pirarubicin and Liver-Neoplasms

Cerebral lipiodol embolism (CLE) is an extremely rare complication of transcatheter arterial chemoembolization for hepatocellular carcinoma (HCC). The authors present a case of CLE that occurred after the second hepatic arterial chemoembolization for HCC, and attempt to introduce several plausible mechanisms of CLE, after reporting the clinical and radiological findings and reviewing the medical literature.

Topics: Adult; Antineoplastic Agents; Carcinoma, Hepatocellular; Chemoembolization, Therapeutic; Contrast Media; Dose-Response Relationship, Drug; Doxorubicin; Humans; Intracranial Embolism; Iodized Oil; Liver Neoplasms; Magnetic Resonance Imaging; Male

This study aimed to investigate the clinical response and short-term survival and further explore the comprehensive factors for predicting clinical outcomes in patients with liver cancer treated by drug-eluting beads transarterial chemoembolization . Forty-nine patients with liver cancer who received drug-eluting beads transarterial chemoembolization treatment were consecutively enrolled in this cohort study. Demographic features, medical histories, clinicopathological properties, biochemical indexes, previous treatments, and chemoembolization reagents were recorded. Ten (20.4%) patients achieved complete response and 31 (63.3%) patients achieved partial response after drug-eluting beads transarterial chemoembolization treatment, with overall response rate of 83.7%. Logistic analysis revealed that high aspartate aminotransferase ( P = .041), high carbohydrate antigen 199 ( P = .030), and low hemoglobin ( P = .020) could independently predict less possibility for complete response achievement. As to survival analysis, high alkaline phosphatase ( P = .040), low albumin ( P = .033) low hemoglobin ( P = .018), portal vein invasion ( P = .025), higher Eastern Cooperative Oncology Group performance status ( P = .011), and higher Child-pugh stage ( P = .001) were independent predictors for worse overall survival. In conclusion, the present study validated that drug-eluting beads transarterial chemoembolization was effective and well tolerated for patients with liver cancer, and high aspartate aminotransferase, high alkaline phosphatase, low albumin, low hemoglobin, portal vein invasion, higher Child-pugh stage, higher Barcelona Clinic Liver Cancer stage, higher Eastern Cooperative Oncology Group performance status were correlated with worse outcomes.

Topics: Adult; Aged; Antineoplastic Agents; Chemoembolization, Therapeutic; Cohort Studies; Doxorubicin; Epirubicin; Female; Humans; Kaplan-Meier Estimate; Liver Neoplasms; Male; Middle Aged; Proportional Hazards Models; Treatment Outcome

To explore the efficiency of single application of lobaplatin in tran-scatheter arterial chemoembolization (TACE) for patients with a primary hepatic carcinoma who were unable or unwilling to undergo surgery.. 173 patients with primary hepatic carcinoma diagnosed by imaging or pathology were randomly divided into experimental and control groups and respectively treated with lobaplatin and pirarubicin hydrochloride as chemotherapeutic drugs for TACE. The amount of iodipin was regulated according to the tumor number and size, and then gelatin sponge or polyvinyl alcohol particles were applied for embolisms. The efficiency of treatment in the two groups was compared with reference to survival time and therapeutic response.. The experimental group (single lobaplatin as chemotherapy drug) was superior to control group (single pirarubicin hydrochloride as chemotherapy drug) in the aspects of survival time and therapeutic response, with statistical significance.. Single lobaplatin can be as a chemotherapy drug in TACE and has better efficiency in the aspects of mean survival time and therapeutic response, deserving to be popularized in the clinic.

Topics: Antineoplastic Agents; Carcinoma, Hepatocellular; Case-Control Studies; Chemoembolization, Therapeutic; Cyclobutanes; Doxorubicin; Female; Follow-Up Studies; Hepatic Artery; Humans; Infusions, Intra-Arterial; Liver Neoplasms; Male; Middle Aged; Neoplasm Staging; Organoplatinum Compounds; Prognosis; Survival Rate

The Japanese Study Group for Pediatric Liver Tumor (JPLT) has conducted cooperative treatment studies on hepatoblastoma (HBL) since 1991. The JPLT2 protocol was launched in 1999 to evaluate the efficacy of cisplatin/pirarubicin (CITA) under risk stratification. European and North American groups showed the improvement of HBL patients by pre- and postoperative chemotherapeutic regimens. Therefore, we evaluated the results of JPLT study and considered the future aspect of JPLT.. A total of 389 children with malignant hepatic tumors were enrolled in JPLT-2 until 2010. Data from 331 HBL cases were analyzed.. Of the 331 patients enrolled, their 5-year overall survival and event-free survival rates were 83.3 and 68.0%, respectively. While outcomes of standard-risk cases (tumors involving 3 or fewer sectors of the liver) were excellent, those of high-risk cases (tumors involving 4 sectors of the liver or with distant metastases) remained poor. For 26 high-risk or relapse/refractory HBL cases, high-dose chemotherapy (HDC) with stem cell transplantation (SCT) was carried out. Among them, 6 of 12 relapse or refractory cases died. Compared with other regimens, the CITA regimen achieved similar or superior rates of survival among children with standard-risk HBL, while HDC with SCT was not effective in patients with high-risk HBL. Presently, a global Children's Hepatic Tumor International Consortium (CHIC) project is ongoing, with a focus on international cooperation and risk stratification in the field of rare liver cancers in children. More promising strategies, including liver transplantation and new targeting drugs under global risk stratification, are being proposed.

Topics: Antineoplastic Agents; Child; Cisplatin; Disease-Free Survival; Doxorubicin; Drug Therapy, Combination; Follow-Up Studies; Hepatoblastoma; Humans; Immunosuppressive Agents; Incidence; Liver Neoplasms; Neoplasm Recurrence, Local; Retrospective Studies; Survival Rate; Treatment Outcome

There is no consensus about the most effective method for transarterial chemoembolisation of hepatocellular carcinoma.. The aim of this phase II trial was to compare the efficacy and toxicity of lipiodol transarterial chemoembolisation with amiodarone in association with pirarubicin or doxorubicin versus lipiodol transarterial chemoembolisation with anthracycline alone in a control group.. Patients with unresectable hepatocellular carcinoma and Child-Pugh A/B7 were considered eligible for the trial. transarterial chemoembolisation was repeated every 6 weeks for a maximum of 4 sessions.. Thirteen patients were randomised in the amiodarone group, and 14 were randomised in the control group. The two groups were comparable with respect to their baseline characteristics. The objective response rate according to the EASL criteria was 62% (95% CI 35-88) in the amiodarone group and 50% (95% CI 24-76) in the control group. At 1 and 2 years, survival rates were 77% (95% CI 44-92) and 52% (95% CI 22-75) in the amiodarone group, and 57% (95% CI 28-78) and 40% (95% CI 15-65) in the control group, respectively. There was no difference between the two groups in terms of toxicity.. The results of this study suggest that lipiodol transarterial chemoembolisation with anthracycline and amiodarone was safe but did not increase survival compared with lipiodol transarterial chemoembolisation with anthracycline alone in patients with hepatocellular carcinoma.

