A network meta-analysis (NMA) of randomized controlled trials (RCT) of chemotherapy regimens for metastatic pancreatic cancer (mPC).

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 4050-4050 ◽  
Author(s):  
Gillian Gresham ◽  
Sharlene Gill ◽  
George A Wells ◽  
Derek J. Jonker
Keyword(s):  
Pancreatic Cancer ◽  
Survival Benefit ◽  
Meta Analysis ◽  
Locally Advanced ◽  
Advanced Pancreatic Cancer ◽  
Phase Iii ◽  
Significant Heterogeneity ◽  
Treatment Protocols ◽  
Significant Difference ◽  
Safety Outcomes

4050 Background: Recent RCTs suggest a survival benefit for combination therapy in mPC compared to gemcitabine alone. Such combinations include FOLFIRINOX and gemcitabine plus nab-paclitaxel (G+nab-P). Survival and safety outcomes of these regimens were analyzed using gemcitabine as the reference comparator. Methods: Systematic review and NMA included data from reported phase III RCTs meeting quality standards and compared chemotherapy treatment to gemcitabine for mPC between 2000 and 2013. Excluded were trials assessing locally advanced pancreatic cancer. Following inter-trial heterogeneity assessment (patient characteristics, trial methodologies, treatment protocols), Bayesian NMAs were conducted for primary (overall survival [OS]) and secondary (progression free survival [PFS]) outcomes, overall response rate [ORR], and safety. Results: 27 studies were included involving 10 429 patients and 18 different treatments. No significant heterogeneity was observed between trials. When indirectly compared, FOLFIRINOX, PEFG and G+nab-P were top ranked for OS, PFS and ORR (Table). Comparing FOLFIRINOX and G +nab-P, there was no significant difference in odds ratios (OR) for febrile neutropenia, diarrhea or sensory neuropathy. FOLFIRINOX caused more gr3-4 neutropenia (OR 1.85 (95%Cl 1.1-3.4),p<0.05), and G+nab-P trended more gr3-4 fatigue (OR 2.03 95% Cl 0.95-3.8). Conclusions: Survival and safety outcomes were comparable amongst the three regimens identified from this network meta-analysis for mPC. FOLFIRINOX tended towards a greater survival benefit over G+nab-P and PEFG although comparisons did not reach statistical significance.Head-to-head trials between FOLFIRINOX, G+nab-P and PEFG are needed to further compare the survival benefits and safety profiles of these treatments. [Table: see text]

Phase III Randomized Comparison of Gemcitabine Versus Gemcitabine Plus Capecitabine in Patients With Advanced Pancreatic Cancer

2009 ◽  
Vol 27 (33) ◽  
pp. 5513-5518 ◽  
Author(s):  
David Cunningham ◽  
Ian Chau ◽  
Deborah D. Stocken ◽  
Juan W. Valle ◽  
David Smith ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Meta Analysis ◽  
Performance Status ◽  
Objective Response ◽  
Locally Advanced ◽  
Advanced Pancreatic Cancer ◽  
Progression Free Survival ◽  
Primary Outcome Measure ◽  
Phase Iii ◽  
Open Label

PurposeBoth gemcitabine (GEM) and fluoropyrimidines are valuable treatment for advanced pancreatic cancer. This open-label study was designed to compare the overall survival (OS) of patients randomly assigned to GEM alone or GEM plus capecitabine (GEM-CAP).Patients and MethodsPatients with previously untreated histologically or cytologically proven locally advanced or metastatic carcinoma of the pancreas with a performance status ≤ 2 were recruited. Patients were randomly assigned to GEM or GEM-CAP. The primary outcome measure was survival. Meta-analysis of published studies was also conducted.ResultsBetween May 2002 and January 2005, 533 patients were randomly assigned to GEM (n = 266) and GEM-CAP (n = 267) arms. GEM-CAP significantly improved objective response rate (19.1% v 12.4%; P = .034) and progression-free survival (hazard ratio [HR], 0.78; 95% CI, 0.66 to 0.93; P = .004) and was associated with a trend toward improved OS (HR, 0.86; 95% CI, 0.72 to 1.02; P = .08) compared with GEM alone. This trend for OS benefit for GEM-CAP was consistent across different prognostic subgroups according to baseline stratification factors (stage and performance status) and remained after adjusting for these stratification factors (P = .077). Moreover, the meta-analysis of two additional studies involving 935 patients showed a significant survival benefit in favor of GEM-CAP (HR, 0.86; 95% CI, 0.75 to 0.98; P = .02) with no intertrial heterogeneity.ConclusionOn the basis of our trial and the meta-analysis, GEM-CAP should be considered as one of the standard first-line options in locally advanced and metastatic pancreatic cancer.

