Phase II study of AVR118 in the management of cancer related anorexia/cachexia

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e20631-e20631
Author(s):  
J. T. D'Olimpio ◽  
M. R. Chasen ◽  
R. Sharma ◽  
M. Diego ◽  
V. Gullo ◽  
...  
Keyword(s):  
Karnofsky Performance Status ◽  
Performance Status ◽  
Treatment Phase ◽  
Severity Index ◽  
Active Components ◽  
Skin Fold Thickness ◽  
Skin Fold ◽  
Significant Difference ◽  
Branched Chain ◽  
Index Weight

e20631 Background: AVR118 represents a new class of cytoprotective drugs in managing symptoms associated with anorexia\/ cachexia. In a previous study in patients with advanced HIV-AIDS, an improvement in appetite, strength and alertness was noted. The precise mechanism of action is not understood, but activity may be related to AVR118's adenosine based components. Other active components include guanosine and branched chain amino acids leucine and valine. Objective: To determine the effect of AVR118 on appetite, early satiety and nutritional intake in patients with advanced cancer. Secondary endpoints include changes in performance status, lean muscle mass and quality of Life (QOL). Methods: Eligible adult patients received 4.0 ml of AVR118 subcutaneous daily injections. Patients underwent bi-monthly evaluations during the 28 day initial treatment (phase A) Evaluations included Karnofsky performance status, Edmonton Symptoms Assessment Scale (ESAS), Patient Generated Subjective Global Assessment (PG-SGA), Simmonds Functional Assessment, Dyspepsia Symptom Severity Index, Weight, Lean Body Mass, skin fold thickness and grip strength. Patients who benefited from phase A could elect to continue with therapy (phase B). Results: Currently, of 16 enrolled patients 7 have completed phase A. All 7 patients chose to continue with AVR118 treatment (phase B). Improvements in anorexia and PG-SGA scores were seen in 7/7 and 6/7 patients respectively. Weight stabilization or gain was observed in 5/7 patients. All other parameters showed no significant difference. There was AVR118 has been well tolerated and no serious side effects have been reported. Conclusions: Based on these positive results, the primary endpoints have been achieved and the study will be expanded from 14 to 30 patients. [Table: see text]

Regimen-related toxicity and early posttransplant survival in patients undergoing marrow transplantation for lymphoma.

1989 ◽  
Vol 7 (9) ◽  
pp. 1288-1294 ◽  
Author(s):  
S I Bearman ◽  
F R Appelbaum ◽  
A Back ◽  
F B Petersen ◽  
C D Buckner ◽  
...  
Keyword(s):  
Malignant Lymphoma ◽  
Advanced Disease ◽  
Karnofsky Performance Status ◽  
Performance Status ◽  
Probability Of Survival ◽  
Significant Difference ◽  
Preparative Regimen ◽  
Life Threatening ◽  
Total Body ◽  
Grade 3

Ninety-five patients transplanted for malignant lymphoma were retrospectively evaluated for regimen-related toxicity (RRT) and early posttransplant survival. Nineteen patients developed life-threatening (grade 3) or fatal (grade 4) RRT in one or more organs. Grade 3 or 4 RRT was more common in patients with advanced disease versus those transplanted earlier in their course (P = .008), and was more common in patients with advanced disease conditioned with cytarabine (Ara-C)/total body irradiation (TBI) versus those prepared with cyclophosphamide (CY)/TBI (P = .033). There was no significant difference in the incidence of grade 3 or 4 toxicity in autologous, histocompatibility locus antigen (HLA)-identical, or HLA-mismatched marrow recipients. Grade 3 or 4 RRT tended to be more common and 100-day survival worse in patients with a Karnofsky performance status of less than 90 (P = .063 and .0002, respectively). Patients receiving 20 Gy or more of mediastinal irradiation before coming to transplant had more idiopathic or cytomegalovirus (CMV) interstitial pneumonitis than those who received less than 20 Gy (30% v 9%, P = .027). The probability of survival decreased with the number of organs in which toxicity was observed (P = .0001). Severe or fatal toxicities directly related to the preparative regimen are a significant problem in the treatment of patients with advanced malignant lymphoma and can be reduced by carrying out transplantation earlier in the course of the disease.

