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Hamaya S, Oura K, Morishita A, Masaki T. Cisplatin in Liver Cancer Therapy. Int J Mol Sci 2023; 24:10858. [PMID: 37446035 DOI: 10.3390/ijms241310858] [Citation(s) in RCA: 32] [Impact Index Per Article: 16.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2023] [Revised: 06/19/2023] [Accepted: 06/26/2023] [Indexed: 07/15/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is the most common primary liver tumor and is often diagnosed at an unresectable advanced stage. Systemic chemotherapy as well as transarterial chemoembolization (TACE) and hepatic arterial infusion chemotherapy (HAIC) are used to treat advanced HCC. TACE and HAIC have long been the standard of care for patients with unresectable HCC but are limited to the treatment of intrahepatic lesions. Systemic chemotherapy with doxorubicin or chemohormonal therapy with tamoxifen have also been considered, but neither has demonstrated survival benefits. In the treatment of unresectable advanced HCC, cisplatin is administered transhepatic arterially for local treatment. Subsequently, for cisplatin-refractory cases due to drug resistance, a shift to systemic therapy with a different mechanism of action is expected to produce new antitumor effects. Cisplatin is also used for the treatment of liver tumors other than HCC. This review summarizes the action and resistance mechanism of cisplatin and describes the treatment of the major hepatobiliary cancers for which cisplatin is used as an anticancer agent, with a focus on HCC.
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Affiliation(s)
- Sae Hamaya
- Department of Gastroenterology and Neurology, Kagawa University Faculty of Medicine, Kita-gun 761-0793, Japan
| | - Kyoko Oura
- Department of Gastroenterology and Neurology, Kagawa University Faculty of Medicine, Kita-gun 761-0793, Japan
| | - Asahiro Morishita
- Department of Gastroenterology and Neurology, Kagawa University Faculty of Medicine, Kita-gun 761-0793, Japan
| | - Tsutomu Masaki
- Department of Gastroenterology and Neurology, Kagawa University Faculty of Medicine, Kita-gun 761-0793, Japan
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Hoshiai S, Irie T, Mori K, Hasegawa N, Fukuda K, Ishige K, Mori K, Arai H, Takahashi N, Nakajima T. A Transarterial Chemoembolization of Balloon-Occluded Alternate Infusions of Cisplatin and Gelatin Particles for Hepatocellular Carcinoma: A Phase I/II Multicenter Prospective Study of Safety and Efficacy. J Vasc Interv Radiol 2021; 33:169-176.e1. [PMID: 34715322 DOI: 10.1016/j.jvir.2021.10.015] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/14/2021] [Revised: 08/18/2021] [Accepted: 10/18/2021] [Indexed: 10/20/2022] Open
Abstract
PURPOSE To evaluate the safety and efficacy of a newly developed technique of balloon-occluded alternate infusions of cisplatin and gelatin particles in transarterial chemoembolization (BOAI-TACE) for hepatocellular carcinoma (HCC), and to evaluate liver damage following BOAI-TACE. MATERIALS AND METHODS Forty-three patients with HCC from four medical centers were enrolled in this multicenter, prospective study. Of these, 41 patients were observed for 6 months following BOAI-TACE. The primary endpoint was the safety of BOAI-TACE, and the secondary endpoint was the objective response rate (ORR) of the HCCs at 2 months following treatment. RESULTS Three patients experienced adverse events, including one patient with facial swelling and skin rash, dissection of the celiac artery, and a bland portal vein thrombus. No major adverse events were identified. 4.9% of the patients regressed from a Child-Pugh classification of A to B. The BOAI-TACE treatment achieved a 22.0% complete response (CR) rate and a 73.2% ORR (95% confidence interval [CI]: 57.9-84.4%). In a retrospective analysis of 23 patients with HCCs above the up-to-7 criteria, the CR rate and ORR of the BOAI-TACE were 21.7% and 82.6% (95% CI: 62.3-93.6%), respectively. CONCLUSIONS BOAI-TACE is safe and effective for achieving a high ORR while preserving liver function.
