Chemoradiotherapy for pancreatic cancer: current status and perspectives

Oya, Natsuo

doi:10.1007/s10147-004-0449-6

Cited by 13 publications

(8 citation statements)

References 47 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…7–9 In the ESPAC-1 study, clinicians were allowed to deliver “background” chemoradiation or chemotherapy separate from the study regimens, and 30% of patients assigned to receive radiation did not receive a uniform dose of radiation or radiation at all. With regard to radiation therapy, current treatment typically consists of radiation doses of 45–54 gray (Gy) rather than the 40 Gy used in the three studies above, and the split course technique is no longer used because of prolonged treatment time and inferior radiobiologic efficiency.…”

Section: Introductionmentioning

confidence: 99%

“…6 Interpretation of the results from these 3 major studies, especially ESPAC-1, varies considerably because of several limitations, including statistical design issues and the suboptimal, relatively out-of-date chemoradiation protocols. [7][8][9] In the ESPAC-1 study, clinicians were allowed to deliver ''background'' chemoradiation or chemotherapy separate from the study regimens, and 30% of patients who were assigned to receive radiation either did not receive a uniform dose of radiation or did not receive radiation at all. With regard to radiation therapy, current treatment typically consists of radiation doses from 45 grays (Gy) to 54 Gy rather than the 40 Gy used in the 3 studies described above, and the split-course technique no longer is used because of prolonged treatment time and inferior radiobiologic efficiency.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Results and patterns of failure in patients treated with adjuvant combined chemoradiation therapy for resected pancreatic adenocarcinoma

Hattangadi

Hong

Yeap

et al. 2009

Cancer

View full text Add to dashboard Cite

Background While adjuvant chemoradiation is commonly used in the United States for treatment of resected pancreatic cancer, there is no consensus on the benefit of this therapy as results from randomized trials are conflicting. We reviewed our experience in a consecutive, unselected series of patients treated with adjuvant 5-FU and radiation therapy for resected pancreatic adenocarcinoma. Methods 86 patients with resected pancreatic adenocarcinoma who underwent adjuvant therapy from 1998–2005 were identified. Medical records were reviewed. 93% of patients were treated with external beam RT to ≥ 50.4 Gy and 91% of patients received concurrent 5-FU by continuous infusion. 45% of patients went on to receive adjuvant gemcitabine. Results Median follow-up was 31 months (range 21–62) among the 20 patients still alive. Fewer than half of patients had positive (33%) or close (<1mm, 15%) resection margins. 81% of the tumors were T3; 66% had involved lymph nodes. The median overall survival (OS) for all patients was 22 months; negative lymph node status (p=0.016) was a significant prognostic factor for improved OS, while treatment with gemcitabine trended towards improved OS (p=0.080). Median disease-free survival (DFS) for all patients was 10 months, and treatment with gemcitabine (p=0.044) or any chemotherapy (p=0.047) were significant predictors of DFS. 75 patients (87%) had disease recurrence, the majority of whom recurred with peritoneal (55%) or liver (53%) metastases. Negative lymph nodes trended towards a lower rate of distant failure (p=0.060). Conclusions The median survival of this cohort is greater than that of the chemoradiation arms of the EORTC and ESPAC-1 trials, and comparable to the survival observed on the GITSG chemoradiation arm. Lymph node status and treatment with adjuvant chemotherapy were significant predictors of OS and DFS, respectively. Future survival improvements should be directed at reducing peritoneal and liver metastases. Further randomized trials are required to define the role of adjuvant therapy for pancreatic adenocarcinoma.

show abstract

Section: Introductionmentioning

confidence: 99%

mentioning

confidence: 99%

Results and patterns of failure in patients treated with adjuvant combined chemoradiation therapy for resected pancreatic adenocarcinoma

Hattangadi

Hong

Yeap

et al. 2009

Cancer

View full text Add to dashboard Cite

show abstract

“…Pancreatic cancer is a fatal disease, with a 5-year survival rate of less than 5% 14. In the majority of cases (> 80%), at first diagnosis, pancreatic cancer has already become metastatic so that conventional treatment regimens provide minimal, if any, clinical benefit in prolonging life or ameliorating the negative prognosis of this disease 15.…”

