Pemetrexed alone as salvage treatment in metastatic colorectal cancer patients who were failed after standard chemotherapy: A phase II single arm prospective study
Ontology highlight
ABSTRACT:
DISEASE(S): Neoplasms
PROVIDER: 2511545 | ecrin-mdr-crc |
REPOSITORIES: ECRIN MDR
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Project description:Interventions: Drug : Petrexed 500 mg/m2 IV Q 3 weeks + Tarceva 100mg once daily, continous
Primary outcome(s): Overall Response Rate
| 2511765 | ecrin-mdr-crc
Project description:Background: We designed a single-arm, open-label phase II study to determine the efficacy and toxicity of pemetrexed monotherapy with vitamin supplementation in patients with refractory colorectal cancer (CRC) that failed to respond to standard treatments including 5-fluorouracil, oxaliplatin, and irinotecan with or without biologic agents. Methods: Patients were treated with pemetrexed 500 mg/m2 on day 1 every 3 weeks, with folic acid and vitamin B12 supplementation. Treatment was continued until disease progression or intolerable toxicity. Between June 2016 and October 2016, 24 patients were enrolled in this study. Results: One patient withdrew consent, leaving a total of 23 patients for evaluation. The median age of the patients was 54.0 years (range, 23.0 to 67.0), and the median ECOG performance status was 1 (1-2). The median number of previous systemic chemotherapies was 3 (range, 2 to 5). There was no patient with complete response (CR) or partial response (PR). However, stable disease was observed in 10 patients (43.4%) and maintained more than 6 months in 7 of 10 patients. The median progression-free survival was 1.6 months (95% CI, 1.1-2.0) and the median overall survival was 9.8 months (95% CI, 5.9-13.6). Grade 3 treatment-related adverse events occurred in one patient with elevated liver enzymes and hematologic adverse event of grade 2 anemia was observed in one patient. There were no cases of dose reduction or treatment-related deaths and all toxicities were manageable. Conclusions: Pemetrexed monotherapy showed moderate disease control and acceptable toxicity profile as salvage therapy for refractory CRC.
| S-EPMC6096381 | biostudies-literature
Project description:Pemetrexed is an anticancer agent that exerts its action by disrupting crucial folate-dependent metabolic processes essential for cell replication. In vitro studies have shown that pemetrexed behaves as a multitargeted antifolate by inhibiting thymidylate synthase (TS), dihydrofolate reductase (DHFR), and glycinamide ribonucleotide formyltransferase (GARFT), which are key folate-dependent enzymes for the de novo biosynthesis of thymidine and purine nucleotides.Pemetrexed is used as a standard therapeutic agent for lung cancer, pleural mesothelioma, peritoneal mesothelioma.In addition to these effective anti-cancer effect, Pemetrexed is not severe side effects of the medicine.
Pemetrexed has been research in colon cancer. Zhang, etc., demonstrated the anti-cancer effect of Pemetrexed in human colon cancer Cells.
Although sometimes made also two or more clinical studies, Pemetrexed was reported 15-17% of the treatment response rate in these two studies.
| 2201098 | ecrin-mdr-crc
Project description:The growth of diffraction-quality single crystals is of primary importance in protein X-ray crystallography. Chemical modification of proteins can alter their surface properties and crystallization behavior. The Midwest Center for Structural Genomics (MCSG) has previously reported how reductive methylation of lysine residues in proteins can improve crystallization of unique proteins that initially failed to produce diffraction-quality crystals. Recently, this approach has been expanded to include ethylation and isopropylation in the MCSG protein crystallization pipeline. Applying standard methods, 180 unique proteins were alkylated and screened using standard crystallization procedures. Crystal structures of 12 new proteins were determined, including the first ethylated and the first isopropylated protein structures. In a few cases, the structures of native and methylated or ethylated states were obtained and the impact of reductive alkylation of lysine residues was assessed. Reductive methylation tends to be more efficient and produces the most alkylated protein structures. Structures of methylated proteins typically have higher resolution limits. A number of well-ordered alkylated lysine residues have been identified, which make both intermolecular and intramolecular contacts. The previous report is updated and complemented with the following new data; a description of a detailed alkylation protocol with results, structural features, and roles of alkylated lysine residues in protein crystals. These contribute to improved crystallization properties of some proteins.
| S-EPMC4078742 | biostudies-literature
Project description:This study is single center single arm prospective phase II study. In this study, efficacy and side effects of pemetrexed as salvage regimen on patients who failed all standard chemotherapy and total of 29 patients will be enrolled. Pemetrexed will be continued until disease progression is happened.
