Pretreatment serum ferritin and overall survival in metastatic pancreatic cancer.

2013 ◽  
Vol 31 (4_suppl) ◽  
pp. 171-171
Author(s):  
Lindsey Zubritsky ◽  
Ahmed Alkhateeb ◽  
Kim Leitzel ◽  
Suhail M. Ali ◽  
Cynthia Campbell-Baird ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Overall Survival ◽  
Serum Ferritin ◽  
Predictive Factor ◽  
Serum Ferritin Level ◽  
Ferritin Level ◽  
Advanced Pancreatic Cancer ◽  
Phase Iii ◽  
Metastatic Pancreatic Cancer ◽  
Pretreatment Serum

171 Background: Ferritin, an iron storage protein, is elevated in the serum of certain types of cancers, including breast and pancreatic. Ferritin has been shown to play a role in tumorigenesis and cancer cell growth and survival through angiogenesis, immune regulation, and iron delivery. Ferritin may serve as a potential biomarker in evaluating survival of pancreatic cancer patients. Methods: This study determined pretreatment ferritin levels in a phase III clinical trial of 162 patients with advanced pancreatic cancer. A quantitative sandwich ELISA (Human Ferritin ELISA (Assaypro, St. Charles, Missouri) was used to measure pretreatment serum ferritin levels in 162 patients with advanced pancreatic cancer. Serum ferritin level was correlated with overall patient survival using log-rank regression and Kaplan-Meier analysis on a continuous and categorical dichotomous basis (median cutpoint). Results: The median pretreatment serum ferritin in 162 patients was 832.6 ng/ml, a 25th and 75th percentile of 446 and 1735 ng/ml, respectively, and ranged from 51 ng/ml to 35914 ng/ml. When analyzed on a continuous basis, patients with higher serum ferritin had reduced overall survival (p= 0.001). When analyzed on a categorical basis (median 832.6 ng/ml), patients with higher ferritin had shorter overall survival (median 121 days vs. 180 days) (p=0.003). In multivariate analysis with pretreatment serum ferritin, TIMP-1, uPA, and VEGF, TIMP-1 remained the only significant predictive factor (p<0.0001), with ferritin trending toward significance (p= 0.076). Conclusions: Pretreatment serum ferritin in 162 patients with advanced pancreatic cancer was quantified using ELISA. Pretreatment serum ferritin predicted for significantly shorter overall survival in a phase III trial of metastatic pancreatic cancer. Pretreatment serum ferritin level has prognostic biomarker utility in pancreatic cancer, and should be evaluated as a predictive factor for response to novel treatment regimens.

Elevated pretreatment serum IL-8 and PD-L1 and overall survival in a phase III randomized advanced pancreatic cancer clinical trial.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 4131-4131
Author(s):  
Ashok Maddukuri ◽  
Prashanth Reddy Moku ◽  
Hyma Vani Polimera ◽  
Vinod Nagabhairu ◽  
Suhail M. Ali ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Clinical Trial ◽  
Overall Survival ◽  
Advanced Pancreatic Cancer ◽  
Serum Levels ◽  
Phase Iii ◽  
Cancer Trial ◽  
Biomarker Analysis ◽  
Combined Pretreatment ◽  
Pretreatment Serum