A prospective study to evaluate the efficacy and safety of oral acetyl-L-carnitine (ALC) in treatment of chemotherapy-induced peripheral neuropathy (CPIN).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 9017-9017 ◽  
Author(s):  
Yuanjue Sun ◽  
Baorui Liu ◽  
Ping Liu ◽  
Changping Wu ◽  
Rongsheng Zheng ◽  
...  
Keyword(s):  
Peripheral Neuropathy ◽  
Oral Administration ◽  
Primary Endpoint ◽  
Side Effect ◽  
Karnofsky Performance Status ◽  
Performance Status ◽  
Controlled Study ◽  
Efficacy And Safety ◽  
Cancer Related Fatigue ◽  
Significant Difference

9017 Background: Chemotherapy-induced peripheral neuropathy (CIPN) is a major side effect of many commonly used chemotherapeutic. This side effect of chemotherapy can be debilitating and effective treatment for CIPN remains elusive. Previous studies demonstrated that Acetyl-L-Carnitine (ALC) is effective in attenuating CIPN, controlled study is needed to substantiate ALC’s effect in treatment of CIPN. Methods: This study was designed to evaluate the efficacy and safety of Acetyl-L-Carnitine (ALC) Hydrochloride Enteric-coated Tablet (oral administration) in the treatment of CIPN. It was a prospective, randomized, double-blinded, placebo-controlled and paralleled clinical study (registration No. 2007L03540). Of 239 subjects enrolled in the study (NCI grade 2 or above), 118 subjects received 3g/day ALC orally for 8 weeks and 121 received placebo. Primary endpoint was set as improvement of peripheral neuropathy at least 1 grade and assessment was made in week 4, 8 and 12 after enrollment. Results: In full analyses set (FAS) and per-proposal set (PPS), the peripheral sensory neuropathy was significantly ameliorated in ALC group with 50.5% and 51.6% patients meeting the primary endpoint at week 8 and 12 respectively while only 24.1% and 23.1% of patients in the placebo group at week 8 and 12 respectively (p<0.001 in both sets). Secondary endpoint such as nerve electrophysiological test and Physical Condition Score (Karnofsky performance status, KPS) were also significantly improved in patients with ALC treatment (in FAS, P=0.0463 and P=0.022; in PPS, P=0.0076and P=0.0064, respectively). Cancer-related fatigue was significantly alleviated after ALC treatment in PPS (P=0.0135). Safety: 236 subjects were included in safety assessment and 41 patients experienced 62 adverse events during the course of study. There was no significant difference in AE/SAE incidence between the two groups (P=0.3903). Conclusions: Oral administration of ALC is effective in attenuating CIPN as well as in reducing cancer-related fatigue and improving physical conditions in cancer patients. The treatment of oral ALC is safe and well tolerated.

Influence of genetic variants of genes potentially associated with colorectal brain metastases on overall survival.

2014 ◽  
Vol 32 (3_suppl) ◽  
pp. 487-487
Author(s):  
Stefan Stremitzer ◽  
Anna Sophie Berghoff ◽  
Nico Benjamin Volz ◽  
Wu Zhang ◽  
Dongyun Yang ◽  
...  
Keyword(s):  
Overall Survival ◽  
Brain Metastases ◽  
Genetic Variants ◽  
Karnofsky Performance Status ◽  
Performance Status ◽  
Univariate Analysis ◽  
Nucleotide Polymorphisms ◽  
Primary Tumor Site ◽  
Prognostic Effect ◽  
Significant Difference

