scholarly journals Efficacy and safety of tripterygium glycosides for active moderate to severe Graves’ ophthalmopathy: a randomised, observer-masked, single-centre trial

2021 ◽  
Vol 184 (2) ◽  
pp. 277-287
Author(s):  
Xiaozhen Ye ◽  
Heng Zhao ◽  
Jun Liu ◽  
Bin Lu ◽  
Jiaqing Shao ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Overall Response Rate ◽  
Response Rate ◽  
Single Centre ◽  
Eye Muscle ◽  
Overall Response ◽  
Graves Ophthalmopathy ◽  
Tripterygium Glycosides ◽  
To Receive

Background Tripterygium glycosides (TG) has been used to treat a spectrum of inflammatory and autoimmune diseases. Our preliminary studies have shown that TG is effective in the treatment of active Graves’ ophthalmopathy (GO). Objective We aimed to compare the efficacy and tolerability of TG with intravenous methylprednisolone (iv.MP) in patients with active moderate-to-severe GO. Methods This study was an observer-masked, single-centre, block-randomised trial. Patients with active moderate-to-severe GO were randomly assigned to receive iv.MP (500 mg once per week for 6 weeks followed by 250 mg per week for 6 weeks) or with TG (20 mg tablet three times per day for 24 weeks). The primary endpoints were the overall response rate and the patients’ quality of life at 12 and 24 weeks. Results In this study, 161 patients were enrolled and randomised from 2015 to 2019. A total of 79 were randomly assigned to receive iv.MP and 82 to receive TG. A greater overall response rate was found in the TG group compared with the iv.MP group at week 24 (90.2% vs 68.4%, P = 0.000). Similarly, the patients’ quality of life of the TG group showed a significantly higher response than the iv.MP group at week 24 (89.02% vs 72.15%, P = 0.001). The TG therapy showed a better CAS response than the iv.MP (91.5% vs 70.9% improved, P < 0.05), and up to 91.2% of patients were inactive. Also, the TG group showed a significantly higher improved rate of diplopia, proptosis, visual acuity, soft tissue involved and the decrease of eye muscle motility than the iv.MP group at week 24. Significantly more patients in the iv.MP group than the TG group experienced adverse events. Conclusion Compared with iv.MP treatment, TG therapy is more effective and safer for patients with active moderate to severe GO.

Decitabine Low-Dose Schedule (100 mg/m2/Course) in Myelodysplastic Syndrome (MDS). Comparison of 3 Different Dose Schedules.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 2522-2522 ◽  
Author(s):  
Hagop Kantarjian ◽  
Susan O’Brien ◽  
Francis Giles ◽  
Farhad Ravandi-Kashani ◽  
Stefan Faderl ◽  
...  
Keyword(s):  
Low Dose ◽  
Overall Response Rate ◽  
Response Rate ◽  
Optimal Schedule ◽  
Dose Schedule ◽  
Overall Response ◽  
Transfusion Independence ◽  
Secondary Mds ◽  
To Receive