Topics: Adult; Aged; Amiodarone; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Hepatocellular; Chemoembolization, Therapeutic; Disease-Free Survival; Doxorubicin; Ethiodized Oil; Excipients; Female; Humans; Kaplan-Meier Estimate; Liver Neoplasms; Male; Middle Aged; Treatment Outcome

To observe the efficacy and side effects of transarterial chemoembolization (TACE) combined with sorafenib for advanced hepatocellular carcinoma (HCC).. Forty patients with HCC were treated with sorafenib (400 mg bid) after TACE. The efficacy was evaluated according to RECIST 1.1 criteria, and side effects were assessed by NCI CTC 3.0 criteria.. Among the forty cases, one case achieved complete remission (CR), seven cases achieved partial remission (PR), nineteen cases achieved stable disease (SD) and thirteen cases had progressive disease (PD). The disease control rate (DCR) was 67.5%. The overall survival time was 1 - 18 months, and 1-year survival rate was 54.0%. The major adverse events were hand-foot skin reaction, diarrhea and thrombocytopenia.. The combined therapy of TACE and sorafenib is effective and well tolerated for advanced HCC.

Topics: Adolescent; Adult; Aged; Antineoplastic Agents; Benzenesulfonates; Carcinoma, Hepatocellular; Chemoembolization, Therapeutic; Combined Modality Therapy; Diarrhea; Disease Progression; Doxorubicin; Female; Follow-Up Studies; Humans; Liver Neoplasms; Male; Middle Aged; Neoplasm Staging; Niacinamide; Organoplatinum Compounds; Oxaliplatin; Phenylurea Compounds; Pyridines; Remission Induction; Sorafenib; Survival Rate; Thrombocytopenia; Young Adult

A prospective phase II study was performed to determine the feasibility, efficacy and safety of arterial hepatic infusion (HAI) using pirarubicin combined with intravenous chemotherapy.. From December 1991 to April 1994, 75 patients with unresectable colorectal metastases confined to the liver were included in this multicenter study to receive intra-arterial hepatic pirarubicin and a systemic monthly regimen of 5-fluorouracil (5-FU) and folinic acid. Sixty-four patients were analyzed in the intention-to-treat analysis and 61 in the per-protocol analysis.. Tolerance of this regimen was rather good; however, functional catheter problems were observed in 29 patients (45%) resulting in failure of HAI in 21 cases (33%) after a median of three cycles; vomiting grade 3 was present in 12.5% of patients, neutropenia grade 4 in 23% and alopecia grade 3 in 19%. The overall response rate was 31.9% in intention-to-treat analysis, and 39.3% in per-protocol analysis. Extrahepatic progression was reported in only 21.7% of patients. Time to hepatic progression and extra-hepatic progression was 8.3 and 15 months, respectively, in intention-to-treat analysis, and 11 and 18 months, respectively, in per-protocol analysis. Median survival was 19 and 20 months in intention-to-treat analysis and per-protocol, respectively.. In our study, the combination of intra-arterial pirarubicin and intravenous chemotherapy demonstrated some efficacy and good tolerance in the treatment of isolated colorectal liver metastases. This treatment seems to prevent extra-hepatic spread and prolong survival time. The results of this study have to be confirmed by new trials using more active systemic chemotherapy.

Topics: Adolescent; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Colorectal Neoplasms; Disease Progression; Doxorubicin; Feasibility Studies; Female; Fluorouracil; Hepatic Artery; Humans; Infusions, Intra-Arterial; Leucovorin; Liver Neoplasms; Male; Middle Aged; Prospective Studies; Survival Rate; Time Factors

The purpose of this study was to evaluate the tolerance and efficacy of combining i.v. irinotecan, 5-fluorouracil (5-FU) and leucovorin (LV) with hepatic arterial infusion (HAI) of pirarubicin in non-resectable liver metastases from colorectal cancer.. Thirty-one patients were included in a phase II trial with i.v. irinotecan/5-FU/LV administered every 2 weeks, combined with HAI pirarubicin 60 mg/m(2) on day 1 every 4 weeks. In most cases HAI was administered via a percutaneous catheter.. The main grade 3/4 toxicity was neutropenia, encountered in 78% of the patients. When all patients were considered in the analysis, tumour response rate was 15 out of 31 [48%; 95% confidence interval (CI) 32% to 65%]. Liver resection was made possible in 11 patients (35%; 95% CI 21% to 53%). There were no toxic death. Median overall survival was 20.5 months, and median progression-free survival was 9.1 months. In patients with completely resected metastases, median overall survival was not reached and median progression-free survival was 20.2 months.. The multimodality approach used in the present study was well-tolerated and yielded dramatic responses. An aggressive approach combining i.v. and HAI chemotherapy deserves further investigation.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Colorectal Neoplasms; Combined Modality Therapy; Disease-Free Survival; Doxorubicin; Drug Administration Schedule; Female; Fluorouracil; Humans; Infusions, Intra-Arterial; Infusions, Intravenous; Irinotecan; Leucovorin; Liver Neoplasms; Male; Middle Aged; Neutropenia

Hepatoblastoma is the most common malignant liver tumor in childhood. Multicenter studies elucidate the optimal pre- or postoperative chemotherapeutic regimens. This report reviews the results of the Japanese Study Group for Pediatric Liver Tumor Protocol-1 (JPLT-1) and compares its outcomes with published reports of other studies.. From March 1991 to December 1999, 154 patients with malignant liver tumor including 145 cases of hepatoblastomas were enrolled in the JPLT study. Data from 134 cases were analyzed in this study. JPLT-1 protocol 91A was used for patients with stage I or II hepatoblastoma. The chemotherapy regimen consisted of repeated courses of cisplatin (CDDP), 40 mg/m(2), and tetrahydropyranyl (THP)-Adriamycin, 30 mg/m(2). JPLT-1 protocol 91B was administered to patients with stage IIIA, IIIB, or IV hepatoblastoma. The chemotherapy regimen consisted of repeated courses of CDDP, 80 mg/m(2), and THP-Adriamycin, 30 mg/m(2)/day for 2 days. Courses were repeated every 4 weeks as tolerated.. Seven patients died of chemotherapy-related side effects. Six of them died of sepsis caused by leukopenia and 1 case of liver failure. Overall survival rate (3-year/6-year) was 100%/100% for stage I (n = 9), 100%/95.7% for stage II (n = 32), 76.6%/73.8% for stage IIIA (n = 48), 50.3%/50.3% for stage IIIB (n = 25), 64.8%/38.9% for stage IV (n = 20), and 77.8%/73.4% overall. For stage IIIA and B disease, intravenous chemotherapy was better than intraarterial chemotherapy (66.4% v 38.1% for event-free survival and 69.3% v. 57.1% for overall survival). Patients less than 1 year of age had a better prognosis than older patients, but age was not a significant prognostic factor by multivariate analysis.. The overall and event-free survival rates of the JPLT-1 study of hepatoblastoma were comparable with the results of other multicenter studies in Europe and the United States. The event-free survival rate at 3 years for stage IIIB and IV disease was under 50%. New treatment strategies are needed for patients with advanced hepatoblastoma.

Topics: Adolescent; Age Factors; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Child; Child, Preschool; Cisplatin; Doxorubicin; Female; Hepatoblastoma; Humans; Infant; Infant, Newborn; Injections, Intra-Arterial; Injections, Intravenous; Liver Neoplasms; Male; Neoplasm Staging; Survival Rate; Treatment Outcome

Long-term results of intra-arterial chemotherapy using a reservoir (IA) for patients with unresectable hepatocellular carcinoma (HCC) were investigated. Ninety-nine patients with unresectable HCC who were treated in our department during the past 7 years were enrolled in this study. Thirty-four out of the 99 patients were treated by IA with a conventional reservoir (SR group), and 21 by IA with a double-lumen reservoir (DR group) by which IA with occlusion of hepatic arterial flow would be possible. The other 44 patients were treated by transcatheter arterial embolization (TAE group). Cumulative 1-and 2-year survival rates were 54.2 and 21.7% in DR group, respectively, and 50.8 and 35.2% in TAE group, respectively. The results of these two groups were statistically equivalent, and were more favorable than those of the SR group. Cumulative patency rate of reservoirs was maintained at 93.7% after one year and at 61.8% after two years. No difference was recognized in this rate according to the type of reservoir. We concluded that IA with a double-lumen reservoir should be taken into consideration as one of the strategies for treatment of unresectable HCC. However, maintenance of catheter-patency would be necessary for satisfactory outcome.