487 Background: Brain metastases (BM) in colorectal cancer (CRC) are rare, developing in only 0.3-9% of the patients, and considered a late-stage manifestation of the disease. The aim of this study was to investigate whether genetic variants of genes involved in BM-related pathways, such as integrin, invasion- and adhesion-mediating, angiogenic and tumor suppressing pathways, are associated with outcome. Methods: Genomic DNA was extracted from formalin-fixed paraffin embedded resected BM from 70 patients with histologically proven CRC. Single nucleotide polymorphisms (SNP) in seven genes (CXCR4, MMP9, ST6GALNAC5, ITGAV, ITGB1, ITGB3, KLF4) were analyzed by direct Sanger DNA sequencing and evaluated for association with overall survival (OS) from resection of BM. Only SNPs with an allele frequency of ≥ 10% were analyzed. Results: In univariate analysis, rs17577 (MMP9) and rs4642 (ITGB3) showed a significant difference in OS [(G/G 7.4 months, G/A 5.1 months; HR (95% CI) 1.83 (0.95-3.53), p = 0.0440) and (A/A 9.4 months, A/G 4.8 months, G/G 4.3 months; HR (95% CI) 0.81 (0.44-1.49) and 2.14 (0.98-4.67), p = 0.0354), respectively]. In multivariate analysis adjusted for baseline characteristics [primary tumor site (right colon, left colon, rectal), chemotherapy before BM (yes/no), BM location (supratentorial, infratentorial, both), Karnofsky performance status (<80, 80-100)], rs2236599 (KLF4), and rs10171481 (ITGAV) are significant in OS [(G/G 7.4 months, G/A or A/A 4.8 months; HR (95% CI) 3.19 (1.55-6.53), p = 0.0016) and (A/A 5.7 months, A/G 4.4 months, G/G 15.5 months; HR (95% CI) 0.61 (0.29-1.29) and 0.25 (0.10-0.60), p = 0.0082), respectively]. Conclusions: This study suggests for the first time a prognostic effect of the SNPs involved in the BM pathway. Further analyses are needed to confirm these findings.

scholarly journals Vasculogenic Mimicry Formation Predicts Tumor Progression in Oligodendroglioma

2021 ◽  
Vol 27 ◽  
Author(s):  
Jing Xie ◽  
Xue Kong ◽  
Wei Wang ◽  
Yuan Li ◽  
Mengyu Lin ◽  
...  
Keyword(s):  
Tumor Progression ◽  
Ataxia Telangiectasia ◽  
Malignant Tumors ◽  
Karnofsky Performance Status ◽  
Performance Status ◽  
Hypoxia Inducible Factor ◽  
Vasculogenic Mimicry ◽  
Treatment Resistance ◽  
Who Grade ◽  
Significant Difference

Vasculogenic mimicry (VM) has been identified as an important vasculogenic mechanism in malignant tumors, but little is known about its clinical meanings and mechanisms in oligodendroglioma. In this study, VM-positive cases were detected in 28 (20.6%) out of 136 oligodendroglioma samples, significantly associated with higher WHO grade, lower Karnofsky performance status (KPS) scores, and recurrent tumor (p &lt; 0.001, p = 0.040, and p = 0.020 respectively). Patients with VM-positive oligodendroglioma had a shorter progress-free survival (PFS) compared with those with VM-negative tumor (p &lt; 0.001), whereas no significant difference was detected in overall survival (OS) between these patients. High levels of phosphorylate serine/threonine kinases Ataxia-telangiectasia mutated (pATM) and phosphorylate Ataxia-telangiectasia and Rad3-Related (pATR) were detected in 31 (22.8%) and 34 (25.0%), respectively out of 136 oligodendroglioma samples. Higher expressions of pATM and pATR were both associated with a shorter PFS (p &lt; 0.001 and p &lt; 0.001). VM-positive oligodendroglioma specimens tended to exhibit higher pATM and pATR staining than VM-negative specimens (rs = 0.435, p &lt; 0.001 and rs = 0.317, p &lt; 0.001). Besides, Hypoxia-inducible factor-1α (HIF1α) expression was detected in 14(10.3%) samples, correlated with higher WHO grade and non-frontal lobe (p = 0.010 and p = 0.029). However, no obvious connection was detected between HIF1α expression and VM formation (p = 0.537). Finally, either univariate or multivariate analysis suggested that VM was an independent unfavorable predictor for oligodendroglioma patients (p &lt; 0.001, HR = 7.928, 95%CI: 3.382–18.584, and p = 0.007, HR = 4.534, 95%CI: 1.504–13.675, respectively). VM is a potential prognosticator for tumor progression in oligodendroglioma patients. Phosphorylation of ATM and ATR linked to treatment-resistance may be associated with VM formation. The role of VM in tumor progression and the implication of pATM/pATR in VM formation may provide potential therapeutic targets for oligodendroglioma treatment.

