Is farnesyltransferase inhibitor effective as adjuvant or neoadjuvant therapy in orthotopic implantation of hamster pancreatic cancer

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 14153-14153
Author(s):  
E. M. Lima ◽  
C. Y. Morioka ◽  
F. P. Costa ◽  
S. Saito ◽  
C. C. Huang ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Adjuvant Therapy ◽  
Neoadjuvant Therapy ◽  
Surgical Resection ◽  
Positive Control ◽  
Histopathological Analysis ◽  
Farnesyltransferase Inhibitor ◽  
Partial Pancreatectomy ◽  
P21 Ras ◽  
Subsequent Activation

14153 Background: p21-Ras participates in signalling events from membrane tyrosine kinase receptors and a variety of intracellular biochemical pathways to downstream therapeutic strategy.Farnesyl transferase inhibitors (FTI) block the main post-translational plasma membrane and subsequent activation of downstream effector.A curative resection model in Syrian golden hamsters has been developed previously. Aim: To evaluate the effectiveness of FTI as adjuvant or neoadjuvant therapy in hamster experimental pancreatic cancer model. Materials and Methods: HaPT-1,a cell line derived from nitrosamine induced pancreatic cancer was used in these experiments.MTT and MTT agarose were performed.Subcutaneous implanted tumor was resected in exponential phase and tissue was implanted into the pancreas.At Day 7 or Day 14, partial pancreatectomy and splenectomy were performed.Hamsters were divided in 7 groups:1.Positive control (PC,n=5),2.Only FTI (FT,n=5),3.Neodjuvant therapy after surgical resection at Day 7 (NT-R7,n=10),4.Adjuvant therapy after resection at Day 7 (AT-S7,n=10),5.Neoadjuvant therapy after resection at Day 7 (NT-S14,n=10),6.Adjuvant therapy after resection at Day 14 (AT-S14,n=10), and 7.Only surgery at Day 14 (SR,n=5).FTI was administered for one week. In FT and NT groups, drug was administered 3 days after orthotopic implantation.Body weight and side effects were recorded.Fourteen days after the surgical resection, sacrifice was done.Four animals of each group were left to study the survival.After 180 days, living hamsters were sacrificed. Resected and necropsied specimens were sent to histopathological analysis. Results: Successful rate of implantation was 100%.PC,FT,NT-S7,AT-S7,NT-S14,AT-S14,and SR survived in average 82,103,119,134,123,132,and 139 days.Two hamsters of AT-S7 (20%),two of AT-S14 (20%),and two of SR (40%) were alive until 180 days.Intra operatory bleeding was higher in NT groups.Loss of body weight was present in all FTI treated groups. Conclusions: Farnesyltransferase inhibitor showed not to be effective in the curative treatment of orthotopically implanted tumors. It may be used to increase the survival time as adjuvant therapy. No significant financial relationships to disclose.

Effectiveness of Adjuvant Therapy in Patients with Pancreatic Cancer Who Underwent Neoadjuvant Therapy

2021 ◽  
Author(s):  
Hiroshi Kurahara ◽  
Yuko Mataki ◽  
Tetsuya Idichi ◽  
Satoshi Iino ◽  
Yota Kawasaki ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Adjuvant Therapy ◽  
Neoadjuvant Therapy

Adjuvant and Neoadjuvant Therapy for Pancreatic Adenocarcinoma

2017 ◽  
Author(s):  
Gregory C Wilson ◽  
Brent T Xia ◽  
Syed A Ahmed
Keyword(s):  
Pancreatic Cancer ◽  
Adjuvant Therapy ◽  
Neoadjuvant Therapy ◽  
Pancreatic Adenocarcinoma ◽  
Locally Advanced ◽  
Neoadjuvant Treatment ◽  
Advanced Pancreatic Cancer ◽  
Treatment Strategies ◽  
Ductal Adenocarcinoma ◽  
Borderline Resectable