Abstract Background Decitabine (DAC), a hypomethylating agent, has shown activity in MDS. DAC 150 mg/m2 by continuous infusion has been associated with CR rates of 10% to 20%. We investigated optimizing the dose schedule of DAC in MDS. Study Group and Methods Patients (pts) with IPSS intermediate 1–2 & high risk MDS were randomized to one of 3 schedules of DAC: 1) 20 mg/m2 IV over 1 hour daily x 5; 2) 10 mg/m2 IV over 1 hour daily x 10; or 3)10 mg/m2 subcutaneously (SQ) BID x 5. A total of 95 pts are to be treated; Bayesian randomization is implemented based on CR rates. Courses were given every 28 days. Delays to allow counts recovery were permitted every 3 courses, or if myelosuppression without disease, or severe myelosuppression complications. Pts were allowed to receive erythropoietin 40,000 units weekly for anemia, or GCSF if needed. Response criteria for CR & PR were as for AML (PR requiring also ↓ blasts by &gt;50%). Clinical benefit (CB) referred to one or more of: platelets î by ≥ 50% and &gt;30 x 109/L, or granulocytes increase by ≥ 100% and to &gt;109/L, or hemoglobin î by ≥ 2 g/dl or transfusion independence, or splenomegaly ↓ by 50% or more, or monocytes ↓ by 50% or more (pretreatment &gt;5 x 109/L). Results 92 pts have been treated; median age 65 (31–90) yrs; 66% &gt;60 yrs old. IPSS: intermediate-1 25%; intermediate-2 38%; high 19%; CMML 17% Cytogenetic abnormalities 57%; secondary MDS 17%; marrow blasts &gt; 10% in 31%. 27 pts had prior erythropoietin; 17 had prior GCSF; 22 had other prior therapies. Presently, 89 pts have received 1 course. Results: 32 CR (36%); 7 PR (8%); 13 marrow CR + CB (15%); 16 CB (18%); overall response 68/89=76%. Median courses to CR 3 (range 1 to 6). Median follow-up of 9 months; 48 pts continue on DAC. Compared with a 114 pts with MDS who received intensive chemotherapy (2000–2004), CR rate was lower with DAC (36% vs. 45%), overall response rate was favorable; 6-week mortality was lower with DAC (1% vs. 21%); and estimated survival favorable (p = 0.00007). CR rates by schedule: 5 days IV 24/58 (41%); 5 days SQ 4/14 (28%); 10 day IV 4/17 (24%). There was more myelosuppression with 10 day IV. After 55 patients were randomized, the 5 day IV arm was determined statistically superior, therefore, remaining patients were not randomized, but were treated with 5 days IV therapy. Conclusions DAC has significant anti-MDS activity; 2) optimal schedule: 20 mg/m2 IV over 1 hour daily x 5; 3) timely repeated courses needed for optimal response.

Pananemia 2008 multicenter observational study on erythropoietin beta treatment in patients with cancer: Efficacy, patient satisfaction, and impact on psychological distress

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e20695-e20695
Author(s):  
S. Del Prete ◽  
R. Addeo ◽  
L. Leo ◽  
S. Cinieri ◽  
V. Lorusso ◽  
...  
Keyword(s):  
Patient Satisfaction ◽  
Psychological Distress ◽  
Cancer Patients ◽  
Overall Response Rate ◽  
Response Rate ◽  
Multicenter Observational Study ◽  
Overall Response ◽  
To Receive ◽  
Self Administered Questionnaire ◽  
Anemia Treatment

e20695 Background: Cancer-related anemia, results in both a need for transfusions and a decreased functional capacity and quality of life. Treating anemia associated with chemotherapy and many cancers is often necessary. However, patient satisfaction with anemia treatment, and the possible correlation between anemia and psychological distress frequently present in these patients is limited by the lack of validated instruments. Methods: Between January 2008 and December 2008, 591 cancer patients in treatment with erythropoietin beta for anemia were targeted to complete the Psychological Distress Inventory (PDI), a 13-item self-administered questionnaire, and the Patient Satisfaction Questionnaire ( PSQ) at 4 week intervals, a 10-item, self-administered questionnaire. Data from weeks 5 and 9 were analyzed. Patients were required to receive at least four weekly injections of Epo, expecting to receive ≥ 8 additional weeks of chemotherapy, and able to complete questionnaires. Results: Among patients fulfilling eligibility criteria and having received at least four Epo Beta administrations, most (57.5%) of them were female, with a median age of 66 (52.4 - 76.5), and a median KPS of 85 (range: 50–100). 399 patients had a stage IV cancers. Hemoglobin values increased from mean baseline levels of 9.55 g/dL, to attain levels 10.31 at week 5, and 11.05 after 8 weeks of therapy; 247 (42%) patients received iron supplementation. For PDI, the overall response rate was 93 % (548/591) at baseline, 100 % (517/517) at week 5, and 99% (491/492) at week 9. The percentage of patients with psychological difficulties decreased during the treatment. For PSQ, the overall response rate was 100% (517/517) at week 5, and 100 % (492/492) at week 9. The PSQ questionnaires showed that a conspicuous group of patients (124/517) marked troubles to accept the treatment. Conclusions: Our results suggest that in anemic cancer patients psychological distress and anemia were related. PSQ reflect the burden of injection anemia treatment on cancer patients. Final data analysis will be presented. No significant financial relationships to disclose.