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.

Survival Benefit Associated With Resection of Locally Advanced Pancreatic Cancer Following Upfront FOLFIRINOX versus FOLFIRINOX Only

2021 ◽  
Vol Publish Ahead of Print ◽  
Author(s):  
L. J. H. Brada ◽  
L. A. Daamen ◽  
L. G. Magermans ◽  
M. S. Walma ◽  
D. Latifi ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Survival Benefit ◽  
Locally Advanced ◽  
Advanced Pancreatic Cancer ◽  
Locally Advanced Pancreatic Cancer

Gemcitabine in the chemoradiotherapy for locally advanced pancreatic cancer: A meta-analysis

2011 ◽  
Vol 99 (2) ◽  
pp. 108-113 ◽  
Author(s):  
Chang-Peng Zhu ◽  
Jian Shi ◽  
Yue-Xiang Chen ◽  
Wei-Fen Xie ◽  
Yong Lin
Keyword(s):  
Pancreatic Cancer ◽  
Meta Analysis ◽  
Locally Advanced ◽  
Advanced Pancreatic Cancer ◽  
Locally Advanced Pancreatic Cancer

Randomized Controlled Trial Of Dalteparin For Primary Thromboprophylaxis For Venous Thromboembolism (VTE) In Patients With Advanced Pancreatic Cancer (APC): Risk Factors Predictive Of VTE

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 580-580 ◽  
Author(s):  
Saroj Vadhan-Raj ◽  
Xiao Zhou ◽  
Gauri R. Varadhachary ◽  
Javle Milind ◽  
David Fogelman ◽  
...  
Keyword(s):  
Risk Factors ◽  
Pancreatic Cancer ◽  
Cancer Patients ◽  
Locally Advanced ◽  
Advanced Pancreatic Cancer ◽  
Baseline Risk ◽  
Activation Markers ◽  
Compression Ultrasound ◽  
Significant Difference ◽  
D Dimer