Section: Introductionmentioning

confidence: 99%

[6]-Gingerol Induces Cell Cycle Arrest and Cell Death of Mutant p53-expressing Pancreatic Cancer Cells

et al. 2006

View full text Add to dashboard Cite

[6]-Gingerol, a major phenolic compound derived from ginger, has anti-bacterial, anti-inflammatory and anti-tumor activities. While several molecular mechanisms have been described to underlie its effects on cells in vitro and in vivo, the underlying mechanisms by which [6]-gingerol exerts anti-tumorigenic effects are largely unknown. The purpose of this study was to investigate the action of [6]-gingerol on two human pancreatic cancer cell lines, HPAC expressing wildtype (wt) p53 and BxPC-3 expressing mutated p53. We found that [6]-gingerol inhibited the cell growth through cell cycle arrest at G1 phase in both cell lines. Western blot analyses indicated that [6]-gingerol decreased both Cyclin A and Cyclin-dependent kinase (Cdk) expression. These events led to reduction in Rb phosphorylation followed by blocking of S phase entry. p53 expression was decreased by [6]-gingerol treatment in both cell lines suggesting that the induction of Cyclin-dependent kinase inhibitor, p21 cip1 , was p53-independent.[6]-Gingerol induced mostly apoptotic death in the mutant p53-expressing cells, while no signs of early apoptosis were detected in wild type p53-expressing cells and this was related to the increased phosphorylation of AKT. These results suggest that [6]-gingerol can circumvent the resistance of mutant p53-expressing cells towards chemotherapy by inducing apoptotic cell death while it exerts cytostatic effect on wild type p53-expressing cells by inducing temporal growth arrest.

show abstract

“…When feasible, the current standard of care involves surgical resection with or without postoperative chemotherapy or chemo−/radiotherapy (for review see [3]). Until recently, the most common chemotherapeutic agent used for treatment of pancreatic cancer is 5-fluorouracil (5-FU), given either alone or in combination with other chemotherapeutic drugs and/or radiotherapy [4], [5], [6]. However, another nucleotide analogue, gemcitabine (Gemzar), brought onto market in 1997 primarily for its palliative effects rather than for improving survival, has rapidly become the chemotherapeutic treatment of choice for pancreatic cancer due to its therapeutic potential alone or in combination [7], [8], [9].…”

Section: Introductionmentioning

confidence: 99%

Evaluation of a Gene-Directed Enzyme-Product Therapy (GDEPT) in Human Pancreatic Tumor Cells and Their Use as In Vivo Models for Pancreatic Cancer

et al. 2012

View full text Add to dashboard Cite

BackgroundGene-directed enzyme prodrug therapy (GDEPT) is a two-step treatment protocol for solid tumors that involves the transfer of a gene encoding a prodrug-activating enzyme followed by administration of the inactive prodrug that is subsequently activated by the enzyme to its tumor toxic form. However, the establishment of such novel treatment regimes to combat pancreatic cancer requires defined and robust animal model systems.MethodsHere, we comprehensively compared six human pancreatic cancer cell lines (PaCa-44, PANC-1, MIA PaCa-2, Hs-766T, Capan-2, and BxPc-3) in subcutaneous and orthotopical mouse models as well as in their susceptibility to different GDEPTs.ResultsTumor uptake was 83% to 100% in the subcutaneous model and 60% to 100% in the orthotopical mouse model, except for Hs-766T cells, which did not grow orthotopically. Pathohistological analyses of the orthotopical models revealed an infiltrative growth of almost all tumors into the pancreas; however, the different cell lines gave rise to tumors with different morphological characteristics. All of the resultant tumors were positive for MUC-1 staining indicating their origin from glandular or ductal epithelium, but revealed scattered pan-cytokeratin staining. Transfer of the cytochrome P450 and cytosine deaminase suicide gene, respectively, into the pancreatic cancer cell lines using retroviral vector technology revealed high level infectibility of these cell lines and allowed the analysis of the sensitivity of these cells to the chemotherapeutic drugs ifosfamide and 5-fluorocytosine, respectively.ConclusionThese data qualify the cell lines as part of valuable in vitro and in vivo models for the use in defined preclinical studies for pancreas tumor therapy.

show abstract

Chemoradiotherapy for pancreatic cancer: current status and perspectives

Cited by 13 publications

References 47 publications

Results and patterns of failure in patients treated with adjuvant combined chemoradiation therapy for resected pancreatic adenocarcinoma

Results and patterns of failure in patients treated with adjuvant combined chemoradiation therapy for resected pancreatic adenocarcinoma

[6]-Gingerol Induces Cell Cycle Arrest and Cell Death of Mutant p53-expressing Pancreatic Cancer Cells

Evaluation of a Gene-Directed Enzyme-Product Therapy (GDEPT) in Human Pancreatic Tumor Cells and Their Use as In Vivo Models for Pancreatic Cancer

Contact Info

Product

Resources

About