Relevance of rapid geriatric assessment for elderly patients with newly diagnosed malignancy.

2017 ◽  
Vol 35 (31_suppl) ◽  
pp. 115-115
Author(s):  
Hina Niranjan Mehta ◽  
Rania Farhat ◽  
Sravanthi Ravulapati ◽  
Yifan Tu
Keyword(s):  
Palliative Care ◽  
Overall Survival ◽  
Pilot Study ◽  
Elderly Patients ◽  
Geriatric Assessment ◽  
Geriatric Patients ◽  
Newly Diagnosed ◽  
Oncology Patients ◽  
Number Of Patients ◽  
Significant Difference

115 Background: The elderly population is the fastest growing segment of the US population, and it is widely affected by cancer and its related sequelae. At St. Louis University (SLU), a simple Rapid Geriatric Assessment (RGA) was developed based on the SLU Mental Status Exam (SLUMS). The RGA includes screening for frailty, sarcopenia, nutrition, and cognition. In this pilot study, we used RGA to assess geriatric patients with newly diagnosed malignancy prior to cancer therapy and its ability to improve outcomes in oncology patients. Methods: Elderly patients (aged 65 and above) with newly diagnosed malignancy completed the RGA either inpatient or outpatient at SLU. A retrospective chart review was done to collect patient's demographics, type of malignancy, number of hospitalizations since diagnosis and referral to palliative care over a 6 month period. Relationship between tolerability and RGA subscores were assessed using general linear models, Kaplan-Meier survival analysis and Chi-square testing. Results: Twenty six patients (mean age 76 [65-90]) were included from December 2015 to 2016 of which 9 were male (n = 35) and 17 female (n = 65). 19 patients (73%) were inpatient, 7 (27%) were outpatient and 13 patients (50%) received chemotherapy. Using the Mann-Whitney U test, no significant difference was seen between RGA subscores (FRAIL p = 1; SNAQ p = 0.69; SARC-F p = 0.71; RCS p = 1) in patients receiving versus not receiving chemotherapy. There was no significant difference in overall survival (OS) over a 20 month period based on chemotherapy status (p = 0.39). In our study, 62% of patients (n = 16) were referred to palliative care and noted to have a significant better OS (p = 0.04). Conclusions: The RGA is a self-explanatory tool that can be used in geriatric oncology patients and it can bedone in 10 minutes. In this pilot study, we used this tool in a small number of patients. We plan to perform a prospective study to evaluate the RGA comparing to ECOG-performance status in geriatric patients prior to standard cancer therapies. Improvement of overall survival with incorporation of palliative care in oncology patients is reaffirmed in our study.

scholarly journals Evaluation of a Standardized Geriatric Assessment at Diagnosis in a Prospective Cohort of Elderly Patients with Newly Diagnosed Acute Myeloid Leukemia

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 2671-2671 ◽  
Author(s):  
Colombe Saillard ◽  
Frederique Rousseau ◽  
Maud Cecile ◽  
Cecile Braticevic ◽  
Anne Etienne ◽  
...  
Keyword(s):  
Overall Survival ◽  
High Risk ◽  
Elderly Patients ◽  
Geriatric Assessment ◽  
Prospective Cohort ◽  
Myeloid Leukemia ◽  
Global Evaluation ◽  
Intensive Chemotherapy ◽  
Newly Diagnosed ◽  
The Impact