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Affiliation(s)
- Sodai Hoshiai
- Department of Diagnostic and Interventional Radiology, University of Tsukuba, Tsukuba, Japan
| | - Toshiyuki Irie
- Department of Radiology, Tsukuba University Hospital Mito Clinical Education and Training Center, Mito Kyodo General Hospital, Mito, Japan
| | - Kensaku Mori
- Department of Diagnostic and Interventional Radiology, University of Tsukuba, Tsukuba, Japan
| | - Naoyuki Hasegawa
- Department of Gastroenterology, University of Tsukuba, Tsukuba, Japan
| | - Kuniaki Fukuda
- Department of Gastroenterology, University of Tsukuba, Tsukuba, Japan; Department of Gastroenterology, Kasumigaura Medical Center, Tsuchiura, Japan
| | - Kazunori Ishige
- Department of Gastroenterology, University of Tsukuba, Tsukuba, Japan; Department of Gastroenterology, Kasumigaura Medical Center, Tsuchiura, Japan
| | - Kouichi Mori
- Department of Radiology, Tsuchiura Kyodo General Hospital, Tsuchiura, Japan
| | - Hirotaka Arai
- Department of Gastroenterology, Maebashi Red Cross Hospital, Maebashi, Japan
| | - Nobuyuki Takahashi
- Department of Radiology, Tsukuba University Hospital Mito Clinical Education and Training Center, Mito Kyodo General Hospital, Mito, Japan; Department of Radiology, Tsukuba Memorial Hospital, Tsukuba, Japan
| | - Takahito Nakajima
- Department of Diagnostic and Interventional Radiology, University of Tsukuba, Tsukuba, Japan
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Fu J, Wang Y, Zhang J, Yuan K, Yan J, Yuan B, Guan Y, Wang M. The safety and efficacy of transarterial chemoembolisation with bleomycin for hepatocellular carcinoma unresponsive to doxorubicin: a prospective single-centre study. Clin Radiol 2021; 76:864.e7-864.e12. [PMID: 34452734 DOI: 10.1016/j.crad.2021.07.013] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2021] [Accepted: 07/15/2021] [Indexed: 02/07/2023]
Abstract
AIM To investigate the safety and efficacy of transarterial chemoembolisation (TACE) with bleomycin for hepatocellular carcinoma (HCC) unresponsive to doxorubicin. MATERIALS AND METHODS A randomised controlled trial was undertaken of HCC patients resistant to TACE with doxorubicin to assess the survival benefits of the experimental group (TACE with bleomycin) compared with the control group (TACE with doxorubicin). One hundred and seventy patients were allocated randomly between December 2015 and December 2017, and 80 patients of each group were analysed. The modified response evaluation criteria in solid tumours (mRECIST) was used to evaluated the tumour response every 4-6 weeks. The primary endpoint was median progression-free survival (mPFS) and median overall survival (mOS). Safety was assessed by post-procedure complications. RESULTS The study was completed in October 2018. Objective response rate (ORR) of the experimental group was 27.5% (22/80), mPFS and mOS was 5.8 and 8.1 months. ORR of the control group was 7.5% (6/80), mPFS and mOS was 2.9 and 4 months. The ORR were significantly different between two groups (χ2 = 0.348, p<0.05). The differences of mPFS and mOS between the two groups were statistically significant (χ2 = 2.865, p<0.05 and χ2 = 0.926, p<0.05, respectively). There were no significant difference in post-procedure complications (p>0.05) and no major complications occurred. CONCLUSION It is suggested that TACE with bleomycin is a safe and effective method for HCC and bleomycin can be a second-line chemotherapeutic agent for the HCC patients unresponsive to TACE with doxorubicin.
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Affiliation(s)
- J Fu
- Department of Interventional Radiology, Chinese PLA General Hospital, 28 Fuxing Road, Beijing 100853, PR China
| | - Y Wang
- Department of Interventional Radiology, Chinese PLA General Hospital, 28 Fuxing Road, Beijing 100853, PR China
| | - J Zhang
- Department of Interventional Radiology, Chinese PLA General Hospital, 28 Fuxing Road, Beijing 100853, PR China
| | - K Yuan
- Department of Interventional Radiology, Chinese PLA General Hospital, 28 Fuxing Road, Beijing 100853, PR China
| | - J Yan
- Department of Interventional Radiology, Chinese PLA General Hospital, 28 Fuxing Road, Beijing 100853, PR China
| | - B Yuan
- Department of Interventional Radiology, Chinese PLA General Hospital, 28 Fuxing Road, Beijing 100853, PR China
| | - Y Guan
- Department of Interventional Radiology, Chinese PLA General Hospital, 28 Fuxing Road, Beijing 100853, PR China
| | - M Wang
- Department of Interventional Radiology, Chinese PLA General Hospital, 28 Fuxing Road, Beijing 100853, PR China.