Topics: Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Hepatocellular; Cisplatin; Doxorubicin; Embolization, Therapeutic; Epirubicin; Female; Humans; Infusion Pumps, Implantable; Infusions, Intra-Arterial; Liver Neoplasms; Male; Middle Aged; Survival Rate

Intra-arterial hepatic (i.a.h.) administration of the doxorubicin analogue pirarubicin was evaluated in a phase I trial, based on preclinical studies that showed an advantage of pirarubicin over doxorubicin after locoregional hepatic administration. Pirarubicin was given to 9 patients with metastatic liver disease with intrapatient dose escalation. Of the 58 cycles evaluable for tolerance, no hepatobiliary or vascular toxicity was observed. The dose-limiting toxicity was granulocytopenia: the maximum administered doses ranged from 50 to 120 mg/m2, suggesting variable rates of pirarubicin hepatic extraction between patients. Pharmacokinetic data obtained in 7 patients, in which a direct comparison of intravenous (i.v.) and i.a.h. administration was possible, indicated a median i.v./i.a.h. ratio of 7.4 for the maximal plasma concentration, and a median ratio of 4 for the area under the plasma concentrations versus time curves, suggesting a high pirarubicin hepatic extraction. An unexpectedly high response rate was observed: two complete (colorectal carcinoma) and two partial responses. These data demonstrate that i.a.h. pirarubicin not only produced high locoregional concentrations and reduced systemic exposure, but can also achieve responses in metastatic liver disease of colorectal origin.

Topics: Agranulocytosis; Antibiotics, Antineoplastic; Colorectal Neoplasms; Doxorubicin; Humans; Injections, Intra-Arterial; Injections, Intravenous; Liver Neoplasms; Treatment Outcome

Twenty patients with unresectable hepatocellular carcinoma were treated by intra-arterial subsegmental injection of Cisplatin/4-0-Tetrahydro-Pyranyl-adriamycin Lipiodol suspension (CTLS). The mean single doses of Lipiodol, cisplatin and THP were 2.3 ml, 85 mg and 8.9 mg, respectively. The therapy was given once in 10 patients, twice in 8 and 3 times in two. Over 25% reduction in tumor size was recognized in 12 patients (60%). Fifty or more % decrease of alfa-feto-protein (AFP) was observed in all of 7 patients (100%) with the initial serum AFP level of more than 200 ng/ml. Although transitional and mild symptoms, such as fever, abdominal pain and vomiting were recognized in some cases, no severe complications were encountered. This method is promising as an excellent procedure for unresectable hepatocellular carcinoma.

Topics: Aged; alpha-Fetoproteins; Antibiotics, Antineoplastic; Carcinoma, Hepatocellular; Chemoembolization, Therapeutic; Cisplatin; Doxorubicin; Female; Humans; Injections, Intra-Arterial; Iodized Oil; Liver Neoplasms; Male; Middle Aged; Suspensions

A clinical trial of transarterial chemoembolization for hepatocellular carcinoma using pirarubicin (4'-0-tetrahydropyranyladriamycin, THP) was performed. Although adriamycin has been widely utilized for chemoembolization on the hepatocellular carcinoma, myocardial toxicity has been occasionally observed as its serious side effect. THP has an advantage that myocardial and gastrointestinal complications are less frequent than adriamycin. Ten patients with hepatocellular carcinoma were included in this study. Emulsion of 30-60 mg of THP and lipiodol was administered through a catheter inserted into the right or left hepatic artery, and thereafter, transarterial embolization was performed. PR was observed in seven of the ten patients and MR in two. Only one patient showed NC. Serum alpha-fetoprotein levels decreased in nine of the ten patients, and PIVKA II in the peripheral blood disappeared in all five patients that had been positive before the chemo-embolization four weeks after the treatment. Side effects included nausea in two patients just after administration of THP, but leukopenia below 2,000/cmm, was not observed in any of the patients. No other serious side effect was observed. From these results, THP was suggested to be a useful chemotherapeutic agent for hepatocellular carcinoma.

Topics: Aged; alpha-Fetoproteins; Biomarkers; Carcinoma, Hepatocellular; Clinical Trials as Topic; Doxorubicin; Embolization, Therapeutic; Female; Hepatic Artery; Humans; Iodized Oil; Liver Neoplasms; Male; Middle Aged; Protein Precursors; Prothrombin

Intra-arterial hepatic chemotherapy (IAHC) with adriamycin (ADM) has not increased its therapeutic index. For our preclinical studies, we selected pirarubicin (THP), an ADM derivative with faster cellular uptake. In rabbits with VX2 tumor in the liver we compared plasmatic and cellular pharmacokinetics of ADM and THP after i.v. and IAH therapy. For ADM, there were no differences in plasma and heart concentrations, with only a slight increase in tumoral levels after IAH compared to i.v. administration; on the other hand, with IAH THP, there was important reduction in systemic exposure with a major increase in tumoral drug distribution. In the phase I study, involving nine patients with implanted catheters, the starting dose of THP was 30 mg/m2 with a 10 mg/m2 intrapatient escalation every 3 weeks in the absence of toxicity. Pharmacokinetics were compared for i.v. and IAH administration in seven patients. The limiting toxicity was neutropenia and the maximal tolerated dose (MTD) ranged from 50 to 110 mg/m2. Moderate nausea-vomiting (grade 1-2) and alopecia (grade 1) occurred at the MTD. No arterial occlusion, gastroduodenal ulcer, hepatitis, or sclerosing cholangitis were seen. In the phase II study, in colorectal cancer patients (CRC) with metastasis confined to the liver, patients were enrolled until June 1990. THP (40 min infusion every 3 weeks) was initiated at 60 mg/m2 with 10 mg/m2 increment until grade 2 hematotoxicity. The median MTD was 85 mg/m2 (range of 60-120 mg/m2), and the median number of cycles was 7 (range of 2-11) with cumulated doses from 180 to 1,030 mg/m2. Grade 2-4 neutropenia was reached in 15 patients. Other toxicities included two arterial occlusions, one episode of gastritis, but no hepatic toxicity and no heart failure. Antitumor effect (in 18 patients) included 1 CR, 5 PR, 3 MR, 6 NC, and 3 PD. The median survival was 18+ months and 1-year survival was 73% +/- 12%. Seven patients had extrahepatic progression at this time. In conclusion, besides 5-FU or Fudr, THP is active in IAHC (probably in relation with high local extraction) on CRC liver metastases usually unresponsive to ADM. It can be given in an outpatient setting with minimal toxicity.

Topics: Animals; Colorectal Neoplasms; Doxorubicin; Drug Administration Schedule; Drug Evaluation; Hepatic Artery; Humans; Infusions, Intra-Arterial; Liver Neoplasms; Liver Neoplasms, Experimental; Neutropenia; Rabbits

Chemoresistance has become a primary hurdle in the therapeutic outcome of hepatocellular carcinoma. Substantial evidences have demonstrated that microRNAs (miRNAs) are closely associated with the chemoresistance of hepatocellular carcinoma (HCC). Our investigation is aimed at testifying the influence of microRNA-15a-5p (miR-15a-5p)/eukaryotic translation initiation factor 4E (eIF4E) on hepatocellular carcinoma resistance to pirarubicin (THP). In our study, miR-15a-5p expression was increased in THP-treated HepG2 cells. Downregulation of miR-15a-5p blocked cell growth and elevated cell apoptosis of HepG2 cells treated with THP. Moreover, eIF4E was verified as a direct target of miR-15a-5p by binding its 3'-UTR, which was confirmed by luciferase report experiment. Additionally, eIF4E was negatively associated with the miR-15a-5p expression in HepG2 cells. Mechanically, eIF4E was proven as a specific downstream of miR-15a-5p and mediated the effects of miR-15a-5p on cell viability and apoptosis of HepG2 cells treated with THP. These findings supported that miR-15a-5p facilitated THP resistance of hepatocellular carcinoma cells by modulating eIF4E, thus providing an experimental basis that miR-15a-5p might act as a novel diagnostic target in hepatocellular carcinoma resistance to THP.

