Preoperative chemoradiation in adenocarcinoma of the pancreas. A single centre experience advocating a new treatment strategy

Golcher, Henriette; Brunner, Thomas; Grabenbauer, Gerhard G.; Merkel, Susanne; Papadopoulos, Thomas; Hohenberger, Werner; Meyer, Thomas

doi:10.1016/j.ejso.2007.11.012

Cited by 53 publications

(35 citation statements)

References 29 publications

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“…Theoretically, these drawbacks may be overcome by employing the neoadjuvant approach, so that more patients can receive potentially beneficial adjuvant treatment. clinical studies of neoadjuvant chemo-(radio)-therapy in pancreatic cancer have recently been reported (16)(17)(18)(19)(20)(21)(22). HAI chemotherapy, using fluorodeoxyuridine or 5-FU, has been studied most extensively in patients with liver metastases from colorectal cancer.…”

Section: Discussionmentioning

confidence: 99%

Pilot study of hepatic arterial infusion chemotherapy with gemcitabine and 5-fluorouracil for patients with postoperative liver metastases from pancreatic cancer

Tajima

Ohta

Kitagawa

et al. 2011

Experimental and Therapeutic Medicine

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Abstract. hepatic metastasis is a common cause of treatment failure after curative resection of pancreatic cancer. We report a pilot study of hepatic arterial infusion (hai) chemotherapy with gemcitabine and 5-fluorouracil (5-FU) for postoperative liver metastases from pancreatic cancer. Five patients who had undergone curative resection of liver metastases from pancreatic cancer received HAI of gemcitabine and 5-FU between October 2008 and September 2010 at Kanazawa university hospital. Gemcitabine at a dose of 800 mg was infused over 30 min via a bedside pump. after gemcitabine administration, 250 mg of 5-FU was infused continuously over 24 h on days 1-5, comprising one cycle of therapy. these treatment cycles were continued biweekly. in the evaluation according to rEciSt criteria, a partial response was obtained in 2 of the 5 cases, with stable disease being achieved in the remaining 3 cases (response rate, 100%). In 4 of the 5 cases, a decrease in serum tumor marker ca19-9 was observed after 10 hai treatment cycles. the median time to treatment failure was 10 months (range 3-17). as to adverse events, leukocytopenia was grade 3 in 1 of 4 affected cases and all 5 were anemic, although 4 of the 5 cases had anemia prior to HAI therapy. Grade 2 thrombocytopenia was observed in 2 cases. no nonhematologic events, such as nausea, diarrhea, liver injury and neuropathy, occurred. there were no life-threatening toxicities, but 4 cases (80%) developed catheter complications, and the hai catheter and subcutaneous implantable port system had to be removed. hai delivers high doses of chemotherapeutic agents directly into tumor vessels, producing increased regional levels with greater efficacy and a lower incidence/ severity of systemic side effects. in conclusion, hai chemotherapy is useful and safe for the treatment of malignancies confined to the liver. Introductionpancreatic cancer is one of the major causes of cancer-related death globally, with a 5-year survival rate of less than 5% (1,2). For patients with localized disease, radical surgery may provide long-term benefits. However, even in patients who undergo resection, the reported 5-year survival rate remains in the range of 7-24%, and median survival is only approximately 1 year in most series, indicating that surgery alone is generally inadequate. Even after curative resection, patients with pancreatic cancer face a 50-80% local recurrence rate and a 25-50% chance of developing distant metastases (3).Gemcitabine, a deoxycytidine analogue that competes for incorporation into dna thereby inhibiting its synthesis, is the key drug employed in the treatment of pancreatic cancer. adjuvant chemotherapy with gemcitabine improves, although to a limited degree, the survival of patients with resectable pancreatic adenocarcinoma as compared to resection alone (4). however, a major drawback of adjuvant therapy for pancreatic cancer is that 20-30% of patients cannot receive the designated therapy as a result of postoperative complications, delayed surgical recovery and/or ear...

