Predictive utility of serum cytokine levels in patients with metastatic renal cell carcinoma (MRCC) treated with interferon alfa (IFNa)

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 14503-14503
Author(s):  
A. J. Montero ◽  
C. Diaz-Montero ◽  
X. Wang ◽  
B. W. McIntyre ◽  
N. Tannir
Keyword(s):  
Clinical Outcome ◽  
Clinical Benefit ◽  
Serum Levels ◽  
Phase Iii ◽  
Gm Csf ◽  
Risk Of Death ◽  
Ifna Therapy ◽  
Increased Risk ◽  
Cytokine Levels ◽  
Th1 Cytokines

14503 Background: IFNa may prolong survival in MRCC patients (pts) due to stimulation of cell-mediated immunity. We hypothesized that IFNa exerts an anti-tumor effect by upregulation of Th1 cytokines and that patients (pts) with elevated serum levels of Th1 cytokines either at baseline (BL) or after treatment with IFNa would have a superior clinical outcome. Methods: Cytokine profiling was performed on 104 pts with MRCC treated in a randomized phase III trial with IFNa 0.5 million units (MU) subcutaneously (SC) twice daily or 5 MU SC daily. Serum samples were collected at BL (n = 104) and after 8 weeks of IFNa therapy (C1) (n = 89). Cytokine concentrations were determined using a 16-plex immunoassay. The linear mixed-effect model was fit to assess the change of cytokine levels from BL to C1. Cox proportional hazards model was fit to evaluate the effect of BL cytokine levels or change of cytokine levels from BL to C1 on the risk of death. Results: Of 16 cytokines evaluated (IL-1b, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12 p40, IL-13, IL-15, IL-17, IFNa, IFNg, GM-CSF, TNFa, VEGF), lower BL TNFa, IL-8 (Th1), and IL-13 (Th2) levels were associated with clinical benefit (major response or progression-free status at 6 months) (p = 0.01 and 0.03, respectively). By multivariate analysis, only extremely low or high levels of IFNa (p = 0.02) and IL-12 (p = 0.002) at BL were associated with an increased risk of death. IFNa therapy after C1 produced higher levels of several Th1 cytokines (IL-8, IL-12 p40, IL-15) (p < .001) and lower levels of Th2 cytokines (IL-4, IL-13). Unexpectedly, there were significantly lower levels of TNFa and GM-CSF (Th1) and higher levels of IL-10 (Th2) with IFNa. Only an increase of IL-2 levels from BL to C1 (RR 1.45; p = 0.05) correlated with an increased risk of death. Conclusions: Lower BL serum levels of TNFa, IL-8, and IL-13 were associated with clinical benefit to IFNa. Although IFNa therapy favored a shift towards a Th1 response, this effect alone did not correlate with clinical outcome. No significant financial relationships to disclose.

scholarly journals Prognostic role of neoplastic markers in Takotsubo syndrome

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Francesco Santoro ◽  
Tecla Zimotti ◽  
Adriana Mallardi ◽  
Alessandra Leopizzi ◽  
Enrica Vitale ◽  
...  
Keyword(s):  
Serum Levels ◽  
Takotsubo Syndrome ◽  
Ca 15.3 ◽  
Risk Of Death ◽  
Increased Risk ◽  
Ca 19.9 ◽  
Long Term Follow Up