scholarly journals FINAL Results of an Phase, Multicenter, Randomied, Controlled OPEN LEVEL Trial: Decitabine Therapy in Patients with Myelodysplastic Syndromes

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 3865-3865
Author(s):  
Zonghong Shao ◽  
Hui Liu ◽  
Hao Jiang ◽  
Hongyan Tong ◽  
Ruixiang Xiang ◽  
...  
Keyword(s):  
Clinical Trials ◽  
High Risk ◽  
Adverse Events ◽  
Myelodysplastic Syndromes ◽  
Overall Response Rate ◽  
Response Rate ◽  
Conflicts Of Interest ◽  
Study Drug ◽  
Overall Response ◽  
To Receive

Abstract Background: DNA hypomethylating agent, decitabine, has become the current standard therapy for patients with higher-risk myelodysplastic syndromes (MDS). Decitabine was launched in China in August 2009 without clinical trials. According to some retrospective studies, the efficacy and safety are similar to those reported in other countries, but there is still a lack of large-scale prospective clinical trials. So we start a prospective clinical trial in China to compare the effect and safety of decitabine in MDS, which was registered at clinicaltrials.gov (NCT02013102). Design: Adults with intermediate or high risk MDS by the International Prognostic Scoring System (IPSS≥0.5) were randomized to receive either decitabine 20 mg/m2 IV daily for 5 days (arm Ⅰ) or decitabine 12 mg/m2 IV daily for 8 days (arm Ⅱ) every four weeks. Patients continued to receive study drug for 4 cycles until death, disease progression, intercurrent illness preventing further administration of treatment, unacceptable adverse event or decision by the patient to withdraw from the study. And supportive care were permitted. The primary end point was overall response rate (ORR, CR+mCR+PR) by International Working Group (IWG 2006) criteria, secondary end points included CR, mCR, PR, HI, safety, et al. Results: We enrolled a total of 198 patients between 8/2013 and 12/2017, among which 7 patients didn't take decitabine, and 191 were included in the analysis. 94 in arm Ⅰ recieved decitabine and 97 in arm Ⅱ. 32.8% of patients withdrew from the study for a variety of reasons, including progression and death (5.1%), personal decision (13.6%), adverse events (6.6%), and other causes (7.6%). The median age of patients in arm Ⅰ was 54.88 years old and 54.82 years old in arm II. The median follow-up was 106 days for patients in both arms. The patients received a mean 2.5 cycles of decitabine therapy for arm Ⅰ and 2.0 cycles for arm Ⅱ. The overall response rate was 39.3% in total, and 41.5% and 38.1% (p=0.6598) for patients in arm Ⅰ and arm Ⅱ, respectively. And CR was 18.1% and 14.4% (p= 0.5584) , PR was 6.4% and 3.1% (p=0.3257) , mCR was 17.0% and 20.6% (p=0.5814) , HI was 3.2% and 1.0% (p=0.3633) , for patients in armⅠand armⅡ, respectively (Table 1). Among all patients, 38.7% were intermediate-1 risk, 40.3% were intermediate-2 risk, 20.4% were high risk. Analysis of response by MDS patient subtypes is shown in Table 2. Those who were higher risk experienced higher ORR and CR, while the difference is not significant between two arms (p>0.05). As expected, cytopenias were the most frequent complications (76.4%). Grade 3-4 neutropenia, thrombocytopenia and anemia considered to be at least possibly related to the study drug occurred at rates of 23.0%, 34.6%, and 34.6% of patients, respectively. Nonhematologic adverse events were also common including abnormal metabolism and nutrition (23.40% vs 18.56%), abnormal gastrointestinal function (29.79% vs 41.24%), cardiac disorders (11.70% vs 14.43%), infection and infectious diseases (32.98% vs 36.08%), abnormal skin and subcutaneous tissue and so on, which were no significant differences between two ams. During the study there were 17 SAE, only 7 cases were possibly related to drug therapy, such as pulmonary infection, Sepsis, myelosuppression, intracranial hemorrhage, hepatic failure, and arrhythmia. Conclusions: The use of 5-day and 8-day schedule decitabine is safe and effective in patients with intermediate and high risk MDS, among which there was no significant differences. Disclosures No relevant conflicts of interest to declare.

