scholarly journals Therapeutic Antibodies for the Treatment of Pancreatic Cancer

2010 ◽  
Vol 10 ◽  
pp. 1107-1120 ◽  
Author(s):  
Patrick Chames ◽  
Brigitte Kerfelec ◽  
Daniel Baty
Keyword(s):  
Pancreatic Cancer ◽  
Target Therapy ◽  
Symptom Control ◽  
Clinical Results ◽  
Phase Iii ◽  
General View ◽  
Cancer Therapies ◽  
Current Standard ◽  
Phase Iii Trials ◽  
Novel Therapeutic Strategies

Pancreatic cancer is a devastating disease with the worst mortality rate and an overall 5-year survival rate lower than 5%. In the U.S., this disease is the fourth leading cause of death and represents 6% of all cancer-related deaths. Gemcitabine, the current standard first-line treatment, offers marginal benefits to patients in terms of symptom control and prolongation of life. Since 1996, about 20 randomized phase III trials have been performed to improve the efficacy of gemcitabine, with little success regarding a significant improvement in survival outcomes. The need for novel therapeutic strategies, such as target therapy, is obvious. Monoclonal antibodies have finally come of age as therapeutics and several molecules are now approved for cancer therapies. This review aims to give a general view on the clinical results obtained so far by antibodies for the treatment of pancreatic cancer and describes the most promising avenues toward a significant improvement in the treatment of this frustrating disease.

Phase III Trials in Pancreatic Cancer in the United States

2010 ◽  
Vol 9 (1) ◽  
pp. 59-60
Author(s):  
Edward Chu ◽  
David Cunningham ◽  
David Watkins
Keyword(s):  
United States ◽  
Pancreatic Cancer ◽  
The United States ◽  
Phase Iii ◽  
Phase Iii Trials

Current status of targeted agents in advanced pancreatic cancer (APC): A pooled analysis of 2,361 patients (pts) enrolled in six phase III trials

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 4126-4126 ◽  
Author(s):  
E. Bria ◽  
P. Carlini ◽  
A. Gelibter ◽  
E. Ruggeri ◽  
A. Ceribelli ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cancer Biology ◽  
Primary Outcome ◽  
Pooled Analysis ◽  
Negative Trend ◽  
Phase Iii ◽  
Current Status ◽  
Secondary Outcome ◽  
Significant Negative Trend ◽  
Phase Iii Trials

4126 Background: Molecular targeting of pathways that are deregulated in pancreatic cancer is a promising approach aimed at improving the dismal prognosis of APC pts. However, the clinical impact of novel “biological” drugs (ND) remains to be defined. Methods: All prospective phase III trials comparing single-agent Gemcitabine (G) with either a ND or a combination of ND and G (ND+G) were considered eligible. A pooled analysis was performed and event-based relative risk ratios (RR) with 95% CI were derived through both a fixed- and a random-effect model approach, exploring OS as the primary outcome and PFS and ORR as secondary outcomes. Heterogeneity between different trials was also taken into account. Results: Six trials involving 2361 pts were identified; ND tested included: FTI inhibitors (1 trial), MMP inhibitors (3 trials), EGFR inhibitors (1 trial), and anti-gastrin vaccine (1 trial). The analysis was conducted considering three different subgroups: 1) overall population (2361 patients, 6 trials), 2) ND+G vs G (1879 patients, 4 trials), and 3) ND vs G (482 patients, 2 trials). As shown in the table, no significant differences in either the primary outcome (OS) or the secondary outcome of PFS were observed in the overall population as well as in ND+G vs G trials, while a significant negative trend for ND was found in ND vs G trials with regard to both endpoints. Conversely the evaluation of the secondary endpoint of ORR significantly favored G in the overall population as well as in ND vs G trials, while a not significant negative trend for ND was observed in ND+G vs G trials. Conclusions: G remains the treatment of choice in APC pts. The ND tested, either alone or combined with G, do not seem to add any benefit over G. A better understanding of pancreatic cancer biology and further clinical evaluation of new agents and is needed to improve prognosis in APC pts. [Table: see text] No significant financial relationships to disclose.

Early tumor shrinkage as a predictor of favorable outcomes in patients (pts) with advanced pancreatic cancer treated with FOLFIRINOX.

2016 ◽  
Vol 34 (4_suppl) ◽  
pp. 237-237
Author(s):  
Yasuhiro Kaga ◽  
Yu Sunakawa ◽  
Yutaro Kubota ◽  
Teppei Tagawa ◽  
Taikan Yamamoto ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Statistical Significance ◽  
Advanced Pancreatic Cancer ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Severe Toxicity ◽  
Tumor Shrinkage ◽  
Current Standard ◽  
Early Tumor Shrinkage ◽  
Early Tumor