Abstract Background Risk of VTE is high in cancer patients, especially, in patients with APC. Treatment with chemotherapy further increases the risk. Purpose of the study was to evaluate the safety and efficacy of primary thromboprophylaxis with dalteparin in reducing the incidence of VTE in APC patients planned to start chemotherapy; and to determine the baseline risk factors/biomarkers predictive of VTE. Methods Patients with metastatic or locally advanced pancreatic cancer planned to start chemotherapy were randomized 1:1 to dalteparin vs control arms, stratified for the presence of metastasis and central venous catheter (CVC). The treatment arm received dalteparin 5000 U SQ daily for 16 weeks during chemotherapy and the control arm received chemotherapy alone. Bilateral compression ultrasound of the lower extremities was performed at baseline, and during study (weeks-8 and-16). In addition, blood was collected to identify biomarkers such as, plasma D-dimer levels, platelet activation markers (P-selectin), thrombin-antithrombin complex (TAT), prothrombin fragments 1 and 2 (F1+2), and cytokine levels. Univariate and multivariate logistic regression analysis of clinical and laboratory parameters were done to identify risk factors associated with the development of VTE. Results Of 87 patients enrolled, 75 were randomized to dalteparin (38 patients) or control (37 patients) arms; 8 did not meet the eligibility criteria (including 6 found positive for incidental VTE on screening ultrasound), and 4 withdrew consents before randomization. There were 41 males and 34 females; with median age 52 (range, 36-77 years). Over half of the patients (55% dalteparin arm and 54% control arm) completed 16 weeks on study. All 75 patients were evaluable for response in an intent-to-treat analysis. During the study, the incidence of VTE was 22% [8/37 patients; 2 pulmonary emboli (PE) and 6 deep vein thrombosis (DVT)] on the control arm as compared to 5% (2/38 patients; both DVT) on the dalteparin arm (p = 0.02). In the multivariate analysis, baseline plasma levels of D-dimer, ECOG performance status, presence of CVC, and prophylaxis with dalteparin were independent factors predictive of risk for VTE, as shown below. There was no statistically significant difference in overall survival between the two arms; however, there were higher proportion of patients with elevated baseline D-dimer levels in the dalteparin arm than the control arm (≥ 5000 ng/mL 16% vs 3%). Elevated baseline D-dimer level (≥ 5000 ng/mL) was also predictive of the presence of silent or asymptomatic VTE at screening for study entry (p=0.001), suggesting its potential value in identifying patients with silent VTE. Treatment with dalteparin was well tolerated; the main adverse events included minimal bruising (5/34, 15%), or pain (2/34, 6%) at the injection sites. There were no clinically significant bleeding episodes in the dalteparin arm. Conclusions The results of this study showed that the incidence of VTE is very high in patients with APC. Primary thromboprophylaxis with dalteparin was well tolerated and was associated with 75% reduction in the incidence of VTE in ambulatory patients with locally advanced or metastatic cancer while receiving chemotherapy. Baseline risk factors such as elevated D-dimer levels may help identify high risk patients for primary thromboprophylaxis as well as patients with the presence of asymptomatic VTE. Disclosures: Vadhan-Raj: Eisai: Research Funding. Off Label Use: Fragmin (Dalteparin): Prophylaxis of VTE in ambulatory cancer patients while receiving chemotherapy.

Multicenter randomized controlled phase III clinical trial using TNFerade (TNF) with chemoradiation (CRT) in patients with locally advanced pancreatic cancer (LAPC): Interim analysis (IA) of overall survival (OS)

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 4605-4605
Author(s):  
K. J. Chang ◽  
W. Fisher ◽  
D. Kenady ◽  
J. Klapman ◽  
M. Posner ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Locally Advanced ◽  
Advanced Pancreatic Cancer ◽  
Human Tumor ◽  
Adenovirus Vector ◽  
Nonparametric Methods ◽  
Phase Iii ◽  
Open Label ◽  
Prognostic Information ◽  
Cancer Trial

4605 Intro: Local control of LAPC with CRT has historically demonstrated survival benefit vs. RT alone. TNF is a nonreplicating adenovirus vector delivering human tumor necrosis factor (TNF-α). Results from a phase II study with TNF in LAPC indicated a possible survival advantage. To confirm these findings, a randomized, open-label, controlled Pancreatic Cancer Trial with TNF (PACT) study was developed. Methods: The TNF arm received a 5 wk treatment of qw intratumoral inj of 4x1011 PU TNF, cont. iv 5-FU and 50.4Gy radiation. The standard of care (SOC) arm received CRT alone. Both groups received adjuvant gemcitabine(G) with the option of erlotinib(E). An IA of OS (primary efficacy endpoint) was planned after the first third (92) of the expected 276 total death events (from a total patient n=330). Nonparametric logrank of OS was planned; in addition, a lognormal model was used to account for an evident separation of the survival curves after the median. Results: 185 pts were available for OS analysis (117-TNF+SOC and 68-SOC). Survival in the TNF+SOC group demonstrated a HR of 0.753 (CI [0.494 - 1.15]) relative to SOC. Best fit parametric lognormal analysis indicated a median survival of 11.1 mo with TNF+SOC and 8.7 mo with SOC; nonparametric methods indicated a MS of 9.9 mo for both arms, with a pronounced “late effect” (75th percentile 19.4 mo with TNF+SOC and 11.8 mo with SOC). Prognostic information (G and E use, stage, etc) indicated equivalent distribution between groups. Conclusions: HR results of the OS IA indicate an encouraging trend in favor of the TNF treated group. Parametric medians may better reflect the true HR than nonparametric methods since the latter do not reflect the shape of the OS distribution. A second IA is planned after 2/3 total events. [Table: see text]

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