scholarly journals The effect of using awake craniotomy combined with multimodal techniques  intraoperative on survival of patients with glioblastoma: a single-center experience

2020 ◽  
Author(s):  
hui zhou ◽  
Li Yang ◽  
Ming Lu ◽  
Xqing Deng ◽  
Mming Yang
Keyword(s):  
Survival Time ◽  
Parietal Lobe ◽  
Karnofsky Performance Status ◽  
Performance Status ◽  
Intraoperative Ultrasound ◽  
Extent Of Resection ◽  
Awake Craniotomy ◽  
Motor Dysfunction ◽  
Tumour Resection ◽  
Significant Difference

Abstract Background :We analysed outcomes of cerebral glioblastoma patients undergoing awake craniotomies combined with multimodal techniques for tumour resection, with regards to the extent of resection, functional preservation, and prognosis. Methods : A retrospective analysis was conducted on adult glioblastoma patients who underwent an awake craniotomy from September 2010 to August 2018 under anaesthesia combined with multimodal techniques. Results: In total, 81 glioblastoma patient charts were analysed. The most common lesion sites were the frontal lobe (n=36), temporal lobe (n=17), and parietal lobe (n=6). The main symptoms were headache (n=51), dyskinesia (n=11), speech disorder (n=9), and epilepsy (n=10). The extent of resection was gross total for 91.36% patients, subtotal for 7.41%, and partial for 1.23%. No deaths occurred 30 days post-operation. Intracranial haemorrhage occurred in 2 patients, seizures in 5 patients, and intracranial infections in 3 patients. There was no significant difference between preoperative and postoperative Karnofsky Performance Status scores (P>0.05). There were no significant changes in postoperative neurological function in 50 patients. Symptoms improved in 24 patients. Three patients exhibited motor dysfunction, 2 exhibited speech deficits, and 2 exhibited sensory deficits. The average duration of hospitalization was 6.89±2.66 days. The shortest survival time was 4 months, the longest survival time was 26 months, and the median survival time was 12 months. Conclusions: Awake craniotomy using multimodal techniques such as neuronavigation, intraoperative ultrasound, electrophysiology, and tumour fluorescence during an operation can maximize safety during the cerebral glioblastoma resection, thus protecting brain function and improving surgical efficacy and patients’ postoperative quality of life.

scholarly journals Budesonide Prophylaxis Reduces Engraftment Syndrome (ES) after Autologous Hematopoietic Cell Transplantation (autoHCT) in Multiple Myeloma (MM)

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 35-36
Author(s):  
Bicky Thapa ◽  
Huaying Dong ◽  
Sergey Tarima ◽  
Binod Dhakal
Keyword(s):  
Research Funding ◽  
Large Scale ◽  
Hematopoietic Cell Transplantation ◽  
Karnofsky Performance Status ◽  
Performance Status ◽  
Advisory Board ◽  
Prophylaxis Group ◽  
Significant Difference ◽  
Chi Squared ◽  
Engraftment Syndrome

