BACKGROUNDTransarterial chemoembolization (TACE) is the most widely used primary treatment for unresectable hepatocellular carcinoma (HCC) due to its survival benefit, though its clinical effect is still far from satisfactory. Jiedufang (JDF) granule preparation is a commonly used Chinese herbal medicine formula for HCC. The aim of this study was to evaluate the effect of combined therapy with TACE and JDF granule preparation in treatment of unresectable HCC on survival.

METHODSA retrospective study of TACE was performed in 165 patients with unresectable HCC who were admitted between January 2002 and December 2007 in Changhai Hospital, Shanghai, China. Of the 165 patients, 80 patients (study group) received combined therapy consisting of TACE and a long-term maintenance treatment with oral JDF granule preparation, and the remaining 85 patients (control group) received TACE alone. The survival rates of both groups were calculated by the Kaplan-Meier method. Factors possibly affecting survival were assessed by multivariate analysis in the Cox proportional hazard model, such as maximum tumor size, number of lesions, portal vein invasion, and etc.

RESULTSThe median overall survival was 9.2 months (95% CI: 6.94 - 11.46) in the study group versus 5.87 months (95% CI: 4.21 - 7.52) in the control group. In the study group,survival rates of the 1-, 2- and 3-year follow-up were 41.2%, 18.4%, and 9.6%, respectively. Significant independent prognostic factors identified by the Cox regression analysis were as follows: serum hepatitis B surface antigen (HBsAg) (P = 0.014), maximum tumor size (P = 0.027), number of lesions (P < 0.001), portal vein invasion (P < 0.001), and the therapy model (P = 0.006).

CONCLUSIONCombination therapy of TACE and JDF granule preparation may significantly prolong survival of patients with unresectable HCC.

Adult ; Aged ; Antineoplastic Agents ; therapeutic use ; Carcinoma, Hepatocellular ; drug therapy ; mortality ; pathology ; therapy ; Chemoembolization, Therapeutic ; methods ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Humans ; Liver Neoplasms ; drug therapy ; mortality ; pathology ; therapy ; Male ; Middle Aged ; Retrospective Studies ; Survival Rate ; Treatment Outcome

OBJECTIVETo explore the inhibitory effect of combined administration of bear bile powder (BBP) and cyclophosphamide (Cytoxan, CTX) on colorectal cancer liver metastasis by regulating tumor promotion inflammation microenvironment.

METHODThe CRC liver metastasis mode in mice was established through in situ spleenic injection of SL4 tumor cells into spleens. The mice were randomly divided into 5 groups: the model group, the CTX (80 mg x kg(-1)) treatment group, the CTX + BBP high dose (300 mg x kg(-1)) group, the CTX + BBP middle dose (150 mg x kg(-1)) group and the CTX + BBP low dose (75 mg x kg(-1)) group. Mice were orally administered with drugs for 12 days, and sacrificed on the 13'h day for weighing their spleens and lives, HE staining, and immunofluorescence analysis. Their peripheral blood, and metastatic tumor in spleens and lives were analyzed with flow cytometry.

RESULTSpleen and liver weights of the: CTX treatment group and other doses groups were significantly lower than that of the model group. HE staining and immunofluorescence analysis showed that lymphocyte infiltration was detected in normal tissues, and macrophages infiltration was observed around the tumor tissues. Flow cytometry analysis showed that the number of T-lymphocytes in peripheral blood of different doses groups were much higher than that of the CTX treatment group (P < 0.05), with the rise in the ratio of CD4/CD8; the total number of lymphocytes in spleen cell suspension increased in different doses groups, compared to the CTX treatment group, with notable increase in B cells (P < 0.05) and significant decrease in CD11b, F4/80 cells (P < 0.05). The combined treatment showed less monocyte macrophages in liver metastasis than that of the CTX treatment group.

CONCLUSIONThe combined treatment of bear bile powder and cyclophosphamide has the effect in not only protecting liver and increase immunity, but also in anti-inflammation and antitumor by regulating tumor microenvironment and reducing the collection of mononuclear macrophages. Particularly, the combined administration of low dose of bear bile powder and CTX shows the most significant effect in reducing inflammatory cell infiltration.

