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Hatoum H, Rosemurgy A, Bastidas JA, Zervos E, Muscarella P, Edil BH, Cynamon J, Johnson DT, Thomas C, Swinson BM, Nordgren A, Vitulli P, Nutting C, Gipson M, Tsobanoudis A, Agah R. Treatment of locally advanced pancreatic cancer using localized trans-arterial micro perfusion of gemcitabine: combined analysis of RR1 and RR2. Oncologist 2024; 29:690-698. [PMID: 39049803 PMCID: PMC11299923 DOI: 10.1093/oncolo/oyae178] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2023] [Accepted: 06/18/2024] [Indexed: 07/27/2024] Open
Abstract
BACKGROUND Locally advanced pancreatic cancer (LAPC) comprises 40% of pancreatic cancer diagnoses and has a relatively poor prognosis. Trans-arterial micro perfusion (TAMP)-mediated chemotherapy delivery to the primary tumor is a novel approach worthy of investigation. The RR1 (dose escalation) and RR2 (observational) studies examined the safety and preliminary efficacy of TAMP-delivered gemcitabine for LAPC. PATIENTS AND METHODS RR1 and RR2 data were pooled. Both studies enrolled patients with LAPC with histologically confirmed adenocarcinoma. Participant data, including age, sex, race, stage, previous treatments, toxicity, disease progression, and death, were collected. Median number of cycles and average treatment dosage were calculated. Overall survival (OS) was determined for the whole group and separately for patients who received and did not receive previous treatments. Aims of the analysis were to assess procedure safety, OS, and evaluate factors associated with OS. RESULTS The median age of the 43 patients enrolled in RR1 and RR2 was 72 years (range, 51-88 years). Median OS for the 35 eligible patients with stage III disease was 12.6 months (95% CI, 2.1-54.2 months). Previous chemoradiation was associated with significantly longer OS [27.1 months (95% CI, 8.4-40.6 months)] compared to previous systemic chemotherapy [14.6 months (95% CI, 6.4-54.2 months)] or no prior treatment [7.0 months (95% CI, 2.1-35.4 months)] (P < .001). The most common adverse events were GI related (abdominal pain, emesis, and vomiting); the most common grade 3 toxicity was sepsis. CONCLUSION Study results indicate that TAMP-mediated gemcitabine delivery in patients with LAPC is potentially safe, feasible, and provides potential clinical benefits. CLINICAL TRIAL REGISTRATION NCT02237157 (RR1) and NCT02591082 (RR2).
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Affiliation(s)
- Hassan Hatoum
- Department of Internal Medicine Hematology-Oncology Section, University of Oklahoma College of Medicine, Oklahoma City, OK, United States
| | | | | | - Emmanuel Zervos
- Division of Surgical Oncology, Brody School of Medicine, East Carolina University, Greenville, NC, United States
| | - Peter Muscarella
- Montefiore Medical Center, Bronx, NY, United States
- Niagara Falls Memorial Medical Center, Niagara Falls, NY, United States
| | - Barish H Edil
- Department of Surgery, University of Oklahoma College of Medicine, Oklahoma City, OK, United States
| | | | - D Thor Johnson
- University of Colorado Hospital, Aurora, CO, United States
- Sarah Cannon, Nashville, TN, United States
| | | | | | - Aaron Nordgren
- Fawcett Memorial Hospital, Port Charlotte, FL, United States
| | - Paul Vitulli
- Florida Hospital, Tampa, Tampa, FL, United States
- Duval Vascular Center, Jacksonville, FL, United States
| | - Charles Nutting
- Endovascular Consultants of Colorado, Lone Tree, CO, United States
| | | | | | - Ramtin Agah
- RenovoRx, Inc., Los Altos, CA, United States
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2
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Serhal M, Riaz A, Salem R, Lewandowski RJ. Locoregional Therapies for Primary and Secondary Hepatic Malignancies. Cancer Treat Res 2024; 192:207-232. [PMID: 39212923 DOI: 10.1007/978-3-031-61238-1_11] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 09/04/2024]
Abstract
Management of hepatic malignancies is a multidisciplinary task with the involvement of hepatologists, medical/surgical/radiation oncologists, transplant surgeons, and interventional radiologists. Patients should be selected for a specific targeted therapy after multidisciplinary consensus. Interventional oncology, with image-guided locoregional cancer therapies, can decrease systemic toxicity without compromising tumoricidal effect.
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Affiliation(s)
- Muhamad Serhal
- Department of Radiology, Section of Interventional Radiology, Robert H Lurie Comprehensive Cancer Center, Northwestern University, Chicago, IL, USA
| | - Ahsun Riaz
- Department of Radiology, Section of Interventional Radiology, Robert H Lurie Comprehensive Cancer Center, Northwestern University, Chicago, IL, USA
| | - Riad Salem
- Department of Radiology, Section of Interventional Radiology, Robert H Lurie Comprehensive Cancer Center, Northwestern University, Chicago, IL, USA
| | - Robert J Lewandowski
- Department of Radiology, Section of Interventional Radiology, Robert H Lurie Comprehensive Cancer Center, Northwestern University, Chicago, IL, USA.
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3
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Bourien H, Pircher CC, Guiu B, Lamarca A, Valle JW, Niger M, Edeline J. Locoregional Treatment in Intrahepatic Cholangiocarcinoma: Which Treatment for Which Patient? Cancers (Basel) 2023; 15:4217. [PMID: 37686493 PMCID: PMC10486617 DOI: 10.3390/cancers15174217] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2023] [Revised: 08/08/2023] [Accepted: 08/14/2023] [Indexed: 09/10/2023] Open
Abstract
For unresectable intrahepatic cholangiocarcinoma (iCC), different locoregional treatments (LRT) could be proposed to patients, including radiofrequency ablation (RFA) and microwave ablation (MWA), external beam radiotherapy (EBRT) or transarterial treatments, depending on patient and tumor characteristics and local expertise. These different techniques of LRT have not been compared in a randomized clinical trial; most of the relevant studies are retrospective and not comparative. The aim of this narrative review is to help clinicians in their everyday practice discuss the pros and cons of each LRT, depending on the individual characteristics of their patients.
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Affiliation(s)
- Héloïse Bourien
- Medical Oncology Department, Centre Eugène Marquis, 35000 Rennes, France;
| | - Chiara Carlotta Pircher
- Medical Oncology Department, Fondazione IRCCS Istituto Nazionale Tumori, 20133 Milano, Italy; (C.C.P.); (M.N.)
| | - Boris Guiu
- Interventional Radiology Department, CHU de Montpellier, 34090 Montpellier, France;
| | - Angela Lamarca
- Oncology Department, Fundación Jiménez Díaz University Hospital, 28022 Madrid, Spain;
- Medical Oncology Department, Division of Cancer Sciences, University of Manchester, Manchester M13 9PL, UK;
- The Christie NHS Foundation Trust, Manchester M20 4BX, UK
| | - Juan W Valle
- Medical Oncology Department, Division of Cancer Sciences, University of Manchester, Manchester M13 9PL, UK;
- The Christie NHS Foundation Trust, Manchester M20 4BX, UK
| | - Monica Niger
- Medical Oncology Department, Fondazione IRCCS Istituto Nazionale Tumori, 20133 Milano, Italy; (C.C.P.); (M.N.)
| | - Julien Edeline
- Medical Oncology Department, Centre Eugène Marquis, 35000 Rennes, France;
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4
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Endo S, Kawaguchi S, Terada S, Shirane N. Hepatic Arterial Infusion Chemotherapy for Liver Metastases Following Standard Chemotherapy for Pancreatic Cancer. Intern Med 2021; 60:223-229. [PMID: 32963157 PMCID: PMC7872812 DOI: 10.2169/internalmedicine.5449-20] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/20/2022] Open
Abstract
A 65-year-old man diagnosed with locally advanced pancreatic cancer underwent distal pancreatectomy and combined portal vein resection. One month after surgery, contrast-enhanced magnetic resonance imaging revealed multiple liver metastases. We administered two courses of gemcitabine plus nab-paclitaxel combination therapy followed by 17 modified FOLFIRINOX courses. However, the response was insufficient, and the patient thereafter developed grade 3 neutropenia, which made it difficult to continue the treatment regimen. As a result, we administered hepatic arterial infusion chemotherapy comprising gemcitabine plus 5-fluorouracil because the residual tumor was limited to liver metastases. The progression-free survival period was 7 months, and no drug-related adverse effects were noted during the treatment.