AbstractTakotsubo syndrome (TTS) is an acute heart failure syndrome with significant rates of in and out-of-hospital mayor cardiac adverse events (MACE). To evaluate the possible role of neoplastic biomarkers [CA-15.3, CA-19.9 and Carcinoembryonic Antigen (CEA)] as prognostic marker at short- and long-term follow-up in subjects with TTS. Ninety consecutive subjects with TTS were enrolled and followed for a median of 3 years. Circulating levels of CA-15.3, CA-19.9 and CEA were evaluated at admission, after 72 h and at discharge. Incidence of MACE during hospitalization and follow-up were recorded. Forty-three (46%) patients experienced MACE during hospitalization. These patients had increased admission levels of CEA (4.3 ± 6.2 vs. 2.2 ± 1.5 ng/mL, p = 0.03). CEA levels were higher in subjects with in-hospital MACE. At long term follow-up, CEA and CA-19.9 levels were associated with increased risk of death (log rank p < 0.01, HR = 5.3, 95% CI 1.9–14.8, HR = 7.8 95% CI 2.4–25.1, respectively, p < 0.01). At multivariable analysis levels higher than median of CEA, CA-19.9 or both were independent predictors of death at long term (Log-Rank p < 0.01). Having both CEA and CA-19.9 levels above median (> 2 ng/mL, > 8 UI/mL respectively) was associated with an increased risk of mortality of 11.8 (95% CI 2.6–52.5, p = 0.001) at follow up. Increased CEA and CA-19.9 serum levels are associated with higher risk of death at long-term follow up in patients with TTS. CEA serum levels are correlated with in-hospital MACE.

Phase III Trial Adding Vincristine-Topotecan-Cyclophosphamide to the Initial Treatment of Patients With Nonmetastatic Ewing Sarcoma: A Children's Oncology Group Report

2021 ◽  
Author(s):  
Patrick J. Leavey ◽  
Nadia N. Laack ◽  
Mark D. Krailo ◽  
Allen Buxton ◽  
R. Lor Randall ◽  
...  
Keyword(s):  
Ewing Sarcoma ◽  
Tumor Volume ◽  
Phase Iii ◽  
Pelvic Bone ◽  
Experimental Therapy ◽  
Survival Outcomes ◽  
Primary Tumors ◽  
Risk Of Death ◽  
Increased Risk ◽  
To Receive

PURPOSE The primary aim of this phase III randomized trial was to test whether the addition of vincristine, topotecan, and cyclophosphamide (VTC) to interval compressed chemotherapy improved survival outcomes for patients with previously untreated nonmetastatic Ewing sarcoma. METHODS Patients were randomly assigned to receive standard five-drug interval compressed chemotherapy (regimen A) for 17 cycles or experimental therapy with five cycles of VTC within the 17 cycles (regimen B). Patients were stratified by age at diagnosis (< 18 years and ≥18 years) and tumor site (pelvic bone, nonpelvic bone, and extraosseous). Tumor volume at diagnosis was categorized as < 200 mL or ≥ 200 mL. Local control occurred following six cycles. Histologic response was categorized as no viable or any viable tumor. Event-free survival (EFS) and overall survival (OS) were compared between randomized groups with stratified log-rank tests. RESULTS Of 642 enrolled patients, 309 eligible patients received standard and 320 received experimental therapy. The 5-year EFS and OS were 78% and 87%, respectively. There was no difference in survival outcomes between randomized groups (5-year EFS regimen A v regimen B, 78% v 79%; P = .192; 5-year OS 86% v 88%; P = .159). Age and primary site did not affect the risk of an EFS event. However, age ≥ 18 years was associated with an increased risk of death at 5 years (hazard ratio 1.84; 95% CI, 1.15 to 2.96; P = .009). The 5-year EFS rates for patients with pelvic, nonpelvic bone, and extraosseous primary tumors were 75%, 78%, and 85%, respectively. Tumor volume ≥ 200 mL was significantly associated with lower EFS. CONCLUSION While VTC added to five-drug interval compressed chemotherapy did not improve survival, these outcomes represent the best survival estimates to date for patients with previously untreated nonmetastatic Ewing sarcoma.

scholarly journals Which factors are associated with sarcopenia and frailty in elderly persons residing in the community?