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Section: Discussionmentioning

confidence: 99%

Pilot study of hepatic arterial infusion chemotherapy with gemcitabine and 5-fluorouracil for patients with postoperative liver metastases from pancreatic cancer

Tajima

Ohta

Kitagawa

et al. 2011

Experimental and Therapeutic Medicine

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“…Pancreatic ductal adenocarcinoma is characterized by its high malignant potential, showing rapid progression, early metastasis, and limited response to chemotherapy and radiotherapy (18). The efficacies of adjuvant and neoadjuvant chemotherapy with gemcitabine for pancreatic cancer (7,8) and the induction of apoptotic cell death in vitro by chemotherapy and radiotherapy in malignant tumors (9) were reported. Caspase-mediated cleavage of the cytokeratin 18 (CK18) contributes to the degradation of the intracellular cytoskeleton if epithelial cells undergo apoptosis.…”

Section: Discussionmentioning

confidence: 99%

“…Gemcitabine, a pyrimidine analog, was launched in 1996, and has been used as the first-line agent for the treatment of pancreatic cancer (6). Recently, the efficacies of adjuvant and neoadjuvant chemotherapy (NAC) with gemcitabine for pancreatic cancer were reported (7,8).…”

Section: Introductionmentioning

confidence: 99%

Neoadjuvant chemotherapy with gemcitabine for pancreatic cancer increases in situ expression of the apoptosis marker M30 and stem cell marker CD44

Tajima¹,

Ohta²,

Kitagawa³

et al. 2012

Oncology Letters

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Abstract. We examined the pathological effects of preoperative neoadjuvant chemotherapy (NAC) and the expression of markers of apoptosis, epithelial-to-mesenchymal transition (EMT) and cancer stem cells in resected pancreatic cancer specimens from patients treated with gemcitabine as NAC. Immunohistochemical expression of the apoptosis marker M30, EMT marker Snail and stem cell marker CD44 in surgically resected pancreatic cancer specimens were compared between patients treated (NAC group n=13) and not treated (control group n=21) with gemcitabine. In the NAC group, the tumor specimens showed tumor cell injury; however, there was no significant reduction of serosal, retroperitoneal, perineural or vascular invasion, lymph node metastasis or tumor size. The expression frequencies of M30 and CD44 were significantly higher in the NAC group (61.5 and 53.8%) compared to the control group (9.5 and 14.3%); however, no significant difference in Snail expression was noted between the two groups (53.8 versus 42.9%). Gemcitabine induced apoptosis of pancreatic cancer cells in vivo; however, it did not reduce the tumor burden. Moreover, the residual cancer tissues were rich in chemoresistant cancer stem cells. By contrast, marked EMT of cancer cells was observed in the specimens from the groups treated and not treated with gemcitabine.

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“…[23][24][25] Continuous intravenous infusion of fluorouracil has become standard, and, to get better results, some institutions have reported co-use of MMC and CDDP to be effective. 25,26 pCR to NACRT is rare in pancreatic cancer, which is thought to be chemoradioresistant relative to other gastrointestinal malignancies. 8 In our institution, 25 patients with locally invasive PDA without distant metastasis underwent fluorouracil-based NACRT (5-FU+MMC+CDDP+radiation 40 Gy) between 2003 and 2011.…”

Section: Discussionmentioning

confidence: 99%

Two Cases of Pathological Complete Response to Neoadjuvant Chemoradiation Therapy in Pancreatic Cancer

et al. 2015

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Neoadjuvant chemoradiation therapy (NACRT) is increasingly used in patients with a potentially or borderline resectable pancreatic ductal adenocarcinoma (PDA) and it has been shown to improve survival and reduce locoregional metastatic disease. It is rare for patients with PDA to have a pathological complete response (pCR) to NACRT, but such patients reportedly have a good prognosis. We report the clinicopathological findings of two cases of pCR to NACRT in PDA. Both patients underwent pancreatectomy after NACRT (5-fluorouracil, mitomycin C, cisplatin, and radiation). Neither had residual invasive carcinoma and both showed extensive fibrotic regions with several ducts regarded as having pancreatic intraepithelial neoplasia 3/carcinoma in situ in their post-therapy specimens. It is noteworthy that both patients had a history of a second primary cancer. They both had comparatively good outcomes: one lived for 9 years after the initial pancreatectomy and the other is still alive without recurrence after 2 years.

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Preoperative chemoradiation in adenocarcinoma of the pancreas. A single centre experience advocating a new treatment strategy

Cited by 53 publications

References 29 publications

Pilot study of hepatic arterial infusion chemotherapy with gemcitabine and 5-fluorouracil for patients with postoperative liver metastases from pancreatic cancer

Pilot study of hepatic arterial infusion chemotherapy with gemcitabine and 5-fluorouracil for patients with postoperative liver metastases from pancreatic cancer

Neoadjuvant chemotherapy with gemcitabine for pancreatic cancer increases in situ expression of the apoptosis marker M30 and stem cell marker CD44

Two Cases of Pathological Complete Response to Neoadjuvant Chemoradiation Therapy in Pancreatic Cancer

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