Introduction: ES after autoHCT encompasses a continuum of peri-engraftment complications characterized by non-infectious fever, rash, diarrhea, and capillary leak features. ES is an increasingly recognized complication after autoHCT in MM, with the varying incidence reported, based on the diagnostic criteria used. ES is typically mild and self-limited in most patients, while a subset can develop severe complications. In this study, we explored whether the use of budesonide prophylaxis reduces ES rates in MM patients undergoing autoHCT. Methods: All patients who underwent autoHCT for MM from 12/2017 to 11/2019 were included after IRB approval at our institution. Beginning on 12/15/2018, as a quality improvement institutional initiative to reduce ES, budesonide 3 mg orally three times a day was initiated at day +5 post autoHCT and continued until the time of discharge. In patients developing ES, systemic steroids were started, and budesonide was discontinued. The efficacy of the intervention was compared with patients who did not receive prophylaxis prior to the study period. ES was defined according to the previously published criteria [T R Spitzer BMT 50, 469-475(2015)]. Patient demographics, disease, and treatment outcomes between the 2 groups were compared using Mann-Whitney and Chi-squared tests when appropriate. The primary outcome was the ES rates between the 2 groups. Multiple logistic regression was used to model ES rates with other predictors, including budesonide prophylaxis as the main effect. Length of stay (LOS) and 30-day readmission were the secondary endpoints. Results: Table 1 shows the patient-, disease- and treatment characteristics between no prophylaxis (N=148) and prophylaxis (N=109) groups. The two groups were well matched overall except for induction therapy and Karnofsky performance status (KPS). The rates of ES were significantly higher in the no prophylaxis group vs. prophylaxis group [69 (75%) vs. 23 (25%); p&lt;0.001]. All patients in both groups were able to achieve neutrophil and platelet engraftment at day 28 and day 100, respectively. There was no significant difference in LOS [mean 15 (±3.2) vs. 16 (±2.8); p=0.27] and 30-day readmission [9 (6%) vs. 8 (7%); p=0.81] between the no prophylaxis and prophylaxis groups, respectively. On adjusted analysis, budesonide prophylaxis was associated with a significantly lower risk of developing ES compared to no prophylaxis groups [Odds ratio, OR 0.30 (95%CI: 0.17-0.53); p&lt;0.0001]. No other significant predictors were identified for the development of ES. There was no difference in the 30-day readmission rates [OR 1.12 (95%CI: 0.41-3.03); p= 0.75], but a trend for shorter LOS in the prophylaxis group [7.3% reduction in LOS (95%CI: 14.4%- 0%); p=0.052] (Table 2). Conclusion: Our study concludes that the use of budesonide prophylaxis significantly reduces the risk of ES in MM patients undergoing autoHCT. Future large-scale randomized studies are needed to confirm these findings in patients undergoing autoHCT for MM and other diseases. Disclosures Dhakal: Celgene: Consultancy, Honoraria; Takeda: Consultancy, Other: Advisory Board; Sanofi: Research Funding; Amgen: Consultancy, Other: AdvIsory Board, Research Funding; Janssen: Consultancy, Other: Advisory Board, Research Funding; GSK: Consultancy, Research Funding, Speakers Bureau.

scholarly journals PO-010 Effects of kickboxing on body composition of adolescents with obesity

2018 ◽  
Vol 1 (3) ◽  
Author(s):  
Ziwen Chu
Keyword(s):  
Body Composition ◽  
Body Fat ◽  
Fat Content ◽  
Point Of View ◽  
Hip Circumference ◽  
Obese People ◽  
Muscle Weight ◽  
Skin Fold Thickness ◽  
Skin Fold ◽  
Significant Difference