Topics: 3' Untranslated Regions; Antineoplastic Agents; Apoptosis; Binding Sites; Carcinoma, Hepatocellular; Cell Proliferation; Computational Biology; Doxorubicin; Drug Resistance, Neoplasm; Eukaryotic Initiation Factor-4E; Gene Expression Regulation, Neoplastic; Hep G2 Cells; Humans; Liver Neoplasms; MicroRNAs

To retrospectively analyze the safety and long-term clinical efficacy of gelatin sponge microparticles combined with the chemotherapy drug pirarubicin for hepatic transcatheter arterial chemoembolization (GSMs-TACE) in order to treat breast cancer liver metastasis (BCLM).. Twenty-seven BCLM patients who underwent GSMs-TACE from July 2010 to July 2016 were enrolled. Tumor target blood vessels were slowly and regionally embolized with absorbable gelatin sponge particles and pirarubicin injections. Plain computed tomography (CT) scans and biochemical indexes were re-examined at 4 days after treatment, and enhanced CT scans or magnetic resonance images and biochemical indexes, 1 month later. For patients with stable tumors, the follow-up period was 2 to 3 months, and the tumor response was evaluated using Modified Response Evaluation Criteria in Solid Tumors. Adverse reactions, survival time, and prognostic factors were assessed.. By October 2019, 27 patients with BCLM had undergone GSMs-TACE, with an average of 2.44 ± 1.58 treatments. The 1-, 3-, and 5-year survival rates were 62.96%, 22.22%, and 14.81%, respectively, and the mOS was 22.0 months. No serious complications, such as acute liver failure and liver abscess, had occurred. There were two cases of acute cholecystitis that recovered after symptomatic treatment. Multivariate analysis of the prognosis showed that the primary tumor size, number of metastatic lymph nodes, estrogen receptor/progesterone receptor (ER/PR) status, and time to postoperative liver metastasis and combination therapy were statistically significant.. The overall prognosis of BCLM was poor. GSMs-TACE was safe and effective for BCLM treatment and could prolong the median survival time of patients. Therefore, it is worthy of widespread clinical application.

Topics: Breast Neoplasms; Carcinoma, Hepatocellular; Chemoembolization, Therapeutic; Doxorubicin; Female; Gelatin; Humans; Liver Neoplasms; Prognosis; Retrospective Studies

To investigate the possibility that the antioxidant stress protein Heme oxygenase-1 (HO-1) is involved in the acquisition of chemoresistance in cisplatin and pirarubicin (CITA) therapy.. Human hepatoblastoma-derived cell line (HepG2) was used to generate a knockdown cell line of HO-1 by small interfering RNA (siRNA). Expression of HO-1, epidermal growth factor receptor (EGFR), Akt, and extracellular signal-regulated kinase1/2 (ERK1/2) was examined by Western blot. The cytotoxic effect of cisplatin, pirarubicin, and EGFR inhibitor was examined by trypan blue staining. In human hepatoblastoma specimens (n = 5), changes of HO-1 expression were examined immunohistochemically before and after CITA therapy.. HO-1 expression in HepG2 cells was increased by the treatment of cisplatin (CDDP) and pirarubicin (THP) dose-dependently. In HO-1 knockdown HepG2 cells, the HO-1 was not expressed and the percentage of trypan blue-positive cells (dead cells) was significantly increased after treatment of CDDP and THP. The EGFR inhibitor decreased the levels of HO-1, phospho-Akt and phospho-ERK1/2 in HepG2 cells. Combination treatment of EGFR inhibitor with CDDP and THP increased the cytotoxic effect in HepG2 cells. In human hepatoblastoma specimens, 4 of the 5 patients (80%) showed HO-1 expression changed much stronger in the viable tumor cells after CITA therapy.. The cytotoxic effects of CDDP and THP were both enhanced under HO-1 knockdown conditions as well as under conditions that inhibit the activation pathway of HO-1 by EGFR inhibitors. EGFR/HO-1 axis may be involved in acquiring chemoresistance in HepG2 cell lines as well as in human hepatoblastoma.

Topics: Antineoplastic Agents; Cell Line; Cells, Cultured; Child, Preschool; Cisplatin; Doxorubicin; Drug Resistance, Neoplasm; ErbB Receptors; Female; Heme Oxygenase-1; Hep G2 Cells; Hepatoblastoma; Humans; Infant; Liver Neoplasms; Male

This study aimed to investigate the efficacy and safety of drug-eluting beads transarterial chemoembolization (DEB-TACE) treatment in Barcelona Clinic Liver Cancer (BCLC) stage C liver cancer patients. In 39 patients with BCLC stage C liver cancer, after the first cycle of DEB-TACE, 2 (5.1%) and 24 (61.5%) patients achieved complete response (CR) and partial response (PR) to give an overall objective response rate (ORR) of 66.7%. With respect to the second cycle of therapy, the ORR was higher in patients receiving DEB-TACE compared with those receiving cTACE (57.1% vs. 11.1%). After the first cycle of DEB-TACE treatment, the percentages of abnormal albumin (ALB), total protein (TP), total bilirubin (TBIL), and alanine aminotransferase (ALT) worsened at 1 week and recovered at 1 month. The number of patients with abnormal aspartate aminotransferase (AST) did not increase at 1 week but elevated at 1 month. After the second cycle of DEB-TACE or cTACE treatment, no difference was observed between cTACE and DEB-TACE in terms of all adverse events (AEs) at all visits, and most of the AEs did not change after the second cycle in both groups. The most common AEs after the first and second treatment cycles were pain, fever, and nausea/vomiting. These results demonstrate that DEB-TACE offers patients with BCLC stage C liver cancer a clinically active short-term treatment that is safe and relatively well tolerated.

Topics: Adult; Aged; Alanine Transaminase; Antineoplastic Agents; Aspartate Aminotransferases; Carcinoma, Hepatocellular; Chemoembolization, Therapeutic; Doxorubicin; Drug Delivery Systems; Drug-Related Side Effects and Adverse Reactions; Female; Humans; Liver Neoplasms; Male; Microspheres; Middle Aged; Neoplasm Staging; Treatment Outcome

Pirarubicin (THP) is a new generation cell cycle nonspecific anthracycline anticancer drug. Pirarubicin and pirarubicin-based combination therapies have been demonstrated to be effective against HCC in TACE. However, the drug resistance limits its therapeutic efficacy. Receptor-interacting protein kinase 1 (RIPK1) displays a critical role in cell death. Here we found that RIPK1 and p21 may participate in the resistance to pirarubicin. In this study, we first found that inhibition of RIPK1 significantly decreased pAKT and increased p21, accompanied by G0/G1 phase cell cycle arrest and cell anti-proliferation in pirarubicin-treated hepatocellular carcinoma cells. Moreover, phosphorylation of AKT reversed the anti-proliferative effect of RIPK1 inhibitor in HCC, which proved that RIPK1-AKT-P21-dependent pathway played a key role in pirarubicin resistance. Using a mouse xenograft model, we further found that RIPK1 inhibitor combined with pirarubicin exerted synergistic anti-tumor effect