2018 ◽  
Vol 21 (6) ◽  
pp. 755-766
Author(s):  
Ana Paula Pillatt ◽  
Rutiana Silva Patias ◽  
Evelise Moraes Berlezi ◽  
Rodolfo Herberto Schneider
Keyword(s):  
Systematic Review ◽  
Vitamin D ◽  
Frail Elderly ◽  
Serum Vitamin ◽  
Serum Levels ◽  
Elderly Persons ◽  
Risk Of Death ◽  
Increased Risk ◽  
Vitamin D Levels ◽  
Low Serum

Abstract Objective: to broaden knowledge about the factors associated with sarcopenia and frailty in elderly persons residing in the community. Method: an integrative systematic review based on the PRISMA recommendations was carried out, using articles published from 2012 to March 2017 in the PubMED, SciELO, Virtual Health Library, CINAHL and Springer electronic databases with the following descriptors: frail elderly, sarcopenia and etiology and their synonyms. The articles identified by the initial search strategy were independently assessed by two researchers, according to the eligibility criteria, and the articles selected were evaluated for methodological quality. Results: the results of this survey show that frailty may be associated with sarcopenia, low serum vitamin D levels, anemia, subclinical hyperthyroidism in men, while the greatest evolution in women was for osteoporosis. An association between sarcopenia and advanced age was also observed, with worsening quality of life, physical-functional capacity, nutritional status and comorbidities, as well as an increased risk of death in sarcopenic elderly persons. Conclusion: this systematic review showed that low serum levels of vitamin D are associated with frailty and factors that predispose this condition. It is therefore important to monitor the serum levels of this vitamin in the elderly population, and it is suggested that new studies are carried out related to supplements of this vitamin in frail elderly persons.

scholarly journals Homozygous Deletion of the p16/MTS1 Gene in Pediatric Acute Lymphoblastic Leukemia Is Associated With Unfavorable Clinical Outcome

Blood ◽  
1997 ◽  
Vol 89 (11) ◽  
pp. 4161-4166 ◽  
Author(s):  
Ursula R. Kees ◽  
Paul R. Burton ◽  
Changlong Lü ◽  
David L. Baker
Keyword(s):  
Risk Factors ◽  
Acute Lymphoblastic Leukemia ◽  
Clinical Outcome ◽  
Lymphoblastic Leukemia ◽  
Homozygous Deletion ◽  
Cell Phenotype ◽  
P16 Gene ◽  
Childhood All ◽  
Risk Of Death ◽  
Increased Risk

Abstract The p16 gene (MTS1, CDKN2, p16INK4A, CDKI) encoding an inhibitor of cyclin-dependent kinase 4 (cdk4) has been found to be deleted in various types of tumors, including leukemia, and is thought to code for a tumor suppressor gene. Our preliminary findings on eight pediatric patients with acute lymphoblastic leukemia (ALL) suggested that the survival of patients carrying a homozygous p16 gene deletion was significantly inferior to that of those without a deletion. The present study on 48 patients tested the hypothesis that the clinical outcome for pediatric ALL patients is correlated with the presence or absence of the p16 gene. Overall, nine of 48 children (18.3%) carried a homozygous p16 deletion. Such deletions were significantly more common (P = .003) among T-ALL patients (five of eight, 62.5%) than among precursor-B-ALL patients (four of 40, 10.0%). Of nine patients exhibiting p16 deletions, eight (88.9%) were classified as high-risk patients by the recognized prognostic factors of age, white blood cell count, and T-cell phenotype. The 4-year event-free survival in the study population as a whole was 72.7%. Without adjustment for other risk factors (univariate model), the presence of a homozygous p16 deletion was associated with a markedly increased probability of both relapse (P = .0003) and death (P = .002). These findings raise the question of whether the p16 deletion itself confers an increased risk of relapse after adjusting for the known risk factors. In this analysis, the estimated risk multiplier factor for relapse in patients carrying the p16 deletion was 14.0 (P = .0004) and for the risk of death 15.6 (P = .0008). We therefore conclude that the presence of a homozygous p16 deletion may well be an important risk factor for both relapse and death in childhood ALL, and that its prognostic effect is not a consequence of confounding by other factors already known to influence outcome in this disease.

