scholarly journals Anlotinib Combined with Temozolomide Therapy for Recurrent Glioblastoma (IDH-wt and TERTp-mut) After Standard Treatment

Author(s):  
Tianwei Wang ◽  
Zhijun Liao ◽  
Ruizhi Wang ◽  
Ming Ye ◽  
Keman Liao ◽  
...  

Abstract Purpose IDH1-wt glioblastoma patients with TERTp-mut had the worst prognosis, and no effective management strategy was established after tumor recurrence. The median overall survival (OS) of recurrent GBM patients who only received supportive therapy was approximately 1.0 month. We reported survival outcomes of recurrent glioblastoma (rGBM) treated with anlotinib combined with temozolomide therapy (ACTT), and to explore the management strategy of rGBM. Methods The clinical data of 14 rGBM patients treated with ACTT was collected. Therapeutic efficacy and adverse effects were evaluated in every 2 months of treatment. We also included 16 patients treated with bevacizumab (Bev), 22 with TMZ, 28 with re-operation, 21 with re-irradiation, and 75 with supportive care to make comparison. Kaplan-Meier analysis was used to compare the survival of ACTT group versus other treatment groups. Results Fourteen rGBM patients treated with ACTT were enrolled. After 2-month of ACTT, the overall response and disease control rate were 50.0% and 92.9%, respectively. The 6-months PFS rate was 78.6%, and the 1-year survival rate was 50.0%. The median PFS and OS in ACTT group were 11.0 and 13.0 months, respectively. The median PFS and OS in Bev-group was 4.0 and 8.0 months. The patients treated with ACTT had better PFS than that in Bev-group. And compared to all the others treatment groups, ACTT could prolong survival. Conclusion The treatment regimen of ACTT maybe reliable, safe, and effective for rGBM. The patients can gain survival benefits from ACTT, and prolonged survival were observed compared with other treatment regimens.

2019 ◽  
Vol 145 (3) ◽  
pp. 531-540
Author(s):  
Wolfgang Wick ◽  
Andriy Krendyukov ◽  
Klaus Junge ◽  
Thomas Höger ◽  
Harald Fricke

Abstract Purpose Glioblastoma is an aggressive malignant cancer of the central nervous system, with disease progression associated with deterioration of neurocognitive function and quality of life (QoL). As such, maintenance of QoL is an important treatment goal. This analysis presents time to deterioration (TtD) of QoL in patients with recurrent glioblastoma receiving Asunercept plus reirradiation (rRT) or rRT alone. Methods Data from patients with a baseline and ≥ 1 post-baseline QoL assessment were included in this analysis. TtD was defined as the time from randomisation to the first deterioration in the EORTC QLQ-C15, PAL EORTC QLQ-BN20 and Medical Research Council (MRC)-Neurological status. Deterioration was defined as a decrease of ≥ 10 points from baseline in the QLQ-C15 PAL overall QoL and functioning scales, an increase of ≥ 10 points from baseline in the QLQ-C15 PAL fatigue scale and the QLQ-BN20 total sum of score, and a rating of “Worse” in the MRC-Neurological status. Patients without a deterioration were censored at the last QoL assessment. Kaplan–Meier estimates were used to describe TtD and treatment groups (Asunercept + rRT or rRT alone) were compared using the log-rank test. Results Treatment with Asunercept + rRT was associated with significant improvement of TtD compared with rRT alone for QLQ-CL15 PAL overall QoL and physical functioning, and MRC Neurological Status (p ≤ 0.05). In the Asunercept + rRT group, QoL was maintained beyond progresison of disease (PoD). Conclusion Treatment with Asunercept plus rRT significantly prolongs TtD and maintains QoL versus rRT alone in recurrent glioblastoma patients.