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Affiliation(s)
- Shinya Endo
- Department of Gastroenterology, Shizuoka General Hospital, Japan
| | - Shinya Kawaguchi
- Department of Gastroenterology, Shizuoka General Hospital, Japan
| | - Shuzo Terada
- Department of Gastroenterology, Shizuoka General Hospital, Japan
| | - Naofumi Shirane
- Department of Gastroenterology, Shizuoka General Hospital, Japan
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5
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Ettrich TJ, Seufferlein T. Liver Metastases of Neuroendocrine Tumors and CCC. LOCOREGIONAL TUMOR THERAPY 2018:107-127. [DOI: 10.1007/978-3-319-69947-9_5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/06/2025]
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6
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Gruber-Rouh T, Langenbach M, Naguib NNN, Nour-Eldin NEM, Vogl TJ, Zangos S, Beeres M. Trans-arterial chemoperfusion for the treatment of liver metastases of breast cancer and colorectal cancer: Clinical results in palliative care patients. World J Clin Oncol 2017; 8:343-350. [PMID: 28848701 PMCID: PMC5554878 DOI: 10.5306/wjco.v8.i4.343] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/19/2016] [Revised: 02/14/2017] [Accepted: 05/05/2017] [Indexed: 02/06/2023] Open
Abstract
AIM To evaluate the clinical value and efficiency of trans-arterial chemoperfusion (TACP) in patients with liver metastases from breast cancer (BC) and colorectal cancer (CRC).
METHODS We treated 36 patients with liver metastases of BC (n = 19, 19 females) and CRC (n = 17; 8 females, 9 males) with repeated TACP. The treatment interval was 4 wk. TACP was performed with gemcitabine (1000 mg/m2) and mitomycin (10 mg/m2), administered within 1 h after positioning the catheter tip in the hepatic artery. Before treatment, the size, location, tumour volume, vascularization and number of liver tumours were evaluated using magnetic resonance imaging (MRI). Tumour response was evaluated according to the Response Evaluation Criteria in Solid Tumors guidelines.
RESULTS TACP using gemcitabine and mitomycin for metastases from CRC and BC was performed without any serious side effects. The follow-up MRI showed a therapeutic response in 84.2% of the BC patients - stable disease 47.4% and partial response 36.8%. A progression was seen in 15.8%. CRC patients showed a therapeutic response in 52.9% of cases. A progression of the disease was documented in 47.1% of the patients with CRC. These data show that TACP in patients with liver metastases of BC leads to a significantly better therapeutic response compared with CRC patients (P = 0.042). The median survival time was 13.2 mo for the BC patients, which is significantly longer than for CRC patients at 9.3 mo (P = 0.001).
CONCLUSION TACP for liver metastases of BC appears to be a safe and effective palliative treatment with improved outcomes in comparison to patients with CRC.
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Bian JL, Wang MM, Tong EJ, Sun J, Li M, Miao ZB, Li YL, Zhu BH, Xu JJ. Benefit of everolimus in treatment of an intrahepatic cholangiocarcinoma patient with a PIK3CA mutation. World J Gastroenterol 2017; 23:4311-4316. [PMID: 28694672 PMCID: PMC5483506 DOI: 10.3748/wjg.v23.i23.4311] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/26/2017] [Revised: 04/22/2017] [Accepted: 05/19/2017] [Indexed: 02/06/2023] Open
Abstract
Intrahepatic cholangiocarcinoma (ICC) is a relatively rare form of liver cancer with a poor prognosis. The therapeutic options for patients with advanced ICC are limited and usually ineffective. There is currently no approved targeted therapy for ICC, although accumulating evidence supports inhibition of the PI3K/Akt/mTOR signaling pathway as a promising therapeutic strategy in the treatment of ICC. Here, we report a patient with stage IV ICC harboring a PIK3CA mutation who responded well to the mTOR inhibitor everolimus. Computed tomography and magnetic resonance imaging demonstrated shrinkage of the tumor and maintenance of a partial response for 6.5 mo after everolimus treatment as the best response. To the best of our knowledge, this is the first clinical case report in the literature of clinical benefit from everolimus treatment in an ICC patient with PIK3CA mutation.
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Yamaguchi T, Seki T, Inokuchi R, Kawamura R, Murata M, Matsuzaki K, Nakashima O, Kumabe T, Okazaki K. S-1 monotherapy in a patient with cholangiolocellular carcinoma: A case report. Mol Clin Oncol 2016; 5:762-766. [PMID: 28105354 DOI: 10.3892/mco.2016.1049] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2015] [Accepted: 06/21/2016] [Indexed: 11/05/2022] Open
Abstract
A 71-year-old man with alcoholic cirrhosis was found to have multiple hypervascular lesions in the liver on enhanced computed tomography. An ultrasound-guided biopsy of the lesion was performed. Immunohistochemical analysis for hepatocyte paraffin 1 expression was negative; cytokeratin (CK) 7, CK19, epithelial cell adhesion molecule and epithelial membrane antigens were positive; mucicarmine staining was negative. The tumor was thus histologically diagnosed as cholangiolocellular carcinoma (CoCC). The tumor was inoperable due to the associated advanced liver disease. In addition, the patient preferred systemic chemotherapy using only orally administered agents. Thus, S-1 monotherapy was recommended. S-1 was initially administered orally at a dose of 80 mg/day. Although the levels of tumor marker (prothrombin induced by vitamin K absence/antagonist-II and carbohydrate antigen 19-9) levels were marginally elevated, their values did not change over the entire course. The patient achieved a partial response according to the Response Evaluation Criteria In Solid Tumors (RECIST) and modified RECIST 1 year after chemotherapy initiation. In conclusion, S-1 monotherapy exhibited promising efficacy against unresectable CoCC.
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Affiliation(s)
- Takashi Yamaguchi
- Department of Gastroenterology and Hepatology, Kansai Medical University, Hirakata, Osaka 573-1191, Japan; Liver Disease Center, Kansai Medical University Medical Center, Moriguchi, Osaka 570-8507, Japan
| | - Toshihito Seki
- Department of Gastroenterology and Hepatology, Kansai Medical University, Hirakata, Osaka 573-1191, Japan; Liver Disease Center, Kansai Medical University Medical Center, Moriguchi, Osaka 570-8507, Japan
| | - Ryosuke Inokuchi
- Department of Gastroenterology and Hepatology, Kansai Medical University, Hirakata, Osaka 573-1191, Japan; Liver Disease Center, Kansai Medical University Medical Center, Moriguchi, Osaka 570-8507, Japan
| | - Rinako Kawamura
- Department of Gastroenterology and Hepatology, Kansai Medical University, Hirakata, Osaka 573-1191, Japan; Liver Disease Center, Kansai Medical University Medical Center, Moriguchi, Osaka 570-8507, Japan
| | - Miki Murata
- Department of Gastroenterology and Hepatology, Kansai Medical University, Hirakata, Osaka 573-1191, Japan; Liver Disease Center, Kansai Medical University Medical Center, Moriguchi, Osaka 570-8507, Japan
| | - Koichi Matsuzaki
- Department of Gastroenterology and Hepatology, Kansai Medical University, Hirakata, Osaka 573-1191, Japan; Liver Disease Center, Kansai Medical University Medical Center, Moriguchi, Osaka 570-8507, Japan
| | - Osamu Nakashima
- Department of Clinical Laboratory Medicine, Kurume University Hospital, Kurume, Fukuoka 830-0011, Japan
| | | | - Kazuichi Okazaki
- Department of Gastroenterology and Hepatology, Kansai Medical University, Hirakata, Osaka 573-1191, Japan
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9
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Karaosmanoglu AD, Onur MR, Ozmen MN, Akata D, Karcaaltincaba M. Magnetic Resonance Imaging of Liver Metastasis. Semin Ultrasound CT MR 2016; 37:533-548. [PMID: 27986172 DOI: 10.1053/j.sult.2016.08.005] [Citation(s) in RCA: 42] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Liver magnetic resonance imaging (MRI) is becoming the gold standard in liver metastasis detection and treatment response assessment. The most sensitive magnetic resonance sequences are diffusion-weighted images and hepatobiliary phase images after Gd-EOB-DTPA. Peripheral ring enhancement, diffusion restriction, and hypointensity on hepatobiliary phase images are hallmarks of liver metastases. In patients with normal ultrasonography, computed tomography (CT), and positron emission tomography (PET)-CT findings and high clinical suspicion of metastasis, MRI should be performed for diagnosis of unseen metastasis. In melanoma, colon cancer, and neuroendocrine tumor metastases, MRI allows confident diagnosis of treatment-related changes in liver and enables differential diagnosis from primary liver tumors. Focal nodular hyperplasia-like nodules in patients who received platinum-based chemotherapy, hypersteatosis, and focal fat can mimic metastasis. In cancer patients with fatty liver, MRI should be preferred to CT. Although the first-line imaging for metastases is CT, MRI can be used as a problem-solving method. MRI may be used as the first-line method in patients who would undergo curative surgery or metastatectomy. Current limitation of MRI is low sensitivity for metastasis smaller than 3mm. MRI fingerprinting, glucoCEST MRI, and PET-MRI may allow simpler and more sensitive diagnosis of liver metastasis.
