Pretreatment serum TIMP-1 levels and survival in advanced pancreatic cancer

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e15568-e15568
Author(s):  
R. Vargas ◽  
V. Shrivastava ◽  
K. Leitzel ◽  
S. M. Ali ◽  
W. Carney ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cancer Patients ◽  
Growth Promotion ◽  
Advanced Pancreatic Cancer ◽  
Tissue Inhibitor Of Metalloproteinase ◽  
Phase Iii ◽  
Double Blind ◽  
Treatment Regimens ◽  
Pretreatment Serum ◽  
Cutpoint Analysis

e15568 Background: Tissue inhibitor of metalloproteinase-1 (TIMP-1) has been shown to have diverse multifunctional roles in tumorigenesis such as inhibition of the catalytic activity of MMPs, growth promotion, inhibition of apoptosis and regulation of angiogenesis. Elevated TIMP-1 has been associated with an unfavorable prognosis in many cancers including breast, colorectal, gastric, head and neck, lung, and lymphoma. VEGF is also intimately associated with angiogenesis. Methods: This study determined serum TIMP-1 and VEGF levels in a phase III clinical trial of 157 patients with advanced pancreatic cancer. ELISAs for TIMP-1 and VEGF (Oncogene Science / Siemens HealthCare Diagnostics, Cambridge, MA) were employed to measure pretreatment serum TIMP-1 levels in 157 pancreatic cancer patients enrolled in a randomized, double-blind, placebo-controlled phase III trial. Statistical analysis was performed with TIMP-1 and VEGF on a continuous and cutpoint basis. Serum biomarker levels were then correlated with patient survival using Kaplan -Meier life table analysis. Results: Serum TIMP-1 levels in 157 pancreatic patients had a median of 409.9 ng/mL, and ranged from 144 to 1078 ng/mL. Patients with higher serum TIMP-1 had significantly shorter survival on a continuous basis (p = 0.001), on quartile analysis (p = 0.004), and on a dichotomous cutpoint analysis of upper 25 % vs lower 75 % (median survival 101 days vs. 197 days)(p< 0.001). Serum VEGF level was not associated with survival on a continuous (p = 0.57) or cutpoint analysis (p= 0.93). Conclusions: Pancreatic cancer patients with higher serum TIMP-1 levels had significantly shorter overall survival. Serum TIMP-1 level should be evaluated as a predictive factor for response to novel treatment regimens. [Table: see text]

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 III trial of virulizin plus gemcitabine vs. gemcitabine alone in advanced pancreatic cancer: Results of subgroup analysis

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 4116-4116 ◽  
Author(s):  
J. A. Wright ◽  
J. Osterlee ◽  
S. Fekete ◽  
Y. Lee ◽  
A. H. Young
Keyword(s):  
Pancreatic Cancer ◽  
Metastatic Cancer ◽  
Performance Status ◽  
Locally Advanced ◽  
Advanced Pancreatic Cancer ◽  
Phase Iii ◽  
Double Blind ◽  
Significant Difference ◽  
Ecog Ps ◽  
To Receive

4116 Background: Virulizin (V) is a novel antitumor immune modulator that improves survival in pancreatic cancer patients (pts) as monotherapy. A double-blind, multicenter, randomized, phase III study was conducted to evaluate the survival benefits and safety of V in combination with gemcitabine (G) in pts with advanced pancreatic cancer. Methods: Chemo-naive pts with locally advanced or metastatic pancreatic cancer with ECOG Performance Status (PS) of 0, 1 or 2 were enrolled. Pts were randomized to receive intramuscular injections of either V or placebo (P) 3 times weekly + G (1,000 mg/m2 weekly ×7 with 1 week rest, then weekly ×3 q4w). Randomization was stratified according to ECOG PS (0 or 1, and 2) and extent of disease (locally advanced and metastatic). Pts who showed no clinical benefit or were intolerant to G entered 2nd-line therapy (stage 3), in which pts continued to receive either V or P alone or with 5-FU, or best supportive care. The primary endpoint was survival, defined as time from baseline/treatment day 1 to time of death from any cause. Results: The intent to treat (ITT) population comprised 434 pts, of which 377 were efficacy evaluable (EE). Median overall survival for V + G was 6.3 months for the ITT population (6.8 months for EE pts) and 6 months for P + G for both ITT and EE pts. While differences in survival times were not statistically significant, exploratory analysis showed encouraging results in specific subgroups treated with V + G ( table ). Importantly, a significant difference was found in stage 3 pts who received V in a salvage setting compared to pts who received P. Conclusions: Pancreatic cancer pts with either low ECOG PS or metastatic cancer showed a survival benefit when treated with V + G, which was significant in pts who continued to receive V as a salvage therapy. Further studies in these targeted patient populations are being considered. [Table: see text] No significant financial relationships to disclose.