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Efficacy of a Glass Membrane Emulsification Device to Form Mixture of Cisplatin Powder with Lipiodol on Transarterial Therapy for Hepatocellular Carcinoma. Cardiovasc Intervent Radiol 2021; 44:766-773. [PMID: 33415417 DOI: 10.1007/s00270-020-02757-2] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/22/2020] [Accepted: 12/23/2020] [Indexed: 02/07/2023]
Abstract
PURPOSE To examine physiochemical characteristics and drug release properties of cisplatin powder and lipiodol mixtures formed by a glass membrane emulsification device compared with a 3-way stopcock. MATERIALS AND METHODS Seven different types of mixtures were evaluated: cisplatin powder and lipiodol directly mixed (suspension), complete cisplatin solution and lipiodol mixed by a 3-way stopcock or the device (emulsion), incomplete cisplatin solution and lipiodol mixed by a 3-way stopcock or the device (solid-in-water emulsion), and contrast material and cisplatin suspension mixed by a 3-way stopcock or the device (solid-in-oil emulsion). RESULT The percentages of water-in-oil were 98.08 ± 0.27% in the emulsion formed by the device, while 70.3 ± 4.63% in the emulsion formed by a 3-way stopcock (P = 0.037). Solid-in-water and solid-in-oil emulsions formed by the device showed 98.09 ± 0.38% and 98.70 ± 0.40% of water-in-oil, respectively, whereas both solid-in-water and solid-in-oil emulsions formed by a 3-way stopcock showed 0.00%. Homogenous droplet sizes were shown by using the device. The half release times of cisplatin in the emulsions formed by the device were 197 ± 19, 244 ± 24 and 478 ± 52 min, respectively, which were significantly longer than the emulsion formed by a 3-way stopcock of 8 ± 8 min (P = 0.046-0.050). Suspension showed the longest release time; however, the viscosity was lowest. CONCLUSION The glass membrane emulsification device formed almost 100% water-in-oil, whereas 3-way stopcock produced 100% oil-in-water when incomplete solution or suspension was mixed. Slower cisplatin release was shown in the emulsions formed by the device.
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Kim MS, Hong HP, Park K, Kang KA, Lee SR. In Vitro Bovine Liver Experiment of Cisplatin-Infused and Normal Saline-Infused Radiofrequency Ablation with an Internally Cooled Perfusion Electrode. Cardiovasc Intervent Radiol 2019; 42:886-892. [PMID: 30761412 DOI: 10.1007/s00270-019-02178-w] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/30/2018] [Accepted: 02/02/2019] [Indexed: 12/22/2022]
Abstract
PURPOSE To evaluate the efficacy of cisplatin-infused and normal saline-infused radiofrequency ablation (RFA) with internally cooled perfusion (ICP) electrode. MATERIALS AND METHODS Using a 200 W generator, thirty ablation zones were created and divided into three groups of 10 each as follows: group A, RFA alone with 16 gauge monopolar internally cooled (IC) electrode; group B, cisplatin-infused RFA with 16 gauge ICP electrode; and group C, normal saline-infused RFA with 16 gauge ICP electrode. Radiofrequency was applied to the explanted bovine liver for 12 min. During RFA, cisplatin and normal saline were injected into tissue at a rate of 0.5 mL/min through the ICP electrode by injection pump. Dimensions of the ablation zone and technical parameters were compared between the three groups. RESULT In the cisplatin-infused RFA group, the ablation zone size was significantly larger than that of the RFA-alone group but significantly smaller than normal saline-infused RFA group. The width of longitudinal section and volume were 3.39 ± 0.22 cm2 and 26.55 ± 4.62 cm3 in RFA-alone group, 3.88 ± 0.32 cm2 and 36.45 ± 5.46 cm3 in cisplatin-infused RFA group, and 4.52 ± 0.50 cm2 and 49.44 ± 7.55 cm3 in normal saline-infused RFA group, respectively (p < 0.05 between any two groups). The mean impedance in group A, B, and C were 60.0 ± 7.2, 50.3 ± 2.5, and 40.3 ± 4.0 Ω, respectively (p < 0.05 between any two groups). CONCLUSION Cisplatin-infused RFA with ICP electrode created the larger size of ablation zone than that of monopolar RFA with an IC electrode, but created the smaller size of ablation zone than that of normal saline-infused RFA.
