelosuppression, and multiple other side effects....
Doxorubicin (DOX) is a prevalent anticancer agent; however, it is unfortunately characterized by high cardiotoxicity, myelosuppression, and multiple other side effects. To overcome DOX limitations, two novel pyridoxine-derived doxorubicin derivatives were synthesized (DOX-1 and DOX-2). In the present study, their antitumor activity and mechanism of action were investigated. Of these two compounds, DOX-2, in which the pyridoxine fragment is attached to the doxorubicin molecule via a C3 linker, revealed higher selectivity against specific cancer cell types compared to doxorubicin and a promising safety profile for conditionally normal cells. However, the compound with a C1 linker (DOX-1) was not characterized by selectivity of antitumor action. It was revealed that DOX-2 obstructs cell cycle progression, induces apoptosis via the mitochondrial pathway without the development of necrosis, and showcases antioxidant capabilities, underlining its cell-regulatory roles. In contrast to doxorubicin's DNA-centric mechanism, DOX-2 does not interact with nuclear DNA. Given these findings, DOX-2 presents a new promising direction in cancer therapeutics, which is deserving of further in vivo exploration.
PubMed: 38541608
DOI: 10.3390/life14030282 -
Phytotherapy Research : PTR Jun 2024As a complementary and alternative therapy, traditional Chinese medicine (TCM) has been playing a significant role in gastric cancer treatment. Data from individual...
As a complementary and alternative therapy, traditional Chinese medicine (TCM) has been playing a significant role in gastric cancer treatment. Data from individual systematic reviews have not been comprehensively summarized, and the relationship between certain interventions and outcomes are ill-defined. This study aimed to analyze the advantages of TCM interventions for gastric cancer by the method of evidence mapping. We searched PubMed, Embase, Web of Science, China National Knowledge Infrastructure, Chinese Scientific Journals Database, and Wanfang Database for systematic reviews of TCM treating gastric cancer up to December 31, 2023. We used Excel, Endnote 20, and Python software for the analysis of incorporated studies. We assessed the quality of included SRs by AMSTAR-2 and performed evidence mapping including 89 SRs, 1648 RCTs and 122,902 patients, identifying 47 types of interventions and 39 types of outcomes. From a visual overview, we displayed that most SRs reported beneficial effects in improving short- and long-term survival, myelosuppression, and immune function, even though the quality of evidence was generally low. The benefits of Brucea javanica Oil Emulsion Injection, ShenQiFuZheng Injection, XiaoAiPing, Astragalus-Containing TCM and Guben Xiaoji Therapy were found the most solid in corresponding aspects. Our findings suggest that although more rigorous clinical trials and SRs are needed to identify the precise effectiveness, integrating such evidence into clinical care of gastric cancer is expected to be beneficial.
Topics: Stomach Neoplasms; Humans; Medicine, Chinese Traditional; Drugs, Chinese Herbal
PubMed: 38517014
DOI: 10.1002/ptr.8155