Topics: Animals; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Hepatocellular; Cell Line, Tumor; Chemoembolization, Therapeutic; Cyclin-Dependent Kinase Inhibitor p21; Doxorubicin; Drug Resistance, Neoplasm; Humans; Imidazoles; Indoles; Liver Neoplasms; Male; Mice; Mice, Nude; Phosphorylation; Proto-Oncogene Proteins c-akt; Receptor-Interacting Protein Serine-Threonine Kinases; RNA, Small Interfering; Xenograft Model Antitumor Assays

We aimed to clarify whether surgical resectability and tumor response after preoperative chemotherapy (preCTx) represented prognostic factors for patients with hepatoblastoma (HBL) in the JPLT-2 study (1999-2012).. Patients (N=342) with HBL who underwent preCTx were eligible. PRETEXT, CHIC risk stratification (standard [SR], intermediate [IR] and high risk [HR]) at diagnosis, POST-TEXT, and tumor resectability were evaluated by imaging. Tumor response was classified into responders (CR or PR) and nonresponders (NC or PD) according to RECIST criteria.. There were 7 PRETEXT I, 106 II, 143 III, and 86 IV, including 71 metastatic HBLs. In POST-TEXT, 12 PRETEXT II, 42 III, and 58 IV were down-staged. The 5-year EFS/OS rates of 198 SR, 73 IR, and 71 HR-HBLs were 82/94%, 49/64%, and 28/34%, respectively. In 198 SR, 154 of 160 responders and 24 of 38 nonresponders survived event-free (P<0.01). In 73 IR, 12 of 24 whose tumors remained unresectable experienced recurrence, 9 of whom were nonresponders (P<0.01). In 71 HR, chemoresponders and tumor resectability after preCTx correlated with favorable outcomes (P<0.05).. Evaluation of response and tumor resectability after preCTx is useful for predicting prognosis in HBLs. To improve outcomes, we should reconsider surgical procedures according to resectability and chemoresponsiveness.. Level II.

Topics: Adolescent; Antineoplastic Combined Chemotherapy Protocols; Carboplatin; Child; Child, Preschool; Cisplatin; Clinical Protocols; Combined Modality Therapy; Doxorubicin; Etoposide; Female; Hepatoblastoma; Humans; Ifosfamide; Infant; Liver Neoplasms; Male; Neoadjuvant Therapy; Prognosis; Treatment Outcome

Topics: Abdominal Injuries; Accidents, Traffic; Aged; Antineoplastic Agents; Carcinoma, Hepatocellular; Chemoembolization, Therapeutic; Contrast Media; Doxorubicin; Ethiodized Oil; Humans; Intracranial Embolism; Liver Neoplasms; Male

MicroRNAs function as oncomiRs and tumor suppressors in diverse cancers. However, the utility of specific microRNAs in predicting the clinical benefit of chemotherapy has not been well-established. Here, we investigated the correlation between microRNA-21 expression and hepatic arterial infusion chemotherapy with 5-fluorouracil and pirarubicin (HAIC) for hepatocellular carcinoma (HCC). We found that HCC patients with low microRNA-21 levels in tumors tended to have a longer time to recurrence and disease-free survival. We demonstrated that microRNA-21 suppression in combination with 5-fluorouracil and pirarubicin treatment inhibited tumor growth in subcutaneous xenograft mice models. Mechanistically, the AP-1 and microRNA-21-mediated axis was verified to be a therapeutic target of cytotoxic drugs and deregulation of this axis led to an enhanced cell growth in HCC. Taken together, our findings demonstrate that microRNA-21 is a chemotherapy responsive microRNA and can serve as a prognostic biomarker for HCC patients undergoing HAIC. Targeting microRNA-21 enhances the effect of chemotherapeutic drugs, thereby suggesting that microRNA-21 suppression in combination with HAIC may be a novel approach for HCC treatment.

Topics: Animals; Antineoplastic Combined Chemotherapy Protocols; Blotting, Western; Carcinoma, Hepatocellular; Cell Line, Tumor; Cell Proliferation; Disease-Free Survival; Doxorubicin; Female; Fluorouracil; Gene Expression Regulation, Neoplastic; Humans; Immunohistochemistry; Immunosuppressive Agents; Liver Neoplasms; Male; Mice, Inbred BALB C; Mice, Nude; MicroRNAs; Middle Aged; Prognosis; Reverse Transcriptase Polymerase Chain Reaction; Transcription Factor AP-1; Tumor Burden; Xenograft Model Antitumor Assays

Pirarubicin, a derivative of doxorubicin, induces tumor destruction via the production of reactive oxygen species (ROS) but is associated with cardiotoxicity. As a macromolecule (conjugated to styrene-maleic acid [SMA]), SMA-pirarubicin is selective to tumors resulting in improved survival with decreased systemic toxicity. Tumor destruction is, however incomplete, and resistant cells at the periphery of the tumor contribute to recurrence. Tumor hypoxia is a major factor in tumor resistance. Understanding the effect of oxidative stress induced by SMA-pirarubicin on the tumor microenvironment may be key to overcoming resistance. This study investigated the pattern of ROS production and tumor hypoxia after treatment with SMA-pirarubicin in a murine model of colorectal liver metastases.. Liver metastases were induced in male, CBA mice using a murine-derived colon cancer cell line. SMA-pirarubicin (maximum tolerated dose, 100 mg/kg) or pirarubicin, (maximum tolerated dose, 10 mg/kg) were administered intravenously 14 days after tumor induction. Systemic oxidative stress in serum, liver, and cardiac tissue was quantified using the thiobarbituric acid reactive substances assay. Flow cytometry and fluorescence microscopy were used to assess ROS production for 48 hours after treatment. Tumor hypoxia was quantified using immunohistochemistry for pimonidazole adducts.. SMA-pirarubicin (100 mg/kg) induced ROS exclusively in tumors with minimal levels in serum and cardiac tissue. ROS levels were induced in a time-dependent and dose-dependent manner optimal between 4 and 24 hours after drug administration. Although tumor hypoxia was decreased overall, residual tumor cells adjacent to patent vessels were hypoxic.. This study provides insight into the tumor microenvironment after chemotherapy. SMA-pirarubicin inhibits the growth of colorectal liver metastases by inducing ROS, which seems to be largely tumor selective. The temporal pattern of ROS production can be used to improve future dosing regimens. Furthermore, the observation that residual tumor cells are hypoxic clarifies the need for a multimodal approach with agents that can alter the hypoxic state to effect complete tumor destruction.

Topics: Animals; Antineoplastic Combined Chemotherapy Protocols; Cell Hypoxia; Colorectal Neoplasms; Disease Models, Animal; Doxorubicin; Liver Neoplasms; Male; Maleates; Mice; Mice, Inbred CBA; Oxidative Stress; Polystyrenes; Reactive Oxygen Species; Tumor Microenvironment

Golgi protein 73 (GP73) is a promising biomarker of hepatocellular carcinoma (HCC). It decreases after surgical resection, and resumes upon recurrence, indicating a potential indicator for the effectiveness of the treatment. But changes of GP73 after transcatheter arterial chemoembolization (TACE) have not been reported so far. This study was to investigate the dynamic changes of GP73 in HCC patients after TACE treatment, and the possible underlying mechanisms in the cell cultures.. Blood samples were collected from 72 HCC patients, before TACE, at day 1 and day 30 after TACE. GP73 levels were measured by Western blotting. The dynamic changes of GP73 were analyzed and compared with image changes and clinical data. The effects of chemotherapeutic agents (5-FU and pirarubicin) on GP73 expression were tested in three HCC cell lines (HepG2, HCCLM3 and MHCC97H).. The GP73 level was significantly elevated at day 1 and day 30 after TACE in HCC patients compared with that before the procedure (P<0.05). There was no statistical difference between the two time points after TACE, nor correlation between GP73 levels and clinicopathological features, tumor metastasis, and patient survival. Pirarubicin, not 5-FU, significantly increased GP73 expression in three cell lines.. Unlike surgical resection which decreases the GP73 level, TACE significantly increased GP73 expression in patients with HCC. No correlations were observed among GP73 levels, tumor characteristics and prognosis of patients with HCC.