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Affiliation(s)
- Myung Sub Kim
- Department of Radiology, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, 29 Saemunan-ro, Jongno-gu, Seoul, 03181, Republic of Korea
| | - Hyun Pyo Hong
- Department of Radiology, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, 29 Saemunan-ro, Jongno-gu, Seoul, 03181, Republic of Korea.
| | - Kyungmin Park
- Department of Radiology, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, 29 Saemunan-ro, Jongno-gu, Seoul, 03181, Republic of Korea
| | - Kyung A Kang
- Department of Radiology, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, 29 Saemunan-ro, Jongno-gu, Seoul, 03181, Republic of Korea
| | - Sung Ryol Lee
- Department of Surgery, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
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Ikeda K. Recent advances in medical management of hepatocellular carcinoma. Hepatol Res 2019; 49:14-32. [PMID: 30308081 DOI: 10.1111/hepr.13259] [Citation(s) in RCA: 51] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/19/2018] [Revised: 09/20/2018] [Accepted: 10/02/2018] [Indexed: 12/18/2022]
Abstract
Transcatheter arterial therapies for hepatocellular carcinoma (HCC) have developed during the last decade. A fine powder formulation of cisplatin and the new platinum agent miriplatin became standard medicines in addition to anthracyclines in transcatheter arterial chemoembolization (TACE) in Japan. Recent prospective and retrospective studies supported the usefulness of platinum agents as a chemotherapeutic at the time of varied TACE therapy. Although balloon-occluded TACE is an effective therapy for localized HCC and drug-eluting microspheres seemed to show a higher response rate in certain HCCs, the definite advantages of those procedures still remain uncertain. Intermediate stage HCC, or Barcelona Clinic Liver Cancer stage B, is regarded as a heterogeneous category with a wide spectrum of tumors and patients, and several subclassifications of the stage have been proposed to show different prognoses; there are also different recommended therapies in each subgroup. Authors have subclassified patients based on combinations of tumor size, tumor number, and liver function, with or without performance status. Because of differences of available medical resources and techniques in treatment procedures between countries, the most ideal and useful subgrouping remains inconclusive at present. Recently, a few systemic chemotherapies proved to be effective for advanced stage HCC in phase III studies: lenvatinib as the first line of therapy, and regorafenib, cabozantinib, and ramucirumab as second-line therapy. Other molecular-targeted and immune-oncological medicines are expected to follow in the near future. Some studies have suggested an advantage of early introduction of molecular-targeted therapy for TACE-resistant HCC in the intermediate stage.
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Affiliation(s)
- Kenji Ikeda
- Department of Hepatology, Toranomon Hospital, Tokyo, Japan
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He SH, Xu W, Sun ZW, Liu WB, Liu YJ, Wei HF, Xiao JR. Selective Arterial Embolization for the Treatment of Sacral and Pelvic Giant Cell Tumor: A Systematic Review. Orthop Surg 2018. [PMID: 28644557 DOI: 10.1111/os.12336] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/28/2022] Open
Abstract
Giant cell tumor of the bone (GCTB) is a locally aggressive tumor with a certain distant metastatic rate. For sacral GCT (SGCT) and pelvic GCT (PGCT), surgery has its limitations, especially for unresectable or recurrent tumors. Selective arterial embolization (SAE) is reported to be an option for treatment in several cases, but there are few systematic reviews on the effects of SAE on SGCT and/or PGCT. Medline and Embase databases were searched for eligible English articles. Inclusion and exclusion criteria were conducted before searching. All the clinical factors were measured by SPSS software, with P-values ≤0.05 considered statistically significant. A total of 9 articles were retrieved, including 44 patients receiving SAE ranging from 1 to 10 times. During the mean follow-up period of 85.8 months, the radiographic response rate was 81.8%, with a local control and overall survival rate of 75% and 81.8%, respectively. No bowel, bladder, or sexual dysfunction was observed. Three patients developed distant metastases and finally died. Patients with primary tumors tended to have better prognosis than those with recurrence (P = 0.039). The favorable outcomes of SAE suggest that it may be an alternative treatment for SGCT and PGCT patients for whom surgery is not appropriate.