Animals ; Bile ; chemistry ; Colorectal Neoplasms ; drug therapy ; mortality ; pathology ; Combined Modality Therapy ; Cyclophosphamide ; administration & dosage ; Humans ; Liver Neoplasms ; drug therapy ; mortality ; physiopathology ; secondary ; Male ; Mice ; Mice, Inbred C57BL ; Tumor Microenvironment ; drug effects ; Ursidae

Primary hepatic cancer is one of common malignant tumors. When being diagnosed, most patients were in middle and advanced stage and missed opportunities for surgical treatment. Therefore, chemotherapy and Chinese medicines become the main therapies for advanced primary hepatic cancer. This study was designed to observe the efficacy of Ganfule prescription combined with chemotherapy in treating advanced primary hepatic cancer. In the study, 58 cases of advanced primary hepatic cancer were randomly divided into the treatment group (30 cases) and the control group (28 cases). The treatment group was administered with Ganfule prescription combining with chemotherapy, while the control group was given chemotherapy alone. The tumors progress, quality of life, serum AFP level were evaluated in every three treatment cycles; and the survival rate was followed up for one year. According to the results of this study, after the treatment, there was no statistical significance in the comparison between the two groups in terms of response rate (RR) and disease control rate (DCR) (30.0% vs 25.0%, P = 0.670; 66.7% vs 60.7%, P = 0.637). The improvement rate of KPS score in the treatment group was significantly higher than that of the control group (43.33% vs 21.43%, P < 0.05). The reduction of serum AFP level in the treatment group was more significant than that of the control group (P < 0.05). During the one-year follow-up visit, the survival rate of the treatment group was 26.67%, and the control group was 25.00%, which indicated no statistical significance. This study drew the following conclusion that the oral administration of Ganfule prescription could improve the quality of life of patients of primary hepatic cancer, decrease the serum AFP level and maintain the disease control rate and the one-year survival rate.
Administration, Oral ; Adult ; Aged ; Drugs, Chinese Herbal ; administration & dosage ; Female ; Humans ; Liver Neoplasms ; drug therapy ; mortality ; pathology ; Male ; Middle Aged ; Prospective Studies ; Treatment Outcome

Although continuous low-dose (metronomic [MET]) therapy exerts anti-cancer efficacy in various cancer models, the effect of long-term MET therapy for hepatocellular carcinoma (HCC) remains unknown. This study assessed the long-term efficacy of MET on suppression of tumor growth and spontaneous metastasis in a rat model of HCC induced by administration of diethylnitrosamine for 16 wk. The rats were divided into 3 groups: MTD group received intraperitoneal (i.p.) injections of 40 mg/kg cyclophosphamide on days 1, 3, and 5 of a 21-day cycle; Control and MET groups received i.p. injections of saline and 20 mg/kg cyclophosphamide twice a week, respectively. Anti-tumor and anti-angiogenic effects and anti-metastatic mechanisms including matrix metalloproteinases (MMPs) and tissue inhibitors of MMPs (TIMPs) were evaluated. Twelve wk of MET therapy resulted in a significant reduction in intrahepatic tumors than control or MTD therapy. The MET group had fewer proliferating cell nuclear antigen-positive cells and decreased hypoxia-inducible factor-1alpha levels and microvessel density. Lung metastases were detected in 100%, 80%, and 42.9% in the control, MTD, and MET groups, respectively. MET therapy significantly decreased expression of TIMP-1, MMP-2 and -9. For mediators of pro-MMP-2 activation, MET therapy induced significant suppression in the TIMP-2 and MMP-14 level. The survival in the MET group was significantly prolonged compared to the control and MTD groups. Long-term MET scheduling suppresses tumor growth and metastasis via its potent anti-angiogenic properties and a decrease in MMPs and TIMPs activities. These results provide a rationale for long-term MET dosing in future clinical trials of HCC treatment.
Animals ; Antineoplastic Agents/*administration & dosage/*pharmacology ; Carcinoma, Hepatocellular/chemically induced/*drug therapy/mortality/pathology ; Cell Proliferation/drug effects ; Cyclophosphamide/*administration & dosage/*pharmacology ; Diethylnitrosamine ; Disease Models, Animal ; Gene Expression Regulation, Neoplastic/*drug effects ; Liver Cirrhosis/chemically induced ; Liver Neoplasms/chemically induced/*drug therapy/mortality/pathology ; Lung Neoplasms/drug therapy/pathology/secondary ; Male ; Matrix Metalloproteinases/metabolism ; Neovascularization, Pathologic/enzymology/physiopathology ; Rats ; Rats, Sprague-Dawley ; Survival Analysis ; Tissue Inhibitor of Metalloproteinases/metabolism ; Tumor Burden/drug effects

OBJECTIVETo evaluate the efficacy and safety of combination chemotherapy with paclitaxel and carboplatin for advanced breast cancer (ABC).