Abstract Introduction: Acute myeloid leukemia (AML) in the elderly is a therapeutic challenge, and global evaluation of comorbidity, performance status, fitness and frailty is crucial for therapeutic decision of treatment intensity. Accurately predicting risks and benefits of available therapies is particularly difficult, as it relies on subjective criteria, no geriatric scores being validated so far. The aim of this study was to evaluate the impact of a standardized geriatric assessment at diagnosis in a prospective cohort of newly diagnosed AML in elderly patients, and to investigate correlations between geriatric scores and overall survival. Methods: All patients aged ≥ 70 years with newly diagnosed AML were prospectively included in this cohort. They all benefited from an exhaustive geriatric assessment in addition to standard AML workup, including ADL, IADL, ECOG, comorbidities, nutritional status (assessed by BMI and mini-MNA), cognitive impairment (mini-COG, mini-GDS), quality of life (QLQ-C30), functional scales (physical, role, emotional, cognitive and social functioning), symptom scales (fatigue, nausea and vomiting, pain, dyspnea, insomnia, appetite loss, constipation, diarrhea, financial difficulties) and frailty criteria (physical activity, energy visual scale, mobility, nutrition). Patients were treated according to international guidelines, with intensive chemotherapy, hypomethylating agents, subcutaneous low-dose cytarabine, palliative oral chemotherapy or best supportive care only, according to physician choice. The impact of geriatric scores on 6-months overall survival was analyzed. Results: Between 2010 and 2015, 94 patients were enrolled, including 61.7% of males and 38.3% of females. Median age was 75.5 years (70-96). Initial median leucocytes, neutrophils, hemoglobin, and platelets counts were respectively 4.7 G/L (0.4-174), 1.3 G/L (0.1-5.4), 9.3 g/dL (5.3-13.2), 51 G/L (5-520). Median bone marrow blasts percentage was 55% (20-96). Cytogenetics was favorable, intermediate and adverse in 18%, 62% and 20% respectively. Intensive chemotherapy was chosen in 57.4% of patients, and low intensity or palliative approach in 42.6% of patients. Patients spent a median of 30.5 days in hospital (0-119), received a median of 12 (0-44) red blood cells units and 2 (0-33) platelets units. Global geriatric assessment of patients is reported in Table 1. By univariate analysis, prognostic factors associated with a reduced survival were high dementia risk (HR=3.63, 95% CI=1.4-9.3, p=0.004), high ECOG score (HR=2.1, 95% CI=1.1-4, p=0.02) and high risk of denutrition (HR=3.43, 95% CI=1.33-8.9, p=0.007), while intensive chemotherapy was associated with a better outcome (HR=0.45, 95% CI=0.2-0.9, p=0.014). Multivariate analysis identified high risk of denutrition as independently associated with reduced survival (HR=3.08, 95% CI=1.17-8.11, p=0.02). Intensive chemotherapy treatment tended to impact prognosis but was not statistically significant (HR=0.54, 95% CI=0.27-1.01, p=0.08). Conclusions: In a prospective cohort of newly diagnosed AML elderly patients, an exhaustive standardized geriatric assessment at diagnosis identified high risk patients for mortality. The most relevant prognostic factor was nutritional status, which correlated with overall survival. Other geriatric scores and scales did not impact prognosis, which highlights the difficulty of global evaluation in this population. Patients treated with intensive chemotherapy tended to have a better outcome. Disclosures No relevant conflicts of interest to declare.

Limited stage mantle cell lymphoma: Results of overall survival based on treatment modality using SEER database.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e19566-e19566
Author(s):  
Apoorva Jayarangaiah ◽  
Shuai Wang ◽  
Tarek N. Elrafei ◽  
Lewis Steinberg ◽  
Abhishek Kumar
Keyword(s):  
Overall Survival ◽  
Mantle Cell Lymphoma ◽  
Cell Lymphoma ◽  
Stage I ◽  
Close Monitoring ◽  
Seer Database ◽  
Limited Stage ◽  
Number Of Patients ◽  
Significant Difference ◽  
Mantle Cell

e19566 Background: Limited stage mantle cell lymphoma (MCL) (stage I-II) is rare and occurs in 5-15% of patients. The ideal treatment approach among radiation (RT), chemotherapy (CT), chemoradiotherapy (CRT) or close monitoring (NT) has not been defined. Methods: A retrospective analysis of SEER database (1975 to 2018) was conducted for patients with stage I-II MCL to compare overall survival (OS) among the various treatment modalities in patients >18 years. We excluded patients lacking information on demographic characteristics and survival. Patients were analyzed in 4 groups; RT only, CT only, CRT and no treatment groups. ANOVA test and Chi-square test were used to evaluate parametric and non-parametric variables between groups, respectively. Cancer specific survival (CSS) and OS were assessed by Kaplan-Meier. SPSS 26.0 was used for data analysis. Results: There were in total 2266 patients with limited stage MCL. Median age was 71 years (61-78.25) and predominantly male (65.7%). Stage I MCL was noted in 55.6% and stage II in 44.4% of the patients. The number of patients in each group; RT only, CT only, CRT and NT along with the OS are presented in Table. CSS among these four groups showed no statistically significant differences (p <0.26). OS showed that CT only group has worse survival compared to RT only and CRT groups (p <0.001). CRT has no significant difference in survival compared to RT only (p<0.001). NT was associated with poorest survival rates (p<0.001). Conclusions: In limited stage MCL, RT only and CRT resulted in superior OS compared to CT only. Results suggest a role for incorporation of RT in treatment regimens. One limitation of the study is that the SEER database lacks the ability to distinguish between no receipt of therapy versus lack of availability of data.[Table: see text]