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Affiliation(s)
- Shao-Hui He
- Department of Orthopaedic Oncology, Spinal Tumor Center, Changzheng Hospital, Second Military Medical University, Shanghai, China
| | - Wei Xu
- Department of Orthopaedic Oncology, Spinal Tumor Center, Changzheng Hospital, Second Military Medical University, Shanghai, China
| | - Zheng-Wang Sun
- Department of Orthopaedic Oncology, Spinal Tumor Center, Changzheng Hospital, Second Military Medical University, Shanghai, China
| | - Wei-Bo Liu
- Department of Orthopaedic Oncology, Spinal Tumor Center, Changzheng Hospital, Second Military Medical University, Shanghai, China.,Department of Spine Surgery, Central Hospital of Qingdao, Qingdao, China
| | - Yu-Jie Liu
- Department of Orthopaedic Oncology, Spinal Tumor Center, Changzheng Hospital, Second Military Medical University, Shanghai, China
| | - Hai-Feng Wei
- Department of Orthopaedic Oncology, Spinal Tumor Center, Changzheng Hospital, Second Military Medical University, Shanghai, China
| | - Jian-Ru Xiao
- Department of Orthopaedic Oncology, Spinal Tumor Center, Changzheng Hospital, Second Military Medical University, Shanghai, China
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Goda Y, Morimoto M, Irie K, Kobayashi S, Ueno M, Moriya S, Tezuka S, Ohkawa S, Morinaga S, Numata K, Tanaka K, Maeda S. Switch to miriplatin for multinodular hepatocellular carcinoma unresponsive to transarterial chemoembolization with epirubicin: a prospective study. Jpn J Clin Oncol 2017; 47:1151-1156. [DOI: 10.1093/jjco/hyx131] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2017] [Accepted: 08/21/2017] [Indexed: 01/05/2023] Open
Affiliation(s)
- Yoshihiro Goda
- Hepatobiliary and Pancreatic Oncology, Kanagawa Cancer Center
| | - Manabu Morimoto
- Hepatobiliary and Pancreatic Oncology, Kanagawa Cancer Center
| | - Kuniyasu Irie
- Hepatobiliary and Pancreatic Oncology, Kanagawa Cancer Center
| | | | - Makoto Ueno
- Hepatobiliary and Pancreatic Oncology, Kanagawa Cancer Center
| | - Satoshi Moriya
- Hepatobiliary and Pancreatic Oncology, Kanagawa Cancer Center
| | - Shun Tezuka
- Hepatobiliary and Pancreatic Oncology, Kanagawa Cancer Center
| | - Shinichi Ohkawa
- Hepatobiliary and Pancreatic Oncology, Kanagawa Cancer Center
| | | | - Kazushi Numata
- Gastroenterological Center, Yokohama City University Medical Center
| | - Katsuaki Tanaka
- Gastroenterological Center, Yokohama City University Medical Center
| | - Shin Maeda
- Department of Gastroenterology, Yokohama City University Graduate School of Medicine, Yokohama, Japan
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Imai N, Ishigami M, Ishizu Y, Kuzuya T, Honda T, Hayashi K, Hirooka Y, Goto H. Transarterial chemoembolization for hepatocellular carcinoma: A review of techniques. World J Hepatol 2014; 6:844-850. [PMID: 25544871 PMCID: PMC4269903 DOI: 10.4254/wjh.v6.i12.844] [Citation(s) in RCA: 49] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/12/2014] [Revised: 10/07/2014] [Accepted: 10/29/2014] [Indexed: 02/06/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is one of the most common malignant diseases worldwide. While curative therapies, including resection, liver transplantation, and percutaneous ablation (percutaneous ethanol injection and radiofrequency ablation), are applicable for only a portion of the HCC population, transcatheter arterial chemoembolization (TACE) has been recognized as an effective palliative treatment option for patients with advanced HCC. TACE is also used even for single HCCs in which it is difficult to perform surgical resection or locoregional treatment due to systemic co-morbidities or anatomical problems. TACE has become widely adopted in the treatment of HCC. By using computed tomography-angiography, TACE is capable of performing diagnosis and treatment at the same time. Furthermore, TACE plays an important role in the multidisciplinary treatment for HCC when combined with other treatment. In this review, we first discuss the history of TACE, and then review the previous findings about techniques of achieving a locoregional treatment effect (liver infarction treatment, e.g., ultra-selective TACE, balloon-occluded TACE), and the use of TACE as a drug delivery system for anti-cancer agents (palliative, e.g., platinum complex agents, drug-eluting beads) for multiple lesions.
