MXELOXIRI Combined With Molecular Targeting Drug as First-line Therapy in Patients With Initially Unresectable Metastatic Colorectal Cancer: A Phase II, Single-arm, Prospective Clinical Study
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ABSTRACT:
DISEASE(S): Initially Unresectable Metastatic Colorectal Cancer
PROVIDER: 2684302 | ecrin-mdr-crc |
REPOSITORIES: ECRIN MDR
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Project description:Interventions: Experimental group:mXELOXIRI;Control group:FOLFOX/FOLFIRI Combined With Molecular Targeting Drug
Primary outcome(s): Objective response rate
Study Design: Parallel
| 2687497 | ecrin-mdr-crc
Project description:Backgrounds/aimsSurgical resection is the only curative treatment for biliary tract cancers; however, most patients undergo palliative chemotherapy because they are contraindicated for surgery. Conversion surgery, a treatment strategy for downsizing chemotherapy and subsequent surgical resection, is feasible for initially unresectable biliary tract cancers following the introduction of effective chemotherapeutic agents.MethodsPatients initially diagnosed with unresectable biliary tract cancers, and treated with conversion surgery after palliative chemotherapy between 2013 and 2019, were reviewed retrospectively.ResultsTwelve patients underwent conversion surgery after palliative chemotherapy for initially unresectable biliary tract cancers. The final pathological diagnosis included six perihilar cholangiocarcinomas, four distal common bile duct cancers, and two gallbladder cancers. Different chemotherapy regimens were used, but all the patients were treated with gemcitabine at some point during their treatment. The median overall survival was 28 months, which was longer than that of patients treated with isolated palliative chemotherapy in previous studies.ConclusionsConversion surgery represents a therapeutic alternative for specific cases of unresectable biliary tract cancers. Palliative chemotherapy for initially unresectable biliary tract cancers is recommended for downsizing the tumor and expanding the indications for surgery. Further studies and clinical trials are required to develop new and effective chemotherapeutic regimens.
| S-EPMC8382869 | biostudies-literature
Project description:The NAD hydrolase (NADase) SARM1 acts as a central executioner of programmed axon death and is a possible therapeutic target for neurodegenerative disorders. While orthosteric inhibitors of SARM1 have been described, this multi-domain enzyme is also subject to intricate forms of autoregulation, suggesting the potential for allosteric modes of inhibition. Previous studies have identified multiple cysteine residues that support SARM1 activation and catalysis, but which of these cysteines, if any, might be selectively targetable by electrophilic small molecules remains unknown. Here we describe the chemical proteomic discovery of a series of tryptoline acrylamides that site-specifically and stereoselectively modify cysteine-311 (C311) in the non-catalytic, autoregulatory armadillo repeat (ARM) domain of SARM1. These covalent compounds inhibit the NADase activity of WT-SARM1, but not C311A or C311S SARM1 mutants, show a high degree of proteome-wide selectivity for SARM1_C311, and stereoselectively block vincristine- and vacor-induced neurite degeneration in primary rodent dorsal root ganglion neurons. Our findings describe selective, covalent inhibitors of SARM1 targeting an allosteric cysteine, pointing to a potentially attractive therapeutic strategy for axon degeneration-dependent forms of neurological disease.
2022-08-22 | PXD035400 | Pride
Project description:PurposeStereotactic body radiotherapy (SBRT) may have significant immunomodulatory effects that enhance tumor response to immune checkpoint inhibitors. This phase 2 clinical trial was conducted to evaluate the safety and efficacy of combining palliative SBRT with camrelizumab (an anti-PD1 monoclonal antibody) in patients with unresectable hepatocellular carcinoma (uHCC).MethodsPatients with uHCC, Child-Pugh A/B liver function, and at least one measurable lesion were enrolled between April 2020 and August 2022. Patients were administered 200 mg camrelizumab intravenously from the first day of palliative SBRT and then every 3 weeks. Palliative SBRT was delivered daily over five fractions per week, with a dose range of 30-50 Gy. The primary endpoints were objective response rate (ORR) and safety. This trial was registered at ClinicalTrials.gov (NCT04193696).ResultsTwenty-one patients were enrolled; the median radiation dose was 40 Gy, and the median number of cycles of camrelizumab was five. The ORR was 52.4%. After a median follow-up of 19.7 months, the median progression-free and overall survival were 5.8 and 14.2 months, respectively. The overall survival probability was 85.7% at 6 months, 76.2% at 9 months, and 59.9% at 12 months. All grade 3 treatment-related adverse events (TRAEs) occurred in five patients (23.8%) and were manageable. No grade 4/5 TRAEs were observed.ConclusionPalliative SBRT plus camrelizumab showed promising antitumor activity against uHCC. Toxicities were manageable with no unexpected safety issues. This study provides evidence of a new therapeutic method for the treatment of uHCC.