METHODSFrom January 2001 to March 2006, 45 patients with ABC were treated with combination chemotherapy of paclitaxel and carboplatin. Patients received infusion of paclitaxel 175 mg/m2 on day 1 every 3 weeks or 75 mg/m2 on day 1, 8, 15 every 4 weeks. Carboplatin was administrated on day 2 with a dose of area under the time-concentration curve (AUC) being 5.

RESULTSThe median number of cycles was 3 (range, 2-6). The overall response rate was 62.2%. Median time to progression was 7.0 months (95% CI: 5.1-8.9). Median overall survival was 29.0 months (95% CI: 20.1-37.9). One year survival rate was 73.3%. Response rate for first line and second line treatment were 62.1% and 62.5% , respectively. No significant difference in response existed between visceral metastasis and soft tissue metastasis. The main side effects included nausea/vomiting, neurotoxicity, and hematologic toxicities. Grade III to IV adverse events included nausea/vomiting in 2 cases (4.4%), leukopenia in 17 cases (37.8%) , and alopecia in 6 cases (13.3%).

CONCLUSIONCombination of paclitaxel and carboplatin is active in treatment of ABC with an acceptable toxicity profile.

Alopecia ; chemically induced ; Antineoplastic Combined Chemotherapy Protocols ; adverse effects ; therapeutic use ; Breast Neoplasms ; drug therapy ; mortality ; pathology ; Carboplatin ; administration & dosage ; Drug Administration Schedule ; Female ; Humans ; Leukopenia ; chemically induced ; Liver Neoplasms ; drug therapy ; secondary ; Lung Neoplasms ; drug therapy ; secondary ; Middle Aged ; Nausea ; chemically induced ; Neoplasm Metastasis ; Paclitaxel ; administration & dosage ; Postmenopause ; Premenopause ; Soft Tissue Neoplasms ; drug therapy ; secondary ; Survival Rate ; Vomiting ; chemically induced

BACKGROUNDRegional intra-arterial infusion chemotherapy (RIAC) has been more valuable to improve prognosis and quality of life of patients with inoperable pancreatic adenocarcinomas, and adjuvant RIAC plays an important role in prolonging survival and reducing risk of liver metastasis after radical resection of pancreatic cancer, but the effect of preoperative or multiple-phase RIAC (preoperative combined with postoperative RIAC) for resectable pancreatic cancers has not been investigated. In this prospective study, the effect of multiple-phase RIAC for patients with resectable pancreatic head adenocarcinoma was evaluated, and its safety and validity comparing with postoperative RIAC were also assessed.

METHODSPatients with resectable pancreatic head cancer were randomly assigned to two groups. Patients in group A (n=50) were treated with new therapeutic mode of extended pancreaticoduodenectomy combined with multiple-phase RIAC, and those in group B (n=50) were treated with extended pancreaticoduodenectomy combined with postoperative RIAC in the same period. The feasibility, compliance and efficiency of the new therapeutic mode were evaluated by tumor size, serum tumor markers, clinical benefit response (CBR), surgical complications, mortality and toxicity of RIAC. The disease-free survival time, median survival time, incidence of liver metastasis, survival rate at 1, 2, 3 and 5 years were also observed. Life curves were generated by the Kaplan-Meier method.

RESULTSThe pain relief rate and CBR in group A was 80% and 84% respectively. Serum tumor markers decreased obviously and tumors size decreased in 26% of patients after preoperative RIAC in group A. No more surgical complications, mortality or severe systemic side effects were observed in group A compared with group B. The incidence of liver metastasis in group A was 34% which was lower than 50% in group B. The disease-free survival time and median survival time in group A were 15.5 months and 18 months respectively. The 1-, 2-, 3- and 5-year survival rates were 54.87%, 34.94%, 24.51% and 12.25% respectively. There was no significant difference of survival time or survival rates between two groups.

CONCLUSIONSMultiple-phase RIAC is effective in combined therapy of resectable pancreatic head carcinomas by enhancing inhibition of tumor growth and reduction of liver metastasis, without negative effect on patients' safety or surgical procedure.

Adenocarcinoma ; drug therapy ; mortality ; pathology ; surgery ; Adult ; Aged ; Deoxycytidine ; analogs & derivatives ; therapeutic use ; Disease-Free Survival ; Female ; Fluorouracil ; therapeutic use ; Humans ; Infusions, Intra-Arterial ; methods ; Liver Neoplasms ; secondary ; Male ; Middle Aged ; Mitomycin ; therapeutic use ; Neoplasm Metastasis ; Pancreas ; drug effects ; pathology ; surgery ; Pancreatic Neoplasms ; drug therapy ; mortality ; pathology ; surgery ; Pancreaticoduodenectomy

OBJECTIVETo observe the short-term efficacy and safety of Shenqi mixture (SQM) combined with microwave coagulation in treating primary hepatocellular carcinoma (HCC).