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Dong J, Li W, Dong A, Mao S, Shen L, Li S, Gong X, Wu P. Gene therapy for unresectable hepatocellular carcinoma using recombinant human adenovirus type 5. Med Oncol 2014; 31:95. [PMID: 24990099 DOI: 10.1007/s12032-014-0095-4] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/20/2014] [Accepted: 06/21/2014] [Indexed: 12/21/2022]
Abstract
The objective of this study was to assess the clinical efficacy of genetically engineered recombinant human adenovirus type 5 (rhAd5) plus transcatheter arterial chemoembolization in patients with unresectable hepatocellular carcinoma (HCC). Data from two groups of patients with unresectable HCC were retrospectively reviewed. One group included 149 patients treated with rhAd5 injection, and the other included 150 control patients without gene therapy. Differences in short-term treatment effectiveness and adverse events were recorded and compared between the two groups. Our results indicated that for patients with higher tumor staging in the treatment group, the overall response rate and the disease control rate were higher than those in the control group, but not statistically significant (P > 0.05). The total progression free survival (PFS) and overall survival (OS) were significantly longer in the treatment group than the control group (240 vs. 196 days, P < 0.05; and 1,526 vs. 1,236 days, P = 0.000; respectively). The overall incidence rate of treatment-related adverse effects was similar (P > 0.05). No serious complications were observed. In conclusion, this study suggests that rhAd5 is a safe, effective gene therapy that prolongs the PFS and OS time of patients with unresectable HCC.
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Affiliation(s)
- Jun Dong
- Department of Medical Imaging and Image Guided Therapy, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, East Dong Feng Road 651, Guangzhou, 510060, Guangdong, People's Republic of China
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Yoshimitsu K. Transarterial chemoembolization using iodized oil for unresectable hepatocellular carcinoma: perspective from multistep hepatocarcinogenesis. Hepat Med 2014; 6:89-94. [PMID: 25114603 PMCID: PMC4086665 DOI: 10.2147/hmer.s31440] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/21/2022] Open
Abstract
Transarterial chemoembolization (TACE) using iodized oil (Lipiodol®) (Lp-TACE) as a carrier of chemotherapeutic agents has been routinely performed to control hepatocellular carcinomas (HCC) in Japan, and its use has yielded fairly beneficial therapeutic results. Lipiodol is thought to pass through the tumor sinusoids of HCC and reach the outflow drainage areas, namely, the portal venous side of the tumor. By doing this, Lipiodol blocks not only the tumor’s arterial inflow but also its portal venous outflow, providing sufficient ischemic effects. It is known that the inflow blood system, tumor sinusoids, and outflow blood system change drastically during the process of multistep hepatocarcinogenesis; thus, it is reasonable to postulate that the distribution of Lipiodol and the subsequent therapeutic effect of Lp-TACE may also change during that process. Arterial inflow to HCC is highest for moderately differentiated HCC (mHCC) and is relatively low in well or poorly differentiated HCC (wHCC and pHCC, respectively). It has been suggested that the metabolic state of wHCC and mHCC is aerobic, while that of pHCC is anaerobic. The tumor sinusoids in wHCC and mHCC are small in size and large in number, while those in pHCC are large in size and small in number. This finding results in a greater chance of tumor cell exposure to chemotherapeutic agents in the former and a lesser chance in the latter. The outflow tract, namely, the drainage system via the residual portal venous branches within the pseudocapsule, is more complete in mHCC and pHCC and less so in wHCC. Considering all of these components of HCC of different histological grades, Lp-TACE should have the greatest effect on mHCC and a relatively low effect on wHCC and pHCC. To achieve consistently high therapeutic results, it is important to consider these components, which affect the sensitivity of HCC to Lp-TACE, to maximize both the chemotherapeutic and ischemic effects of this therapy.
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Affiliation(s)
- Kengo Yoshimitsu
- Department of Radiology, Faculty of Medicine, Fukuoka University, Fukuoka, Japan
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12
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McNamara MG, Knox JJ. Systemic therapy for hepatocellular carcinoma. Hepat Oncol 2014; 1:23-38. [PMID: 30190939 PMCID: PMC6114012 DOI: 10.2217/hep.13.10] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022] Open
Abstract
Optimal treatment of hepatocellular carcinoma (HCC) is clinically challenging. Systemic treatment for advanced HCC was limited until the approval of sorafenib. This discovery resulted in the advent of many clinical trials. An ongoing Phase III trial is examining the benefit of adjuvant sorafenib. Utilization of doxorubicin-eluting bead embolization may offer safer treatment in eligible HCC patients. The use of systemic treatment peritransarterial chemoembolization is also being investigated. Many targeted therapies are being explored as first-/second-line treatment options in advanced HCC. The potential benefit of c-MET inhibitors, particularly in those with advanced, MET high expression HCC, may result in new systemic patient-directed targeted medicinal approaches. Remaining dilemmas query the appropriate management of patients with advanced Child-Pugh B, HCC and those recurring post-transplant.