237 Background: Results from the phase III PRODIGE 4/ACCORD 11 trial provided one of current standard regimens for advanced pancreatic cancer (PC), consisting of oxaliplatin, irinotecan, fluorouracil, and leucovorin (FOLFIRINOX), which has superior response rate (RR) and survival benefit even with severe toxicity (Thierry C, et al. N Engl J Med 2011;364:1817-1825). There are several reports on the correlation between early tumor shrinkage (ETS) or depth of response (DpR) and survival in chemotherapies for colorectal cancer; however, few studies have investigated it in PC. We therefore analyzed retrospectively whether the ETS will predict outcomes in pts with PC treated with FOLFIRINOX therapy. Methods: Advanced PC pts with ECOG PS of 0 or 1, who received FOLFIRINOX as 1st- or 2nd-line treatment between November 2012 and July 2015 in 3 institutes of Showa University were included in this analysis. ETS was defined as a reduction ≥ 20% of target lesions’ diameters measured at 8 weeks from treatment start. We evaluated the association of ETS with progression-free survival (PFS) and overall survival (OS) but also addressed the correlation between outcomes and DpR, which was percentage of maximal tumor shrinkage observed at the nadir diameter compared with baseline. Results: Fifty-nine PC pts with median age of 63 (range 34-76) years and males of 68% were enrolled: 80% of pts had metastatic disease. In the population, RR, median PFS, and OS were 28%, 5.4 months, and 10.7 months, respectively. Among 46 (78%) evaluable pts for the ETS, 12 (26%) pts experienced ETS. The PFS was significantly longer in pts with ETS compared to pts with no ETS (9.0 vs. 4.2 months, HR 0.43, 95%CI 0.17-0.96, log-rank P= 0.045). Moreover, pts with ETS had a better OS although no statistical significance (HR 0.53, log-rank P= 0.25). Median DpR was 11.1% (from -75.7 to 100), and the correlation of DpR with clinical outcome was observed (P= 0.024 for PFS, P= 0.22 for OS). Conclusions: This retrospective analysis suggests that the early response to FOLFIRINOX treatment may predict better outcomes in pts with advanced PC. The ETS may serve as a novel predictor of prolonged survival time in PC pts treated with FOLFIRINOX.

scholarly journals Pattern of care and effectiveness of treatment for glioblastoma patients in the real world: Results from a prospective population-based registry. Could survival differ in a high-volume center?

2014 ◽  
Vol 1 (4) ◽  
pp. 166-171 ◽  
Author(s):  
Alba A. Brandes ◽  
Enrico Franceschi ◽  
Mario Ermani ◽  
Alicia Tosoni ◽  
Fiorenzo Albani ◽  
...  
Keyword(s):  
Methylation Status ◽  
High Volume ◽  
Population Based ◽  
Phase Iii ◽  
Treatment Center ◽  
Current Standard ◽  
Pattern Of Care ◽  
Phase Iii Trials ◽  
Emilia Romagna Region ◽  
High Volume Center

Abstract Background As yet, no population-based prospective studies have been conducted to investigate the incidence and clinical outcome of glioblastoma (GBM) or the diffusion and impact of the current standard therapeutic approach in newly diagnosed patients younger than aged 70 years. Methods Data on all new cases of primary brain tumors observed from January 1, 2009, to December 31, 2010, in adults residing within the Emilia-Romagna region were recorded in a prospective registry in the Project of Emilia Romagna on Neuro-Oncology (PERNO). Based on the data from this registry, a prospective evaluation was made of the treatment efficacy and outcome in GBM patients. Results Two hundred sixty-seven GBM patients (median age, 64 y; range, 29–84 y) were enrolled. The median overall survival (OS) was 10.7 months (95% CI, 9.2–12.4). The 139 patients ≤aged 70 years who were given standard temozolomide treatment concomitant with and adjuvant to radiotherapy had a median OS of 16.4 months (95% CI, 14.0–18.5). With multivariate analysis, OS correlated significantly with KPS (HR = 0.458; 95% CI, 0.248–0.847; P = .0127), MGMT methylation status (HR = 0.612; 95% CI, 0.388–0.966; P = .0350), and treatment received in a high versus low-volume center (HR = 0.56; 95% CI, 0.328–0.986; P = .0446). Conclusions The median OS following standard temozolomide treatment concurrent with and adjuvant to radiotherapy given to (72.8% of) patients aged ≤70 years is consistent with findings reported from randomized phase III trials. The volume and expertise of the treatment center should be further investigated as a prognostic factor.

scholarly journals Preclinical Rationale for the Phase III Trials in Metastatic Pancreatic Cancer

Pancreas ◽  
2017 ◽  
Vol 46 (2) ◽  
pp. 143-150 ◽  
Author(s):  
Ramya Thota ◽  
Anirban Maitra ◽  
Jordan D. Berlin
Keyword(s):  
Pancreatic Cancer ◽  
Phase Iii ◽  
Metastatic Pancreatic Cancer ◽  
Phase Iii Trials