scholarly journals Tobacco Smoking and Increased Risk of Death and Progression for Patients With p16-Positive and p16-Negative Oropharyngeal Cancer

2012 ◽  
Vol 30 (17) ◽  
pp. 2102-2111 ◽  
Author(s):  
Maura L. Gillison ◽  
Qiang Zhang ◽  
Richard Jordan ◽  
Weihong Xiao ◽  
William H. Westra ◽  
...  
Keyword(s):  
Cancer Progression ◽  
Tobacco Smoking ◽  
Oropharyngeal Cancer ◽  
Radiation Therapy Oncology Group ◽  
Phase Iii ◽  
Tobacco Exposure ◽  
Primary Tumors ◽  
Risk Of Death ◽  
Oropharynx Cancer ◽  
Increased Risk

Purpose Tobacco smoking is associated with oropharynx cancer survival, but to what extent cancer progression or death increases with increasing tobacco exposure is unknown. Patients and Methods Patients with oropharynx cancer enrolled onto a phase III trial of radiotherapy from 1991 to 1997 (Radiation Therapy Oncology Group [RTOG] 9003) or of chemoradiotherapy from 2002 to 2005 (RTOG 0129) were evaluated for tumor human papillomavirus status by a surrogate, p16 immunohistochemistry, and for tobacco exposure by a standardized questionnaire. Associations between tobacco exposure and overall survival (OS) and progression-free survival (PFS) were estimated by Cox proportional hazards models. Results Prevalence of p16-positive cancer was 39.5% among patients in RTOG 9003 and 68.0% in RTOG 0129. Median pack-years of tobacco smoking were lower among p16-positive than p16-negative patients in both trials (RTOG 9003: 29 v 45.9 pack-years; P = .02; RTOG 0129: 10 v 40 pack-years; P < .001). After adjustment for p16 and other factors, risk of progression (PFS) or death (OS) increased by 1% per pack-year (for both, hazard ratio [HR], 1.01; 95% CI, 1.00 to 1.01; P = .002) or 2% per year of smoking (for both, HR, 1.02; 95% CI, 1.01 to 1.03; P < .001) in both trials. In RTOG 9003, risk of death doubled (HR, 2.19; 95% CI, 1.46 to 3.28) among those who smoked during radiotherapy after accounting for pack-years and other factors, and risk of second primary tumors increased by 1.5% per pack-year (HR, 1.015; 95% CI, 1.005 to 1.026). Conclusion Risk of oropharyngeal cancer progression and death increases directly as a function of tobacco exposure at diagnosis and during therapy and is independent of tumor p16 status and treatment.

Characteristics of Immunoglobulin Deficiency in Patients with Untreated Multiple Myeloma Stage II and III.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4861-4861
Author(s):  
Markus Hamel ◽  
Wolfram Poenisch ◽  
Dirk Hasenclever ◽  
Goetz Gelbrich ◽  
Markus Loeffler ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Light Chain ◽  
Normal Values ◽  
Serum Levels ◽  
Stage Ii ◽  
Phase Iii ◽  
Myeloma Protein ◽  
Randomised Study ◽  
Median Serum ◽  
Increased Risk