Despite decades of advancement and research into the multimodal care of pancreatic cancer, mortality after the diagnosis of pancreatic ductal adenocarcinoma remains grim. The role of adjuvant therapy following surgical resection has been well established in the literature. However, adjuvant therapy is imperfect, and outside of a clinical trial, there are high rates of omission or delayed initiation of therapy. Neoadjuvant treatment strategies continue to be explored in the management of resectable, borderline-resectable, and locally advanced unresectable pancreatic adenocarcinoma. With improved resection rates and the possibility for tumor downstaging, neoadjuvant therapy has become standard for patients with borderline-resectable and locally advanced unresectable tumors. Additional benefits of neoadjuvant therapy in the treatment of resectable tumors include improved completion rates of systemic therapy and R0 resection rates. Future clinical trials, including the use of novel treatment agents and combination treatment strategies in both neoadjuvant and adjuvant regimens, will add value to the treatment of pancreatic adenocarcinoma. Key words: adjuvant therapy, borderline-resectable pancreatic cancer, locally advanced pancreatic cancer, neoadjuvant therapy, pancreatic adenocarcinoma, resectable disease 

scholarly journals Neoadjuvant therapy versus upfront surgery in resectable pancreatic cancer according to intention-to-treat and per-protocol analysis: A systematic review and meta-analysis

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Yoon Suk Lee ◽  
Jong-Chan Lee ◽  
Se Yeol Yang ◽  
Jaihwan Kim ◽  
Jin-Hyeok Hwang
Keyword(s):  
Pancreatic Cancer ◽  
Adjuvant Therapy ◽  
Neoadjuvant Therapy ◽  
Protocol Analysis ◽  
Meta Analysis ◽  
Statistical Significance ◽  
Supporting Evidence ◽  
Resectable Pancreatic Cancer ◽  
Survival Gain ◽  
Intention To Treat

Abstract The effectiveness of neoadjuvant therapy (NAT) remains unclear in resectable pancreatic cancer (PC) as compared with upfront surgery (US). The aim of this study was to investigate the survival gain of NAT over US in resectable PC. PubMed and EMBASE were searched for studies comparing survival outcomes between NAT and US for resectable PC until June 2018. Overall survival (OS) was analyzed according to treatment strategy (NAT versus US) and analytic methods (intention-to-treat analysis (ITT) and per-protocol analysis (PP)). In 14 studies, 2,699 and 6,992 patients were treated with NAT and US, respectively. Although PP analysis showed the survival gain of NAT (HR 0.72, 95% CI 0.68–0.76), ITT analysis did not show the statistical significance (HR 0.96, 95% CI 0.82–1.12). However, NAT completed with subsequent surgery showed better survival over US completed with adjuvant therapy (HR 0.82, 95% CI 0.71–0.93). In conclusion, the supporting evidence for NAT in resectable PC was insufficient because the benefit was not demonstrated in ITT analysis. However, among the patients who completed both surgery and chemotherapy, NAT showed survival benefit over adjuvant therapy. Therefore, NAT could have a role of triaging the patients for surgery even in resectable PC.

scholarly journals Survival in Locally Advanced Pancreatic Cancer After Neoadjuvant Therapy and Surgical Resection

2019 ◽  
Vol 270 (2) ◽  
pp. 340-347 ◽  
Author(s):  
Georgios Gemenetzis ◽  
Vincent P. Groot ◽  
Alex B. Blair ◽  
Daniel A. Laheru ◽  
Lei Zheng ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Neoadjuvant Therapy ◽  
Surgical Resection ◽  
Locally Advanced ◽  
Advanced Pancreatic Cancer ◽  
Locally Advanced Pancreatic Cancer

Effect of body mass index (BMI) on outcomes after surgical resection and adjuvant therapy for pancreatic cancer patients.

2011 ◽  
Vol 29 (4_suppl) ◽  
pp. 185-185
Author(s):  
M. R. Khawaja ◽  
N. Zyromski ◽  
M. Yu ◽  
H. R. Cardenes ◽  
C. M. Schmidt ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Adjuvant Therapy ◽  
Cancer Patients ◽  
Surgical Resection ◽  
Survival Rates ◽  
Disease Free Survival ◽  
University Hospital ◽  
Rank Test ◽  
Kaplan Meier ◽  
Significant Difference