Evaluating the benefit of adaptive randomization in the CC-115 arm of the Individualized Screening Trial of Innovative Glioblastoma Therapy (INSIGhT): A phase II randomized Bayesian adaptive platform trial in newly diagnosed MGMT unmethylated glioblastoma.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 2006-2006
Author(s):  
Rifaquat Rahman ◽  
Lorenzo Trippa ◽  
Geoffrey Fell ◽  
Eudocia Quant Lee ◽  
Isabel Arrillaga-Romany ◽  
...  
Keyword(s):  
Mammalian Target Of Rapamycin ◽  
Progression Free Survival ◽  
Newly Diagnosed ◽  
Adaptive Randomization ◽  
Number Of Patients ◽  
Significant Difference ◽  
Enrollment Rates ◽  
Dependent Protein ◽  
The Impact ◽  
Screening Trial

2006 Background: Adaptive randomization adjusts enrollment rates based upon early trial results, which can allow for decreased enrollment for therapies less likely to meet the primary endpoint of a trial. CC-115, a CNS-penetrant, oral inhibitor of mammalian target of rapamycin kinase (mTOR) and deoxyribonucleic acid-dependent protein kinase (DNA-PK), was evaluated in the Individualized Screening Trial of Innovative Glioblastoma Therapy (INSIGhT) trial. As CC-115 was discontinued due to concerns about toxicity and unfavorable risk-to-benefit ratio, we sought to investigate the impact of adaptive randomization in its testing. Methods: In INSIGhT, adults with newly diagnosed MGMT-unmethylated glioblastoma and available genomic data are adaptively randomized to an experimental arm or the control arm of standard radiotherapy with concurrent and adjuvant temozolomide. Patients randomized to CC-115 received it (10mg po BID) with radiotherapy and as adjuvant monotherapy, and a safety lead-in 3+3 design was used for this arm. By simulating the INSIGhT trial with standard uniform randomization, we estimated the reduction of enrollment rate and sample size of the CC-115 arm that was attributable to adaptive randomization. Results: Twelve patients were randomized to CC-115; 58% (n = 7) patients had possible treatment-related CTCAE grade > 3 toxicity. Compared to the control arm, there was no significant difference in progression-free survival (PFS, HR 0.66, 95% CI 0.32-1.36, p = 0.3) or overall survival (OS, HR 0.93, 95% CI 0.43-2.03, p = 0.8). Based on early PFS results, randomization probability to CC-115 decreased from 25% to 16%. At the time of the CC-115 arm closure, 14% of enrolled INSIGhT patients had been randomized to this arm. Compared to average expected enrollment by standard randomization, the use of adaptive randomization decreased the number of patients randomized to CC-115 by 50% (12 patients vs. 18 patients [95% CI 11-25 patients]). Conclusions: The INSIGhT trial, designed with adaptive randomization, facilitated more efficient testing of CC-115 and decreased the number of patients allocated to the CC-115 arm relative to a standard randomization design. Clinical trial information: NCT02977780.

scholarly journals A Comprehensive Overview of Polypharmacy in Elderly Patients in Saudi Arabia