4131 Background: We previously reported the prognostic and predictive utility of pretreatment serum PD-L1 in the CCTG MA.31 serum bank (SABCS 2018, abstr PD3-10). IL-8 (CXCL8) is a pro-inflammatory cytokine that binds to CXCR1 and CXCR2 and promotes tumor immune escape and progression. High serum IL-8 levels are associated with poor prognosis in many cancers, and have recently been reported to predict for reduced OS to nivolumab in lung cancer and melanoma (ASCO 2018, abstr #3025). In this study, we retrospectively evaluated combined pretreatment serum IL-8 and PD-L1 on overall survival (OS) from a phase III randomized pancreatic cancer trial of first-line therapy (octreotide + 5-FU vs. 5-FU) that had reported no significant OS difference between treatment arms. Methods: This study had 147 patients with serum available for this retrospective biomarker analysis from an advanced pancreatic cancer phase III clinical trial.TheELLA immunoassay platform (ProteinSimple, San Jose, CA) was utilized to quantitate serum levels of IL-8 and PD-L1. Kaplan-Meier life table analysis was used to correlate serum biomarkers with overall survival (OS). Results: In univariate analysis, pretreatment serum IL-8 was a significant biomarker as a continuous variable (HR = 1.004; p = 0.012) and trended significant at the median cutpoint (HR = 1.379; p = 0.098) for OS, however serum PD-L1 was not significant at any cutpoint. When serum PD-L1 and IL-8 levels were analyzed as combined biomarkers (median cutpoints), the serum IL-8 high / PD-L1 high cohort had a significantly shorter OS vs the serum IL-8 low / PD-L1 low cohort (HR = 1.816; p = 0.017). Conclusions: In this phase III randomized clinical trial in advanced pancreatic cancer, pretreatment serum IL-8 was a significant biomarker for OS, but serum PD-L1 was not. Higher combined pretreatment serum levels of PD-L1 and IL-8 (both biomarkers high vs. both low) were prognostic for reduced OS in this phase III pancreatic cancer trial. Further study of circulating IL-8 and PD-L1 is warranted in pancreatic cancer for evaluation of targeted and investigational therapies, including the immune checkpoint inhibitors and anti-IL8 therapy.

Gemcitabine Plus Capecitabine Compared With Gemcitabine Alone in Advanced Pancreatic Cancer: A Randomized, Multicenter, Phase III Trial of the Swiss Group for Clinical Cancer Research and the Central European Cooperative Oncology Group

2007 ◽  
Vol 25 (16) ◽  
pp. 2212-2217 ◽  
Author(s):  
Richard Herrmann ◽  
György Bodoky ◽  
Thomas Ruhstaller ◽  
Bengt Glimelius ◽  
Emilio Bajetta ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Performance Status ◽  
Single Agent ◽  
Advanced Pancreatic Cancer ◽  
Phase Iii ◽  
Metastatic Pancreatic Cancer ◽  
Karnofsky Performance Score ◽  
Phase Iii Trial ◽  
Good Performance Status ◽  
Grade 3

PurposeThis phase III trial compared the efficacy and safety of gemcitabine (Gem) plus capecitabine (GemCap) versus single-agent Gem in advanced/metastatic pancreatic cancer.Patients and MethodsPatients were randomly assigned to receive GemCap (oral capecitabine 650 mg/m2twice daily on days 1 to 14 plus Gem 1,000 mg/m2by 30-minute infusion on days 1 and 8 every 3 weeks) or Gem (1,000 mg/m2by 30-minute infusion weekly for 7 weeks, followed by a 1-week break, and then weekly for 3 weeks every 4 weeks). Patients were stratified according to center, Karnofsky performance score (KPS), presence of pain, and disease extent.ResultsA total of 319 patients were enrolled between June 2001 and June 2004. Median overall survival (OS) time, the primary end point, was 8.4 and 7.2 months in the GemCap and Gem arms, respectively (P = .234). Post hoc analysis in patients with good KPS (score of 90 to 100) showed a significant prolongation of median OS time in the GemCap arm compared with the Gem arm (10.1 v 7.4 months, respectively; P = .014). The overall frequency of grade 3 or 4 adverse events was similar in each arm. Neutropenia was the most frequent grade 3 or 4 adverse event in both arms.ConclusionGemCap failed to improve OS at a statistically significant level compared with standard Gem treatment. The safety of GemCap and Gem was similar. In the subgroup of patients with good performance status, median OS was improved significantly. GemCap is a practical regimen that may be considered as an alternative to single-agent Gem for the treatment of advanced/metastatic pancreatic cancer patients with a good performance status.