The analysis of EGFR expression and EGFR mutations in advanced pancreatic cancer

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e15629-e15629 ◽  
Author(s):  
M. Ueno ◽  
S. Ohkawa ◽  
Y. Sakamoto ◽  
K. Miyakawa ◽  
Y. Miyagi
Keyword(s):  
Lung Cancer ◽  
Pancreatic Cancer ◽  
Cancer Patients ◽  
Direct Sequencing ◽  
Advanced Pancreatic Cancer ◽  
Phase Iii ◽  
Egfr Mutations ◽  
Egfr Expression ◽  
Sequencing Method ◽  
Direct Sequencing Method

e15629 Background: The standard chemotherapy of advanced pancreatic cancer is still gemcitabine and recently gemcitabine + EGFR tyrosine kinase inhibitor (TKI)is noted to be positive on Phase III study. In lung cancer, EGFR mutations (the deletion of exon 19, the point mutation of exon 18, 21) have been reported to be correlated with the effect of EGFR TKI. On the other hand, such EGFR mutations were not reported to be recognized by the direct sequencing method in pancreatic cancer. This time we examined EGFR expressions and EGFR mutations in advanced pancreatic cancer. Methods: We examined EGFR expressions immunohistochemically and EGFR mutations by Loop-Hybrid Mobility Shift Assay (LH-MSA) which is more sensitive than the direct sequencing method in the tissue obtained from percutaneous biopsies in advanced pancreatic cancer patients. In addition we examined the correlation between EGFR expressions and survivals by the log-rank test. Results: The subjects were 31 inoperable pancreatic cancer patients. Patients received chemotherapy (gemcitabine: 10, S-1: 8, gemcitabine+S-1: 12, no treatment: 1).The UICC stages were as follows:stage II; 2, stage III; 6, stage IV; 23. The tissues were obtaind from liver; 12, pancreas; 19. EGFR expressions were positive; 15, negative; 16. EGFR expressions were not correlated with survival (p=0.386). Although LH-MSA were performed successfully in all patients, the same EGFR mutations as lung cancer were not detected. Conclusions: EGFR expressions were not correlated with survivals and the same EGFR mutations as lung cancer were not detected in inoperable advanced pancreatic cancer. No significant financial relationships to disclose.

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.

PANOVA: A phase II study of TTFields (150 kHz) concomitant with standard chemotherapy for front-line therapy of advanced pancreatic adenocarcinoma—Updated efficacy results.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e15790-e15790 ◽  
Author(s):  
Manuel Benavides ◽  
Carmen Guillen ◽  
Fernando Rivera ◽  
Javier Gallego ◽  
Jose A. Lopez-Martin ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cancer Patients ◽  
Metastatic Disease ◽  
Locally Advanced ◽  
Advanced Pancreatic Cancer ◽  
Skin Toxicity ◽  
Distant Metastases ◽  
Phase Iii ◽  
Prior Therapy ◽  
Grade 3

e15790 Background: TTFields are a non-invasive, regional antimitotic treatment modality, which has been approved for the treatment of glioblastoma by the FDA. TTFields predominantly act by disrupting the formation of the mitotic spindle during metaphase. TTFields were effective in multiple preclinical models of pancreatic cancer. PANOVA was the first trial testing TTFields in pancreatic cancer patients. Results from the first arm of the study, testing TTFields in combination with gemcitabine, have demonstrated superiority in efficacy compared to historical controls (Rivera F. et al, J Clin Oncol 34, 2016 (suppl 4S; abstr 269). Methods: Twenty advanced pancreatic cancer patients were enrolled in the second arm of PANOVA and treated with TTFields in combination with gemcitabine concomitant to nab-paclitaxel. All patients had unresectable tumors, an ECOG performance score of 0-1 and no prior therapy. The primary endpoint was the incidence and severity of adverse events. Results: The median age was 68.2 (range – 58-81) and most patients (65%) had an ECOG score of 1. Twelve patients (60%) had distant metastases. Ten patients (50%) had serious AEs during the study period. Eleven patients (55%) had treatment-related skin toxicity, of which 5 had grade 3 toxicity. No TTFields-related serious AEs were reported. The median PFS was 12.7 months (95% CI 5.4, NA): 9.3 months in patients with metastatic disease, and not reached in locally-advanced patients. PFS rate at 6 months was 65%: 50% in metastatic disease and 87.5% in locally advanced patients. Of the evaluable tumors, 40% had partial response and another 47% stable disease. The median OS was not reached, and the 1-year survival rate was 72% (62.5% in metastatic disease and 87.5% in locally advanced disease). Conclusions: TTFields concomitant to gemcitabine and nab-paclitaxel are safe for advanced pancreatic cancer patients, with promising clinical outcome which doubled historical data. A phase III trial is planned, testing the efficacy of TTFields combined with gemcitabine and nab-paclitaxel in locally-advanced pancreatic cancer patients. Clinical trial information: NCT01971281.