Geriatrics ◽  
2019 ◽  
Vol 4 (2) ◽  
pp. 36 ◽  
Author(s):  
Aseel Alsuwaidan ◽  
Norah Almedlej ◽  
Sawsan Alsabti ◽  
Omamah Daftardar ◽  
Fawzi Al Deaji ◽  
...  
Keyword(s):  
Risk Factors ◽  
Health Care ◽  
Adverse Drug Reaction ◽  
Saudi Arabia ◽  
Drug Reaction ◽  
Elderly Patients ◽  
Care Management ◽  
Geriatric Patients ◽  
Health Care Management ◽  
Significant Difference

Background/Objectives: Saudi Arabia has a great percentage of geriatric patients associated with multiple chronic diseases who require close attention and monitoring for their medications. The purpose of this study is to develop a full-framed picture about the utilization of medications for geriatric patients and how to provide better health-care management. Methodology: A retrospective cross-sectional study targeting patients 65 years of age and older, who are taking multiple chronic medications for different indications. Descriptive analysis and frequency of the main variables were used as appropriate. Only qualified and professional candidates were chosen for data entry to present the quality and accuracy of data. Results: A total of 3009 patient profiles were analyzed, with the patients’ average age in years being 73.26 ± 6.6 (SD). It was found that 55% of the patients have polypharmacy. An average of 6.4 medications were prescribed for patients aged between 65 and 70 years compared with a significant difference for patients aged 71 years and above, while a linear correlation between age and comorbidity diseases associated with all elderly patients. Hypertension, hyperlipidemia, and diabetes mellitus are the most common comorbidity diseases for elderly patients aged 65 years and older. Conclusion: Polypharmacy in geriatrics is defined as a patient aged 65 years and older receiving five or more appropriate medications. It is the responsibility of health-care professionals to reduce the number of medications in elderly patients. Awareness of geriatric medications and diagnosed diseases will improve managing adverse drug reaction and other risk factors. Awareness of geriatric medications should elaborate on how to avoid adverse drug reaction and other risk factors. It is the responsibility of physicians and pharmacists to reduce the number of medications in elderly patients. We also prove that the number of medications will not necessarily increase with age. The main impact of this study is to follow the main recommendations to improve health care management in geriatrics.

Immediate or Deferred Androgen Deprivation for Patients With Prostate Cancer Not Suitable for Local Treatment With Curative Intent: European Organisation for Research and Treatment of Cancer (EORTC) Trial 30891

2006 ◽  
Vol 24 (12) ◽  
pp. 1868-1876 ◽  
Author(s):  
Urs E. Studer ◽  
Peter Whelan ◽  
Walter Albrecht ◽  
Jacques Casselman ◽  
Theo de Reijke ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Overall Survival ◽  
Local Treatment ◽  
Androgen Deprivation ◽  
Cancer Specific Survival ◽  
Deferred Treatment ◽  
Symptomatic Disease ◽  
Androgen Ablation ◽  
Number Of Patients ◽  
Significant Difference

Purpose This study (EORTC 30891) attempted to demonstrate equivalent overall survival in patients with localized prostate cancer not suitable for local curative treatment treated with immediate or deferred androgen ablation. Patients and Methods We randomly assigned 985 patients with newly diagnosed prostate cancer T0-4 N0-2 M0 to receive androgen deprivation either immediately (n = 493) or on symptomatic disease progression or occurrence of serious complications (n = 492). Results Baseline characteristics were well balanced in the two groups. Median age was 73 years (range, 52 to 81). At a median follow-up of 7.8 years, 541 of 985 patients had died, mostly of prostate cancer (n = 193) or cardiovascular disease (n = 185). The overall survival hazard ratio was 1.25 (95% CI, 1.05 to 1.48; noninferiority P > .1) favoring immediate treatment, seemingly due to fewer deaths of nonprostatic cancer causes (P = .06). The time from randomization to progression of hormone refractory disease did not differ significantly, nor did prostate-cancer specific survival. The median time to the start of deferred treatment after study entry was 7 years. In this group 126 patients (25.6%) died without ever needing treatment (44% of the deaths in this arm). Conclusion Immediate androgen deprivation resulted in a modest but statistically significant increase in overall survival but no significant difference in prostate cancer mortality or symptom-free survival. This must be weighed on an individual basis against the adverse effects of life-long androgen deprivation, which may be avoided in a substantial number of patients with a deferred treatment policy.