Phase III Trial of Gemcitabine Plus Tipifarnib Compared With Gemcitabine Plus Placebo in Advanced Pancreatic Cancer

2004 ◽  
Vol 22 (8) ◽  
pp. 1430-1438 ◽  
Author(s):  
E. Van Cutsem ◽  
H. van de Velde ◽  
P. Karasek ◽  
H. Oettle ◽  
W.L. Vervenne ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Overall Survival ◽  
Single Agent ◽  
Survival Rates ◽  
Advanced Pancreatic Cancer ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Controlled Study ◽  
Double Blind ◽  
Free Survival

Purpose To determine whether addition of the farnesyltransferase inhibitor tipifarnib (Zarnestra, R115777; Johnson and Johnson Pharmaceutical Research and Development, Beerse, Belgium) to standard gemcitabine therapy improves overall survival in advanced pancreatic cancer. Patients and Methods This randomized, double-blind, placebo-controlled study compared gemcitabine + tipifarnib versus gemcitabine + placebo in patients with advanced pancreatic adenocarcinoma previously untreated with systemic therapy. Tipifarnib was given at 200 mg bid orally continuously; gemcitabine was given at 1,000 mg/m2 intravenously weekly × 7 for 8 weeks, then weekly × 3 every 4 weeks. The primary end point was overall survival; secondary end points included 6-month and 1-year survival rates, progression-free survival, response rate, safety, and quality of life. Results Six hundred eighty-eight patients were enrolled. Baseline characteristics were well balanced between the two treatment arms. No statistically significant differences in survival parameters were observed. The median overall survival for the experimental arm was 193 v 182 days for the control arm (P = .75); 6-month and 1-year survival rates were 53% and 27% v 49% and 24% for the control arm, respectively; median progression-free survival was 112 v 109 days for the control arm. Ten drug-related deaths were reported for the experimental arm and seven for the control arm. Neutropenia and thrombocytopenia grade ≥ 3 were observed in 40% and 15% in the experimental arm versus 30% and 12% in the control arm. Incidences of nonhematologic adverse events were similar in two groups. Conclusion The combination of gemcitabine and tipifarnib has an acceptable toxicity profile but does not prolong overall survival in advanced pancreatic cancer compared with single-agent gemcitabine.

A phase II study of lapatinib and capecitabine in first-line treatment of metastatic pancreatic cancer (ICORG 08- 39).

2011 ◽  
Vol 29 (4_suppl) ◽  
pp. 315-315 ◽  
Author(s):  
R. S. McDermott ◽  
P. Calvert ◽  
M. Parker ◽  
G. Webb ◽  
B. Moulton ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Overall Survival ◽  
Cancer Patients ◽  
Advanced Pancreatic Cancer ◽  
Metastatic Pancreatic Cancer ◽  
Survival Duration ◽  
Synergistic Activity ◽  
Line Treatment ◽  
First Line ◽  
First Line Treatment

315 Background: The combination of capecitabine plus erlotinib in gemcitabine-refractory advanced pancreatic cancer patients has proved beneficial in terms of median survival duration, objective radiological response rate and decrease in tumour marker levels from baseline. In the phase I study of capecitabine and lapatinib carried out in advanced solid tumors, the optimal tolerated regimen was determined to be lapatinib 1,250 mg plus capecitabine 2,000 mg/m2/day. At these dose levels, the combination was well tolerated with few grade 3 toxicities and no grade 4 toxicity. Our preclinical work suggested synergistic activity of capecitabine and lapatinib in pancreatic cancer. We initiated a study of this combination in the first-line therapy of metastatic pancreas cancer. Methods: This was a single-arm multicenter study in patients with chemotherapy-naive metastatic pancreatic cancer. The primary endpoint was overall survival. The study was designed as a Simons two-stage optimal design and was divided into two stages. The first stage was to recruit up to 12 patients. If at least seven of these patients survived for at least six months, then a further 20 patients would be enrolled into the study. If six or fewer of the initial 12 patients met the specified study survival criteria, the study would be halted. Treatment was to be administered until disease progression or until withdrawal from the study due to unacceptable toxicity or other reasons. Clinical and laboratory parameters were assessed to evaluate disease response and toxicity of therapy. The study patients received lapatinib 1,250 mg/day, plus capecitabine 2000 mg/m2/day on days 1-14 every 21 days. Results: Nine patients were enrolled. Seven of these patients did not achieve the interim protocol response requirement of survival for at least 6 months, to allow for the study to continue to the second cohort of patients. Median overall survival from first dose was 4 months. Median time on treatment was 2 months. There were no objective responses. There were no unexpected toxicities. Conclusions: The addition of lapatinib to capecitabine does not improve overall survival in the first-line treatment of advanced pancreatic cancer patients. [Table: see text]

