Regional chemotherapy for unresectable primary liver cancer: results of a phase II clinical trial and assessment of DCE-MRI as a biomarker of survival

Jarnagin, William R.; Schwartz, Lawrence H.; Gültekin, David H.; Gönen, Mithat; Haviland, Dana; Shia, Jinru; D’Angelica, M.I.; Fong, Yuman; DeMatteo, Ronald P.; Tse, Archie; Blumgart, Leslie H.; Kemeny, Nancy E.

doi:10.1093/annonc/mdp029

Cited by 157 publications

(134 citation statements)

References 34 publications

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“…The initial report from MSKCC showed a response rate of 47.1% (50% updated), overall PFS of 7.3 months (CI 5.30–9.28), hepatic PFS of 10.1 months (CI 7.14–12.86), and overall survival of 29.5 months (CI 21.28–32.70). One patient was converted to resectability and was found to have a complete pathologic response [16]. …”

Section: Discussionmentioning

confidence: 99%

“…A recent phase II study at Memorial Sloan-Kettering Cancer Center (MSKCC) evaluated HAI of floxuridine (FUDR) plus dexamethasone (Dex) with no concomitant systemic therapy in patients with unresectable primary liver cancer [16]. In the updated results of this trial, there was a 50% partial response rate (53.8% for ICC and 25% for HCC) with a median survival of 29.5 months for the entire cohort.…”

Section: Introductionmentioning

confidence: 99%

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Treating Primary Liver Cancer with Hepatic Arterial Infusion of Floxuridine and Dexamethasone: Does the Addition of Systemic Bevacizumab Improve Results

Kemeny¹,

Schwartz

Gönen

et al. 2011

Oncology

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Objectives: This study investigated the efficacy and safety of adding systemic (IV) bevacizumab (Bev) to hepatic arterial infusion (HAI) with floxuridine (FUDR)/dexamethasone (Dex) in unresectable primary liver cancer. Methods: Patients with unresectable intrahepatic cholangiocarcinoma (ICC) or hepatocellular carcinoma (HCC) were treated with HAI FUDR/Dex plus IV Bev. Results were compared to a recent study of HAI without Bev in a similar patient population. Results: Twenty-two patients (18 ICC, 4 HCC) were treated with HAI FUDR/Dex plus Bev; 7 (31.8%) had partial response and 15 (68.2%) had stable disease. Median survival was 31.1 months (CI 14.14–33.59), progression-free survival (PFS) 8.45 months (CI 5.53–11.05), and hepatic PFS 11.3 months (CI 7.93–15.69). In the previous trial with HAI alone (no Bev), the response was 50%; median survival, PFS, and hepatic PFS were 29.5, 7.3, and 10.1 months. In the present trial, bilirubin elevation (>2 mg/dl) was seen in 24% of patients and biliary stents were placed in 13.6%, versus 5.8 and 0%, respectively, in the HAI trial without Bev. Due to increased biliary toxicity, the trial was prematurely terminated. Conclusion: Adding Bev to HAI FUDR/Dex appeared to increase biliary toxicity without clear improvement in outcome (median PFS 8.45 vs. 7.3 months, and median survival 31.1 vs. 29.5 months, for HAI + Bev vs. HAI alone groups, respectively).

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Treating Primary Liver Cancer with Hepatic Arterial Infusion of Floxuridine and Dexamethasone: Does the Addition of Systemic Bevacizumab Improve Results

Kemeny¹,

Schwartz

Gönen

et al. 2011

Oncology

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“…Male morbidity is higher compared with female morbidity (1). A report from 2006 revealed that 662,000 patients succumb to HLC annually (2). The morbidity of HLC varies across regions; Eastern and Southeast Asia, a number of Western Pacific islands, and Saharan and Southern Africa have high morbidity rates compared with other countries.…”

Section: Introductionmentioning

confidence: 99%

Effects of harmaline on cell growth of human liver cancer through the p53/p21 and Fas/FasL signaling pathways