2019 ◽  
Vol 37 (4_suppl) ◽  
pp. 284-284 ◽  
Author(s):  
Ben M. Chue ◽  
Bryce D. La Course

284 Background: mPC has a poor prognosis with a median overall survival (mOS) ranging from 8.5 to 11.1 months (mo) with standard treatment, outlining the need for new innovative treatments. MC regimens utilize lower doses of chemotherapy that are administered more frequently which can maintain dose intensity while reducing toxicity. MC with paclitaxel (P) or nab-paclitaxel (N) may have effects on the tumor microenvironment. Methods: A retrospective analysis of treatment regimens and survival of patients (pts) with biopsy proven mPC who received treatment between August 2004 and August 2018 was performed. Results: 30 pts with biopsy proven mPC were identified. 14 pts received prior chemotherapy. mOS of this cohort was 18.9 mo after diagnosis and 14.2 mo after beginning MC. 70% of pts (21/30) survived longer than 12 mo, 37% (11/30) greater than 24 mo, and 27% (8/30) greater than 30 mo. All MC regimens were given on a weekly basis and included: P 60 mg/m² and G 600 mg/m² (PaG); P 60 mg/m², O 50 mg/m², folinic acid (L) 20 mg/m², and 5-fluorouracil (F) 425 mg/m² (POLF); P 60 mg/m², I 100 mg/m², and cisplatin (C) 20 mg/m² (PIC) or P 60 mg/m², I 100 mg/m², L 20 mg/m², and F 425 mg/m² (PILF). 21 pts received N instead of P at some point during their treatment. PaG, POLF, and PIC or PILF were purposely switched before disease progression after a median length of 13, 11 and 13 weeks respectively. 16 pts received PaG as their first regimen. 12 of these 16 pts then received POLF as their second regimen, and 7 of these 12 pts subsequently received PIC or PILF as their third regimen. These 7 pts had a mOS of 21.7 mo after diagnosis and 19.1 mo after beginning MC. 10 pts were successfully able to receive PaG, POLF, or PIC/PILF more than once. Conclusions: Weekly MC regimens such as PaG, POLF, and PIC/PILF that are given sequentially are an effective treatment for mPC. Switching regimens may prevent the development of chemotherapy resistance, allowing for chemotherapy regimens to be used again in the future. There are limitations of retrospective studies so further investigation of this treatment strategy should be done with a large randomized clinical trial.


2012 ◽  
Vol 56 (4) ◽  
pp. 1974-1978 ◽  
Author(s):  
Judith M. Wenisch ◽  
Daniela Schmid ◽  
Hung-Wei Kuo ◽  
Franz Allerberger ◽  
Verena Michl ◽  
...  

ABSTRACTIn a hospital-based, prospective cohort study, the effects of the three standard treatment regimens for mildClostridium difficileinfection (CDI), oral (p.o.) metronidazole at 500 mg three times/day, intravenous (i.v.) metronidazole at 500 mg three times/day, and oral (p.o.) vancomycin at 250 mg four times/day, were compared with respect to the risk of occurrence of complications, sequelae, and all-cause death within 30 days after the date of starting treatment. Differences in the incidence of these outcomes were tested by χ2or Fisher's exact tests. A Poisson regression model was performed to control for possible confounding effects of sex, age, and severity of comorbidity categorized according to the Charlson comorbidity index. The highest mortality was observed in the metronidazole i.v. group, with a mortality rate 38.1% (16/42) compared to mortality rates of 7.4% (9/121) in the metronidazole p.o. group and 9.5% (4/42) in the vancomycin p.o. group (P< 0.001). After adjustment for possible effects of sex, age (>65 years), and severity of comorbidity, the relative risk of a 30-day fatal outcome for patients receiving metronidazole i.v. was 4.3 (95% confidence interval [CI] = 1.92 to 10;P< 0.0001) compared to patients treated with metronidazole p.o. and 4.0 (95% CI = 1.31 to 5.0;P< 0.015) compared to patients treated with vancomycin p.o. There were no significant differences in the risk of complications between the three treatment groups. This study generates the hypothesis that treatment with i.v. metronidazole is inferior to the oral alternatives metronidazole and vancomycin.