| S-EPMC9525355 | biostudies-literature
Project description:Background and purpose: Research on the efficacy of conversion therapy for initially unresectable mid-low rectal cancer (IURC) remained limited. This study aimed to assess the efficacy and safety of the conversion regimen for IURC and analyze the long-term outcomes of these patients. Methods: We retrospectively analyzed the data of clinically diagnosed IURC patients who received conversion therapy between October 2010 and April 2017. The conversion therapy consisted of long-term radiation, concurrent chemotherapy, delayed surgery and consolidation chemotherapy. The primary end point was the rate of R0 resection, and other short- and long-term outcomes were analyzed. Results: Sixty-one patients were enrolled in this study. After conversion therapy, 51 (83.6%) patients received R0 resection. The rates of pathologic complete response and downstaging were 16.4% and 62.3%, respectively. The rate of grade 3-4 chemoradiotherapy-related toxicity events was 13.1%. The overall survival at 3 years was 75.4% in all patients, and the disease-free survival at 3 years was 72.5% in patients who received R0 resection. Conclusion: The conversion regimen showed a high conversion resection rate and good survival outcomes in IURC patients, and might benefit the patients if recommended in clinical practice.
| S-EPMC8176423 | biostudies-literature
Project description: Not available
| S-EPMC10932671 | biostudies-literature
Project description:Molecular basis for condensin targeting to chromosomal loci [Hi-C]
| PRJNA1121927 | ENA
Project description:Most patients with hepatocellular carcinoma (HCC) are diagnosed when the disease is already at an advanced stage, so they are not eligible for resection and their prognosis is poor. The combination of transarterial chemoembolization (TACE) with immune checkpoint inhibitors or tyrosine kinase inhibitors can improve unresectable HCC to the point that patients can be treated with surgery. Here we describe two cases of such "conversion therapy". One patient was a 52-year-old man in Child-Pugh class A with treatment-naive HCC whose 11.3-cm tumor had invaded the middle hepatic vein and right branch of the portal vein. He was treated with TACE plus camrelizumab, and radical resection was performed 3 months later. No evidence of recurrence was observed during 5-month follow-up. The other patient was a 42-year-old man in Child-Pugh class A with HCC involving a 11.4-cm tumor and severe liver cirrhosis. The patient was treated with TACE and lenvatinib, but the embolic effect after one month was unsatisfactory, so the regional treatment was changed to hepatic artery infusion chemotherapy and transcatheter arterial embolization. Radical resection was performed 2 months later, and no recurrence was evident at 1-month follow-up. These cases demonstrate two conversion therapies that may allow patients with initially unresectable HCC to benefit from resection.
| S-EPMC9583878 | biostudies-literature
Project description:BackgroundSquamous cell carcinoma of the anal canal (SCCA) is a rare malignancy associated with infection by human papillomavirus (HPV). No consensus treatment approach exists for the treatment of metastatic disease. Because intratumoral HPV oncoproteins upregulate immune checkpoint proteins such as PD-1 to evade immune-mediated cytotoxicity, we did a trial of the anti-PD-1 antibody nivolumab for patients with metastatic SCCA.MethodsWe did this single-arm, multicentre, phase 2 trial at ten academic centres in the USA. We enrolled patients with treatment-refractory metastatic SCCA, who were given nivolumab every 2 weeks (3 mg/kg). The primary endpoint was response according to Response Evaluation Criteria in Solid Tumors, version 1.1, in the intention-to-treat population. At the time of data cutoff, the study was ongoing, with patients continuing to receive treatment. The study is registered with ClinicalTrials.gov, number NCT02314169.ResultsWe screened 39 patients, of whom 37 were enrolled and received at least one dose of nivolumab. Among the 37 patients, nine (24% [95% CI 15-33]) had responses. There were two complete responses and seven partial responses. Grade 3 adverse events were anaemia (n=2), fatigue (n=1), rash (n=1), and hypothyroidism (n=1). No serious adverse events were reported.InterpretationTo our knowledge, this is the first completed phase 2 trial of immunotherapy for SCCA. Nivolumab is well tolerated and effective as a monotherapy for patients with metastatic SCCA. Immune checkpoint blockade appears to be a promising approach for patients with this orphan disease.FundingNational Cancer Institute/Cancer Therapy Evaluation Program, the HPV and Anal Cancer Foundation, the E B Anal Cancer Fund, The University of Texas MD Anderson Moon Shots Program, and an anonymous philanthropic donor.
| S-EPMC5809128 | biostudies-literature
Project description:Targeting Pyrimidine Synthesis Accentuates Molecular Therapy Response in Glioblastoma Stem Cells
| PRJNA531324 | ENA