Efficacy of Melphalan and Prednisone Plus Thalidomide in Patients Older Than 75 Years With Newly Diagnosed Multiple Myeloma: IFM 01/01 Trial

2009 ◽  
Vol 27 (22) ◽  
pp. 3664-3670 ◽  
Author(s):  
Cyrille Hulin ◽  
Thierry Facon ◽  
Philippe Rodon ◽  
Brigitte Pegourie ◽  
Lotfi Benboubker ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
Elderly Patients ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Standards Of Care ◽  
Newly Diagnosed ◽  
Grade 3 ◽  
To Receive

Purpose Until recently, melphalan and prednisone were the standards of care in elderly patients with multiple myeloma. The addition of thalidomide to this combination demonstrated a survival benefit for patients age 65 to 75 years. This randomized, placebo-controlled, phase III trial investigated the efficacy of melphalan and prednisone plus thalidomide in patients older than 75 years with newly diagnosed myeloma. Patients and Methods Between April 2002 and December 2006, 232 previously untreated patients with myeloma, age 75 years or older, were enrolled and 229 were randomly assigned to treatment. All patients received melphalan (0.2 mg/kg/d) plus prednisone (2 mg/kg/d) for 12 courses (day 1 to 4) every 6 weeks. Patients were randomly assigned to receive 100 mg/d of oral thalidomide (n = 113) or placebo (n = 116), continuously for 72 weeks. The primary end point was overall survival. Results After a median follow-up of 47.5 months, overall survival was significantly longer in patients who received melphalan and prednisone plus thalidomide compared with those who received melphalan and prednisone plus placebo (median, 44.0 v 29.1 months; P = .028). Progression-free survival was significantly prolonged in the melphalan and prednisone plus thalidomide group (median, 24.1 v 18.5 months; P = .001). Two adverse events were significantly increased in the melphalan and prednisone plus thalidomide group: grade 2 to 4 peripheral neuropathy (20% v 5% in the melphalan and prednisone plus placebo group; P < .001) and grade 3 to 4 neutropenia (23% v 9%; P = .003). Conclusion This trial confirms the superiority of the combination melphalan and prednisone plus thalidomide over melphalan and prednisone alone for prolonging survival in very elderly patients with newly diagnosed myeloma. Toxicity was acceptable.

scholarly journals Comprehensive geriatric assessment is correlated to overall survival among gynaecologic oncology patients

2019 ◽  
Vol 50 (3) ◽  
pp. 276-281
Author(s):  
Nadav Michaan ◽  
Sang Yoon Park ◽  
Myong Cheol Lim
Keyword(s):  
Overall Survival ◽  
Multivariate Analysis ◽  
Activities Of Daily Living ◽  
Geriatric Assessment ◽  
Comprehensive Geriatric Assessment ◽  
Daily Living ◽  
Nutritional Assessment ◽  
Mini Nutritional Assessment ◽  
Cancer Type ◽  
Oncology Patients

Abstract Objective To investigate the correlation of comprehensive geriatric assessment to overall survival among older gynaecologic oncology patients. Methods Between 2011 and 2017, patients &gt;70 years had geriatric assessment before treatment. Geriatric assessment included the following tests: Old American resource and services, instrumental activities of daily living, modified Barthels index, mini-mental state examination, geriatric depression scale, mini-nutritional assessment, risk of falling and medication use. Overall survival was calculated for patients’ groups below and above median tests scores. Univariate as well as multivariate analysis was done to evaluate the association between each variable and survival. Results About 120 patients had geriatric assessment. Mean patients’ age was 76.4 ± 5. A total of 78 Patients had ovarian cancer, 16 uterine cancer, 17 cervical cancer and 9 had other gynaecologic malignancies. No correlation was found between age, BMI (body mass index) and cancer type to overall survival. Patients with scores below cut-off values of modified Barthels index, instrumental activities of daily living, mini-nutritional assessment and mini-nutritional assessment had significantly shorter overall survival (P = 0.004, 0.031, 0.046 and 0.004, respectively). This remained significant in both univariate and multivariate analysis. Conclusions Gynaecologic oncology patients with lower geriatric assessment scores have significantly lower overall survival, irrespective of cancer type. Geriatric assessment tests allow objective assessment of older patients with worst prognosis before treatment planning.