METHODSSeventy-two patients with primary HCC of stage II-III, Karnofsky scoring > or = 50 scores and predicted survival period > or = 3 months were selected and randomly assigned into two groups, the treated group and the control group, 36 in each. Microwave therapy was applied to both groups by double leads, 60 W, 800 sec once a week for two weeks. To the treated group, SQM was given additionally through oral intake of 20 ml, three times a day for 1 month. The changes in tumor size, main symptoms, serum level of alpha-fetoprotein (AFP), immune function and adverse reaction were observed after treatment and the immune parameters of the patients were compared with 30 healthy persons in the normal control group.

RESULTS(1) In the SQM treated group, after treatment 3 patients got completely remitted (CR), 24 partial remitted (PR), 4 unchanged (NC) and 5 progressively deteriorated (PD), the effective rate being 75.00%; while in the control group, 1 got CR, 19 PR, 9 NC and 7 PD, the effective rate being 55.56%. Comparison of the effective rate between the two groups showed significant difference (P < 0.05). (2) AFP level decreased after treatment in both groups, but the decrement in the treated group was significantly higher than that in the control group (P < 0.01). (3) After treatment, in the treated group, CD3(+), CD4(+), CD4(+)/CD8(+) and NK activity were improved, Karnofsky scores increased and liver function bettered, with these improvements significantly superior to those in the control group (P < 0.01). (4) The improvement in symptoms such as hepatic region pain, fever, weakness, poor appetite and jaundice in the treated group after treatment was also superior to that in the control group (P < 0.01). (5) The 12-month, 18-month and 24-month survival rates were higher and the recurrence rate was lower in the treated group than those in the control group, showing significant difference (P < 0.05).

CONCLUSIONCombined therapy with SQM and microwave coagulation could not only kill the tumor and residue tumor cells to prevent recurrence, but also enhance the cellular immunity of organism. It is one of the effective therapies for patients with middle-advanced hepatocarcinoma, who have lost the chance of surgical operation. It could improve clinical symptoms, elevate the quality of life, prolong the survival period of patients, but shows no evident adverse reaction.

Adult ; Carcinoma, Hepatocellular ; drug therapy ; immunology ; mortality ; pathology ; Combined Modality Therapy ; Drugs, Chinese Herbal ; administration & dosage ; adverse effects ; Electrocoagulation ; methods ; Female ; Humans ; Leukocyte Count ; Liver Function Tests ; Liver Neoplasms ; drug therapy ; immunology ; mortality ; pathology ; Male ; Microwaves ; therapeutic use ; Middle Aged ; Neoplasm Recurrence, Local ; Survival Rate ; alpha-Fetoproteins ; metabolism

BACKGROUND/AIMS: Limited options remain for patients with metastatic colorectal cancer (CRC) after failure of standard systemic chemotherapy. Readministration of chemotherapeutic agents by hepatic arterial infusion (HAI) has the rationale of providing higher concentrations of chemotherapeutic agents to hepatic metastases. The present study was conducted to evaluate the efficacy and safety of HAI of fluorouracil with leucovorin (HAI 5-FU/LV) for patients with liver metastases from CRC. METHODS: Fourteen patients with liver metastases from CRC who received HAI 5-FU/LV after failure of systemic chemotherapy containing fluorouracil and leucovorin were identified and their medical records were reviewed. RESULTS: Of 10 patients evaluable for response, one partial response, six stable disease, and three progressive disease were reported. Additionally, the overall response and disease control rates were 7% and 50%, respectively. The median time to progression was 4.3 months (range, 2.9 to 5.6), to hepatic progression was 5.8 months (range, 4.7 to 6.9), and to extrahepatic progression was 5.8 months (range, 2.3 to 9.2). No grade 3/4 hematologic toxicities occurred and one case of abdominal pain and two cases of oral mucositis were the only grade 3 nonhematologic toxicities. Catheter-related complications occurred in three patients: one thrombosis, one infection, and one displacement. CONCLUSIONS: HAI 5-FU/LV was well tolerated and showed modest efficacy for patients with liver metastases from refractory CRC. Readministration of previously used chemotherapeutic agents via the hepatic artery could be an effective salvage option and warrants further investigation in a prospective trial.
Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols/*administration & dosage/adverse effects ; Colorectal Neoplasms/*pathology ; Female ; Fluorouracil/administration & dosage/*therapeutic use ; Humans ; *Infusions, Intra-Arterial ; Leucovorin/administration & dosage/*therapeutic use ; Liver Neoplasms/*drug therapy/mortality/*secondary ; Male ; Middle Aged ; *Salvage Therapy