2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi157-vi157
Author(s):  
Manik Chahal ◽  
Brian Thiessen

Abstract BACKGROUND Bevacizumab (Bev) has been publicly funded in British Columbia (BC) since 2011 for treatment of recurrent glioblastoma (rGBM). We performed a retrospective outcomes assessment of patients with rGBM treated with Bev. METHODS Patients with rGBM treated at BC Cancer centers with Bev between January 2011 and December 2016 were reviewed. Patient demographics, tumor characteristics, treatment regimens, and dates of radiographic progression and death were collected. Kaplan-Meier method was used to assess survival, and comparisons were made using the log-rank test. RESULTS 138 patients were reviewed. There were 136 reported deaths with median PFS 3 months (CI95 = 2.5 - 3.5) and OS 7 months (CI95 = 6.1-8.0) from Bev initiation. 64% of patients on corticosteroids prior to Bev reduced their dose shortly after initiation. The majority of patients (72%) were treated with multiple lines of therapy prior to Bev, with a median time from chemoradiation to Bev initiation of 8 months (range 1-67). Patients started on Bev &lt; 6 months from chemoradiation (prior to completion of adjuvant temozolomide) had improved OS compared to those who started Bev later (p = 0.05), but there was no association between extent of treatment prior to Bev and outcomes (p = 0.182). Addition of chemotherapy to Bev did not improve survival over Bev monotherapy (p = 0.175). CONCLUSIONS Despite limited benefits to overall survival, Bev is associated with reduction in corticosteroid use and likely improvement in quality of life. Bev combinations with chemotherapy did not confer survival advantage over Bev monotherapy. Furthermore, our results show that patients receiving Bev before completion of adjuvant chemotherapy have better outcomes, suggesting pseudoprogression may have prompted the therapeutic switch. Further research is required to optimize patient selection for and administration of Bev. Additional analysis of rGBM patients prescribed Bev until 2020 in BC is currently underway.


2009 ◽  
Vol 24 (S1) ◽  
pp. 1-1
Author(s):  
R. de Arce ◽  
E. Eding ◽  
J. Marques-Teixeira ◽  
V. Milanova ◽  
E. Rancans ◽  
...  

Objective:A recent randomized, open-label, relapse prevention trial (ConstaTRE) of risperidone long-acting injectable (RLAI) versus quetiapine and the oral atypical antipsychotic aripiprazole was carried out. Here we report the descriptive analysis of the aripiprazole arm.Methods:Clinically stable adults with schizophrenia or schizoaffective disorder previously treated with oral risperidone, olanzapine, or oral conventional antipsychotic were randomized to treatment with RLAI, quetiapine, or aripiprazole (in some countries). Efficacy and tolerability were monitored for up to 24 months of treatment.Results:A total of 45 patients were treated with aripiprazole (10-30 mg/day) and 329 patients with RLAI. Relapse occurred in 27.3% aripiprazole and 16.5% RLAI-treated patients. Kaplan-Meier estimates of mean relapse-free period were 314 versus 607 days for aripiprazole and RLAI patients, respectively. Full-remission, as defined by Andreasen et al, (2005), was achieved by 34% aripiprazole and 51% RLAI patients and was maintained until the end of the trial by 30% aripiprazole and 44% RLAI patients. According to Clinical Global Impression-Severity, there were 61% aripiprazole and 62% RLAI patients moderately ill or worse at baseline, and 59% aripiprazole and 45% RLAI at endpoint, respectively. Tolerability was generally similar between aripiprazole and RLAI treatment groups. However, weight gain, extrapyramidal adverse events (AEs), and possibly prolactin-related AEs were more common with RLAI treatment. Gastrointestinal disorders were more common in aripiprazole-treated patients.Conclusions:Time-to-relapse in stable patients with schizophrenia or schizoaffective disorder tended to be longer in RLAI-treated patients when compared with aripiprazole-treated patients. both RLAI and aripiprazole treatments were generally well tolerated.