TIMP-1 and TIMP-2 Levels Are Directly Correlated with Neoangiogenesis and Are Prognostic Factors in Multiple Myeloma Patients.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4866-4866
Author(s):  
Luciana Correa Oliveira de Oliveira ◽  
Juliana Alves Uzuelli ◽  
Ana Paula Alencar de Lima Lange ◽  
Barbara Amelia Aparecida Santana-Lemos ◽  
Marcia Sueli Baggio ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Overall Survival ◽  
Prognostic Factors ◽  
Bone Disease ◽  
Cox Regression ◽  
Conflicts Of Interest ◽  
Newly Diagnosed ◽  
Significant Difference ◽  
The Impact

Abstract Abstract 4866 Background Multiple myeloma (MM) is an incurable malignant disease, characterized by increased angiogenesis in the bone marrow (BM) microenvironment and aberrant BM metabolism. Matrix metalloproteinases (MMP) are a family of zinc-dependent endopeptidases implicated in tumour progression, invasion, metastasis and angiogenesis, via proteolytic degradation of extracellular matrix. MMPs are inhibited by tissue inhibitors of metalloproteinase (TIMP). Although recent studies have implicated MMP 9 in MM bone disease, little is known about the role of the TIMPs. Objectives a) to compare levels of sRANKL, OPG, MMP-2, MMP-9, TIMP-1, TIMP-2, VEGF, bFGF, microvessel density (MVD) between newly diagnosed MM patients and healthy controls; b) to determine the association of these molecules with disease progression, bone disease and neoangiogenesis and c) to evaluate the impact of these variables on survival. Patients and Methods As of July 2009 38 newly diagnosed and untreated multiple myeloma patients were enrolled in the study. The median age was 61years-old (range 39-91) with 24 (63%) males. Patients were diagnosed and categorized according The International Myeloma Working Group criteria and ISS, respectively. Bone involvement was graded according to standard X-ray: patients with no lesions, or with one/ two bones involved or diffuse osteoporosis were classified as low score, whereas patients with lesions in more than two bones or presence of bone fracture were classified as high score. MMP-2 and MMP-9 were determined by PAGE gelatin zymography from plasma as previously described. MMP-9, TIMP-1 and TIMP-2, OPG and sRANKL concentrations were measured by ELISA. The levels of VEGF, bFGF were obtained using cytometric bead array. Ten healthy volunteers were used as controls. Bone marrow MVD measured in hotspots was evaluated in 26 out of 38 patients at diagnosis and 15 patients with Hodgkin Lymphoma stage IA and IIA (used as controls) by staining immunohistochemically for CD34. Comparisons among groups were analyzed by ANOVA and the correlation by the Spearman's correlation coefficient. Cox regression were performed for overall survival (OS) analysis. Results Patients with MM had elevated TIMP-1, TIMP-2 and OPG values compared with controls. No significant difference was found between plasma sRANKL, pro-MMP2, pro-MMP9 and MMP-9 levels. We found that plasma TIMP-1 levels correlated positively with bFGF, VEGF, MVD, beta-2 microglobulin (B2M) and OPG (r: 0.514, p=0,001, r: 0.350, p=0,031; r: 0.610, p<0.0001; r: 0.760, p<0.0001 and r: 0.701, p<0.0001, respectively) and TIMP-2 levels with bFGF, DMV, B2M and OPG (r: 0.512, p=0.002; r: 0.595, p<0.0001; r: 0.587, p<0.0001 and r: 0.552, p<0.0001, respectively). TIMP-1 and TIMP-2 levels correlated with the ISS stage (p<0.0001, p=0.006, respectively). The only variables that correlated with clinical bone disease staging were hemoglobin, B2M and albumin levels, whereas TIMP-1, TIMP-2, bFGF, VEGF and OPG correlated with DMV. On the univariate analyses, age, gender, proMMP2, TIMP-1, TIMP-2, creatinine, B2M and MVD were significantly associated with overall survival. In Cox regression model, TIMP-1, TIMP-2 and B2M levels remained to be significantly associated with OS. In conclusion, our results suggest that TIMP-1 and TIMP-2 levels are strongly associated with neoangiogenesis and are independent prognostic factors in MM. Disclosures No relevant conflicts of interest to declare.