Objective In order to find a scientific and effective way to lose weight, the effect of kickboxing exercise was studied by the method of experiment. Through research, it is found that kickboxing can effectively change the body shape and body composition of the human body and achieve a better weight loss effect. This study further enriches and improves the theory of exercise and fitness, which can provide scientific guidance for obese children and adolescents to lose weight and provide a good reference for obesity of other age groups and special populations.  Methods In this paper, 20 students of 12~14 years old in the summer class of Wuhan diet training camp were selected as the subjects. Through the test of height and weight, the 20 subjects of drug induced obesity or non secondary obesity were selected by BMI as the main basis, including 8 girls and 12 boys. kickboxing training time is 8 weeks, 3 times a week, each class 60 minutes，from warming up, basically, relax three parts. In order to study the effects of kickboxing on body composition of obese people, skin fold thickness, girth and body fat were monitored and tested.  Results After 8 weeks of kickboxing exercise, there was a significant difference in the thickness of the upper arm skin fold of the boys P < 0.05, and the thickness of the skin fold of the lower scapula was P < 0.01, but the changes in the abdomen were not obvious. While the skin thickness of the upper arm and the abdominal skin fold were P < 0.05, and there was no significant difference in the skin fold thickness of the scapula. Male hip circumference P < 0.05 had a very significant change, chest circumference, waist circumference and waist hip ratio P > 0.05 did not change significantly. The waist circumference and waist hip ratio were significantly changed, but there was no significant change in chest circumference and hip circumference. After exercise, the changes in fat content, muscle weight and BMI were the most significant. Girls' weight, fat content, body fat percentage and BMI were the most significant changes, followed by a slight change in muscle weight. Conclusions From the qualitative point of view, it can be concluded that the practice of kickboxing exercises can effectively develop flexibility, balance, coordination and so on. It has a significant effect on improving human posture and sports ability. From a quantitative point of view, aerobics can also reduce fat content, increase muscle weight, make the percentage of BMI, body fat change significantly, and have a significant impact on maintaining muscle content and muscle / weight ratio and laying a solid foundation for future exercise. It can be concluded that kickboxing is a suitable exercise for obese people to lose weight.

scholarly journals Comparative analysis of measuring the body fat percentage by anthropometric methods and bioimpedance

2020 ◽  
pp. 65-65
Author(s):  
Jelena Jovic ◽  
Aleksandar Corac ◽  
Maja Nikolic ◽  
Danijela Ilic ◽  
Aleksandra Ilic ◽  
...  
Keyword(s):  
Body Fat ◽  
The Body ◽  
Body Fat Percentage ◽  
Fat Percentage ◽  
Mean Values ◽  
Skin Fold Thickness ◽  
Contemporary Method ◽  
Skin Fold ◽  
Significant Difference ◽  
Post Hoc

Introduction/Objective. Body fat percentage (BFP) is the most reliable indicator of a nutritional status. For clinical practice it is important but scarcely investigated whether to exclusively use contemporary methods of BFP measurement, or classic anthropometric methods are also reliable. The aim was to investigate the correlation between the results of BFP measuring using a contemporary method of bioimpedance (Bio) and classic methods of skin fold thickness (SFT) and body mass index (BMI). Method. There were 279 patients of the Dietetic Counseling Center of the Institute for Public Health in Nis who were included in the research during 2015. Body fat percentage was determined using three classic anthropometric methods of ST over the triceps, and the scapula and BMI. Apparatus OMRON BF 302 was used for BFP measuring with bioimpedance method. Results. Using a one factorial analysis of variance we found a statistically significant difference between the mean values of the BFP obtained with bioimpedance and with anthropometric methods (F = 24.19, p < 0.05). Post hoc analysis revealed a statistically significant difference between the BFP determined with bioimpedance and SFT over the triceps and the scapula, while the anthropometric method based on BMI gave the results similar to those from bioimpedance. Conclusion. We show that the most reliable anthropometric method of determination of BFP is that based on BMI, as its results correlate best with those obtained with a contemporary method of bioimpedance.

The effect of using awake craniotomy combined with multimodal techniques intraoperatively on the survival of patients with glioblastoma: A retrospective single-centre study

2020 ◽  
Author(s):  
hui zhou ◽  
Li Yang ◽  
Ming Lu ◽  
Xqing Deng ◽  
Mming Yang
Keyword(s):  
Survival Time ◽  
Parietal Lobe ◽  
Karnofsky Performance Status ◽  
Performance Status ◽  
Intraoperative Ultrasound ◽  
Extent Of Resection ◽  
Awake Craniotomy ◽  
Motor Dysfunction ◽  
Tumour Resection ◽  
Significant Difference