2021 ◽  
Vol 2 (1) ◽  
pp. 15-17
Author(s):  
Maiorova M.O.

41 women with osteoporosis were examined. The age of the examined people ranged from 50 to 60 years. All the women were postmenopausal. As a result of the study, it was found that the most effective management strategy for such patients is a combination of menopausal hormone therapy and non-hormonal drugs that affect calcium metabolism in bone tissue, improve its metabolism and reduce resorption. If there are contraindications to MGT, prevention and treatment of osteoporosis should also be carried out using the appointment of non-hormonal drugs. In this case, the use of ipriflavone is effective.


2017 ◽  
Vol 102 (7) ◽  
pp. 954-958 ◽  
Author(s):  
Giovanni Staurenghi ◽  
Nicolas Feltgen ◽  
Jennifer J Arnold ◽  
Todd A Katz ◽  
Carola Metzig ◽  
...  

Background/aimsTo evaluate intravitreal aflibercept versus laser in subgroups of patients with baseline Diabetic Retinopathy Severity Scale (DRSS) scores ≤43, 47, and ≥53 in VIVID-DME and VISTA-DME.MethodsPatients with diabetic macular oedema were randomised to receive intravitreal aflibercept 2 mg every 4 weeks (2q4), intravitreal aflibercept 2 mg every 8 weeks after five initial monthly doses (2q8), or macular laser photocoagulation at baseline with sham injections at every visit. These post hoc analyses evaluate outcomes based on baseline DRSS scores in patients in the integrated dataset. The 2q4 and 2q8 treatment groups were also pooled.Results748 patients had a baseline DRSS score based on fundus photographs (≤43, n=301; 47, n=153; ≥53, n=294). At week 100, the least squares mean difference between treatment groups (effect of intravitreal aflibercept above that of laser, adjusting for baseline best-corrected visual acuity) was 8.9 (95% CI 5.99 to 11.81), 9.7 (95% CI 5.54 to 13.91), and 11.0 (95% CI 7.96 to 14.1) letters in those with baseline DRSS scores ≤43, 47, and ≥53, respectively. The proportions of patients with ≥2 step DRSS score improvement were greater in the intravitreal aflibercept group versus laser, respectively, for those with baseline DRSS scores of ≤43 (13% vs 5.9%), 47 (25.8% vs 4.5%), and ≥53 (64.5% vs 28.4%).ConclusionsRegardless of baseline DRSS score, functional outcomes were superior in intravitreal aflibercept-treated patients, demonstrating consistent treatment benefit across various baseline levels of retinopathy.Trial registration numbersNCT01331681 and NCT01363440, Post-results.


2018 ◽  
Vol 52 (6) ◽  
pp. 599-610 ◽  
Author(s):  
Sally A Sharpe ◽  
Donna Smyth ◽  
Anthony McIntyre ◽  
Fergus Gleeson ◽  
Mike J Dennis

Until validated correlates of protection are identified, animal models remain the only way to test the efficacy of the new vaccines and drugs urgently needed to fight the global epidemic caused by infection with Mycobacterium tuberculosis. Non-human primates (NHP) offer the most relevant models of human tuberculosis (TB) and are central to the development process for new interventions. Efficacy evaluations are dependent on the capability of the test model to discriminate improved outcomes between treated groups after experimental exposure to M. tuberculosis and therefore the ability to measure TB-induced disease burden is central to the process. We have developed a score system that allows us to quantify the disease burden induced in macaques by infection with M. tuberculosis, based on the extent and features of disease visible on computed tomography (CT) images. The CT determined disease burden was then verified against that obtained using an established pathology-based approach. Trials of the system as a tool to measure disease burden have shown the approach capable of revealing differences between treatment groups in order to: (a) characterise outcome of infection and enable model refinement; (b) demonstrate the efficacy of drug treatment regimens by showing differences in outcome between test groups. Initial trials suggest that the imaging-based score system provides a valuable additional tool for the measurement of TB-induced disease burden that offers the opportunity to apply both refinement and reduction within studies.


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