scholarly journals Impact of dihydropyrimidine dehydrogenase and γ-glutamyl hydrolase on the outcomes of patients treated with gemcitabine or S-1 as adjuvant chemotherapy for advanced pancreatic cancer

2011 ◽  
Vol 2 (6) ◽  
pp. 1097-1103 ◽  
Author(s):  
AYAKO NAKAMURA ◽  
KAZUHIKO HAYASHI ◽  
GO NAKAJIMA ◽  
HIROTAKA KAMIKOZURU ◽  
RYUJI OKUYAMA ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Adjuvant Chemotherapy ◽  
Dihydropyrimidine Dehydrogenase ◽  
Advanced Pancreatic Cancer

Phase I Study of Capecitabine With Concomitant Radiotherapy for Patients With Locally Advanced Pancreatic Cancer: Expression Analysis of Genes Related to Outcome

2005 ◽  
Vol 23 (34) ◽  
pp. 8679-8687 ◽  
Author(s):  
M. Wasif Saif ◽  
Mohammaed A. Eloubeidi ◽  
Suzanne Russo ◽  
Adam Steg ◽  
Jennifer Thornton ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Dihydropyrimidine Dehydrogenase ◽  
Locally Advanced ◽  
Three Dimensional ◽  
Advanced Pancreatic Cancer ◽  
Needle Aspiration ◽  
Mrna Levels ◽  
Necrosis Factor Alpha ◽  
Tnf Α ◽  
Grade 3

Purpose To establish the feasibility of capecitabine with concurrent radiotherapy (XRT) in patients with locally advanced (LA) pancreatic cancer and evaluate the effect of XRT on thymidine phosphorylase (TP), dihydropyrimidine dehydrogenase (DPD), and tumor necrosis factor-alpha (TNF-α). Patients and Methods Fifteen patients with LA pancreatic cancer received three-dimensional conformal XRT to a dose of 50.4 Gy with capecitabine at escalating doses from 600 to 1,250 mg/m2 bid (Monday through Friday). Following chemo-XRT, stable and responding patients were treated with capecitabine 2,000 mg/m2 orally bid for 14 days every 21 days. Tumor specimens were procured with endoscopic ultrasound–guided fine-needle aspiration 1 week before and 2 weeks after chemo-XRT to evaluate TP, DPD, and TNF-α mRNA levels. Results Dose-limiting grade 3 diarrhea was observed in two of six patients treated at a capecitabine dose of 1,000 mg/m2 with XRT. Three patients (20%) achieved partial response. Mean percent difference in TP pre- and post-XRT was 119.2% (P = .1934). There was no significant differences in mean TNF-α, or DPD levels pre- and post-XRT (P = .1934 and .4922, respectively). TP and TNF-α levels were not significantly correlated both at pre- and post-XRT (P = .670 and P < .154, respectively). Median value of TP:DPD ratios at baseline was 2.65 (range, 0.36 to 11.08). No association between TP:DPD ratio and efficacy of capecitabine or severity of toxicities was identified. Conclusion The recommended dose for phase II evaluation is capecitabine 800 mg/m2 bid (Monday through Friday) with concurrent XRT. This approach offers an easy alternative to intravenous fluorouracil as a radiosensitizer in these patients. Role of TP and TP:DPD ratio warrants further investigation in a larger clinical trial.

The impact of dihydropyrimidine dehydrogenase expression in pancreatic cancer patients who undergo curative resection with S-1 adjuvant chemotherapy

Pancreatology ◽  
2016 ◽  
Vol 16 (4) ◽  
pp. S142
Author(s):  
Masaaki Murakawa ◽  
Toru Aoyama ◽  
Yohei Miyagi ◽  
Yosuke Atsumi ◽  
Keisuke Kazama ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Adjuvant Chemotherapy ◽  
Cancer Patients ◽  
Curative Resection ◽  
Dihydropyrimidine Dehydrogenase ◽  
The Impact

A randomized phase II trial of adjuvant chemotherapy with uracil / tegafur (UFT) and gemcitabine (GEM) vs. gemcitabine alone in patients with resected pancreatic cancer

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 4542-4542 ◽  
Author(s):  
H. Yoshitomi ◽  
A. Togawa ◽  
F. Kimura ◽  
H. Shimizu ◽  
H. Yoshidome ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Adjuvant Chemotherapy ◽  
Advanced Pancreatic Cancer ◽  
Disease Free Survival ◽  
Residual Tumor ◽  
Rank Test ◽  
Randomized Phase Ii ◽  
Significant Difference ◽  
Secondary Endpoints ◽  
Ductal Pancreatic Cancer