Topics: Adult; Aged; Antineoplastic Agents; Biomarkers, Tumor; Carcinoma, Hepatocellular; Chemoembolization, Therapeutic; Disease Progression; Disease-Free Survival; Doxorubicin; Female; Fluorouracil; Hep G2 Cells; Humans; Kaplan-Meier Estimate; Liver Neoplasms; Male; Membrane Proteins; Middle Aged; Prospective Studies; Time Factors; Treatment Outcome; Up-Regulation

A 13-year-old boy was referred to us for investigation of a giant liver mass, approximately 16 cm in diameter. Sonographically guided percutaneous needle biopsy was performed and histological examination revealed a fetal-type hepatoblastoma. After four courses of chemotherapy, we performed a left hepatic trisegmentectomy. Follow-up computed tomography, 55 months after the surgery, showed a 1-cm tumor on the route of the preoperative needle biopsy. A second laparotomy revealed a peritonealised tumor, which was excised. The histology of this tumor was identical to that of the primary hepatoblastoma. To our knowledge, this is only the second report of needle tract implantation of hepatoblastoma after percutaneous needle biopsy.

Topics: Adolescent; alpha-Fetoproteins; Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Biopsy, Needle; Cisplatin; Combined Modality Therapy; Doxorubicin; Follow-Up Studies; Hepatectomy; Hepatoblastoma; Humans; Liver Neoplasms; Male; Neoplasm Metastasis; Time Factors; Tomography, X-Ray Computed; Treatment Outcome

To assess the effect and safety of lobaplatin combinated floxuridine /pirarubicin in transcatheter hepatic arterial chemoembolization(TACE) of unresectable primary liver cancer.. TACE combined with the chemotherapy regimen was used to treat 34 unresectable primary liver cancer patients. DSA/ MRI/CT/blood routine examinations were used to evaluate short term activity and toxicity after 4-5 weeks, the process being repeated if necessary.. Among the 34 cases, 1 (2.9%) showed a complete response, 21 (61.7%) a partial response, 8 (23.5%) stable disease, and 4 progressive disease, with a total effective rate of 67.6%. The content of alpha fetoprotein dropped by over 50% in 20 cases (58.8%). The rate of recovery was hepatalgia (88.2%), ascites (47.1%), appetite (55.9%), Performance Status(30.4%). The median follow-up time (MFT) was 281 days (63-558 days), and median progression-free survival was 118.5 days (95%, CI:88.8-148.2 days). Adverse reactions (III-IV grade) were not common, with only 4 cases of vomiting and 2 cases of thrombocytopenia (III grade).. Lobaplatin-based TACE is an effective and safe treatment for primary liver cancer.

Topics: Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Hepatocellular; Chemoembolization, Therapeutic; Cyclobutanes; Disease-Free Survival; Doxorubicin; Female; Floxuridine; Hepatic Artery; Humans; Liver Neoplasms; Male; Middle Aged; Organoplatinum Compounds

Topics: Adult; Angiography, Digital Subtraction; Antineoplastic Agents; Carcinoma, Hepatocellular; Collateral Circulation; Doxorubicin; Embolization, Therapeutic; Ethiodized Oil; Humans; Liver Neoplasms; Male; Mitomycin; Skin; Skin Ulcer; Time Factors; Tomography, X-Ray Computed; Treatment Outcome; Wound Healing

In the recent years, surgical resection with pre- and/or postoperative chemotherapy has markedly improved the survival rate of hepatoblastoma patients. We herein report the results of patients treated with the current protocol of the Japanese Study Group for Pediatric Liver Tumor, JPLT-2.. A total of 279 patients with malignant liver tumor were enrolled in JPLT-2. Data from 212 hepatoblastoma cases were analyzed. PRETEXT I patients were treated with primary resection followed by low doses of cisplatin-pirarubicin (tetrahydropyranyl-adriamycin). Otherwise, patients received preoperative cisplatin-pirarubicin (CITA), followed by surgery and postoperative chemotherapy. Ifosfamide, pirarubicin, etoposide, and carboplatin (ITEC) were given as a salvage treatment. High-dose chemotherapy with hematopoietic stem cell transplantation (SCT) was reserved for patients with metastatic diseases.. The 5-year overall survival rate (OS) in non-metastatic cases was 100% for PRETEXT I, 87.1% for PRETEXT II, 89.7% for PRETEXT III, and 78.3% for PRETEXT IV. The 5-year OS in metastatic cases was 43.9%. The outcome in non-metastatic PRETEXT IV cases was markedly improved, while the results of metastatic tumors remained poor.. JPLT-2 protocol achieved satisfactory survival among children with non-metastatic hepatoblastoma. New approaches are needed for patients with metastatic diseases.

Topics: Adolescent; Antineoplastic Agents, Alkylating; Antineoplastic Agents, Phytogenic; Antineoplastic Combined Chemotherapy Protocols; Carboplatin; Child; Child, Preschool; Cisplatin; Doxorubicin; Etoposide; Female; Hematopoietic Stem Cell Transplantation; Hepatoblastoma; Humans; Ifosfamide; Infant; Infant, Newborn; Japan; Liver; Liver Neoplasms; Male; Survival Analysis; Treatment Outcome

Hepatocellular carcinoma (HCC) in children is rare, and the prognosis has been poor because of its advanced stage at diagnosis and unresponsiveness to chemotherapy. We report a 13-year-old boy with ruptured HCC in the left trisegment. When hemostasis of the ruptured surface was achieved in the emergency operation, the left branch of the portal vein and the left hepatic artery were ligated at the same time. The volume of the future liver remnant (FLR), that is, his right posterior sector, increased from 56% on admission to 70% of his standard liver volume on day 2. Blood level of serum protein induced by vitamin K absence or antagonist ІІ started to decrease immediately. Left trisegmentectomy was successfully performed 10 days later, followed by chemotherapy. He has been well with a 2-year survival without recurrence. When the FLR is considered relatively small for a major hepatic resection, the selective ligation of the portal vein and the hepatic artery, which feed HCC, seems to be beneficial. This is because it may induce enlargement of the FLR, increasing the safety of the hepatectomy as preoperative portal vein embolization does before a major hepatectomy in adult patients with HCC, and the latter suppresses the tumor while waiting for the planned hepatectomy.