Use of electrochemotherapy in women with vulvar cancer to improve quality-of-life in the palliative setting: a meta-analysis

2019 ◽  
Vol 30 (1) ◽  
pp. 107-114 ◽  
Author(s):  
Anastasios Tranoulis ◽  
Dimitra Georgiou ◽  
Christina Founta ◽  
Gautam Mehra ◽  
Ahmad Sayasneh ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Palliative Care ◽  
Partial Response ◽  
Treatment Modality ◽  
Vulvar Cancer ◽  
Response Rate ◽  
Meta Analysis ◽  
Overall Response ◽  
Moderate Quality

IntroductionElectrochemotherapy involves the use of transient tumor permeabilization via electric pulses in combination with low-dose chemotherapeutic agents. It has recently emerged as an alternative treatment modality in vulvar cancer. The aim of this meta-analysis was to ascertain the effectiveness of electrochemotherapy in the context of palliative care.MethodsThe following databases were searched: MEDLINE, Scopus, and Cochrane Database, to identify all registered articles pertaining to palliative vulvar cancer treatment with electrochemotherapy from inception until August 2019, in line with PRISMA guidelines. A single-proportion meta-analysis was performed for the outcomes of overall response, complete response, partial response, stable disease, and progressive disease raterespectively, using the random-effect model. Sensitivity analysis was performed to address heterogeneity.ResultsFour studies were included totaling 104 women. The studies were of moderate quality. Pooled results from four studies rendered a summary proportion of 78.8% (95% CI 70.4% to 86.1%) for the outcome of overall response. The median age ranged between 68 and 85 years. The sample size per study ranged between eight and 61 women. The tumors’ histological types included: squamous-cell carcinoma (96.2%), Paget’s disease (2.9%), and malignant melanoma (0.9%). A total of 65 patients (62.5%) presented with a single nodule, whilst 39 patients (37.5%) presented with multiple nodules. Eighty-nine women (85.6%) were previously submitted to other treatment modalities. The overall response rate ranged from 73.2% to 80.9%. The pooled proportion for the outcomes of complete and partial response rate was 48.7% (95% CI 30.74% to 61.5%) and 30.2% (95% CI 21.7% to 39.4%), respectively. The follow-up ranged from 1 to 51 months. No severe adverse effects were reported. The safety profile of electrochemotherapy was favorable.ConclusionsElectrochemotherapy is an effective and minimally invasive treatment modality in the palliative care management of patients with vulvar cancer. The effective control of vulvar tumors by electrochemotherapy may contribute to improvement of quality-of-life. In light of the moderate quality of evidence, a multi-center cooperation is warranted to confirm its palliative benefit.

Hochrisiko-CLL: Zielgerichtete Kombinationstherapie verbessert das Überleben

2021 ◽  
pp. 1-3
Author(s):  
Katja Zirlik
Keyword(s):  
Cardiac Arrest ◽  
High Risk ◽  
Adverse Events ◽  
Chronic Lymphocytic Leukaemia ◽  
Overall Response Rate ◽  
Lymphocytic Leukaemia ◽  
Response Rate ◽  
Complete Response ◽  
Overall Response ◽  
To Receive