Prolongation of the average survival time in pancreatic cancer (a new measure of effect): Pooled analysis of adjuvant chemotherapy trials.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e16723-e16723
Author(s):  
Eduardo Ceballos Barbancho ◽  
Galo Sánchez Robles
Keyword(s):  
Pancreatic Cancer ◽  
Adjuvant Treatment ◽  
Area Under The Curve ◽  
Pooled Analysis ◽  
National Institutes Of Health ◽  
Phase Iii ◽  
Processing Application ◽  
Average Survival ◽  
Phase Iii Trials

e16723 Background: With the aim of improving the prognosis of the disease, in recent years attempts have been made to optimize the adjuvant treatment of pancreatic cancer, having demonstrated the usefulness of chemotherapy in several phase III trials: CONKO-001, JASPAC-01, ESPAC -4 and PRODIGE. Methods: The method to measure the Area Under the Curve (AUC) is universally known. When the curve is not homogeneous, the AUC is calculated using the traditional method of breaking down the total area into a sum of many polygons. We have calculated the AUC through pixel counting using Image J, which is an image processing application, programmed in Java, developed in the National Institutes of Health and free to access. To estimate the consistency between the pixels and the sum of polygons, we have performed several curves with linear edges to measure the AUC through the sums of the polygons, and then by counting pixels with the Image J application. We have verified that the results are similar, so the pixel count can be used to replace the sum of polygons, especially when the curves are not homogeneous. Entering the areas obtained with Image J in the worksheet, made for this purpose, and available for free at evalmed.es, the measures of the effect are automatically obtained: prolongation of the average surival time (PtS), prolongation of the average event free time (PtSLEv) and time lived without an event (PtvSEV). Results: The median follow-up in all studies was 60 months, with the exception of CONKO-001, for which we have data at an average follow-up time of 136 months, however for our comparative purpose we cite the results in the first 60 months. -CONKO-001: PtS was 5.1 months (24.2 observation vs 29.3 gemcitabine). PtSLEv was 9.6 months (13 observation vs 22.6 gemcitabine). PtvSEv was 22.57 months. -JASPAC-01: PtS was 9.04 months (32.4 gemcitabine vs 41.5 gemcitabine + S1). PtSLEv was 9.75 months (21.6 gemcitabine vs 31.4 gemcitabine + S1). PtvSEv was 31.38 months. -ESPAC-4: PtS was 3.2 months (34 gemcitabine vs 37.2 gemcitabine + capecitabine). PtSLEv was 2.7 months (25.6 gemcitabine + 28.3 gemcitabine + capecitabine). PtvSEv was 24.92 months. -PRODIGE: PtS was 6 months (37 gemcitabine vs 43 FOLFIRINOX). PtSLEv was 8.9 months (22.4 gemcitabine vs 31.2 FOLFIRINOX). PtvSEv was 31.23 months. Conclusions: In the adjuvant treatment with chemotherapy in pancreatic cancer, the transit from observation to gemcitabine, and from here to the most intensive schedules, has meant or contributed an important advance for patients in terms of PtS, PtSLEv and PtvSEv.

scholarly journals Current Prospects for the Fluoroquinolones as First-Line Tuberculosis Therapy

2011 ◽  
Vol 55 (12) ◽  
pp. 5421-5429 ◽  
Author(s):  
Howard Takiff ◽  
Elba Guerrero
Keyword(s):  
Multidrug Resistant ◽  
Phase Iii ◽  
Phase Ii Trials ◽  
First Line ◽  
Current Standard ◽  
Standard Drug ◽  
First Line Therapy ◽  
Development Of Resistance ◽  
Mdr Tb ◽  
Phase Iii Trials

ABSTRACTWhile fluoroquinolones (FQs) have been successful in helping cure multidrug-resistant tuberculosis (MDR TB), studies in mice have suggested that if used as first-line agents they might reduce the duration of therapy required to cure drug-sensitive TB. The results of phase II trials with FQs as first-line agents have been mixed, but in at least three studies where moxifloxacin substituted for ethambutol, there was an increase in the early percentage of sputa that converted to negative for bacilli. Phase III trials are in progress to test the effectiveness of 4-month FQ-containing regimens, but there is concern that the widespread use of FQs for other infections could engender a high prevalence of FQ-resistant TB. However, several studies suggest that despite wide FQ use, the prevalence of FQ-resistant TB is low, and the majority of the resistance is low-level. The principal risk for resistance may be when FQs are used to treat nonspecific respiratory symptoms that are in fact TB, so curtailing this use of FQs could reduce the development of resistance and also the delays in TB diagnosis and treatment that have been documented when an FQ is given in this setting. While the future of FQs as first-line therapy will likely depend upon the results of the ongoing phase III trials, if they are to be effectively employed in high-TB-burden regions their use for community-acquired pneumonias should be restricted, the prevalence of FQ-resistant TB should be monitored, and the cost of the treatment should be comparable to that of current standard drug regimens.

scholarly journals Gemcitabine mono-therapy versus gemcitabine plus targeted therapy in advanced pancreatic cancer: a meta-analysis of randomized phase III trials

2017 ◽  
Vol 56 (3) ◽  
pp. 377-383 ◽  
Author(s):  
Alessandro Ottaiano ◽  
Monica Capozzi ◽  
Chiara De Divitiis ◽  
Alfonso De Stefano ◽  
Gerardo Botti ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Targeted Therapy ◽  
Meta Analysis ◽  
Advanced Pancreatic Cancer ◽  
Phase Iii ◽  
Phase Iii Trials
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