Topics: Adolescent; Antineoplastic Combined Chemotherapy Protocols; Basketball; Carcinoma, Hepatocellular; Chemotherapy, Adjuvant; Cisplatin; Combined Modality Therapy; Doxorubicin; Hemoperitoneum; Hemostasis, Surgical; Hepatectomy; Hepatic Artery; Humans; Ligation; Liver; Liver Neoplasms; Liver Regeneration; Male; Organ Size; Portal Vein; Radiography; Rupture; Shock; Vascular Surgical Procedures

Further to a previous study whereby we reported that an in vitro emulsion of pirarubicin, amiodarone, and lipiodol was more stable and cytotoxic than a classic doxorubicin-lipiodol mixture, we designed a pilot study to evaluate efficacy and toxicity of a transarterial chemoembolization (TACE) procedure using a combination of pirarubicin, amiodarone, lipiodol, and gelatin sponge.. The 43 patients included in this study underwent TACE for unresectable hepatocellular carcinoma. Computed tomography scans were performed to assess tumor response (RECIST) and lipiodol uptake after the first session. Median follow-up lasted 30 months. Endpoints were overall and progression-free survival. Survival was estimated using Kaplan Meier estimations and compared using log-rank tests. Univariate and multivariate Cox analyses were used to calculate hazard ratios with their 95% confidence interval (CI).. Twenty-seven (67.5%) patients had alcoholic cirrhosis. Mean tumor size was 9.5 cm (1-20 cm) and 37/43 were multifocal or diffuse. Cancer of the liver Italian program score was 0 in 7/40 and 1 in 16/40. Mean number of TACE sessions was 3.5 (1-11). There were 3 treatment-related deaths (2 severe sepsis, 1 bowel perforation). A partial response and a stable disease were observed in 12 (28%) and 29 (67%) patients, respectively. Median overall and progression-free survivals were 29 months (95% CI: 13.8-45) and 15 months (95% CI: 11.5-20.8), respectively. Cancer of the liver Italian program score 25% (P = 0.003) were independent prognostic factors for better overall survival.. This new TACE procedure is safe with a high overall survival rate and certainly deserves phase III investigation to compare it with classic treatments such as doxorubicin-lipiodol TACE.

Topics: Aged; Aged, 80 and over; Amiodarone; Antineoplastic Agents; Carcinoma, Hepatocellular; Chemoembolization, Therapeutic; Doxorubicin; Female; Humans; Immunosuppressive Agents; Iodized Oil; Liver Neoplasms; Male; Middle Aged; Pilot Projects; Prognosis; Survival Rate; Tomography, X-Ray Computed; Treatment Outcome

Topics: Antineoplastic Agents; Carcinoma, Hepatocellular; Chemoembolization, Therapeutic; Contrast Media; Diagnosis, Differential; Doxorubicin; Hepatectomy; Humans; Liver Neoplasms; Male; Middle Aged; Myasthenia Gravis; Paraneoplastic Syndromes, Nervous System; Treatment Outcome

Hepatocellular carcinoma arises from hepatocytes, it is the most common primary malignant tumor of the liver and accounts for the majority of liver cancers. Pirarubicin is a compound analog to the antineoplastic anthracycline antibiotic doxorubicin. Thereby as an intercalator of DNA, pirarubicin has shown efficacy in reducing tumor activity of hepatocellular carcinoma. Utilizing in silico optimized similarity of structure search of data base and replacement by isosteres, a total of nine analogs to pirarubicin were generated. The molecular size of ring substituents (approximately a base pair) were preserved and isosteres chosen to preserve the weak electrostatic properties permitting DNA intercalation. Only a small range in molecular weight and volume was permitted in order to preserve intercalation activity. Standard deviations for polar surface area, number of heavy atoms, molecular weight, molecular volume, and number of oxygens and nitrogens, were only 3.98%, 1.76%, 16.5%, 2.51%, and 0%, respectively, of the overall average for these properties. Variation of the target substituent resulted in insignificant changes in many properties; there was a striking variation in the lipophilic property Log P. Values of Log P ranged from 0.142 to 2.078 inclusive of pirarubicin and plays an important role in bioavailability. Hierarchical cluster analysis indicated that all analogs, except analog 6, were substantially similar to pirarubicin. A similar outcome was obtained from non-metric multidimensional scaling of descriptors. However detrended correspondence analysis distinguished both analogs 6 and 5 from the remaining analogs and pirarubicin. Nonhierarchical K-means clustering analysis determined greater differentiation among the analogs and pirarubicin. Analysis of similarity (ANOSIM) affirmed all compounds to be highly similar which shows structural optimization was achieved.

Topics: Antineoplastic Agents; Carcinoma, Hepatocellular; Cluster Analysis; Databases as Topic; DNA; Doxorubicin; Drug Discovery; Humans; Liver Neoplasms; Models, Chemical; Molecular Weight; Multivariate Analysis; Nitrogen Compounds; Oxygen Compounds; Pattern Recognition, Automated; Static Electricity

Topics: Antineoplastic Combined Chemotherapy Protocols; Carboplatin; Chromosomes, Human, Pair 11; Chromosomes, Human, Pair 19; Cisplatin; Doxorubicin; Fatal Outcome; Hepatoblastoma; Humans; Infant; Infant, Newborn; Leukemia, Myelomonocytic, Acute; Liver Neoplasms; Male; Neoplasms, Second Primary; Stem Cell Transplantation; Translocation, Genetic

Clinical study suggests that 72-hour continuous infusion (CIV) of MAID regimen is more effective and achieves longer time of no progression than ADR-based two-drug regimen in advanced soft tissue sarcoma (ASTS) treatment, but has no improvement on the long-term survival. Because of the severe grade 3/4 toxicities as well as treatment-related deaths, the regimen has not been widely applied in ASTS. This study was to investigate the efficacy and toxicity of the modified MAID regimen in ASTS treatment.. In the modified regimen, adriamycin (ADR) was substituted with tetrahydropyranyl adriamycin (THP-ADR) and the application of ifosfamide (IFO) was modified. All enrolled patients received chemotherapy (IFO 2,000 mg . m(-2), 4h, day 1-3; mesna 1,200 mg . m(-2) at 0, 4 and 8 hours of IFO infusion, day 1-3; THP-ADR 20 mg . m-2 and dacarbazine (DTIC) 333.3 mg . m(-2) were mixed in the same bag or pump, CIV for 3 days). The therapy was repeated every 3 weeks for at least 2 cycles before evaluating the effects and toxicities. The patients received follow-up every 2 months after completing 2 cycles until the study was finished. Life table was used to calculate long-term survival rates and time to progression.. Fifty-four cases of evaluable patients had completed at least 2 cycles of modified MAID chemotherapy. The overall response rate was 42.59%. The toxicities were mild. Grade 3/4 neutropenia and thrombocytopenia were 25.93% and 16.17%, respectively. Neutropenia fever was 11.11%. There were no other toxicities, such as hepatic and renal toxicities; no central nervous system toxicity and treatment-related deaths. During 2 year follow-up, time to progression was 7 months, 1- and 2- year survival rates were 61.11% and 36.36%, respectively.. Modified MAID regimen simplifies the application of treatment procedure compared with original regimen, which three drugs have to be CIV simultaneously. Moreover the modified MAID regimen has better survival rates in ASTS, with milder toxicity and better tolerance.