Abstract Introduction: It is well known that multiple myeloma (MM) is often associated with immunoglobulin (Ig) deficiency and increased risk of infection. We evaluated the Ig levels in 150 patients with MM stage II and III as part of a phase III randomised study comparing the effectiveness of melphalane and prednisolone versus bendamustine and prednisolone. Patients and methods: 150 patients at a median age of 68 years, with untreated MM stage II, n = 19, and stage III, n = 131, were evaluated. MM type was IgG, IgA, light chain, and biclonal in 106 (70,7 %), 32 (21,3 %), 11 (7,5 %), 1 (0,7 %) patients respectively. Serum Ig levels were measured in all patients prior to chemotherapy. Normal values for IgG were 7,02 – 14,6 g/l, for IgA 0,24 – 3,81 g/l, and for IgM 0,54 – 2,27 g/l. Only Ig classes other than the myeloma protein class were evaluated. Results: Patients with IgG MM had a median serum IgA of 0,4 g/l (range 0 – 7,9), and a median IgM level of 0,2 g/l (0 – 5,6). In 106 patients with IgG MM, IgA serum levels were below, within normal, and above normal values in 36 (34 %), 69 (65,1 %), and 1 (0,9 %) patients, respectively. On the other hand, IgM levels in these patients were below, within normal, and above normal values in 94 (88,7 %), 9 (8,5 %), and 3 (2,8 %) patients, respectively. Median IgG for IgA MM patients was 3,7 g/l (range 0,1 – 11,8), and median IgM in these 32 patients was 0,2 g/l (range 0 – 1,3). IgG levels were below and within normal in 28 (87,5 %), 4 (12,5 %) patients, respectively. Similarly, IgM level were below, and within normal range in 30 (93,8 %), and 2 (6,3 %) patients with IgA MM. Lastly, median IgG in patients with light chain myeloma was 6,3 g/l (range 2,1 – 9,7), median IgA, and median IgM were 0,4 g/l (range 0,1 – 1,7), and 0,3 g/l (range 0,1 – 0,8), respectively. IgG, IgA, and IgM were below normal values in 8 (72,7 %), 3 (27,3 %), and 9 (81,8 %), respectively. Conclusion: Most patients with untreated MM have markedly reduced serum Ig levels. The correlation of reduced Ig level to the incidence of infections is being evaluated. The effect of chemotherapy on Ig levels is currently being assessed in our phase III study.

A phase III study of xilonix in refractory colorectal cancer patients with weight loss.

2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 685-685 ◽  
Author(s):  
George A. Fisher
Keyword(s):  
Colorectal Cancer ◽  
Cancer Progression ◽  
Human Monoclonal Antibody ◽  
Well Being ◽  
Phase Iii ◽  
Controlled Study ◽  
Open Label ◽  
Risk Of Death ◽  
Increased Risk ◽  
Median Change

685 Background: Xilonix, an anti-interleukin-1α true human monoclonal antibody is being assessed as cancer therapy to improve overall survival (OS) in advanced colorectal cancer (CRC) patients. Methods: An open label multicenter randomized comparator controlled study to evaluate efficacy and safety of Xilonix in CRC complicated with cachexia. Eligible patients had metastatic CRC, failed oxaliplatin or irinotecan based chemotherapy, and lost ≥5% total body weight in the previous 6 months (m). Patients were 1:1 randomized to Xilonix (3.75 mg/kg intravenously every two weeks) or megestrol acetate (MA, oral 800 mg daily) until progression. Primary endpoint was OS. Secondary endpoints included assessment of patient well-being using the EORTC QLQ-C30 questionnaire. Platelets support tumor growth and metastasis and platelet counts increase during cancer progression. IL-1α on platelets may be a target of Xilonix and thus platelet count was a key pharmacodynamic measure. Results: 40 patients were enrolled between March 2013 and July 2014, at which time the study was halted to revise inclusion criteria to reduce screen failures. An eligibility violation excluded 1 Xilonix patient from analysis (Xilonix n=19, MA n=20). MA treatment arm had a 39% shorter median OS (2.0 versus 2.8 months) and a trend in increased risk of death (hazard ratio 2.17, p=0.17). Physical and role function worsened in patients receiving megesterol (median change of -13.3 (p=0.02), -16.7 (p=0.02) respectively), whereas in Xilonix treated patients these functions did not decline during therapy (median change 0, p=0.88 and 0, p=0.69, respectively). Xilonix patients had treatment-related reduction in platelets compared to the MA group (median -60,000/mm3, vs 10,000/mm3, p=0.03). No infusion reactions, no discontinuations due to adverse events (AEs) and no related SAEs were reported for Xilonix. Conclusions: The trend in OS for Xilonix patients was encouraging and consistent with improved function and intended pharmacodynamic activity. An amended Phase III protocol has been developed to simplify enrollment for an ongoing study of Xilonix in an advanced CRC population. (NCT01767857) Clinical trial information: NCT01767857.