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Affiliation(s)
- Ali Devrim Karaosmanoglu
- Liver Imaging Team, Department of Radiology, School of Medicine, Hacettepe University, Ankara, Turkey
| | - Mehmet Ruhi Onur
- Liver Imaging Team, Department of Radiology, School of Medicine, Hacettepe University, Ankara, Turkey
| | - Mustafa Nasuh Ozmen
- Liver Imaging Team, Department of Radiology, School of Medicine, Hacettepe University, Ankara, Turkey
| | - Deniz Akata
- Liver Imaging Team, Department of Radiology, School of Medicine, Hacettepe University, Ankara, Turkey
| | - Musturay Karcaaltincaba
- Liver Imaging Team, Department of Radiology, School of Medicine, Hacettepe University, Ankara, Turkey.
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10
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Riaz A, Lewandowski RJ, Salem R. Locoregional Therapies for Primary and Secondary Hepatic Malignancies. Cancer Treat Res 2016; 168:233-256. [PMID: 29206376 DOI: 10.1007/978-3-319-34244-3_12] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/07/2023]
Abstract
Management of hepatic malignancies is a multidisciplinary task with the involvement of hepatologists, medical/surgical oncologists, transplant surgeons, and interventional radiologists. The patients should be selected for a specific targeted therapy after multidisciplinary consensus. Interventional oncology has established its role in the management of hepatic malignancies. Image-guided locoregional therapies decrease the rate of systemic toxicity without compromising tumoricidal effect.
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11
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Phase I trial of oral S-1 combined with hepatic arterial infusion of gemcitabine in unresectable biliary tract cancer. Cancer Chemother Pharmacol 2015; 75:805-12. [PMID: 25687990 DOI: 10.1007/s00280-015-2704-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/12/2014] [Accepted: 02/11/2015] [Indexed: 10/24/2022]
Abstract
PURPOSE S-1 and gemcitabine (GS) combination therapy is a promising treatment for advanced biliary tract cancer (BTC). However, systemic administration of GS is associated with a high rate of grade 3 and 4 neutropenia. Hepatic arterial infusion (HAI) of gemcitabine may overcome this problem. We conducted a prospective phase 1 trial to determine the maximum tolerated dose (MTD) of S-1 and rates of dose-limiting toxicities (DLTs) associated with HAI of gemcitabine in patients with unresectable BTC. METHODS BTC patients were treated with 21-day cycles of HAI of gemcitabine (1000 mg/m(2) on days 1 and 8) and oral S-1 (60, 70, or 80 mg/m(2) on days 1-14) until disease progression occurred. RESULTS Fifteen patients were enrolled in the study. Grade 3 and 4 neutropenia occurred in five of 15 (33%) patients. Among six patients who were treated with 60 mg/m(2) S-1, one developed grade 4 neutropenia. DLTs (grade 4 neutropenia and bladder infection) occurred in two of six patients who were treated with 70 mg/m(2) S-1. Two of the three patients who were treated with 80 mg/m(2) S-1 experienced DLTs (grade 4 leukopenia and neutropenia and grade 3 febrile neutropenia). Thus, 80 mg/m(2) was defined as the MTD of S-1. CONCLUSION The MTD of oral S-1 in GS therapy is 80 mg/m(2). Furthermore, HAI of gemcitabine may reduce the rate of grade 3 and 4 neutropenia in BTC patients receiving GS therapy.
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Abstract
Over the last decade, transarterial therapies have gained worldwide acceptance as standard of care for inoperable primary liver cancer. Survival times after transarterial chemoembolization (TACE) continue to improve as the technique and selection criteria are refined. Transarterial treatments, frequently provided in an outpatient setting, are now safely and effectively being applied to patients with even advanced malignancy or partially decompensated cirrhosis. In the coming years, newer transarterial therapies such as radiation segmentectomy, boosted-transarterial radioembolzation, combined TACE-ablation, TACE-portal vein embolization, and transarterial infusion of cancer-specific metabolic inhibitors promise to continue improving survival and quality of life.
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13
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Bridgewater J, Galle PR, Khan SA, Llovet JM, Park JW, Patel T, Pawlik TM, Gores GJ. Guidelines for the diagnosis and management of intrahepatic cholangiocarcinoma. J Hepatol 2014; 60:1268-89. [PMID: 24681130 DOI: 10.1016/j.jhep.2014.01.021] [Citation(s) in RCA: 1057] [Impact Index Per Article: 96.1] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/12/2013] [Revised: 01/22/2014] [Accepted: 01/29/2014] [Indexed: 12/11/2022]
Affiliation(s)
- John Bridgewater
- University College, London Cancer Institute, 72 Huntley St., London WC1E 6AA, UK
| | - Peter R Galle
- Department of Internal Medicine I, University Medical Center, Johannes Gutenberg University, Mainz, Germany
| | - Shahid A Khan
- Hepatology and Gastroenterology Section, Department of Medicine, Imperial College London, UK
| | - Josep M Llovet
- HCC Translational Research Laboratory, Barcelona-Clínic Liver Cancer Group, Institut d'Investigacions Biomèdiques August Pi i Sunyer, Hospital Clinic Barcelona, Catalonia, Spain; Mount Sinai Liver Cancer Program, Division of Liver Diseases, Icahn School of Medicine at Mount Sinai, New York, USA
| | - Joong-Won Park
- Center for Liver Cancer, National Cancer Center, Goyang, Republic of Korea
| | - Tushar Patel
- Department of Transplantation, Mayo College of Medicine, Mayo Clinic, 4500 San Pablo Boulevard, Jacksonville, FL 32224, USA
| | - Timothy M Pawlik
- Department of Surgery, Sidney Kimmel Cancer Center, Johns Hopkins University School of Medicine, Harvey 611, 600 N Wolfe Street, Baltimore, MD 21287, USA
| | - Gregory J Gores
- Division of Gastroenterology and Hepatology, Mayo College of Medicine, Mayo Clinic, Rochester, MN, USA.
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Intravital microscopic research of microembolization with degradable starch microspheres. JOURNAL OF DRUG DELIVERY 2013; 2013:242060. [PMID: 24324891 PMCID: PMC3845399 DOI: 10.1155/2013/242060] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/13/2013] [Revised: 09/10/2013] [Accepted: 10/02/2013] [Indexed: 11/18/2022]
Abstract
Treatment efficacy in cancer patients using systemically applied cytostatic drugs is decreased by cytotoxic side effects, which limits the use of efficient dosages. Degradable starch microspheres (DSM) are used to apply drugs into blood vessels which supply the target organ leading to drug accumulation in the target organ by reduction of the blood flow. The present investigations show that DSM is a very effective embolization material leading to effective and enhanced accumulation of 5-FU within the liver tumor tissue of experimental induced liver cancer in rats. By using intravital microscopy, a rapid deceleration of the blood flow into the target organ is observed immediately after application of DSM. The microspheres are stepwise degraded in the direction of the systemic blood flow and are totally dissolved after 25 minutes. These stepwise processes leave the degraded material during the degradation process within the vessels leading to temporally reciprocal blood flow via some of the side-arms of the major blood vessels. By using DMS in transarterial chemoembolization (TACE), severe adverse side effects like postembolization syndrome are rarely observed when compared to other embolization materials. The complete degradation of DSM causes only a short-lasting temporary vascular occlusion, which allows a repeat application of DSM in TACE.
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15
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Maithel SK, Gamblin TC, Kamel I, Corona-Villalobos CP, Thomas M, Pawlik TM. Multidisciplinary approaches to intrahepatic cholangiocarcinoma. Cancer 2013; 119:3929-42. [PMID: 23963845 DOI: 10.1002/cncr.28312] [Citation(s) in RCA: 101] [Impact Index Per Article: 8.4] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2013] [Revised: 07/07/2013] [Accepted: 07/15/2013] [Indexed: 12/16/2022]
Abstract
After hepatocellular carcinoma, intrahepatic cholangiocarcinoma (ICC) is the second most common primary hepatic malignancy. The etiology of ICC in most patients is not known, but its incidence is on the rise worldwide. There are 3 morphologic subtypes of ICC that can be characterized on cross-sectional imaging, mass forming, periductal infiltrating, and intraductal growth; and the radiographic characteristics of ICC may vary based on the subtype. Complete surgical resection remains the only potentially curative option for patients with ICC. Routine lymphadenectomy at the time of surgical resection should be strongly considered, because lymph node status provides important prognostic information. After surgery, the 5-year survival rate for ICC remains poor at only 25% to 35% in most series. Although numerous clinical trials have been conducted using a variety of chemotherapy regimens to treat ICC, systemic options for ICC remain limited. Doublet gemcitabine and cisplatin therapy is currently considered the standard-of-care first-line therapy for patients with advanced disease. Because ICC is typically confined to the liver and systemic chemotherapy traditionally has had only limited efficacy, there has been increasing interest in locoregional therapy. Although locoregional therapy may include intra-arterial therapies, stereotactic radiotherapy, hepatic artery pump therapy, or ablation, most data are limited. The purpose of this article was to provide a multidisciplinary appraisal of the current therapeutic approaches to ICC.