CAG (cytarabine, aclarubicin, G-CSF) Regimen Is Effective and Well Tolerated in 367 Elderly Patients with AML in China and Japan: A Meta-Analysis

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4290-4290
Author(s):  
Guoqing Wei ◽  
Delong Liu
Keyword(s):  
Elderly Patients ◽  
Fixed Effects ◽  
Conflicts Of Interest ◽  
Meta Analysis ◽  
Current Therapy ◽  
Newly Diagnosed ◽  
Fixed Effects Model ◽  
Elderly Aml ◽  
Significant Difference ◽  
China And Japan

Abstract Abstract 4290 Background: Current therapy is still unsatisfactory in elderly patients (pts) with acute myeloid leukemia (AML). CAG regimen (cytarabine, aclarubicin, G-CSF) has been commonly used in China and Japan for the treatment of elderly AML pts. The aim of this study is to summarize the data and to analyze the efficacy as well as the toxic effects of CAG regimen in elderly AML pts. Methods: The databases of PubMed, Wanfang Data, as well as American Society of Hematology (ASH) annual meeting abstracts were searched for articles published in English, Chinese and Japanese languages from January 1995 to December 2010. Eligible studies were relevant clinical trials of elderly AML pts treated with CAG regimen. Complete remission (CR) rate, odds ratio (OR) and 95% confidence intervals (CIs) of chemotherapy were compared through a meta-analysis using a random-effects or fixed-effects model. Results: 19 trials with a total of 367 elderly AML pts were identified and included for analysis. Among the 367 AML pts treated with CAG, 266 pts were newly diagnosed AML, 54 pts were relapsed/refractory (R/R) AML. The AML status was not specified in the rest 47 pts. The CR rate for the 367 elderly AML pts was 52.0% (95% CI 46.8%-57.2%). Interestingly, no significant difference in CR rates was noted between the newly diagnosed (54.7%, 95% CI 48.6%-60.7%) and R/R AML pts (45.7%, 95% CI 32.4%-59.6%) (Q=1.332, p=0.248). Three studies compared the CR rates of elderly AML pts according to the karyotype. The CR rate was significantly higher in pts with intermediate (72.4%, 95% CI 58.0%-83.3%) cytogenetics than those with unfavorable one (35.7%, 95% CI 18.7%-57.2%) (Q=7.803, p=0.005). These elderly AML pts tolerated CAG well with low cardiotoxicity (0.73%, 2/273) and ED (8.48%, 29/342). Conclusions: CAG regimen induced high CR rates in elderly pts with new and relapsed/ refractory AML. This regimen was well tolerated with low cardiotoxicity and early death rate. Disclosures: No relevant conflicts of interest to declare.

Initial Results of the Phase I/II Panobidara Study of Panobinostat in Combination with Idarubicin and Cytarabine in Patients Aged 65 Years or Older with Newly Diagnosed Acute Myeloblastic Leukaemia (AML)

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 1512-1512
Author(s):  
Enrique M Ocio ◽  
Pilar Herrera ◽  
Teresa Olave ◽  
Salut Brunet ◽  
Albert Oriol ◽  
...  
Keyword(s):  
Overall Survival ◽  
Elderly Patients ◽  
Phase I ◽  
Research Funding ◽  
Maintenance Phase ◽  
Newly Diagnosed ◽  
Term Survival ◽  
Deacetylase Inhibitor