| 2239263 | ecrin-mdr-crc
Project description:BackgroundPatients with advanced sarcomas have a poor prognosis and few treatment options that improve overall survival. We assessed the efficacy and tolerability of pemetrexed and cisplatin combination therapy in patients with refractory bone and soft tissue sarcoma (STS).Patients and methodsPatients were included in this multicenter, phase II study (ClinicalTrials.gov identifier NCT03809637) if they progressed after receiving one or more chemotherapy regimens containing an anthracycline and/or ifosfamide. Pemetrexed was first administered intravenously, followed by cisplatin, over a cycle of 21 days, for a maximum of six cycles. The primary endpoint was a progression-free rate (PFR) at 3 months (3-month PFR).ResultsFrom January 2017 to September 2019, we enrolled 37 patients; of these, 73% had previously undergone three or more rounds of chemotherapy. Five patients (13.5%) exhibited objective responses, including two patients (2/6, 33.3%) with malignant peripheral nerve sheath tumors, one patient (1/4, 25%) with synovial sarcoma, one patient (1/4, 25%) with undifferentiated pleomorphic sarcoma, and one patient (1/4, 25%) with angiosarcoma. The median progression-free survival was 2.6 months, and the 3-month PFR was 45.9% (n = 17). None of the four patients with osteosarcoma exhibited objective responses or were progression free at 3 months. The most frequent treatment-related grade 3-4 toxicities included neutropenia (16.2%), anemia (13.5%), thrombocytopenia (13.5%), and fatigue (8.1%). Among 26 patients (70.3%) available for immunohistochemical assessments, patients in the low-excision repair cross-complementation group 1 (ERCC1) and low-thymidylate synthase expression groups showed a tendency for longer overall survival.ConclusionsCombination therapy with pemetrexed and cisplatin was associated with clinically meaningful and sustained responses among patients with advanced and refractory STS. The combination therapy met its predefined primary study endpoint.
| S-EPMC8424216 | biostudies-literature
Project description:BackgroundThe implantation rates of reverse total shoulder arthroplasties (RTSAs) are increasing worldwide, resulting in higher absolute numbers of the associated complications and revision surgeries. This requires the discussion of salvage therapies for failed RTSAs without revision to a new RTSA. Revision to hemiarthroplasty may offer a valid fallback option in certain cases. This study aimed to analyze the incidence, indications, and clinical outcomes, especially the reduction in pain levels compared to a matched control group.MethodsOur prospectively enrolled patient cohort of RTSA implantations at a tertiary referral center between January 2005 and December 2018 was retrospectively queried for revision to a hemiarthroplasty. For clinical outcome evaluation, a minimum follow-up duration of 2 years after revision to hemiarthroplasty was required. Clinical outcome measures were compared to two matching groups, one with RTSA preserving revision and one without any reintervention. The outcome measures were the absolute and relative Constant-Murley score (aCS and rCS), Subjective Shoulder Value (SSV), range of motion, and pain.ResultsA total of 21 out of 1237 RTSAs (1.7%) underwent salvage revision to hemiarthroplasty at a mean time of 20 ± 21 months (range, 1-75 months). Of those, 12 were available for a minimum follow-up of 2 years after revision to a hemiarthroplasty. The main indications were glenoid loosening (8/12), scapular spine fracture (2/12), and instability (2/21). Clinical outcome was analyzed at a mean follow-up period of 46 ± 26 months (24 months to 123 months) after revision to a hemiarthroplasty. The revision significantly reduced CS pain from 6 ± 4 points to 12 ± 3 points (scale 0 to 15 with 15 as optimum, P < .01). The aCS, rCS, SSV, and range of motion did not improve. Comparison with the RTSA preserving revision group and the RTSA group without reintervention showed significantly worse outcome scores for aCS (33 ± 10 vs. 55 ± 19 vs. 69 ± 12 points), rCS (41 ± 14% vs. 67 ± 20% vs. 84 ± 13%), SSV (35 ± 19% vs. 64 ± 20% vs. 81 ± 15%), flexion (53 ± 27° vs. 64 ± 20° vs. 128 ± 24°), and abduction (50 ± 23° vs. 109 ± 42° vs. 142 ± 24°). Pain was similar in all groups at the last follow-up visit.ConclusionIn a few cases, RTSA retention or revision to another RTSA is impossible. For those patients, conversion to hemiarthroplasty is a valid fallback option to reduce the patient's pain levels and provide low-level function.