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Tajima H, Kitagawa H, Tsukada T, Okamoto K, Nakanuma SI, Sakai S, Makino I, Furukawa H, Hayashi H, Oyama K, Inokuchi M, Nakagawara H, Miyashita T, Itoh H, Fujita H, Takamura H, Ninomiya I, Fushida S, Fujimura T, Ohta T, Koda W, Minami T, Ryu Y, Sanada J, Gabata T, Matsui O, Sai Y. Hepatic arterial infusion chemotherapy with gemcitabine and 5-fluorouracil or oral S-1 improves the prognosis of patients with postoperative liver metastases from pancreatic cancer. Mol Clin Oncol 2013; 1:869-874. [PMID: 24649263 PMCID: PMC3916203 DOI: 10.3892/mco.2013.152] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2012] [Accepted: 04/23/2013] [Indexed: 01/13/2023] Open
Abstract
Hepatic metastasis is a common cause of treatment failure following resection of pancreatic cancer. In this study, we report our results of hepatic arterial infusion (HAI) chemotherapy with gemcitabine (GEM) plus 5-fluorouracil (5-FU) or oral S-1 treatment for postoperative liver metastases from pancreatic cancer. Seven patients with postoperative liver metastases from pancreatic cancer received HAI with GEM plus 5-FU or oral S-1 between October, 2008 and September, 2010 at Kanazawa University Hospital (Kanazawa, Japan). Three out of the 7 cases exhibited a partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST) and stable disease (SD) was achieved in 3 out of the 7 cases (response rate, 85.7%). A decrease in serum tumor marker CA 19-9 levels was observed after 10 HAI treatment cycles in 5 out of the 7 cases. The median time to treatment failure was 8 months (range, 0–17 months). Adverse events included grade 3 leukocytopenia in 1 case and anemia in all 7 cases, although 5 out of the 7 patients were anemic prior to HAI therapy. Grade 2 thrombocytopenia was also observed in 2 cases. Non-hematological events, such as nausea, diarrhea, liver injury or neuropathy and life-threatening toxicities were not reported; however, 6 patients (85.7%) developed catheter-related complications and the HAI catheter and subcutaneous implantable port system had to be removed. These findings demonstrated that HAI may deliver high doses of chemotherapeutic agents directly into the tumor vessels, producing increased regional levels with greater efficacy and a lower incidence/severity of systemic side effects. In conclusion, HAI chemotherapy is a safe and effective treatment for liver metastases from pancreatic cancer.
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Affiliation(s)
- Hidehiro Tajima
- Department of Gastroenterological Surgery and, Division of Cancer Medicine, Graduate School of Medical Science, Kanazawa University, Kanazawa, Ishikawa 920-8641, Japan
| | - Hirohisa Kitagawa
- Department of Gastroenterological Surgery and, Division of Cancer Medicine, Graduate School of Medical Science, Kanazawa University, Kanazawa, Ishikawa 920-8641, Japan
| | - Tomoya Tsukada
- Department of Gastroenterological Surgery and, Division of Cancer Medicine, Graduate School of Medical Science, Kanazawa University, Kanazawa, Ishikawa 920-8641, Japan
| | - Koichi Okamoto
- Department of Gastroenterological Surgery and, Division of Cancer Medicine, Graduate School of Medical Science, Kanazawa University, Kanazawa, Ishikawa 920-8641, Japan
| | - Shin-Ichi Nakanuma
- Department of Gastroenterological Surgery and, Division of Cancer Medicine, Graduate School of Medical Science, Kanazawa University, Kanazawa, Ishikawa 920-8641, Japan
| | - Seisho Sakai
- Department of Gastroenterological Surgery and, Division of Cancer Medicine, Graduate School of Medical Science, Kanazawa University, Kanazawa, Ishikawa 920-8641, Japan
| | - Isamu Makino
- Department of Gastroenterological Surgery and, Division of Cancer Medicine, Graduate School of Medical Science, Kanazawa University, Kanazawa, Ishikawa 920-8641, Japan
| | - Hiroyuki Furukawa
- Department of Gastroenterological Surgery and, Division of Cancer Medicine, Graduate School of Medical Science, Kanazawa University, Kanazawa, Ishikawa 920-8641, Japan
| | - Hironori Hayashi
- Department of Gastroenterological Surgery and, Division of Cancer Medicine, Graduate School of Medical Science, Kanazawa University, Kanazawa, Ishikawa 920-8641, Japan
| | - Katsunobu Oyama
- Department of Gastroenterological Surgery and, Division of Cancer Medicine, Graduate School of Medical Science, Kanazawa University, Kanazawa, Ishikawa 920-8641, Japan
| | - Masafumi Inokuchi
- Department of Gastroenterological Surgery and, Division of Cancer Medicine, Graduate School of Medical Science, Kanazawa University, Kanazawa, Ishikawa 920-8641, Japan
| | - Hisatoshi Nakagawara
- Department of Gastroenterological Surgery and, Division of Cancer Medicine, Graduate School of Medical Science, Kanazawa University, Kanazawa, Ishikawa 920-8641, Japan
| | - Tomoharu Miyashita
- Department of Gastroenterological Surgery and, Division of Cancer Medicine, Graduate School of Medical Science, Kanazawa University, Kanazawa, Ishikawa 920-8641, Japan
| | - Hiroshi Itoh
- Department of Gastroenterological Surgery and, Division of Cancer Medicine, Graduate School of Medical Science, Kanazawa University, Kanazawa, Ishikawa 920-8641, Japan
| | - Hideto Fujita
- Department of Gastroenterological Surgery and, Division of Cancer Medicine, Graduate School of Medical Science, Kanazawa University, Kanazawa, Ishikawa 920-8641, Japan
| | - Hiroyuki Takamura
- Department of Gastroenterological Surgery and, Division of Cancer Medicine, Graduate School of Medical Science, Kanazawa University, Kanazawa, Ishikawa 920-8641, Japan
| | - Itasu Ninomiya
- Department of Gastroenterological Surgery and, Division of Cancer Medicine, Graduate School of Medical Science, Kanazawa University, Kanazawa, Ishikawa 920-8641, Japan
| | - Sachio Fushida
- Department of Gastroenterological Surgery and, Division of Cancer Medicine, Graduate School of Medical Science, Kanazawa University, Kanazawa, Ishikawa 920-8641, Japan
| | - Takashi Fujimura
- Department of Gastroenterological Surgery and, Division of Cancer Medicine, Graduate School of Medical Science, Kanazawa University, Kanazawa, Ishikawa 920-8641, Japan
| | - Tetsuo Ohta
- Department of Gastroenterological Surgery and, Division of Cancer Medicine, Graduate School of Medical Science, Kanazawa University, Kanazawa, Ishikawa 920-8641, Japan
| | - Wataru Koda
- Department of Radiology, Division of Cancer Medicine, Graduate School of Medical Science, Kanazawa University, Kanazawa, Ishikawa 920-8641, Japan
| | - Tetsuya Minami
- Department of Radiology, Division of Cancer Medicine, Graduate School of Medical Science, Kanazawa University, Kanazawa, Ishikawa 920-8641, Japan
| | - Yasuji Ryu
- Department of Radiology, Division of Cancer Medicine, Graduate School of Medical Science, Kanazawa University, Kanazawa, Ishikawa 920-8641, Japan
| | - Junichiro Sanada
- Department of Radiology, Division of Cancer Medicine, Graduate School of Medical Science, Kanazawa University, Kanazawa, Ishikawa 920-8641, Japan
| | - Toshifumi Gabata
- Department of Radiology, Division of Cancer Medicine, Graduate School of Medical Science, Kanazawa University, Kanazawa, Ishikawa 920-8641, Japan
| | - Osamu Matsui
- Department of Radiology, Division of Cancer Medicine, Graduate School of Medical Science, Kanazawa University, Kanazawa, Ishikawa 920-8641, Japan
| | - Yoshimichi Sai
- Division of Pharmacy, Kanazawa University Hospital, Kanazawa, Ishikawa 920-8641, Japan
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Radiofrequency ablation for postoperative recurrences of intrahepatic cholangiocarcinoma. Chin J Cancer Res 2013; 23:295-300. [PMID: 23359754 DOI: 10.1007/s11670-011-0295-9] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/25/2010] [Accepted: 05/19/2011] [Indexed: 12/13/2022] Open
Abstract
OBJECTIVE Most recurrent intrahepatic cholangiocarcinoma (RICC) lost the opportunity of radical resection while most nonsurgical management failed to prolong patients' survival. The efficacy and safety of radiofrequency ablation (RFA) as a local treatment for recurrent hepatocellular carcinoma have been confirmed by many clinical studies. The purpose of this study was to evaluate the efficacy, long-term survival and complications of RFA for RICC. METHODS A total of 12 patients with 19 RICCs after radical resection were included in this study. The tumors were 1.9-6.8 cm at the maximum diameter (median, 3.2±1.6 cm). All patients were treated with ultrasound guided RFA. There were two RFA approaches including percutaneous and open. RESULTS A total of 18 RFA treatment sessions were performed. Ablation was successful (evaluated by 1-month CT after the initial RFA procedure) in 18 (94.7%) of 19 tumors. By a median follow-up period of 29.9 months after RFA, 5 patients received repeated RFA because of intrahepatic lesion recurrence. The median local recurrence-free survival period and median event-free survival period after RFA were 21.0 months and 13.0 months, respectively. The median overall survival was 30 months, and the 1- and 3-year survival rates were 87.5% and 37.5%, respectively. The complication rate was 5.6% (1/18 sessions). The only one major complication was pleural effusion requiring thoracentesis. CONCLUSION This study showed RFA may effectively and safely manage RICC with 3-year survival of 37.5%. It provides a treatment option for these RICC patients who lost chance for surgery.