185 Background: Obesity is one of the factors commonly associated with pancreatic cancer risk, but its prognostic role for survival is debatable. This study aimed to determine the role of BMI in treatment outcomes of pancreatic cancer patients (pts) undergoing surgical resection followed by adjuvant therapy. Methods: We retrospectively reviewed 165 consecutive pts with pancreatic cancer undergoing pancreaticoduodenectomy at Indiana University Hospital between 2004 and 2008. Fifty-three pts who received adjuvant treatment [gemcitabine alone (C-group): n=19; gemcitabine + radiotherapy (CRT-group): n=34] at our institution were included in the analysis. The Kaplan-Meier method was used to estimate the disease-free survival (DFS) and overall survival (OS); log-rank test was used to compare these outcomes between BMI groups (normal 18.5-24.99 kg/m2 vs. overweight/obese ≥ 25 kg/m2). Results: The sample comprised 53 pts (28 males; median age 62 yrs) with a median follow-up of 18.6 months (mos). Thirty pts (56.6%) had their BMIs recorded before the date of surgery, and 23 pts prior to starting adjuvant therapy. Two (3.8%) pts were underweight, 21 (39.6%) had a normal BMI and 30 (56.6%) were overweight/obese. There was no statistically significant difference in the median DFS of obese/overweight and normal BMI pts irrespective of adjuvant therapy (C or CRT) (14.47 vs. 11.80 mos; p= 0.111). Obese/overweight pts had a better median OS [25.2 vs. 14.6 mos; p=0.045 overall (25.7 vs. 16.9 mos; p= 0.143 for the CRT-group and 17.3 vs. 13.4 mos; p= 0.050 for the C-group)], 1-year survival [96.7% vs. 61.9%; p < 0.0001 overall (95% vs. 64.3%; p= 0.001 for the CRT-group, and 90% vs. 57.1%; p=0.016 with C)], and 2-year survival [52.6% vs. 25.4%; p < 0.0001 overall (60.0% vs. 30.0%; p=0.0001 for the CRT-group and 37.5% vs. 14.3%; p=0.0002 for the C-group)] than patients with normal BMI. Conclusions: In our experience, overweight/obese pts undergoing surgery followed by adjuvant therapy have better survival rates than patients with normal BMI. [Table: see text] No significant financial relationships to disclose.

Survival impact of neoadjuvant therapy in resected pancreatic cancer.

2016 ◽  
Vol 34 (4_suppl) ◽  
pp. 367-367
Author(s):  
Katelin Anne Mirkin ◽  
Christopher S Hollenbeak ◽  
Joyce Wong
Keyword(s):  
Pancreatic Cancer ◽  
Adjuvant Therapy ◽  
Neoadjuvant Therapy ◽  
Median Survival ◽  
Clinical Stage ◽  
Stage I ◽  
Median Income ◽  
Stage Disease ◽  
Surgery First ◽  
The Impact

367 Background: Pancreatic cancer carries a dismal prognosis, with surgical resection and adjuvant therapy offering the only hope for long-term survival. In recent years, neoadjuvant therapy (NAT) has been employed to optimize outcomes. This study evaluates the impact of NAT on survival in patients with resected stage I-III pancreatic cancer. Methods: The National Cancer Data Base (2003-2011) was analyzed for patients with clinical stage I-III resected carcinoma of the pancreas who underwent NAT or surgery first +/- adjuvant therapy. Univariate statistics were used to compare characteristics between groups. Analysis of variance and Kaplan Meier analyses were used to compare median survival for each clinical stage of disease. Multivariate analyses were performed using a Cox proportional hazards model. Results: 16,122 patients who underwent NAT and 16,869 patients who underwent surgery-first were included. Patients who underwent NAT tended to be younger, covered by private insurance, have a higher median income, greater comorbidities, higher clinical stage disease, and undergo a whipple. Additionally, NAT patients had a greater number of positive regional lymph nodes (9 vs. 6, respectively), although a similar number of nodes retrieved, and higher pathological stage disease. In patients with clinical stage I disease, adjuvant therapy was associated with improved median survival than NAT and surgery-alone (24.8, 18.5, 17.9 months, p < 0.0001, respectively). However, in stage II, adjuvant and NAT offered similar median survival, which was improved over surgery-alone (20.5, 20.1, and 12.4 months, p < 0.0001, respectively). In stage III, NAT had improved median survival than the other groups (19.6, 14.2, 8.6 months, p < 0.0001, respectively). In the multivariate survival analysis, patients who received NAT had a 22% lower hazard of mortality up to 5 years as compared to adjuvant therapy (p < 0.0001). Conclusions: Neoadjuvant therapy in advanced stage pancreatic cancer confers a survival benefit and may allow more patients to undergo surgery; NAT appears to offer similar survival as adjuvant therapy in early stage pancreatic cancer.

Patterns of adjuvant therapy use and survival outcomes in patients with rectal cancer not receiving neoadjuvant therapy in an Australian cohort.

