Effectiveness of Drug Eluting TACE in Primary HCC

Study Overview
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Brief Summary
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the aim of this work to compare effectiveness of drug-eluting bead trans-arterial chemo-embolization and conventional trans-arterial chemo-embolization of hepatic cell carcinoma in the aspect of (Tumor response via m-RECIST criteria), (liver injury via Liver function tests and tumor markers) and (survival outcome) of patients treated in Assiut university .

Detailed Description
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Hepatocellular carcinoma (HCC) is the sixth most common cancer in the world and the third most common cause of cancer-related death .. With improved surveillance of patients with chronic liver disease and advances in imaging, more patients are diagnosed with early-stage HCC . For the treatment of early stage HCC, curative therapies including liver transplantation, hepatic resection, and radio frequency ablation (RFA) are recommended. Liver transplantation is the treatment option especially for patients with decompensated cirrhosis, but potential recipients outnumber donors. Hepatic resection is widely used as the main choice of treatment for resectable HCC. However, the risk of postoperative hepatic dysfunction often precludes surgery. For unresectable patient, trans-arterial chemo-embolization (TACE) was the treatment of choice . At 2014, Yang et al. compared the treatment effects of hepatic resection, RFA, and conventional TACE on long-term survival. It was found that the range of patients treated by TACE in clinical practice reported survivals widely range from 8-26% at 5-years. which was similar to that with hepatic resection and RFA in patients with single-nodule HCC of 3 cm or smaller without vascular invasion when the underlying liver status was balanced among the patients receiving each treatment. In addition, most of the patients initially treated with c-TACE achieved a complete response, which was one of the independent prognostic factors of survival, although some should receive repeated treatments. However, when c-TACE is used as an initial treatment, special care should be taken to obtain a complete response, and surveillance for tumor recurrence should be undertaken. These results are consistent with those of cohort studies demonstrating that TACE provided overall survival similar to hepatic resection in early-stage HCC . Conventional (Lipiodol) TACE Base on technique with emulsified combination of chemotherapy such as Doxorubicin and Lipiodol administrate via arterial feeder. Less in systemic chemotherapy and increase overall survival rate were the most concern in treatment but many studies reported side effects from conventional (Lipiodol) TACE significantly among an improvement of overall survival rate . Conventional TACE may cause side effects because it can damage healthy cells as it kills cancer cells. Side effects can develop any time during, immediately after or a few days or weeks after chemotherapy . in addition to the patient needed frequent ablation after a short time . The most commonly Side Effect of TACE is (Post embolization syndrome) which is a group of symptoms . include : fever, Right upper quadrant pain, nausea, vomiting and fatigue . Other side effects may occur include bruising or bleeding at the catheter site, hair loss, abnormal liver functions, lung infections, gall bladder inflammation and tumor lysis syndrome . Drug-eluting bead TACE is the new method of delivering chemotherapy during TACE which uses special beads that already have the chemotherapy drug in them . after these are injected into the arteries of the liver , they slowly sustained releasing the drug to treat the tumor . The studies showed that TACE with (Hepasphere) less systemic side effect in patient than TACE with (Lipiodol) but no definite statistical difference in treatment and survival outcome. This study compares effectiveness of those methods in treatment of Hepatocellular carcinoma in Assiut university

Official Title
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Effectiveness of Drug Eluting & Conventional Trans-arterial Chemo-embolization in Treatment of Primary Hepatic Cell Carcinoma

Conditions
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Hepatic Cell Carcinoma

Intervention / Treatment
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* Drug: HepaSphere Microspheres/Doxorubicin Hydrochloride
* Drug: Lipiodol


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: patients must be 18 to 75 years old. patients must be diagnosed as primary Hepatocellular carcinoma (HCC) by radiologic imaging revealed angiogenicity pattern . All of the patient have Child-Pugh status A or B . All of the patient have BCLC stage A or B. patients must have adequate renal and liver function accepting the maneuver. patients must have adequate coagulation profile (platelets count ≥ 80 000), (prothrombin concentration ≥ 70 %). patients must haven't previous history of resection of other ablation (alcohol, radio frequency or micro wave ablation). Exclusion Criteria: patients have previous history of resection of other ablation (alcohol, radio frequency or micro wave ablation). patients with impaired coagulation profile (platelets count < 80 000), (prothrombin concentration < 70 %). patients with decompensated liver cell failure having ascites which impedes the maneuver . patients with past history of reaction to the drug used in maneuver patients with poor image quality. patients with lost follow up .

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: drug eluting bead trans arterial chemo embolization<br>the international arm is the patients embolized with drug eluting bead trans arterial chemo embolization using Hepasphere | Drug: HepaSphere Microspheres/Doxorubicin Hydrochloride<br>* evaluation the tumor (size, location and pattern of enhancement) ;and ensure portal vein patency; then evaluation of hepatic arterial anatomy, after that we determine the tumor arterial feeders and the arteries that should be avoided during the maneuver. Selective celiac and superior mesenteric angiograms were performed using 5 Fr. Catheter then superselective angiogram were used microcatheter. then injection of drug-eluting microsphere (25 mg Hepasphere 50-100 micron) loaded with 50 mg doxorubicin solution for 2 hours.<br>|
| Placebo Comparator: conventional trans arterial chemo embolization<br>the control arm is the patients embolized with drug eluting bead trans arterial chemo embolization using Lipiodol | Drug: Lipiodol<br>* evaluation the tumor (size, location and pattern of enhancement) ;and ensure portal vein patency; then evaluation of hepatic arterial anatomy, after that we determine the tumor arterial feeders and the arteries that should be avoided during the maneuver. Selective celiac and superior mesenteric angiograms were performed using 5 Fr. Catheter then superselective angiogram were used microcatheter. then injection of prepared mixture of Lipiodol and (Doxorubicin or 5-FU) vary in dosage depend on operator consideration<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluate the effectiveness of drug-eluting bead trans-arterial chemo-embolization in patients of hepatocellular carcinoma | Evaluate the efficacy and safety of drug-eluting bead trans-arterial chemo-embolization in management of HCC patients in comparison of conventional chemo-embolization in 75 stable patients by evaluating the response of embolized lesions for each drug with modified RECIST criteria. | baseline |