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Affiliation(s)
- Mairéad G McNamara
- Department of Medical Oncology, Princess Margaret Cancer Centre, 610 University Avenue, Toronto, Ontario, M5G 2M9, Canada
| | - Jennifer J Knox
- Department of Medical Oncology, Princess Margaret Cancer Centre, 610 University Avenue, Toronto, Ontario, M5G 2M9, Canada
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Nakanishi K, Osuga K, Hori S, Hamada K, Hashimoto N, Araki N, Yoshikawa H, Tomiyama N. Transarterial embolization (TAE) of sacral giant cell Tumor (GCT) using spherical parmanent embolic material superabsorbant polymer microsphere (SAP-MS). SPRINGERPLUS 2013; 2:666. [PMID: 24353982 PMCID: PMC3866374 DOI: 10.1186/2193-1801-2-666] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/25/2013] [Accepted: 12/06/2013] [Indexed: 11/10/2022]
Abstract
Purpose We retrospectively evaluated our experience of transcatheter arterial embolization (TAE) of the sacral GCT with use of a spherical permanent embolic agent, superabsorbant polymer microsphere (SAP-MS) as an alternative treatment modality. Materials and methods From 1997 to 2011, four patients with sacral GCT were treated with TAE. In all cases, SAP-MS was used as an embolic material. The effects of TAE were evaluated for improvement of patients’ symptoms, radiographic change such as vascularity of tumor, size of tumor and occurrence of reossification. Results Of the four patients, three responded favorably to TAE with improvement in pain and neurologic symptoms with long-term follow up. Diminished vascularity, stabilization of tumor size and reossification were shown radiographically. One patient died because of tumor growth 26 months after the initial TAE. Conclusion In sacral GCT, TAE using SAP-MS might be useful for symptom improvement, reossification of the lesion and stabilization of tumor size.
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Affiliation(s)
- Katsuyuki Nakanishi
- Department of Diagnostic Radiology, Osaka Medical Center for Cancer and Cardiovascular Diseases, 1-3-3, Nakamichi, Higashinari-ku Osaka, 537-8511 Japan
| | - Keigo Osuga
- Department of Diagnostic and Interventional Radiology Osaka University Graduate School of Medicine, Osaka, Japan
| | - Shinichi Hori
- Gate Tower Institute for Image Guided Therapy, Osaka, Japan
| | - Kenichiro Hamada
- Department of Orthopedic Surgery, Osaka University Graduate School of Medicine, Osaka, Japan
| | - Nobuyuki Hashimoto
- Department of Orthopedic Surgery, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, Japan
| | - Nobuhito Araki
- Department of Orthopedic Surgery, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, Japan
| | - Hideki Yoshikawa
- Department of Orthopedic Surgery, Osaka University Graduate School of Medicine, Osaka, Japan
| | - Noriyuki Tomiyama
- Department of Diagnostic and Interventional Radiology Osaka University Graduate School of Medicine, Osaka, Japan
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Kudo M, Tateishi R, Yamashita T, Ikeda M, Furuse J, Ikeda K, Kokudo N, Izumi N, Matsui O. Current status of hepatocellular carcinoma treatment in Japan: case study and discussion-voting system. Clin Drug Investig 2013. [PMID: 22873626 DOI: 10.2165/1163024-s0-000000000-00000] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
The Toward Integrated Treatment of Advanced Hepatocellular Carcinoma with Nexavar (TiTAN) Symposium was held in August 2010 in Tokyo, Japan, during which the position of sorafenib (Nexavar®) in the treatment of HCC in Japan (for which it received approval in 2009) was discussed by a panel of eight expert hepatologists in a session chaired by Dr Kudo. The following article focuses on the discussion that went on during this session, including question and answer sessions regarding the experiences of the 350 conference attendees in treating patients with HCC, as well as some of the more challenging disease management issues. Since 2008, when the phase III Sorafenib Hepatocellular Carcinoma Assessment Randomized Protocol (SHARP) trial demonstrated an increase in the median overall survival (OS) for patients with unresectable HCC treated with sorafenib compared with placebo, international and Japanese guidelines recommend sorafenib as a first-line option for patients with advanced HCC Child-Pugh liver function class A who have extrahepatic metastasis. Sorafenib is also recommended for patients unresponsive to transarterial chemoembolization (TACE) or hepatic arterial infusion chemotherapy (HAIC). Importantly, if HCC is judged to be unresponsive to TACE, treatment should be switched to sorafenib in a timely manner. Almost half of the conference attendees said that they used both the Japan Society of Hepatology clinical practice guidelines and the clinical practice guidelines for HCC when determining treatment strategies for individual HCC patients. Sorafenib should currently not be used as adjuvant therapy or in combination with TACE or HAIC until evidence from ongoing clinical trials shows that it is beneficial in these settings.