Erlotinib Plus Gemcitabine Compared With Gemcitabine Alone in Patients With Advanced Pancreatic Cancer: A Phase III Trial of the National Cancer Institute of Canada Clinical Trials Group

2007 ◽  
Vol 25 (15) ◽  
pp. 1960-1966 ◽  
Author(s):  
Malcolm J. Moore ◽  
David Goldstein ◽  
John Hamm ◽  
Arie Figer ◽  
Joel R. Hecht ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Overall Survival ◽  
Objective Response ◽  
Locally Advanced ◽  
Advanced Pancreatic Cancer ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Pancreatic Tumors ◽  
Double Blind ◽  
Phase Iii Trial

PurposePatients with advanced pancreatic cancer have a poor prognosis and there have been no improvements in survival since the introduction of gemcitabine in 1996. Pancreatic tumors often overexpress human epidermal growth factor receptor type 1 (HER1/EGFR) and this is associated with a worse prognosis. We studied the effects of adding the HER1/EGFR-targeted agent erlotinib to gemcitabine in patients with unresectable, locally advanced, or metastatic pancreatic cancer.Patients and MethodsPatients were randomly assigned 1:1 to receive standard gemcitabine plus erlotinib (100 or 150 mg/d orally) or gemcitabine plus placebo in a double-blind, international phase III trial. The primary end point was overall survival.ResultsA total of 569 patients were randomly assigned. Overall survival based on an intent-to-treat analysis was significantly prolonged on the erlotinib/gemcitabine arm with a hazard ratio (HR) of 0.82 (95% CI, 0.69 to 0.99; P = .038, adjusted for stratification factors; median 6.24 months v 5.91 months). One-year survival was also greater with erlotinib plus gemcitabine (23% v 17%; P = .023). Progression-free survival was significantly longer with erlotinib plus gemcitabine with an estimated HR of 0.77 (95% CI, 0.64 to 0.92; P = .004). Objective response rates were not significantly different between the arms, although more patients on erlotinib had disease stabilization. There was a higher incidence of some adverse events with erlotinib plus gemcitabine, but most were grade 1 or 2.ConclusionTo our knowledge, this randomized phase III trial is the first to demonstrate statistically significantly improved survival in advanced pancreatic cancer by adding any agent to gemcitabine. The recommended dose of erlotinib with gemcitabine for this indication is 100 mg/d.

scholarly journals Gemcitabine Plus Bevacizumab Compared With Gemcitabine Plus Placebo in Patients With Advanced Pancreatic Cancer: Phase III Trial of the Cancer and Leukemia Group B (CALGB 80303)

2010 ◽  
Vol 28 (22) ◽  
pp. 3617-3622 ◽  
Author(s):  
Hedy Lee Kindler ◽  
Donna Niedzwiecki ◽  
Donna Hollis ◽  
Susan Sutherland ◽  
Deborah Schrag ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Overall Survival ◽  
Cancer Patients ◽  
Performance Status ◽  
Eastern Cooperative Oncology Group ◽  
Advanced Pancreatic Cancer ◽  
Phase Iii ◽  
Phase Iii Trial ◽  
Group B ◽  
Leukemia Group

Purpose The combination of gemcitabine plus bevacizumab produced a 21% response rate and a median survival of 8.8 months in a multicenter phase II trial in patients with metastatic pancreatic cancer. These encouraging data led Cancer and Leukemia Group B (CALGB) to conduct a double-blind, placebo-controlled, randomized phase III trial of gemcitabine/bevacizumab versus gemcitabine/placebo in advanced pancreatic cancer patients. Patients and Methods Eligible patients had no prior therapy for advanced disease, Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2, no tumor invasion of adjacent organs, and no increased bleeding risk. The primary end point was overall survival. Patients were stratified by performance status, extent of disease, and prior radiotherapy. Patients received gemcitabine at 1,000 mg/m2 over 30 minutes on days 1, 8, and 15 every 28 days and bevacizumab at 10 mg/kg or placebo on days 1 and 15 every 28 days. Results Between June 2004 and April 2006, 602 patients were enrolled onto the study and 535 were treated. Median overall survival was 5.8 months for gemcitabine/bevacizumab and 5.9 months for gemcitabine/placebo (P = .95). Median progression-free survival was 3.8 and 2.9 months, respectively (P = .07). Overall response rates were 13% and 10%, respectively. Patients with a performance status of 0, 1, and 2 survived a median of 7.9, 4.8, and 2.4 months, respectively. The only statistically significant differences in grades 3 and 4 toxicity occurred for hypertension (10% v 3%; P < .001) and proteinuria (5% v 1%; P = .002); venous thrombosis grade ≥ 3 was equivalent in both arms (14% and 15%, respectively). Conclusion The addition of bevacizumab to gemcitabine does not improve survival in advanced pancreatic cancer patients.

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