BACKGROUND/AIMS: Prognosis of advanced hepatocellular carcinoma (HCC) treated by conventional therapies has been considered to be poor. The aim of this study was to evaluate the efficacy of hepatic arterial infusion therapy (HAIT) using FEM (5-fluorouracil, epirubicin, mitomycin-C) regimen for advanced HCC. METHODS: Eighteen patients received repeated HAIT using an implanted drug delivery system. Of the 18 patients, 8 patients had HCC with portal vein tumor thrombosis, 9 patients had recurrent HCC after transarterial chemoembolization (TACE) and 1 patient after surgical resection. The patients received 5-fluorouracil (330 mg/m2, every week), epirubicin (30 mg/m2, every 4 weeks) and mitomycin-C (2.7 mg/m2, every 2 weeks). RESULTS: Mean age was 51 years. The response rate (complete response+partial response) by tumor size on abdominal CT was 38.9%. Survival ranged from 2 to 24 months and the median survival time was 8 months. The cumulative survival rate of responders group was significantly higher than non-responders group (p=0.0385). The mean levels of serum alpha-FP and PIVKA-II in responders group decreased after HAIT (3,179 ng/mL and 2,850 ng/mL) than before (11,218 ng/mL and 4,396 ng/mL), but not significantly. Chemotherapy-related side effects were nausea, vomiting and alopecia. Three patients had catheter-related complications. One patient developed gastric ulcer. CONCLUSIONS: HAIT using FEM regimen is a useful therapeutic option for patients with advanced HCC with portal vein tumor thrombosis or ineffective response to other therapies.
Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols/*administration & dosage ; Carcinoma, Hepatocellular/*drug therapy/mortality/pathology ; Epirubicin/administration & dosage ; Female ; Fluorouracil/administration & dosage ; Humans ; Infusion Pumps, Implantable ; Infusions, Intra-Arterial ; Liver Neoplasms/*drug therapy/mortality/pathology ; Male ; Middle Aged ; Mitomycin/administration & dosage ; Survival Rate

OBJECTIVETo explore the efficacy and safty of sorafenib in Child-Pugh class B to class C hepatocellular carcinoma (HCC).

METHODSIn this three-center open-label study from November 2011 to May 2013, we randomly assigned 189 patients with advanced Child-Pugh class B or C HCC patients into two groups, one group with 95 patient to receive sorafenib (400 mg a time, twice a day) and the other group with 94 patients to receive best supportive care. The primary end points were progression-free survival and overall survival.

RESULTSThe median progression-free survival was 2.2 months and 1.9 months in the sorafenib group and best supportive care group respectively (Hazard ratio in the sorafenib group, 0.55; 95% confidence interval, 0.40-0.75; P=0.002). The median overall survival was 4.0 months and 3.5 months in the sorafenib group and best supportive care group respectively (Hazard ratio in the sorafenib group, 0.48; 95% confidence interval, 0.35-0.68; P<0.001). The main adverse effect of sorafenib was rash and acne of the skin (in 51.7% patients). The incidences of severe rash, diarrhea, and dry skin were 5.6%, 5.6%, and 2.2% in the sorafenib group. One patient reached partial response in the sorafenib group.

CONCLUSIONSSorafenib is safe in patients with liver function impaired advanced HCC. It is effective in terms of progression-free survival and overall survival compared with best supportive care. Liver functions are the important predictive factors.

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Antineoplastic Agents ; administration & dosage ; adverse effects ; therapeutic use ; Carcinoma, Hepatocellular ; drug therapy ; mortality ; pathology ; Cross-Over Studies ; Disease-Free Survival ; Female ; Humans ; Kaplan-Meier Estimate ; Liver Function Tests ; Liver Neoplasms ; drug therapy ; mortality ; pathology ; Male ; Middle Aged ; Neoplasm Invasiveness ; Neoplasm Staging ; Niacinamide ; administration & dosage ; adverse effects ; analogs & derivatives ; therapeutic use ; Phenylurea Compounds ; administration & dosage ; adverse effects ; therapeutic use ; Treatment Outcome ; Young Adult