Abstract Background :We analysed outcomes of cerebral glioblastoma patients undergoing awake craniotomies combined with multimodal techniques for tumour resection, with regards to the extent of resection, functional preservation, and prognosis. Methods : A retrospective analysis was conducted on adult glioblastoma patients who underwent an awake craniotomy from September 2010 to August 2018 under anaesthesia combined with multimodal techniques. Results: In total, 81 glioblastoma patient charts were analysed. The most common lesion sites were the frontal lobe (n=36), temporal lobe (n=17), and parietal lobe (n=6). The main symptoms were headache (n=51), dyskinesia (n=11), speech disorder (n=9), and epilepsy (n=10). The extent of resection was gross total for 91.36% patients, subtotal for 7.41%, and partial for 1.23%. No deaths occurred 30 days post-operation. Intracranial haemorrhage occurred in 2 patients, seizures in 5 patients, and intracranial infections in 3 patients. There was no significant difference between preoperative and postoperative Karnofsky Performance Status scores (P>0.05). There were no significant changes in postoperative neurological function in 50 patients. Symptoms improved in 24 patients. Three patients exhibited motor dysfunction, 2 exhibited speech deficits, and 2 exhibited sensory deficits. The average duration of hospitalization was 6.89±2.66 days. The shortest survival time was 4 months, the longest survival time was 26 months, and the median survival time was 12 months. Conclusions: Awake craniotomy using multimodal techniques such as neuronavigation, intraoperative ultrasound, electrophysiology, and tumour fluorescence during an operation can maximize safety during the cerebral glioblastoma resection, thus protecting brain function and improving surgical efficacy and patients’ postoperative quality of life.

scholarly journals Randomized Phase III Trial of Ixabepilone Plus Capecitabine Versus Capecitabine in Patients With Metastatic Breast Cancer Previously Treated With an Anthracycline and a Taxane

2010 ◽  
Vol 28 (20) ◽  
pp. 3256-3263 ◽  
Author(s):  
Joseph A. Sparano ◽  
Eduard Vrdoljak ◽  
Oliver Rixe ◽  
Binghe Xu ◽  
Alexey Manikhas ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Cox Regression ◽  
Karnofsky Performance Status ◽  
Performance Status ◽  
Metastatic Breast ◽  
Phase Iii ◽  
Cox Regression Analysis ◽  
Significant Difference ◽  
Previously Treated

PurposeWe sought to determine whether the combination of ixabepilone plus capecitabine improved overall survival (OS) compared with capecitabine alone in patients with metastatic breast cancer (MBC) previously treated with anthracyclines and taxanes.Patients and MethodsA total of 1,221 patients with MBC previously treated with anthracycline and taxanes were randomly assigned to ixabepilone (40 mg/m2intravenously on day 1) plus capecitabine (2,000 mg/m2orally on days 1 through 14) or capecitabine alone (2,500 mg/m2on the same schedule) given every 21 days. The trial was powered to detect a 20% reduction in the hazard ratio (HR) for death.ResultsThere was no significant difference in OS between the combination and capecitabine monotherapy arm, the primary end point (median, 16.4 v 15.6 months; HR = 0.9; 95% CI, 078 to 1.03; P = .1162). The arms were well balanced with the exception of a higher prevalence of impaired performance status (Karnofsky performance status 70% to 80%) in the combination arm (32% v 25%). In a secondary Cox regression analysis adjusted for performance status and other prognostic factors, OS was improved for the combination (HR = 0.85; 95% CI, 0.75 to 0.98; P = .0231). In 79% of patients with measurable disease, the combination significantly improved progression-free survival (PFS; median, 6.2 v 4.2 months; HR = 0.79; P = .0005) and response rate (43% v 29%; P < .0001). Grade 3 to 4 neuropathy occurred in 24% treated with the combination, but was reversible.ConclusionThis study confirmed a previous trial demonstrating improved PFS and response for the ixabepilone-capecitabine combination compared with capecitabine alone, although this did not result in improved survival.

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