Second-Line Oxaliplatin, Folinic Acid, and Fluorouracil Versus Folinic Acid and Fluorouracil Alone for Gemcitabine-Refractory Pancreatic Cancer: Outcomes From the CONKO-003 Trial

2014 ◽  
Vol 32 (23) ◽  
pp. 2423-2429 ◽  
Author(s):  
Helmut Oettle ◽  
Hanno Riess ◽  
Jens M. Stieler ◽  
Gerhard Heil ◽  
Ingo Schwaner ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Overall Survival ◽  
Folinic Acid ◽  
Karnofsky Performance Status ◽  
Advanced Pancreatic Cancer ◽  
Phase Iii ◽  
Second Line ◽  
First Line ◽  
Gemcitabine Refractory

Purpose To assess the efficacy of a second-line regimen of oxaliplatin and folinic acid–modulated fluorouracil in patients with advanced pancreatic cancer who have experienced progression while receiving gemcitabine monotherapy. Patients and Methods A randomized, open-label, phase III study was conducted in 16 institutions throughout Germany. Recruitment ran from January 2004 until May 2007, and the last follow-up concluded in December 2012. Overall, 168 patients age 18 years or older who experienced disease progression during first-line gemcitabine therapy were randomly assigned to folinic acid and fluorouracil (FF) or oxaliplatin and FF (OFF). Patients were stratified according to the presence of metastases, duration of first-line therapy, and Karnofsky performance status. Results Median follow-up was 54.1 months, and 160 patients were eligible for the primary analysis. The median overall survival in the OFF group (5.9 months; 95% CI, 4.1 to 7.4) versus the FF group (3.3 months; 95% CI, 2.7 to 4.0) was significantly improved (hazard ratio [HR], 0.66; 95% CI, 0.48 to 0.91; log-rank P = .010). Time to progression with OFF (2.9 months; 95% CI, 2.4 to 3.2) versus FF (2.0 months; 95% CI, 1.6 to 2.3) was significantly extended also (HR, 0.68; 95% CI, 0.50 to 0.94; log-rank P = .019). Rates of adverse events were similar between treatment arms, with the exception of grades 1 to 2 neurotoxicity, which were reported in 29 patients (38.2%) and six patients (7.1%) in the OFF and FF groups, respectively (P < .001). Conclusion Second-line OFF significantly extended the duration of overall survival when compared with FF alone in patients with advanced gemcitabine-refractory pancreatic cancer.

scholarly journals Role of serum ferritin level on overall survival in patients with myelodysplastic syndromes: Results of a meta-analysis of observational studies

PLoS ONE ◽  
2017 ◽  
Vol 12 (6) ◽  
pp. e0179016 ◽  
Author(s):  
Claudia Pileggi ◽  
Maddalena Di Sanzo ◽  
Valentina Mascaro ◽  
Maria Grazia Marafioti ◽  
Francesco Saverio Costanzo ◽  
...  
Keyword(s):  
Overall Survival ◽  
Serum Ferritin ◽  
Myelodysplastic Syndromes ◽  
Observational Studies ◽  
Serum Ferritin Level ◽  
Ferritin Level ◽  
Meta Analysis
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