<b>Background:</b> Patients with chronic lymphocytic leukaemia and high-risk features have poorer outcomes on ibrutinib than those without high-risk features. The aim of this study was to assess the benefit of adding ublituximab, an anti-CD20 monoclonal antibody, to ibrutinib therapy in this population. <b>Methods:</b> We did a randomised, phase 3, multicentre study (GENUINE) of patients aged 18 years or older with relapsed or refractory chronic lymphocytic leukaemia with at least one of 17p deletion, 11q deletion, or TP53 mutation, at 119 clinics in the USA and Israel. Eligible patients had received at least one previous chronic lymphocytic leukaemia therapy and had an Eastern Cooperative Oncology Group performance status of 2 or lower. We randomised patients (1:1) using permuted block randomisation with a block size of four and stratified by previous lines of therapy (one vs two or more) to receive ibrutinib alone or ibrutinib in combination with ublituximab. Treatment allocation was not masked to patients or investigators. Ibrutinib was given orally daily at 420 mg for all cycles. Ublituximab was given intravenously in 28-day cycles, with increasing doses during cycle 1 (≤150 mg on day 1, 750 mg on day 2, and 900 mg on days 8 and 15) and continuing at 900 mg on day 1 of cycles 2–6. After cycle 6, ublituximab was given at 900 mg every three cycles. The study was initially designed with co-primary endpoints of progression-free survival and overall response rate but due to protracted patient accrual, the protocol was amended to have a single primary endpoint of independent review committee-assessed overall response rate (defined as the proportion of patients who had a partial response, complete response, or complete response with incomplete marrow recovery according to the 2008 International Workshop on CLL criteria) in the intention-to-treat population. Safety was evaluated in the population of patients who received at least one dose of study treatment. This trial is registered with ClinicalTrials.gov, NCT02301156, and the final analysis is presented. <b>Findings:</b> 224 patients were assessed for eligibility, of whom 126 patients were enrolled and randomly assigned to receive ublituximab plus ibrutinib (n = 64) or ibrutinib alone (n = 62) between Feb 6, 2015, and Dec 19, 2016. After a median follow-up of 41·6 months (IQR 36·7–47·3), the overall response rate was 53 (83%) of 64 patients in the ublituximab plus ibrutinib group and 40 (65%) of 62 patients in the ibrutinib group (p = 0·020). 117 patients, including 59 in the ublituximab plus ibrutinib group and 58 in the ibrutinib group, received at least one dose of treatment and were included in safety analyses. Most adverse events were grade 1 or 2. The most common grade 3 and 4 adverse events were neutropenia (11 [19%] patients in the ublituximab plus ibrutinib group and seven [12%] in the ibrutinib group), anaemia (five [8%] and five [9%]), and diarrhoea (six [10%] and three [5%]). The most common serious adverse events were pneumonia (six [10%] in the ublituximab plus ibrutinib group and four [7%] in the ibrutinib group), atrial fibrillation (four [7%] and one [2%]), sepsis (four [7%] and one [2%]), and febrile neutropenia (three [5%] and one [2%]). Two patients in the ublituximab plus ibrutinib group died due to adverse events (one cardiac arrest and one failure to thrive), neither of which were treatment-related. Five patients in the ibrutinib group died due to adverse events, including one cardiac arrest, one cerebral infarction, one intracranial haemorrhage, one Pneumocystis jirovecii pneumonia infection, and one unexplained death; the death due to cardiac arrest was considered to be treatment-related. <b>Interpretation:</b> The addition of ublituximab to ibrutinib resulted in a statistically higher overall response rate without affecting the safety profile of ibrutinib monotherapy in patients with relapsed or refractory high-risk chronic lymphocytic leukaemia. These findings provide support for the addition of ublituximab to Bruton tyrosine kinase inhibitors for the treatment of these patients. <b>Funding:</b> TG Therapeutics.

scholarly journals Forewarned is Forearmed? A Survey-Experiment concerning the Impact of Pre-Notification Letters on Response in a Postal Survey

2014 ◽  
Vol 22 (2) ◽  
pp. 86-95 ◽  
Author(s):  
Bram Spruyt ◽  
Filip Van Droogenbroeck
Keyword(s):  
Large Scale ◽  
Overall Response Rate ◽  
Response Rate ◽  
Positive Impact ◽  
Postal Survey ◽  
Survey Experiment ◽  
Overall Response ◽  
Large Scale Survey ◽  
The Impact

The use of pre-notification letters is thought to increase the response rate of postal surveys. The empirical evidence for that claim, however, is not conclusive. In this research note we assessed the impact of pre-notification by means of data from a large-scale survey-experiment conducted in Flanders (N: 4000). Three outcomes were studied: overall response rate, timing of the response and quality of the response. No significant positive impact was found on the overall response rate and quality of response. However evidence indicated that respondents who received a pre-notification letter were more inclined to respond earlier.

Effect of dietary counseling on food intake, body weight, response rate, survival, and quality of life in cancer patients undergoing chemotherapy: a prospective, randomized study.