2019 ◽  
Vol 37 (4_suppl) ◽  
pp. 675-675
Author(s):  
Kate Jessica Wilkinson ◽  
Sharlyn Kang ◽  
Stephanie Hui-Su Lim ◽  
Cheok Soon Lee ◽  
Ray Asghari ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Adjuvant Chemotherapy ◽  
Adjuvant Therapy ◽  
Neoadjuvant Therapy ◽  
Surgical Resection ◽  
Real World ◽  
Survival Benefit ◽  
Cancer Specific Survival ◽  
Group A ◽  
Group B

675 Background: Consensus international guidelines recommend the use of neoadjuvant chemo-radiotherapy in patients with stage II-III rectal cancer. Despite this, due to factors including inaccurate/under-staging, patient co-morbidities and acute presentations, a proportion will undergo up-front surgical resection. The survival benefit of adjuvant therapy is unclear in this real world, non-trial population. Methods: A retrospective analysis of patients presenting with stage II-III rectal adenocarcinoma in South Western Sydney and Illawarra Shoalhaven Health Districts, Australia, between 2006 to 2015 was performed. Data was extracted from electronic health records, with institutional ethics approval. Treatment modalities, clinicopathological, recurrence and survival data were analyzed. The primary endpoint was overall survival (OS) by treatment modality. Results: 549 patients were identified, of which 295 (54%) underwent up-front surgical resection without neoadjuvant therapy. Of this cohort, 137 (46%) had no adjuvant therapy (Group A), 103 (35%) had adjuvant chemotherapy alone (Group B), and 55 (19%) had adjuvant radiotherapy +/- chemotherapy (Group C). Receipt of any adjuvant treatment was significantly associated with improved OS (5 year OS 56 vs. 79%, HR 0.44, 95% CI 0.3 – 0.6, p < 0.0001) and recurrence free survival (5 yr RFS 25% vs. 47%, HR 0.66, 95% CI 0.5 – 0.9, p=0.01), but not cancer specific survival (5yr CSS 75 vs. 80%, HR 0.78, 95% CI 0.5 – 1.3, p = 0.30). Group B had improved OS compared to Group A (5 yr OS 56% vs. 80%, HR 0.35, 95% CI 0.22 – 0.55, p < 0.0001). There was a trend to improved OS in Group C vs. Group A (5yr OS 56.0% vs. 69.2%, HR 0.79 95% CI 0.6 – 1.01, p = 0.052). The improved OS in Group B versus Group A remained significant in multivariate analysis (HR 0.41, 95% CI 0.22 – 0.77, p = 0.005). Conclusions: Adjuvant chemotherapy improved OS in this real world cohort, and there was a trend to a benefit with adjuvant chemo-radiotherapy. However, the lack of difference in cancer specific survival suggests that this benefit may be partly driven by patient selection bias. Further exploratory analyses to identify sub-groups deriving a cancer specific survival benefit are required.

The Role of Neoadjuvant Versus Adjuvant Therapy for Duodenal Adenocarcinoma: A National Cancer Database Propensity Score Matched Analysis

2020 ◽  
pp. 000313482095482
Author(s):  
Kimberly Linden ◽  
Atlee Melillo ◽  
John Gaughan ◽  
Chioma Obinero ◽  
Alec Kellish ◽  
...  
Keyword(s):  
Overall Survival ◽  
Propensity Score ◽  
Adjuvant Therapy ◽  
Neoadjuvant Therapy ◽  
Surgical Resection ◽  
Retrospective Review ◽  
National Cancer Database ◽  
Tumor Characteristics ◽  
Duodenal Adenocarcinoma

Introduction Adjuvant therapy is recommended in duodenal adenocarcinoma (DA), but the role of neoadjuvant therapy remains undefined. We compared the effect of neoadjuvant therapy to adjuvant therapy on overall survival, 30-day, and 90-day mortality following the resection of DA. Methods A retrospective review of the National Cancer Database was performed on patients with DA who received either adjuvant or neoadjuvant therapy in addition to surgical resection. Propensity score matching was done for patient, socioeconomic, and tumor characteristics. Overall survival, 30-day, and 90-day mortality were compared. Results A total of 112 patients were identified; 55 received adjuvant therapy; 57 received neoadjuvant therapy. There was no difference in 30-day (0% vs. 1.75%; P = 1.00), 90-day mortality (1.82% vs. 7.02%; P = .36), nor overall survival (1 yr: 86% vs. 76; 3 yr: 49% vs. 46%; 5 yr: 42% vs. 39%; P = .28). Conclusions There was no difference in overall survival after propensity score matched analysis.

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