4542 Background: GEM is now the standard therapy for patients with advanced pancreatic cancer (PC). However, there have been few randomized studies of adjuvant chemotherapy with GEM in patients with resected PC. Methods: Patients with invasive ductal pancreatic cancer who underwent radical surgery were enrolled. Within 8weeks after operation, pts were randomized to receive UFT and GEM (GU) or GEM alone (G). GEM was administrated at a dosage of 1g/m2 IV weekly X3 out of 4weeks and UFT at a dosage of 200mg/body/day orally continuously. Eligibility included histological residual tumor (R) 0 or 1, and no previous chemo- or/and radiation therapy. Primary endpoint was 1y disease free survival (DFS) rate and secondary endpoints included overall survival (OS) and side effects in both groups. Results: Between 05/02 and 12/05, 100 patients were randomized into the two arms of the trial (50 pts to GU and 50 to G). No pts were found to be ineligible. Pts characteristics were well balanced (GU/G) with regard to median age (62/63y), tumor status (T3+4 88/94%), nodal status (N positive 77/72%), histological residual tumor status (R0 76/68%). Until 03/06, 1y DFS rate was 50.3% in GU and 45.5% in G and there was no significant difference between two groups. The median OS was 20m in GU and 28m in G (Log rank test: N.S.). Grade 2 or more toxicities were observed in 67.3% of GU pts and 56.3% of G pts (N.S.). No grade 4 or more toxicity was observed in either groups. Leucocytopenia was the most frequently observed side effect in both groups (Grade 2 or more GU/G 49/46%). Conclusion: Preliminary results confirm the efficacy and safety of GEM based adjuvant chemotherapy for pts with resected PC, but addition of UFT with GEM dose not improve DFS as compared with GEM alone, so far. Final results will be presented at the meeting. No significant financial relationships to disclose.

Immunotherapy in pancreatic cancer and the importance of tumour testing

2020 ◽  
Vol 13 (7) ◽  
pp. e235774
Author(s):  
Phuong Ngo ◽  
Mohamed Shanshal ◽  
Adam Rojan
Keyword(s):  
Pancreatic Cancer ◽  
Genetic Testing ◽  
Adjuvant Chemotherapy ◽  
Mismatch Repair ◽  
Poor Prognosis ◽  
Treatment Options ◽  
Locally Advanced ◽  
Advanced Pancreatic Cancer ◽  
Additional Treatment ◽  
Clinical Suspicion

Advanced pancreatic cancer carries a poor prognosis and has traditionally been treated with chemotherapy. However, immunotherapy has made great strides in a subset of patients depending on mismatch repair/microsatellite status. We present a patient with locally advanced pancreatic cancer treated with neoadjuvant chemotherapy followed by surgery and additional adjuvant chemotherapy whose disease progressed while on adjuvant chemotherapy. Tumour testing showed a mismatch repair mutation and high microsatellite instability, making her eligible for treatment with immunotherapy. Germline genetic testing confirmed the clinical suspicion of Lynch syndrome. She has had isolated sites of progression treated with radiation but overall has been receiving immunotherapy for more than 3 years, highlighting the importance of tumour testing as it may allow for additional treatment options and improved survival.

scholarly journals Chemoresistance in Pancreatic Cancer

2019 ◽  
Vol 20 (18) ◽  
pp. 4504 ◽  
Author(s):  
Zeng ◽  
Pöttler ◽  
Lan ◽  
Grützmann ◽  
Pilarsky ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Stem Cells ◽  
Adjuvant Chemotherapy ◽  
Mortality Rate ◽  
Advanced Pancreatic Cancer ◽  
Ductal Adenocarcinoma ◽  
Western World ◽  
Targeted Drugs ◽  
Related Factors ◽  
Pancreatic Cancer Cells

Pancreatic ductal adenocarcinoma (PDAC), generally known as pancreatic cancer (PC), ranks the fourth leading cause of cancer-related deaths in the western world. While the incidence of pancreatic cancer is displaying a rising tendency every year, the mortality rate has not decreased significantly because of late diagnosis, early metastasis, and limited reaction to chemotherapy or radiotherapy. Adjuvant chemotherapy after surgical resection is typically the preferred option to treat early pancreatic cancer. Although 5-fluorouracil/leucovorin with irinotecan and oxaliplatin (FOLFIRINOX) and gemcitabine/nab-paclitaxel can profoundly improve the prognosis of advanced pancreatic cancer, the development of chemoresistance still leads to poor clinical outcomes. Chemoresistance is multifactorial as a result of the interaction among pancreatic cancer cells, cancer stem cells, and the tumor microenvironment. Nevertheless, more pancreatic cancer patients will benefit from precision treatment and targeted drugs. Therefore, we outline new perspectives for enhancing the efficacy of gemcitabine after reviewing the related factors of gemcitabine metabolism, mechanism of action, and chemoresistance.