Yuan

et al. 2017

Oncol Lett

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Abstract. The effects of harmaline on the viability and apoptosis of human liver carcinoma were investigated in vitro. HepG2 cells were treated with harmaline (0-10 µM), and the proliferation and apoptosis of HepG2 cells were investigated using an MTT assay and flow cytometry, respectively. The protein expression of cellular tumor antigen p53 (p53), cyclin-dependent kinase inhibitor 1 (p21), tumor necrosis factor receptor superfamily member 6 (Fas), Fas ligand (FasL) and caspase-8 was subsequently measured using western blotting. In addition, an ELISA was used to analyze caspase-8/3 activity. Harmaline significantly increased p53, p21, Fas and FasL protein expression in HepG2 cells. Additionally, treatment with harmaline significantly increased the expression of caspase-8 and caspase-8/3 activity. The results from the present study suggest that harmaline suppresses the viability, but induces the apoptosis, of human liver carcinoma cells through upregulation of the p53/p21 and Fas/FasL signaling pathways.

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“…Both surgical procedure and stimulation can increase the exfoliation of cancer cells, and metastasis of peritoneal exfoliated cells will directly lead to the recurrence and death in patients after radical resections for gastric cancer and very low 5-year survival rate in patients with progressive gastric cancer. The most common malignant tumours in the abdominal cavity easily occur peritoneal metastasis and liver metastasis, whereas the postoperative conventional treatment including systemic intravenous chemotherapy has very low efficiency (Jarnagin et al, 2009). Currently, intraperitoneally implantation of sustained-release 5-Fu has been widely used in clinic, but its efficacy and safety are still controversial (Chen et al, 2006;Pohlen et al, 2007).…”

Section: Discussionmentioning

confidence: 99%

Experimental Study on Sustained-release 5-Fluorouracil Implantation in Canine Peritoneum and Para-aortic Abdominalis

Guo

Nie²,

Shen³

et al. 2014

Asian Pacific Journal of Cancer Prevention

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Objective: To observe local and systemic toxicity after sustained-release 5-fluorouracil (5-Fu) implantation in canine peritoneum and para-aortic abdominalis and the changes of drug concentration in the local implanted tissue with time. Methods: 300 mg sustained-release 5-Fu was implanted into canine peritoneum and para-aorta abdominalis. Samples were taken 3, 5, 7 and 10 days after implantation for assessment of changes and systemic reactions. High performance liquid chromatography was applied to detect the drug concentrations of peritoneal tissue at different distances from the implanted site, lymphatic tissue of para-aortic abdominalis, peripheral blood and portal venous blood. Results: 10 days after implantation, the drug concentrations in the peritoneum, lymphatic tissue and portal vein remained relatively high within 5 cm of the implanted site. There appeared inflammatory reaction in the local implanted tissue, but no visible pathological changes such as cell degeneration and necrosis, and systemic reaction like anorexia, nausea, vomiting and fever. Conclusions: Sustained-release 5-Fu implantation in canine peritoneum and para-aortic abdominalis can maintain a relatively high tumourinhibiting concentration for a longer time in the local implanted area and portal vein, and has mild local and systemic reactions. Besides, it is safe and effective to prevent or treat recurrence of gastrointestinal tumours and liver metastasis.

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Regional chemotherapy for unresectable primary liver cancer: results of a phase II clinical trial and assessment of DCE-MRI as a biomarker of survival

Abstract: In patients with unresectable primary liver cancer, HAI therapy can be effective and safe. Pretreatment and early post-treatment changes in tumor perfusion characteristics may predict treatment outcome.

Cited by 157 publications

References 34 publications

Treating Primary Liver Cancer with Hepatic Arterial Infusion of Floxuridine and Dexamethasone: Does the Addition of Systemic Bevacizumab Improve Results

Treating Primary Liver Cancer with Hepatic Arterial Infusion of Floxuridine and Dexamethasone: Does the Addition of Systemic Bevacizumab Improve Results

Effects of harmaline on cell growth of human liver cancer through the p53/p21 and Fas/FasL signaling pathways

Experimental Study on Sustained-release 5-Fluorouracil Implantation in Canine Peritoneum and Para-aortic Abdominalis

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