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Affiliation(s)
- Masatoshi Kudo
- Department of Gastroenterology and Hepatology, Kinki University School of Medicine, 377-2 Ohno-Higashi, Osaka-Sayama, Osaka, Japan.
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15
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Kudo M, Tateishi R, Yamashita T, Ikeda M, Furuse J, Ikeda K, Kokudo N, Izumi N, Matsui O. Current status of hepatocellular carcinoma treatment in Japan: case study and discussion-voting system. Clin Drug Investig 2013; 32 Suppl 2:37-51. [PMID: 22873626 DOI: 10.1007/bf03265495] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/19/2023]
Abstract
The Toward Integrated Treatment of Advanced Hepatocellular Carcinoma with Nexavar (TiTAN) Symposium was held in August 2010 in Tokyo, Japan, during which the position of sorafenib (Nexavar®) in the treatment of HCC in Japan (for which it received approval in 2009) was discussed by a panel of eight expert hepatologists in a session chaired by Dr Kudo. The following article focuses on the discussion that went on during this session, including question and answer sessions regarding the experiences of the 350 conference attendees in treating patients with HCC, as well as some of the more challenging disease management issues. Since 2008, when the phase III Sorafenib Hepatocellular Carcinoma Assessment Randomized Protocol (SHARP) trial demonstrated an increase in the median overall survival (OS) for patients with unresectable HCC treated with sorafenib compared with placebo, international and Japanese guidelines recommend sorafenib as a first-line option for patients with advanced HCC Child-Pugh liver function class A who have extrahepatic metastasis. Sorafenib is also recommended for patients unresponsive to transarterial chemoembolization (TACE) or hepatic arterial infusion chemotherapy (HAIC). Importantly, if HCC is judged to be unresponsive to TACE, treatment should be switched to sorafenib in a timely manner. Almost half of the conference attendees said that they used both the Japan Society of Hepatology clinical practice guidelines and the clinical practice guidelines for HCC when determining treatment strategies for individual HCC patients. Sorafenib should currently not be used as adjuvant therapy or in combination with TACE or HAIC until evidence from ongoing clinical trials shows that it is beneficial in these settings.
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Affiliation(s)
- Masatoshi Kudo
- Department of Gastroenterology and Hepatology, Kinki University School of Medicine, 377-2 Ohno-Higashi, Osaka-Sayama, Osaka, Japan.
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16
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Hepatic arterial infusion chemotherapy for advanced hepatocellular carcinoma in Japan. Cancers (Basel) 2012; 4:165-83. [PMID: 24213234 PMCID: PMC3712670 DOI: 10.3390/cancers4010165] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2012] [Revised: 02/08/2012] [Accepted: 02/16/2012] [Indexed: 12/17/2022] Open
Abstract
Transcatheter methods such as transcatheter arterial chemoembolization (TACE) and hepatic arterial infusion chemotherapy (HAIC) have an important role in the treatment for advanced hepatocellular carcinoma (HCC). Recently, sorafenib, an inhibitor of tyrosine kinases, has been found to obtain survival benefits in patients with HCC, leading to major advances in the treatment of advanced HCC. However, it is associated with a low tumor response rate, minimal survival advantage, and high rates of adverse events. On the other hand, high rates of objective treatment response with HAIC for advanced HCC have been reported, although convincing evidence of it contributing to overall survival in HAIC has been lacking. In Japan, HAIC still tends to be the preferred method for the treatment of advanced HCC, even in patients with poor liver function. However, the choice of chemotherapeutic agents in TACE/HAIC for HCC varies between institutions. In this review, based on studies reported to date in the literature, we refer to current knowledge regarding the chemotherapeutic agents used for TACE/HAIC for HCC in Japan and consider the future perspectives for HAIC for this cancer.
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Liapi E, Geschwind JFH. Medium-sized HCC: achieving effective local tumor control with combined chemoebolization and radiofrequency ablation. Ann Surg Oncol 2011; 18:1527-8. [PMID: 21431403 DOI: 10.1245/s10434-011-1679-2] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [MESH Headings] [Grants] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
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