Adjuvant Therapy for Pancreatic Cancer

Swiss Surgery ◽  
2000 ◽  
Vol 6 (5) ◽  
pp. 289-295 ◽  
Author(s):  
Ghaneh ◽  
Slavin ◽  
Sutton ◽  
Neoptolemos
Keyword(s):  
Pancreatic Cancer ◽  
Adjuvant Chemotherapy ◽  
Randomised Controlled Trial ◽  
Adjuvant Therapy ◽  
Survival Benefit ◽  
Controlled Trial ◽  
Advanced Pancreatic Cancer ◽  
The Other ◽  
Cancer Of The Pancreas ◽  
Randomised Controlled

Pancreatic cancer was once considered to be a disease without hope. Advances in regionalisation of treatment in specialist units have resulted in a great improvement in resection outcome. Studies in advanced pancreatic cancer have indicated an advantage for chemotherapy. For 15 years only the GITSG had tested adjuvant therapy in a randomised controlled trial. This small study of only 43 patients suggested a survival benefit for post-operative chemoradiotherapy combined with follow-on chemotherapy. Recently two large trials of over 800 patients, one from the EORTC and the other from ESPAC, have shown no benefit from chemoradiotherapy alone. Results from a Norwegian and from ESPAC suggest that adjuvant chemotherapy (without chemoradiotherapy) prolongs survival. The major randomisation and recruitment centres for ESPAC include Berne, Switzerland, Verona, Italy and Liverpool, UK. The ESPAC-3 Trial plans to recruit 990 patients to definitively answer the chemotherapy question as adjuvant treatment for pancreatic cancer. The new millennium brings hope at last to the most challenging cancer of all-cancer of the pancreas.

Meta-analysis of randomized phase II and phase III trials of gemcitabine with/without S-1 in Asian patients with advanced pancreatic cancer.

2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 311-311 ◽  
Author(s):  
Geoffrey Yuyat Ku ◽  
Benjamin Haaland ◽  
Tatsuya Ioka ◽  
Hiroyuki Isayama ◽  
Yousuke Nakai ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Group Performance ◽  
Meta Analysis ◽  
Performance Status ◽  
Dihydropyrimidine Dehydrogenase ◽  
Eastern Cooperative Oncology Group ◽  
Advanced Pancreatic Cancer ◽  
Phase Iii ◽  
Asian Patients ◽  
Ecog Ps

311 Background: Advanced pancreatic cancer (PC) is a virulent disease, where gemcitabine is considered the standard-of-care. A recent phase III evaluation demonstrated superiority of FOLFIRINOX (bolus and infusional 5-fluorouracil (FU), irinotecan, oxaliplatin) in patients with an Eastern Cooperative Oncology Group performance status (ECOG PS) of ≤1. Recently, three studies were presented in abstract form, comparing gemcitabine/S-1 (GS) to gemcitabine. S-1 is a mixture of tegafur (an oral 5-FU prodrug), a dihydropyrimidine dehydrogenase inhibitor and an agent designed to reduce the gastrointestinal toxicity of 5-FU. All three trials demonstrated significant improvements in progression-free survival (PFS) while one study also showed a statistically significant improvement in overall survival (OS). Methods: We performed a meta-analysis of the three trials. Results: Seven hundred and seventy patients were randomized to receive GS vs. gemcitabine; 75% had metastatic disease and 65% had an ECOG PS of 0. GS was associated with superior RR (hazard ratio (HR) 0.348, p=3.06×10-7), PFS (HR 0.64, p=7.26×10-9) and OS (HR 0.79, p=2.47×10-2) compared to gemcitabine. Patients receiving GS were more likely to experience nausea, diarrhea, rash and stomatitis (mostly grade 1/2); neutropenic fever occurred in <2% of patients. One study demonstrated superior quality-of-life for GS. Conclusions: GS should be considered a first-line option for the treatment of advanced PC in Asian patients. This regimen should serve as the reference for future trials and comparison with FOLFIRINOX in patients with ECOG PS ≤1 is warranted.

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