Abstract Abstract 1512 Introduction: Acute Myeloblastic Leukemia (AML) in elderly patients remains an unmet medical need with a long term survival rate inferior to 10% despite the use of novel drugs. Therefore, there is a need for new agents that could induce higher CR rates and, most importantly, that could prolong the relapse free survival (RFS) and the overall survival (OS) of these poor-prognosis patients. Agents targeting epigenetics such as the hypomethylating drug 5-Azacitidine, have emerged as a promising strategy for elderly patients with AML or MDS. A second group of drugs targeting the epigenome are deacetylase inhibitors. Panobinostat is a pan-deacetylase inhibitor, with clear in vitro activity in AML and which is synergistic with anthracyclines (Maiso et al. Leukemia 2009). Based on these data we designed a phase I/II trial of panobinostat in combination with idarubicine and cytarabine followed by panobinostat maintenance in newly diagnosed AML patients older than 65 years. Methods: The initial schema included one or two induction cycles with idarubicine (8 mg/m2 days 1–3) + cytarabine (100 mg/m2 days 1–7) followed by escalating doses of panobinostat three days per week, per 3 weeks starting at 20 mg. Patients achieving CR/CRi received a consolidation cycle with the same schema. Those patients remaining in CR/CRi started a maintenance phase with 40 mg oral panobinostat in monotherapy three days per week, for 3 weeks in 28-days cycles. This schedule was amended after the six first patients, to reduce the weeks of administration of panobinostat to two weeks in the cycles in combination and to every other week in the maintenance phase. Initially a dose-escalating phase I with the classical 3+3 schema was carried out to define the maximum tolerated dose (MTD) of panobinostat in this combination; and then a phase 2 expansion phase was started to determine the efficacy of this combination in terms of CR rate and RFS. Results: 21 patients have been included after the amendment. Median age was 71 (range 66–83). Median % blasts was 40 (20–93). 35% of patients had AML with dysplastic features while adverse cytogenetics were present in 24%. Two out of 6 evaluable patients in the first cohort developed DLTs with panobinostat 20 mg (G3 hyperbilirrubinaemia in both, and one of them also G3 oedema), accordingly the dose of panobinostat was reduced to 10 mg. No DLTs were observed at this dose level, so 10 mg panobinostat was defined as the MTD in this combination. Treatment was well tolerated in the intensive cycles with the toxicity proper of standard induction chemotherapy. The most common non-hematologic toxicities (occurring in ≥20% of patients) included: fever (90%), infections (62%), mucositis (52%), diarrhoea (62%), constipation (43%), vomiting (57%), skin rash (38%), hepatotoxicity (38%) and hypokalaemia (24%). Grade 3/4 AEs were fever, infection, diarrhoea and hepatotoxicity in 2 patients each (10%) and hypokalaemia in 5 (24%). The median duration of the aplasia was 32 days (range 26–51). Regarding the maintenance phase with panobinostat monotherapy, the most frequent AEs were gastrointestinal: diarrhoea (62%), vomiting (62%) or abdominal pain (25%); as well as asthenia (50%. One of them being G3) and hyporexia (25%). In terms of efficacy, 11 patients (52%) achieved CR plus 2 more (10%) achieving CR with incomplete blood recovery (CRi) (overall 62%). There were 2 deaths in induction (10%), one due to a tumoral lysis syndrome before starting panobinostat and the other secondary to a respiratory infection. From the remaining 6 patients, 2 achieved partial response (10%) and 4 showed refractory disease (19%). With a median follow up of 6 months (range 2–14), among the 11 patients that achieved CR, 10 of them remain in CR and only 1 has progressed (in the 9th maintenance cycle). Both patients that achieved CRi have progressed in the 2nd and 6thmaintenance cycles. The median overall survival for the whole population is 13 months (2.3–23.6), and has not been reached for patients achieving CR. Conclusion: To the best of our knowledge, this is the first report of the use of a histone deacetylase inhibitor with chemotherapy in elderly AML patients. This combination was shown to be safe at the MTD. Although preliminary results are encouraging, particularly for the potential benefit of the maintenance phase, longer follow up is needed to evaluate if panobinostat maintenance is able to prolong RFS and subsequently OS in this poor prognostic population. Disclosures: Ocio: Novartis: Consultancy, Research Funding. Off Label Use: Panobinostat in newly diagnosed AML. Aliseda:Novartis: Employment. Winiger:Novartis: Employment. Hardikar:Novartis: Employment. Mateos:Novartis: Consultancy. San-Miguel:Novartis: Consultancy, Research Funding.

Sign in / Sign up

Export Citation Format

Share Document