1993 ◽  
Vol 11 (10) ◽  
pp. 2043-2049 ◽  
Author(s):  
L Ovesen ◽  
L Allingstrup ◽  
J Hannibal ◽  
E L Mortensen ◽  
O P Hansen
Keyword(s):  
Quality Of Life ◽  
Body Weight ◽  
Protein Intake ◽  
Response Rate ◽  
Oral Intake ◽  
Nutritional Counseling ◽  
Dietary Counseling ◽  
Daily Energy ◽  
To Receive

PURPOSE This study examined the effect of frequent nutritional counseling on oral intake, body weight, response rate, survival, and quality of life in patients with cancer of the lung (small-cell), ovary, or breast undergoing cyclic chemotherapy. PATIENTS AND METHODS Of 105 assessable patients, 57 were randomized to receive nutritional counseling, and 48 to receive no nutritional counseling and consumption of an ad lib oral intake. The intervention group was counseled to achieve a daily energy and protein intake according to recommended dietary allowances. Counseling was standardized and performed by a trained dietitian, and took place twice monthly during a 5-month period from start of chemotherapy. RESULTS Dietary counseling increased daily energy intake by approximately 1 MJ and protein intake by 10 g over the entire study period. There was no change in the control group. Counseling led to an insignificant increase in body weight, but triceps skinfold measurement increased significantly after 5 months. Response rate and overall survival did not differ between the groups. Quality of life measured by the Quality-of-Life index (QL-index) increased significantly in both groups, but did not differ between groups. CONCLUSION No clinical benefit could be demonstrated despite long-term and continuous improved food intake in cancer patients with solid tumors undergoing aggressive chemotherapy.

Efficacy and Safety of Darbepoetin Alfa (DA) in Patients with Myelodysplastic Syndromes (MDS): A Systematic Review and Meta-Analysis

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 5236-5236
Author(s):  
Sophie Park ◽  
Pierre Fenaux ◽  
Peter Greenberg ◽  
Bhakti Mehta ◽  
Fiona Callaghan ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Systematic Review ◽  
Research Funding ◽  
Response Rate ◽  
Meta Analysis ◽  
Response Rates ◽  
Response Criteria ◽  
Overall Response ◽  
Equity Ownership

Abstract Introduction: Erythropoiesis-stimulating agents (ESAs) have been used in treating anemic MDS patients to improve erythropoiesis and reduce the risk of red blood cell (RBC) transfusion. Two previous systematic reviews found that ESA use was efficacious, but these reviews focused on short-acting epoetin alfa (EA). Since then, the results of a number of prospective interventional trials of DA have been reported. We present an updated systematic review and meta-analysis to estimate the efficacy of DA in the treatment of MDS-related anemia. Methods: We conducted a systematic review of the medical literature to identify prospective interventional trials of DA in patients with MDS. The main inclusion-exclusion (IE) criteria were: that studies had to be prospective and interventional in nature; have at least 10 adult subjects with MDS reporting either World Health Organization (WHO), French-American-British (FAB) criteria, or International Prognostic Scoring System (IPSS) status; and report results for the pre-specified primary outcome (proportion of patients with erythroid response) or one of the secondary outcomes (which included major hemoglobin response, changes from baseline in hemoglobin levels, transfusion status, and quality of life (QoL) measures). We recorded and collated all reported adverse events. Two independent reviewers identified the studies and abstracted the information and a third reviewer adjudicated. Clinical and methodological heterogeneity across studies were evaluated with respect to the study population and participant selection method (e.g. MDS diagnosis, history of ESA use, baseline erythropoietin (EPO), hemoglobin, and creatinine levels, transfusion status, and other factors), the intervention (e.g. initial and maintenance ESA dose), and the endpoints of interest including the response criteria. Forest plots with formal testing using Cochran's Q-statistic was also used to assess the heterogeneity across the studies. We used random effects methodology to generate combined estimates when warranted by the data. Subgroup analyses and/or meta-regressions were conducted by dose level, ESA-naïve status, baseline EPO level, hemoglobin level, transfusion status, and other factors. Results: Ten studies (9 single-arm, 1 randomized controlled trial [RCT]) with a total of 647 patients were included in the systematic review, with response rates ranging from 38% to 72%, and the median duration of response varying from 5 to 12 months. The overall response rate for the nine studies that used IWG 2000 response criteria could not be evaluated because of heterogeneity. However, among studies that stratified response rates by baseline endogenous EPO levels, patients with EPO <100 IU/L had an overall response of 81% (95% confidence interval [CI]: 73-90%), and on average a 39% [95% CI: 22-56%] better response than patients with EPO >100 IU/L. Across the studies that reported response stratified by prior ESA use, ESA-naïve patients had a median response rate of 75% compared to 53% for patients previously treated with an ESA. Baseline mean hemoglobin was significantly associated with response (p=0.0204), with higher baseline levels associated with improved response. We also found that response tended to improve with dose (p=0.2; Figure 2): the estimated response for a mean initial dose of 150 μg once weekly (QW) was 57% (95% CI: 49-66%) compared to 64% (95% CI: 55-74%) for 300 μg QW. Baseline transfusion independence (6 studies), and low-risk IPSS status (2 studies) were reported to be significantly associated with better response in several studies. Treatment with DA tended to show an improvement in the quality of life (QoL) measures, transfusion rates, and hemoglobin levels, but the number of studies that reported these outcomes was small. Hypertension, thromboembolism, and progression to acute myeloid leukemia were respectively reported in 2%, 1%, and 1% of the patients. Conclusions: Published studies suggest that treatment with DA yielded high hemoglobin response (38-72%) in MDS patients with anemia. The response was strongest in patients with lower baseline serum EPO level, and ESA naïve patients. Disclosures Park: Hospira: Research Funding; Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Research Funding. Fenaux:Amgen: Honoraria, Research Funding; Novartis: Honoraria, Research Funding; Celgene Corporation: Honoraria, Research Funding; Janssen: Honoraria, Research Funding. Mehta:Amgen Inc.: Employment; Amgen Inc.: Equity Ownership. Callaghan:Amgen Inc.: Employment; Amgen Inc.: Equity Ownership. Kim:Amgen Inc.: Employment; Amgen Inc.: Equity Ownership. Tomita:Amgen Inc.: Employment; Amgen Inc.: Equity Ownership. Xu:Amgen Inc.: Employment; Amgen Inc.: Equity Ownership.