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Fu Y, Yang W, Wu W, Yan K, Xing BC, Chen MH. Radiofrequency ablation in the management of unresectable intrahepatic cholangiocarcinoma. J Vasc Interv Radiol 2012; 23:642-9. [PMID: 22525022 DOI: 10.1016/j.jvir.2012.01.081] [Citation(s) in RCA: 67] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2011] [Revised: 01/13/2012] [Accepted: 01/29/2012] [Indexed: 02/06/2023] Open
Abstract
PURPOSE To evaluate the efficacy of radiofrequency (RF) ablation for treatment of unresectable intrahepatic cholangiocarcinoma (ICC) and to explore the impact of prognostic variables on outcomes. MATERIALS AND METHODS From 2000-2010, 17 patients with 26 ICCs underwent RF ablation at a single institution. None of the patients were surgery candidates. Seven patients had 15 primary ICCs, and 10 patients had 11 recurrent ICCs. The median largest diameter was 4.4 cm (range 2.1-6.8 cm). A percutaneous approach was used in 15 patients, and an open approach was used in 2 patients. Early tumor necrosis, recurrence-free survival, and overall survival were analyzed. Univariate analysis was performed to evaluate 12 clinicopathologic and treatment-related variables associated with recurrence-free survival and overall survival. RESULTS Early tumor necrosis was 96.2% (25 of 26 tumors). The median follow-up period after RF ablation was 29 months. The median recurrence-free survival and overall survival were 17 months and 33 months. The 1-year, 3-year, and 5-year survival rates were 84.6%, 43.3%, and 28.9%, with an overall complication rate of 3.6% (1 of 28 sessions). Three variables were found to be closely associated with recurrence-free survival: lymph node metastases (P = .023), tumor differentiation (P = .034), and tumor number (P = .035). The only variable significantly associated with overall survival was tumor differentiation (P = .033). CONCLUSIONS Preliminary results showed that RF ablation may be an effective treatment for ICC because it achieved an acceptable survival rate in a small population. Prognostic factors might allow better patient selection and outcomes.
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Affiliation(s)
- Ying Fu
- Department of Ultrasound, Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education, Peking University Cancer Hospital & Institute, No 52 Fucheng Road, Haidian District, 100142 Beijing, China
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Rare hepatic malignant tumors: dynamic CT, MRI, and clinicopathologic features: with analysis of 54 cases and review of the literature. ACTA ACUST UNITED AC 2012; 38:511-26. [DOI: 10.1007/s00261-012-9918-y] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/17/2023]
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Treatment of unresectable cholangiocarcinoma: conventional transarterial chemoembolization compared with drug eluting bead-transarterial chemoembolization and systemic chemotherapy. Eur J Gastroenterol Hepatol 2012; 24:437-43. [PMID: 22261548 DOI: 10.1097/meg.0b013e3283502241] [Citation(s) in RCA: 55] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
BACKGROUND Unresectable cholangiocarcinoma (CCC) has a poor prognosis. Patients with intrahepatic CCC have a very limited benefit from systemic chemotherapy (ChT). The aim of this prospective study was to evaluate the feasibility, safety, and efficacy of conventional transarterial chemoembolization (cTACE) with mitomycin-C and of irinotecan-eluting beads (iDEB-TACE), and to retrospectively compare them with ChT with oxaliplatin and gemcitabine. MATERIALS AND METHODS Between June 2002 and June 2010, three independent prospective trials were carried out and compared retrospectively. Following predefined study protocols, 26 patients with histologically proven intrahepatic CCC were treated with iDEB-TACE (200 mg irinotecan), 10 patients were treated with cTACE using 15 mg mitomycin-C mixed with 5-10 ml of ionized oil (lipiodol), followed by embolization with gelfoam, and 31 patients received systemic ChT with gemcitabine and oxaliplatin. Treatment response and progression-free survival (PFS) were assessed by computer tomography or MRI every 2 months according to Response Evaluation Criteria in Solid Tumors. Clinical and laboratory data were assessed for side-effects according to National Cancer Institute-Common Toxicity Criteria. RESULTS iDEB-TACE resulted in PFS of 3.9 months and overall survival (OS) of 11.7 months, compared with a PFS of 1.8 months and OS of 5.7 months, respectively, in patients treated with cTACE, and a PFS of 6.2 months and OS of 11.0 months, respectively, in patients treated with oxaliplatin and gemcitabine. The medium follow-up of patients treated with iDEB-TACE was 12 months; 2 months after treatment, 13 patients (50%) had progressive disease, 11 patients (42%) had stable disease, and one patient had a partial response and became eligible for secondary liver resection. Local tumor control was achieved in 66% of patients; 4% had a partial response, 62% had stable disease, and 27% progressive disease. Common Toxicity Criteria grade III or IV toxicities for iDEB-TACE were abdominal pain (n=7), hepatic abscess (n=1), pleural empyema due to biliary leakage (n=1), and one death due to cholangitis with hepatic failure in a patient with liver cirrhosis. No hematological side-effects were observed. Almost every patient experienced a 'postembolization syndrome' with low-grade fever, nausea, and abdominal pain for up to 2 weeks. CONCLUSION This is the first study demonstrating that treatment of patients suffering from intrahepatic CCC with iDEB-TACE is safe in patients with normal liver function, and results in a prolongation of PFS and OS. Local tumor control, PFS and OS seem similar to systemic ChT with oxaliplatin and gemcitabine, but superior to cTACE.
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21
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Vogl TJ, Naguib NNN, Nour-Eldin NEA, Bechstein WO, Zeuzem S, Trojan J, Gruber-Rouh T. Transarterial chemoembolization in the treatment of patients with unresectable cholangiocarcinoma: Results and prognostic factors governing treatment success. Int J Cancer 2011; 131:733-40. [PMID: 21976289 DOI: 10.1002/ijc.26407] [Citation(s) in RCA: 85] [Impact Index Per Article: 6.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2011] [Accepted: 08/16/2011] [Indexed: 12/15/2022]
Abstract
The aim of the study was to evaluate the effectiveness of transarterial chemoembolization (TACE) with four chemotherapeutic protocols in terms of local tumor control and survival of patients with unresectable cholangiocarcinoma (CCC) and to identify the prognostic factors governing treatment success. In the single-centre study, 115 patients (mean ages = 60.4 years) with unresectable CCC were repeatedly treated with TACE. In total, 819 chemoembolization sessions were performed in 4 week intervals with a mean of 7.1 (range, 3-30) sessions per patient. The chemotherapeutic used was Mitomycin C only in 20.9% of patients, Gemcitabine only in 7%, Mitomycin C with Gemcitabine in 47% and combination of Gemcitabine, Mitomycin C and Cisplatin in 25.1%. Local tumor response was evaluated by MRI according to RECIST. Survival data were calculated according to the Kaplan-Meier method. Prognostic factors for patient's survival were evaluated using log-rank-test. The local tumor controls were: partial response 8.7%, stable disease 57.4% and progressive disease 33.9% of patients. The median and mean survival times from the start of TACE were 13 and 20.8 months. Survival rate from the start of TACE was 52% after 1-year, 29% after 2-years and 10% after 3-years. Initial tumor response, high tumor vascularity and Child-Pugh class A were statistically significant factors for patient's survival. No statistically significant difference between patients treated with different chemotherapy protocols was noted. In conclusion, TACE is a palliative and safe treatment option for patients with unresectable CCC. Child Pugh class B, tumor hypovascularity and initially progressive disease were poor prognostic factors for patient survival.