Clinical outcome and characteristics of patients with cervical cancer submitted to renal replacement therapy.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e21627-e21627
Author(s):  
Diego Reis ◽  
Eduardo Rocha ◽  
Tatiane Cristine Ishida
Keyword(s):  
Cervical Cancer ◽  
Renal Replacement Therapy ◽  
Clinical Outcome ◽  
Replacement Therapy ◽  
Disease Progression ◽  
Stage I ◽  
Intermittent Hemodialysis ◽  
Risk Of Death ◽  
Increased Risk ◽  
Active Disease

e21627 Background: Cervical cancer is the 2nd most prevalent and 4th cause of cancer-related death in Brazil among women. It may cause renal failure due to tumoral growth, the treatments, among other causes. Purpose: To evaluate the clinical outcome and the risk of death in patients with cervical cancer hospitalized submitted to hemodialysis, to describe the clinical characteristics of these patients. Methods: Retrospective observational study. Patients diagnosed with cervical cancer, hospitalized, submitted to renal replacement therapy were identified in a single institution (n = 92). Risk of death was estimated using Kaplan-Meier analysis. The Cox proportional hazards regression model was used to determine the risk of death on the basis of: cancer staging, disease activity, Performance status at admission, oncological surgery before hemodialysis subgroup. Results: 92 patients with cervical cancer hospitalized were submitted to intermittent hemodialysis between January 2007 and December 2008. Data was available for all the 92 patients. Median age at diagnosis 47.8 years (25.4-95.1), 73.9% was diagnosed stage III/IV, 95% had disease progression/ active disease before hemodialysis. 84 patients (91%) were dead at the moment of analysis (Cut-off date 30/03/2010), median interval between first hemodialysis and death 1.1 months (0-24.8). The main cause of death was postrenal kidney failure (82.6%). In multivariate analysis, stage II/III/IV (compared with stage I) and disease progression/active disease were the only independent prognostic factors associated with increased risk of death (HR = 3.149; 95% CI, 1.765 to 5.610; P = .001 and HR = 4.205; 95% CI, 1.002 to 17.65; P = .05). Conclusions: Women with advanced disease and active disease/ disease progression have a significant increased risk of death compared with those with stage I, stable disease/ disease in remission. Prospective studies are warranted to investigate the benefit hemodialysis in patients with cervical cancer.

scholarly journals Persistent Overall Survival Benefit and No Increased Risk of Second Malignancies With Bortezomib-Melphalan-Prednisone Versus Melphalan-Prednisone in Patients With Previously Untreated Multiple Myeloma

2013 ◽  
Vol 31 (4) ◽  
pp. 448-455 ◽  
Author(s):  
Jesús F. San Miguel ◽  
Rudolf Schlag ◽  
Nuriet K. Khuageva ◽  
Meletios A. Dimopoulos ◽  
Ofer Shpilberg ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
Final Analysis ◽  
Incidence Rates ◽  
Phase Iii ◽  
Second Primary ◽  
Risk Of Death ◽  
Increased Risk ◽  
Second Primary Malignancies