scholarly journals An open-label, single-arm, phase 2 (PX-171-004) study of single-agent carfilzomib in bortezomib-naive patients with relapsed and/or refractory multiple myeloma

Blood ◽  
2012 ◽  
Vol 119 (24) ◽  
pp. 5661-5670 ◽  
Author(s):  
Ravi Vij ◽  
Michael Wang ◽  
Jonathan L. Kaufman ◽  
Sagar Lonial ◽  
Andrzej J. Jakubowiak ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Overall Response Rate ◽  
Response Rate ◽  
Phase 1 ◽  
Single Agent ◽  
Phase 2 ◽  
Open Label ◽  
Refractory Multiple Myeloma ◽  
Overall Response ◽  
To Receive

Abstract Carfilzomib is a selective proteasome inhibitor that binds irreversibly to its target. In phase 1 studies, carfilzomib elicited promising responses and an acceptable toxicity profile in patients with relapsed and/or refractory multiple myeloma (R/R MM). In the present phase 2, multicenter, open-label study, 129 bortezomib-naive patients with R/R MM (median of 2 prior therapies) were separated into Cohort 1, scheduled to receive intravenous carfilzomib 20 mg/m2 for all treatment cycles, and Cohort 2, scheduled to receive 20 mg/m2 for cycle 1 and then 27 mg/m2 for all subsequent cycles. The primary end point was an overall response rate (≥ partial response) of 42.4% in Cohort 1 and 52.2% in Cohort 2. The clinical benefit response (overall response rate + minimal response) was 59.3% and 64.2% in Cohorts 1 and 2, respectively. Median duration of response was 13.1 months and not reached, and median time to progression was 8.3 months and not reached, respectively. The most common treatment-emergent adverse events were fatigue (62.0%) and nausea (48.8%). Single-agent carfilzomib elicited a low incidence of peripheral neuropathy—17.1% overall (1 grade 3; no grade 4)—in these pretreated bortezomib-naive patients. The results of the present study support the use of carfilzomib in R/R MM patients. This trial is registered at www.clinicaltrials.gov as NCT00530816.

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