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Affiliation(s)
- Thomas J Vogl
- Institute for Diagnostic and Interventional Radiology, Johann Wolfgang Goethe-University Frankfurt Theodor-Stern-Kai 7, Frankfurt am Main, Germany.
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22
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Tajima H, Ohta T, Kitagawa H, Sakai S, Makino I, Hayashi H, Oyama K, Nakagawara H, Fujita H, Onishi I, Takamura H, Ninomiya I, Fushida S, Tani T, Fujimura T, Koda W, Minami T, Ryu Y, Sanada J, Gabata T, Matsui O. Pilot study of hepatic arterial infusion chemotherapy with gemcitabine and 5-fluorouracil for patients with postoperative liver metastases from pancreatic cancer. Exp Ther Med 2011; 2:265-269. [PMID: 22977495 DOI: 10.3892/etm.2011.190] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/03/2010] [Accepted: 12/28/2010] [Indexed: 01/11/2023] Open
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.
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Cao C, Yan TD, Morris DL, Bester L. Radioembolization with yttrium-90 microspheres for pancreatic cancer liver metastases: results from a pilot study. TUMORI JOURNAL 2010; 96:955-958. [PMID: 21388058 DOI: 10.1177/548.6515] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/01/2025]
Abstract
BACKGROUND Patients with liver metastases from pancreatic adenocarcinomas have a dismal prognosis. Surgical resection remains the only curative option but is appropriate for only a minority of patients as a treatment option. This is the first study to examine the safety and efficacy of radioembolization with yttirum-90 microspheres for these patients. PATIENTS AND METHODS All patients with histologically proven pancreatic carcinoma liver metastases referred to a single institution from 2006-2009 were included in the study. After radioembolization, follow-up abdominal computed tomography scans were performed to assess response according to the Response Criteria in Solid Tumors guidelines. RESULTS Seven patients were identified from our prospectively collected data base. Of the five patients with available computed tomography follow-up, 2 patients achieved a partial response and 1 patient had stable disease. One patient with partial response survived for nearly 15 months after radioembolization therapy. No patient experienced major post-radioembolization complications. CONCLUSIONS Radioembolization with yttrium-90 microspheres may have a useful role in treating patients with pancreatic carcinoma liver metastases in a multimodality setting. Results of the current study warrant further investigation of this novel treatment.
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Affiliation(s)
- Christopher Cao
- Department of Surgery, University of New South Wales, St. George Hospital, Australia
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Tajima H, Ohta T, Kitagawa H, Sakai S, Makino I, Hayashi H, Nakagawara H, Onishi I, Takamura H, Ninomiya I, Fushida S, Tani T, Fujimura T, Kayahara M, Koda W, Minami T, Ryu Y, Sanada J, Matsui O. Hepatic arterial infusion chemotherapy for post-operative liver metastases from pancreatic cancer in a patient with leukocytopenia: A case report. Exp Ther Med 2010; 1:987-990. [PMID: 22993630 DOI: 10.3892/etm.2010.160] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2010] [Accepted: 09/23/2010] [Indexed: 12/22/2022] Open
Abstract
Here, we present a case of post-operative liver metastases from pancreatic head cancer in a patient with leukocytopenia, who was safely treated by hepatic arterial infusion (HAI) chemotherapy consisting of gemcitabine and 5-FU. The patient was a 61-year-old woman who underwent pancreaticoduodenectomy for pancreatic head cancer, but was found to be an unsuitable candidate for adjuvant systemic chemotherapy due to the presence of leukocytopenia. Five months after surgery, a follow-up CT revealed two liver metastases. Intravenous systemic chemotherapy was also contraindicated due to the leukocytopenia. In the apparent absence of recurrence, excepting the liver metastases, we decided to administer HAI chemotherapy, which had already been administered following the curative surgery. HAI chemotherapy has been shown to be associated with a lower incidence of systemic side effects. Gemcitabine at a dose of 400 mg was administered via a bedside pump and infused over 30 min. After gemcitabine infusion, 250 mg of 5-FU was infused continuously over 24 h from days 1 to 5. This comprised 1 cycle of therapy. The treatment cycles were continued biweekly. After 10 cycles without severe side effects, it was found that though the size of the metastatic tumors was not reduced, tumor vascularity was. However, after the 13th treatment cycle, local recurrence and lymph node metastases were detected. By this time, the patient had recovered from the leukocytopenia, and could thus be administered systemic chemotherapy. In conclusion, HAI chemotherapy is useful and safe for the treatment of malignancies confined to the liver, even in cases where the patient is in a reduced physical condition.
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Intrahepatic cholangiocarcinoma: primary liver resection and aggressive multimodal treatment of recurrence significantly prolong survival. Ann Surg 2010; 252:107-14. [PMID: 20531002 DOI: 10.1097/sla.0b013e3181e462e6] [Citation(s) in RCA: 124] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
OBJECTIVE To evaluate the results of surgical therapy for intrahepatic cholangiocarcinoma (ICC), the incidence and the management of recurrence, and to analyze the change in approach during 2 different periods. DESIGN Retrospective study. PATIENTS AND METHODS Patient and tumor characteristics, and overall and disease-free survival were analyzed in a series of 72 consecutive patients who underwent hepatic resection for ICC. Several factors likely to influence survival after resection were evaluated. Patients were divided into 2 groups according to the year of operation (before and after 1999). Management of recurrence and survival after recurrence were also analyzed. RESULTS The 3- and 5-year overall survival rates were 62% and 48%, whereas the 3- and 5-year disease-free survival rates were 30% and 25%, respectively. The median survival time was 57.1 months. Patient and histologic characteristics before and after 1999 were similar. Survival was significantly better among patients operated after 1999, who were node-negative, did not receive blood transfusion, and underwent adjuvant chemotherapy. The overall recurrence rates before and after 1999 were comparable (66.6% and 50%, P = 0.49). The most frequent site of recurrence was the liver. A significantly large number of patients received treatment for recurrence after 1999 (81.5%) compared with the first period (8.3%). The overall 3-year survival rate after recurrence was 46%. After 1999, there was a significant improvement in 3-year survival after recurrence (56%) compared with patients operated before 1999 (0%, P = 0.004); the median survival time from the diagnosis of recurrence increased from 20 months to 66 months in the second group. CONCLUSIONS Although recurrence rate represents a frequent problem in ICC, an aggressive approach to recurrence can significantly prolong survival.
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Nishimura M. A successful treatment by hepatic arterial infusion therapy for advanced, unresectable biliary tract cancer. World J Hepatol 2010; 2:192-7. [PMID: 21160995 PMCID: PMC2999280 DOI: 10.4254/wjh.v2.i5.192] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/30/2009] [Revised: 03/23/2010] [Accepted: 03/30/2010] [Indexed: 02/06/2023] Open
Abstract
Biliary tract cancers (BTC) are relatively rare tumors, and the prognosis is extremely poor. There has been no standard chemotherapy for advanced BTC. However, recently, gemcitabine (GEM) have been used against BTC as the most active agent, and promising response rates and overall survival times with tolerable drug toxicities have been observed. In this article, two cases of advanced intrahepatic cholangiocarcinoma and unresectable metastatic gallbladder (GB) cancer are reported. They were treated with hepatic arterial infusion (HAI) chemotherapy using a combination of GEM and cisplatin, along with the systemic administration of GEM. As a consequence, multiple liver tumors, the GB cancer and metastatic lymph nodes regressed without severe drug toxicities, and favorable results (the overall survival times were 16 and 14 mo, respectively) were achieved. In conclusion, HAI therapy using GEM combined with cisplatin may be a useful and well-tolerated option for advanced BTC, especially in cases where multiple liver metastases are detected.