Purpose This final analysis of the phase III VISTA trial (Velcade As Initial Standard Therapy in Multiple Myeloma: Assessment With Melphalan and Prednisone) was conducted to determine whether the overall survival (OS) benefit with bortezomib-melphalan-prednisone (VMP) versus melphalan-prednisone (MP) in patients with myeloma who were ineligible for transplantation was maintained after 5 years of follow-up and to explore the risk of second primary malignancies. Patients and Methods In all, 682 patients received up to nine 6-week cycles of VMP or MP and were then observed every 12 weeks or less. Data on second primary malignancies were collected by individual patient inquiries at all sites from 655 patients. Results After median follow-up of 60.1 months (range, 0 to 74 months), there was a 31% reduced risk of death with VMP versus MP (hazard ratio [HR], 0.695; P < .001; median OS 56.4 v 43.1 months). OS benefit with VMP was seen across prespecified patient subgroups (age ≥ 75 years, stage III myeloma, creatinine clearance < 60 mL/min). Sixty-three percent of VMP patients and 73% of MP patients had received subsequent therapy. Time to next therapy (median, 30.7 v 20.5 months; HR, 0.557; P < .001) was longer with VMP than with MP. Among patients who received subsequent therapies, survival from start of subsequent therapy was similar following VMP (median, 28.1 months) or MP (median, 26.8 months; HR, 0.914). Following VMP/MP, incidence proportions of hematologic malignancies (1%/1%) and solid tumors (5%/3%) and exposure-adjusted incidence rates (0.017/0.013 per patient-year) were similar and were consistent with background rates. Conclusion VMP resulted in a significant reduction in risk of death versus MP that was maintained after 5 years' follow-up and despite substantial use of novel-agent-based salvage therapies. There is no emerging safety signal for second primary malignancies following VMP.

Analysis of cytokines in ECOG E4Z02: A phase III randomized study of l-carnitine supplementation for fatigue in patients with cancer

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 9635-9635
Author(s):  
T. A. Rich ◽  
M. J. Fisch ◽  
J. Manola ◽  
D. Cella ◽  
B. Ansari ◽  
...  
Keyword(s):  
Proinflammatory Cytokines ◽  
Randomized Study ◽  
Serum Levels ◽  
Pain Severity ◽  
Phase Iii ◽  
Carnitine Supplementation ◽  
Severe Fatigue ◽  
Cytokine Levels ◽  
Lower Pain ◽  
Ifn Γ

9635 Background: The purpose of the study was to investigate associations between fatigue, depression and pain and serum levels of proinflammatory cytokines among pts randomized to l-carnitine supplementation or placebo. Methods: 376 cancer pts with normal hemoglobin and fatigue assessed as moderate or severe were randomized to 4 wks of supplementation with oral carnitine (n=189) or placebo (n=187) 1000 mg bid. Serum levels of 10 inflammatory cytokines and growth factors were measured with Luminex bead ELISA at baseline and 4 wks for 98 pts. Wilcoxon rank sum tests were used to compare cytokine levels between arms and between pts with/without symptoms. Multivariable models of fatigue, depression and pain at 4 wks were examined, adjusting for treatment arm, baseline symptoms and baseline cytokine levels. Results: There were no statistically significant differences in cytokine levels between pts with or without severe fatigue, pain, or depression at baseline. Levels of IL-1rα were higher at baseline among pts randomized to placebo (p=0.01) and increased after 4 wks, while levels among pts randomized to l-carnitine declined (p <0.001). Levels of IFN-γ, TGF-α, IL-6, and TNF-α decreased more among pts randomized to placebo (p=0.008, p=0.006, p=0.01, and p=0.05, respectively). Pts with severe pain at 4 wks had greater declines in levels of EGF, IFN-γ, IL-1α, and IL-1rα than pts without (p=0.05, 0.05, 0.02 and 0.03, respectively). Reductions in IL-1α and TGF-α predicted lower pain severity at 4 wks (p=0.02 and p=0.04, respectively). Conclusions: Levels of proinflammatory cytokines or EGFR ligands failed to distinguish between patients with moderate vs. severe fatigue or levels of depression and pain (severe vs. not) prior to treatment intervention. Lower levels of IL-1α and TGF-α appear to be associated with improvement of pain severity but are not associated with treatment. Mechanisms for these findings require exploration. No significant financial relationships to disclose.

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