| S-EPMC8568842 | biostudies-literature
Project description:BackgroundDue to extended life expectancy and recent improvements in surgical techniques, limb salvage has replaced amputation as the gold standard and is now performed in 90-95% of upper extremity malignancies. However, many of these salvage procedures are associated with significant postsurgical complications. In particular, the clavicula pro humero (CPH) procedure is associated with high rates of nonunion. We present our experience with upper extremity salvage using the free vascularized fibular flap (VFF) after failure or nonunion of the original CPH procedure in the pediatric population.MethodsFive patients under the age of 18 diagnosed with upper extremity sarcoma who underwent tumor resection with immediate CPH reconstruction complicated with nonunion, and subsequent revision with free VFF were included. Data on patient demographics, oncologic characteristics, surgical procedures, intraoperative details, postoperative complications, and time to graft union were recorded.ResultsFive patients (average age = 8.4 years; range = 5-10 years at surgery date) underwent secondary limb salvage procedure with free VFF reconstruction following failed CPH reconstruction for proximal humeral osteosarcoma (n = 4) or Ewing sarcoma (n = 1). The mean follow-up was 3.7 years. Complications occurred in five patients (100%), with three patients requiring reoperation (60%). Four patients achieved graft union (average union time = 3.7 months) and successful limb reconstruction. Four patients were alive with no local recurrence of the disease. One patient did not achieve union and was lost to follow-up.ConclusionPrimary bone tumors in the pediatric population require wide surgical resection, and reconstruction often has high complication rates that can warrant further procedures. A free VFF is a viable option for upper extremity salvage after previously failed reconstructions because it provides vascularized tissue to a scarred tissue bed and allows for the replacement or augmentation of large bony defects.
| S-EPMC9110248 | biostudies-literature
Project description:Flexor hallucis longus (FHL) transfer is a well-established treatment option in failed Achilles tendon (AT) repair and has been routinely performed as an open procedure. We detail the surgical steps needed to perform an arthroscopic transfer of the FHL for a chronic AT rupture. The FHL tendon is harvested as it enters in its tunnel beneath the sustentaculum tali; a tunnel is then drilled in the calcaneus as near to the AT footprint as possible. By use of a suture-passing device, the free end of the FHL is advanced to the plantar aspect of the foot. After adequate tension is applied to the construct, the tendon is fixed in place with an interference screw in an inside-out fashion. This minimally invasive approach is a safe and valid alternative to classic open procedures with the obvious advantages of preserving the soft-tissue envelope and using a biologically intact tendon.
| S-EPMC4661491 | biostudies-literature
Project description:IntroductionTo evaluate the efficacy and safety of etanercept treatment in adult patients with moderate to severe rheumatoid arthritis (RA) who failed to respond (primary failure) or lost a satisfactory response (secondary failure) to adalimumab.MethodsAll patients discontinued prior adalimumab treatment and continued methotrexate with etanercept 50 mg once weekly for 24 weeks. The primary study endpoint was American College of Rheumatology 20% improvement criteria (ACR20) at week 12.ResultsEighty-five patients (mean age 56.6 years; female 80.0%) were evaluated for safety and 84 for efficacy. Thirty (35.7%) patients achieved ACR20 at week 12; the lower bound of the 95% confidence interval (CI; 25.6, 46.9) was greater than the prespecified goal of 24% based on previous research. Improvements from baseline in clinical outcomes and patient-reported outcomes were observed at each study visit. In planned subgroup analyses, patients with anti-adalimumab antibodies and secondary adalimumab failure had the highest ACR20 response to etanercept at week 12 (11/17 patients; 64.7%). Among the patients with secondary adalimumab failure, those with anti-adalimumab antibodies were fivefold more likely to have an ACR20 response to etanercept than those without anti-adalimumab antibodies (odds ratio 5.2; 95% CI 2.0, 13.5; P < 0.001). Adverse events were reported for 62 (72.9%) patients and were consistent with previous studies of etanercept. Most adverse events were mild or moderate in severity.ConclusionSwitching to etanercept is a therapeutic option in patients with RA who fail adalimumab treatment. The presence of anti-adalimumab antibodies may provide additional support for switching to etanercept, particularly in patients with secondary adalimumab failure.Trial registrationClinicalTrials.gov identifier, NCT01927757.
| S-EPMC5696291 | biostudies-literature