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Affiliation(s)
- Masako Nishimura
- Masako Nishimura, Department of Gastroenterology, Otsu Red Cross Shiga Hospital, 298 Wani- naka, Otsu, Shiga 520-0580, Japan
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Hong K, Geschwind JFH. Locoregional Intra-arterial Therapies for Unresectable Intrahepatic Cholangiocarcinoma. Semin Oncol 2010; 37:110-7. [DOI: 10.1053/j.seminoncol.2010.03.002] [Citation(s) in RCA: 32] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
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Guiu B, Vincent J, Guiu S, Ladoire S, Ortega-Deballon P, Cercueil JP, Chauffert B, Ghiringhelli F. Hepatic arterial infusion of gemcitabine-oxaliplatin in a large metastasis from colon cancer. World J Gastroenterol 2010; 16:1150-4. [PMID: 20205288 PMCID: PMC2835794 DOI: 10.3748/wjg.v16.i9.1150] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Hepatic arterial infusion (HAI) of chemotherapy can be performed in cases of liver-confined metastatic disease, resulting in increased local drug concentrations. Here we report the case of a 61-year-old man who presented with an isolated large unresectable liver metastasis of colon cancer after failure of surgery and multiple administration of systemic chemotherapy. The patient was treated with a combination of gemcitabine and oxaliplatin using HAI. The tolerance was excellent and a radiological complete response was obtained after 8 cycles of HAI. The rationale for the use of gemcitabine and oxaliplatin as well as that for the combination of the 2 drugs is discussed in this paper. HAI of gemcitabine-oxaliplatin should be evaluated in further clinical trials.
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Poggi G, Amatu A, Montagna B, Quaretti P, Minoia C, Sottani C, Villani L, Tagliaferri B, Sottotetti F, Rossi O, Pozzi E, Zappoli F, Riccardi A, Bernardo G. OEM-TACE: a new therapeutic approach in unresectable intrahepatic cholangiocarcinoma. Cardiovasc Intervent Radiol 2010; 32:1187-92. [PMID: 19727937 DOI: 10.1007/s00270-009-9694-4] [Citation(s) in RCA: 63] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/09/2009] [Accepted: 07/22/2009] [Indexed: 12/30/2022]
Abstract
Intrahepatic cholangiocarcinoma (ICC) is a rare life-threatening disease, whose only treatment with potential for cure is surgical resection. However, only 27% of patients at most are suitable for surgery when first diagnosed. For patients with unresectable disease, therapeutic options are chemotherapy or chemoradiation. We evaluated the feasibility and safety of oxaliplatin-eluting microspheres transarterial chemoembolization (OEM-TACE) associated with chemotherapy (ChT) in patients affected by unresectable ICC. Between December 2005 and May 2008 we treated nine patients (six female and three male) with unresectable ICC. All patients had undergone OEM-TACE associated with chemotherapy with oxaliplatin and gemcitabine. A retrospective comparison was carried out with a historical group of 11 patients treated with ChT only, estimating the prevalence of adverse effects and the median survival of the two groups. A total of 30 TACEs were performed during the observational time (ranging from one to seven procedures per patient). OEM-TACEs were followed by few adverse effects (AEs), without G4 AEs, according to CTACAE 3.0. According to RECIST criteria, 44% (4/9) of patients achieved partial responses and 56% (5/9) stabilization of disease. Overall survival analysis in the two groups showed a significantly increased survival in patients treated with ChT and OEM-TACE, with respect to those treated with ChT (30 vs. 12.7 months; p=0.004). In conclusion, in our experience OEM-TACE associated with ChT in the treatment of advanced unresectable ICC is a safe and feasible treatment causing no major adverse events. Although RECIST criteria can underestimate the rate of responses in patients treated with locoregional therapies, we achieved very encouraging results. A randomized multicentric trial is warranted to assess the actual superiority of OEM-TACE associated with ChT compared to conventional chemotherapy.
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Affiliation(s)
- Guido Poggi
- Division of Medical Oncology II, Department of Interventional Radiology, IRCCS S. Maugeri Foundation, Maugeri Street 10, 27100 Pavia, Italy.
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van Riel JM, Peters GJ, Mammatas LH, Honeywell RJ, Laan AC, Ruyter R, van den Berg FG, Giaccone G, van Groeningen CJ. A phase I and pharmacokinetic study of gemcitabine given by 24-h hepatic arterial infusion. Eur J Cancer 2009; 45:2519-2527. [PMID: 19556122 DOI: 10.1016/j.ejca.2009.05.025] [Citation(s) in RCA: 15] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2009] [Accepted: 05/15/2009] [Indexed: 11/23/2022]
Abstract
PURPOSE This study was performed to assess the toxicities, the maximum-tolerated dose (MTD), the pharmacokinetics and the anti-tumour activity of gemcitabine given by 24-h hepatic arterial infusion (HAI). PATIENTS AND METHODS Patients with liver malignancies received gemcitabine by 24-h HAI, weekly x 3, every 4 weeks. On day 1 or day 8 of the first cycle, patients received one administration by 24-h intravenous infusion for pharmacokinetic comparison and to determine hepatic extraction. RESULTS Thirteen patients received gemcitabine at the dose levels of 75, 135 and 180 mg/m(2). The MTD was 180 mg/m(2) with thrombocytopaenia as the dose-limiting toxicity. Pharmacokinetic analysis showed a significantly lower maximum gemcitabine plasma concentration (C(max): HAI, 26, 80 and 128 nM, respectively; IV, 229, 264 and 293 nM, respectively) and area under the plasma-concentration-versus-time curve (AUC(0-24h): HAI, 386, 1247 and 2033 nmol x h/L, respectively; IV, 3526, 4818 and 5363 nmol x h/L, respectively) during HAI, compared with intravenous infusion (both P<0.001). Additionally, the mean hepatic extraction ratios of gemcitabine at the 75, 135 and 180 mg/m(2) dose level were 0.89, 0.75 and 0.55, respectively. Hepatic extraction decreased linearly with increasing dose. The C(max) and AUC(0-24h) of 2',2'-difluoro-2'-deoxyuridine, the deaminated product of gemcitabine, were similar for HAI and intravenous infusion. Seven patients had stable disease for a median duration of 9 months (range: 2-11 months). CONCLUSIONS Gemcitabine given by 24-h HAI was well tolerated and resulted in significantly lower systemic gemcitabine plasma concentrations than intravenous infusion due to a relatively high hepatic extraction.
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Affiliation(s)
- J M van Riel
- Department of Medical Oncology, VU University Medical Center, de Boelelaan 1117, 1081 HV Amsterdam, The Netherlands
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A phase I study of gemcitabine given via intrahepatic pump for primary or metastatic hepatic malignancies. Cancer Chemother Pharmacol 2009; 64:935-44. [DOI: 10.1007/s00280-009-0945-5] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/03/2008] [Accepted: 01/21/2009] [Indexed: 12/27/2022]
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Ibrahim SM, Mulcahy MF, Lewandowski RJ, Sato KT, Ryu RK, Masterson EJ, Newman SB, Benson A, Omary RA, Salem R. Treatment of unresectable cholangiocarcinoma using yttrium-90 microspheres: results from a pilot study. Cancer 2008; 113:2119-28. [PMID: 18759346 DOI: 10.1002/cncr.23818] [Citation(s) in RCA: 210] [Impact Index Per Article: 12.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
BACKGROUND The objective of this report was to present data from an open-label cohort study in which patients with intrahepatic cholangiocarcinoma (ICC) underwent radioembolization with yttrium-90 ((90)Y) microspheres. METHODS Twenty-four patients with histologically proven ICC were treated. The planned target dose was 120 Gray. Patients were stratified according to Eastern Cooperation Oncology Group (ECOG) performance status, tumor morphology (infiltrative vs peripheral), tumor distribution (solitary vs multifocal), and the presence or absence of portal vein thrombosis (PVT). Before and after the procedure, the following variables were assessed: 1) biochemical and clinical toxicity, 2) imaging (computed tomography/magnetic resonance imaging) response according to World Health Organization and European Association for the Study of Liver Disease (EASL) criteria, and 3) median survival after the first treatment using Kaplan-Meier methodology. RESULTS In total, 48 (90)Y treatments were administered to hepatic segments or lobes. Fatigue and transient abdominal pain were reported in 18 patients (75%) and 10 patients (42%), respectively. One patient (4%) developed grade 3 bilirubin toxicity. One patient (4%) developed a treatment-related gastroduodenal ulcer. On imaging follow-up of 22 patients, tumors demonstrated a partial response in 6 patients (27%), stable disease in 15 patients (68%), and progressive disease in 1 patient (5%). By using EASL guidelines, 17 patients (77%) showed >50% tumor necrosis on imaging follow-up. Two patients (9%) demonstrated 100% tumor necrosis. The median overall survival for the entire cohort (n = 24) was 14.9 months. The median survival for patients with an ECOG performance status of 0, 1, and 2 was 31.8 months, 6.1 months, and 1 month, respectively (P < .0001); the median survival for patients without and with PVT was 31.8 months and 5.7 months, respectively (P = .0003); and the median survival for patients with peripheral versus periductal-infiltrative tumors was 31.8 months and 5.7 months, respectively (P = .0005). CONCLUSIONS Radioembolization with (90)Y may be a therapeutic option for the treatment of unresectable ICC. Cancer 2008.
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Affiliation(s)
- Saad M Ibrahim
- Department of Radiology, Section of Interventional Radiology, Northwestern Memorial Hospital, Robert H. Lurie Comprehensive Cancer Center, Chicago, Illinois 60611, USA
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Hammill CW, Wong LL. Intrahepatic cholangiocarcinoma: a malignancy of increasing importance. J Am Coll Surg 2008; 207:594-603. [PMID: 18926465 DOI: 10.1016/j.jamcollsurg.2008.04.031] [Citation(s) in RCA: 50] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2008] [Revised: 04/14/2008] [Accepted: 04/22/2008] [Indexed: 02/07/2023]
Affiliation(s)
- Chet W Hammill
- Departments of Surgery, University of Hawaii John A Burns School of Medicine, and Hawaii Medical Center-East, Honolulu, HI 96817, USA
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Gusani NJ, Balaa FK, Steel JL, Geller DA, Marsh JW, Zajko AB, Carr BI, Gamblin TC. Treatment of unresectable cholangiocarcinoma with gemcitabine-based transcatheter arterial chemoembolization (TACE): a single-institution experience. J Gastrointest Surg 2008; 12:129-37. [PMID: 17851723 DOI: 10.1007/s11605-007-0312-y] [Citation(s) in RCA: 96] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/31/2007] [Accepted: 08/16/2007] [Indexed: 02/06/2023]
Abstract
BACKGROUND Survival for patients with unresectable cholangiocarcinoma is reported to range from only 5-8 months without treatment. Systemic chemotherapy has not been shown to significantly improve survival, but newer regimens involving gemcitabine have shown increased response rates. Transcatheter arterial chemoembolization (TACE) has been shown to prolong survival in hepatocellular carcinoma patients, but experience using TACE in the treatment of cholangiocarcinoma is limited. We report our experience treating cholangiocarcinoma with TACE using chemotherapeutic regimens based on the well-tolerated drug gemcitabine. METHODS Forty-two patients with unresectable cholangiocarcinoma were treated with one or more cycles of gemcitabine-based TACE at our institution. Chemotherapy regimens used for TACE included: gemcitabine only (n=18), gemcitabine followed by cisplatin (n=2), gemcitabine followed by oxaliplatin (n=4), gemcitabine and cisplatin in combination (n=14), and gemcitabine and cisplatin followed by oxaliplatin (n=4). RESULTS Patients were 59 years of age (range 36-86) and received a median of 3.5 TACE treatments (range 1-16). Thirty-seven patients (88%) had central cholangiocarcinoma, and five (12%) had peripheral tumors. Nineteen patients (45%) had extrahepatic disease. Grade 3 adverse events (AEs) after TACE treatments were seen in five patients, whereas grade 4 AEs occurred in two patients. No patients died within 30 days of TACE. Median survival from time of first treatment was 9.1 months overall. Results did not vary by patient age, sex, size of largest initial tumor, or by the presence of extra-hepatic disease. Treatment with gemcitabine-cisplatin combination TACE resulted in significantly longer survival (13.8 months) compared to TACE with gemcitabine alone (6.3 months). CONCLUSIONS Our report represents the largest series to date regarding hepatic-artery-directed therapy for unresectable cholangiocarcinoma and provides evidence in favor of TACE as a promising treatment modality in unresectable cholangiocarcinoma. Our results suggest that gemcitabine-based TACE is well tolerated and confers better survival when given in combination therapy (with cisplatin or oxaliplatin) for patients with unresectable cholangiocarcinoma.
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Affiliation(s)
- Niraj J Gusani
- Division of Surgical Oncology, Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA 15213, USA
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Vogl TJ, Zangos S, Eichler K, Selby JB, Bauer RW. Palliative hepatic intraarterial chemotherapy (HIC) using a novel combination of gemcitabine and mitomycin C: results in hepatic metastases. Eur Radiol 2007; 18:468-76. [PMID: 17938935 DOI: 10.1007/s00330-007-0781-0] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2007] [Revised: 07/04/2007] [Accepted: 09/04/2007] [Indexed: 01/16/2023]
Abstract
To evaluate repeated hepatic intraarterial chemotherapy (HIC) as a palliative treatment option for unresectable cholangiocarcinoma and liver metastases of various origins that were progressive under systemic chemotherapy. Between 2002 and 2006, 55 patients were treated in 4-week intervals (mean five sessions). Combined gemcitabine/mitomycin was administered intraarterially within 1 h. Tumor response was evaluated after the third session according to RECIST. Treated tumor entities were colorectal carcinoma (CRC) (n = 12), breast cancer (BC) (n = 12), cholangiocarcinoma (CCC) (n = 10), pancreatic (n = 4), ovarian (n = 3), gastric, cervical, papillary (each n = 2), prostate, esophageal carcinoma, leiomyosarcoma (each n = 1), cancer of unknown primacy (CUP) (n = 5). All patients tolerated the treatment well without any major side effects or complications. In total, there were 1 complete response (CR), 19 partial responses (PR), 19 stable (SD) and 16 progressive diseases (PD). We observed 5 PR, 3 SD and 4 PD in CRC; 1 CR, 4 PR, 6 SD in BC; and 2 PR, 2 SD and 6 PD in CCC. Median survival after first HIC was 9.7 months for CRC, 11.4 months for BC and 6.0 months for CCC. HIC with gemcitabine/mitomycin is a safe, minimally invasive, palliative treatment for hepatic metastases that are progressive under systemic chemotherapy. The treatment yields respectable tumor control rates in CRC and BC patients.
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Affiliation(s)
- Thomas J Vogl
- Institute of Diagnostic and Interventional Radiology, Johann Wolfgang Goethe University Clinic, Theodor-Stern-Kai 7, 60590, Frankfurt am Main, Germany.
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Herber S, Otto G, Schneider J, Manzl N, Kummer I, Kanzler S, Schuchmann A, Thies J, Düber C, Pitton M. Transarterial chemoembolization (TACE) for inoperable intrahepatic cholangiocarcinoma. Cardiovasc Intervent Radiol 2007; 30:1156-65. [PMID: 17508242 DOI: 10.1007/s00270-007-9032-7] [Citation(s) in RCA: 75] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/27/2007] [Revised: 03/27/2007] [Accepted: 03/28/2007] [Indexed: 12/17/2022]
Abstract
The aim of this retrospective study was to determine the safety and efficacy of chemoembolization (TACE) as palliative treatment for patients with unresectable intrahepatic cholangiocarcinoma (CCA) and to compare the results with those in the literature. Fifteen patients with histology-proven CCA (5 men, 10 women) had received palliative treatment with TACE over a 6-year period. The treatment protocol comprised repeated TACE at a minimum of 8-week intervals. TACE was performed with a mixture of 10 ml Lipiodol and 10 mg mitomycin C injected into the tumor-supplying vessels. Follow-up investigations after 8-10 weeks comprised contrast-enhanced multislice spiral CT and laboratory control. Statistical evaluation included survival analysis using the Kaplan-Meier method. During the investigation period 58 TACEs (3.9 +/- 3.8; 1-15) were performed in 15 patients. Mean tumor size was 10.8 +/- 4.6 cm (range, 2.0-18.0 cm). Unifocal tumor disease was diagnosed in eight patients, and multifocal disease in seven. Mean survival was 21.1 months (95% CI, 9.4-32.5 months). At the end of the investigation period 3 patients are still alive, and 12 patients have died. The 1-, 2-, and 3-year survival rate was 51.3%, 27.5%, and 27.5% respectively. According to RECIST criteria interim best response to therapy was stable disease in 9 of 15 patients, a partial response in 1 of 15 patients, and tumor progression in 4 of 15 patients. No deaths and no acute liver failure occurred under TACE therapy. Major complications were observed in two patients, comprising anaphylactic shock owing to contrast medium administration in one and gastric ulceration due to lipiodol displacement in the second patient. These results demonstrate that TACE is a safe procedure with a moderate number of complications for patients suffering from inoperable CCA. According to recently published data on i.v. chemotherapy we suggest that TACE might be able to prolong survival in selected patients who would succumb under other palliative treatment modalities.
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Affiliation(s)
- S Herber
- Department of Diagnostic and Interventional Radiology, University of Mainz, Langenbeckstr. 1, 55131 Mainz, Germany.
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