Topics: Adolescent; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Dacarbazine; Doxorubicin; Female; Fibrosarcoma; Follow-Up Studies; Humans; Ifosfamide; Infusions, Intravenous; Liver Neoplasms; Lung Neoplasms; Male; Middle Aged; Nausea; Neoplasm Staging; Neutropenia; Remission Induction; Rhabdomyosarcoma; Sarcoma, Synovial; Soft Tissue Neoplasms; Survival Rate; Thrombocytopenia; Young Adult

To investigate the value of in vivo proton magnetic resonance spectroscopy (MRS) in the assessment of hepatocellular carcinoma (HCC) and monitor its metabolic change shortly after transcatheter arterial chemoembolization (TACE).. In this prospective study, 28 consecutive patients with large HCC (> or = 3 cm in diameter) confirmed by fine needle aspiration biopsy were recruited. The 1H MRS of all hepatic lesions and some uninvolved liver parenchyma were performed with 1. 5T whole body MR scanner. Among them, 15 cases were evaluated again about one week after TACE. The main metabolites such as choline and lipid before and after interventional therapy were measured to assess the early response of the tumor.. The technical success rate of 1H MRS in liver was high (33/41, 80%), closely related to breath motion, location of lesion, and size of voxel. In spectra, the choline compound peak of HCC elevated compared with uninvolved liver parenchyma. After TACE, both the amplitude and the area of choline resonance peak significantly descended (choline-to-lipid ratios from 0.352 +/- 0.080 to 0.167 +/- 0.030, P = 0.026; from 0.205 +/- 0.060 to 0.070 +/-0.020, P = 0.042, respectively); yet lipid resonance peak ascended.. In vivo 1H MRS is technically feasible for the evaluation of large focal hepatic lesions, however, the reproducibility and stability are not as good as routine MR scan. 1H MRS can monitor the early stage metabolic changes of HCC after TACE but limitation like quantification still exists.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Hepatocellular; Chemoembolization, Therapeutic; Cisplatin; Doxorubicin; Female; Humans; Liver; Liver Neoplasms; Magnetic Resonance Spectroscopy; Male; Middle Aged

Hepatorblastoma is an uncommon childhood malignant tumor of hepatic origin and recent progress of treatment strategy resulted in improved prognosis of patients with hepatoblastoma. Although patients within one year of age were considered to have better prognosis than those over that age, the treatment related deaths have been reported to be the only cause of the treatment failure of the infantile hepatoblastoma. We have successfully treated 4 infants including one with spontaneous rupture and the other with recurrence. Treatment protocol was preoperative chemotherapy using cisplatin and THP-ADR, doses of which were modified according to the age, with optional radiological interventions followed by resection of the primary tumor. This report would describe their clinical courses and experienced side effects of the treatment in order to demonstrate its risk. Trans-arterial embolizations were beneficial to stop bleeding due to rupture and to reduce intraoperative blood loss. In spite of dose modifications high hematological side effects were inevitable and cisplatn-induced hearing loss persisted in one case. In conclusion, for small infants with hepatoblastoma, controlling the inevitable side effects and active but strategic surgical and radiological interventions are essential for successful treatment.

Topics: Antineoplastic Combined Chemotherapy Protocols; Child, Preschool; Cisplatin; Combined Modality Therapy; Doxorubicin; Embolization, Therapeutic; Female; Hepatoblastoma; Humans; Infant; Liver Neoplasms; Male; Prognosis; Radiology, Interventional

To investigate the optimal strategy of preoperative transcatheter arterial chemoembolization (TACE) for hepatoblastoma.. Between 1992 and 2001, 7 children with hepatoblastoma (aged 9 months to 13 years) underwent preoperative TACE. The chemoembolic agent used was an emulsion of pirarubicin and lipiodol. Four patients without distant metastasis underwent "primary" TACE without systemic chemotherapy. The other 3 with distant metastases underwent "delayed" TACE following systemic chemotherapy. These patients were all examined retrospectively using clinical data.. The average dosage of lipiodol was 0.6 ml per tumor maximal diameter (cm). All the primary cases showed a significant decrease in alpha-fetoprotein (AFP) and a reduction in the tumor size. They consequently underwent a complete surgical resection and are now disease free. All the delayed cases showed a slight decrease in AFP and underwent complete surgical resection; however, two of them died of lung metastases, and the other died of a second malignancy. Regarding complications, liver dysfunction and pulmonary embolism occurred in one patient each.. For patients without distant metastasis, regardless of the resectability of the primary tumor, TACE may be considered the initial and only preoperative treatment, and it may be repeated. For patients with distant metastases, their complete eradication with systemic chemotherapy prior to TACE is essential.

Topics: Adolescent; Antineoplastic Agents; Chemoembolization, Therapeutic; Child, Preschool; Doxorubicin; Female; Hepatectomy; Hepatoblastoma; Humans; Infant; Iodized Oil; Liver Neoplasms; Male; Preoperative Care

Topics: Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Clinical Trials as Topic; Colorectal Neoplasms; Doxorubicin; Fluorouracil; Health Care Costs; Hepatic Artery; Humans; Immunosuppressive Agents; Infusions, Intra-Arterial; Irinotecan; Leucovorin; Liver Neoplasms; Patient Selection; Treatment Outcome

Advanced pancreatic cancer is mainly treated by chemotherapy with poor prognosis. This study was designed to evaluate clinical efficacy and application of selective continuous transarterial infusion chemotherapy in treating patients with advanced pancreatic cancer.. Twenty patients with advanced pancreatic cancer were treated by selective continuous transarterial infusion chemotherapy. The interventional treatment was performed with Seldinger technique,12 patients received percutaneous femoral artery cannulization and catheter retention, 8 received percutaneous left subclavian artery port-catheter system implantation. Chemotheraputic drugs were continuously infused when the catheter was selectively placed in turner feeding artery. Nine patients were treated with pirarubicin (THP)/adriamycin (ADM) plus hydroxycamptothecin (HCPT),and 5-fluorouracil (5-FU)/calcium folinate (CF) regimen,and 11 were treated with gemcitabine (GEM) plus carboplatin (CBP),and 5-FU/CF regimen. Treatment regimens were repeated every 4-6 weeks with each cycle of 4 days. Tumor response rate,clinical benefit response (CBR),and survival time were observed.. Objective response rate was 10% with 1 case of complete remission (CR), and 1 case of partial remission (PR), CBR was 70% (14/20), 6-,and 9-month survival rates were 58.8%,and 39.2%. Median survival time for all patients was 8.8 months. No complication related to cannulization was found.. Selective continuous transarterial infusion chemotherapy is safe,and has good efficacy in treating patients with advanced pancreatic cancer, it may prolong survival time of patients.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Carboplatin; Deoxycytidine; Doxorubicin; Female; Fluorouracil; Gemcitabine; Humans; Infusion Pumps, Implantable; Infusions, Intra-Arterial; Leucovorin; Liver Neoplasms; Lymphatic Metastasis; Male; Middle Aged; Neoplasm Staging; Pancreatic Neoplasms; Remission Induction; Survival Rate

Although chemoembolization is known to be an effective palliative treatment in hepatocellular carcinoma, it has a limited effect in large tumors. We report the case of a patient with a large hepatocellular carcinoma of the left liver who had a significant and sustained clinical response after six sessions of chemoembolization with a pirarubicin/amiodarone/lipiodol emulsion. Pirarubicin is an anthracycline which penetrates faster than doxorubicin into cancer cells. Amiodarone is a multidrug resistance inhibitor. Polysorbate 80, an excipient of injectable amiodarone stabilizes the anthracycline/lipiodol emulsion. The clinical efficacy of this new formulation could be evaluated in a phase II clinical trial.

Topics: alpha-Fetoproteins; Amiodarone; Carcinoma, Hepatocellular; Chemoembolization, Therapeutic; Contrast Media; Doxorubicin; Enzyme Inhibitors; Humans; Immunosuppressive Agents; Injections, Intra-Arterial; Iodized Oil; Liver Neoplasms; Male; Middle Aged

A patient with liver metastasis of pancreatic cancer received chemotherapy using mitomycin C and degradable starch microspheres. The patient was a 52-year-old woman who had undergone surgery for cancer of the head of the pancreas in October 1996. She had stage III disease and was followed up as an outpatient on oral therapy with a combined uracil and tegafur preparation. In October 2000, abdominal computed tomography (CT) scans detected multiple liver metastases. Three courses of intra-arterial infusion of mitomycin C and microspheres (1000 mg) resulted in regression of her tumor and a decrease of tumor marker levels. After three more courses of this therapy, the patient developed bile duct necrosis and died of disseminated intravascular coagulation. As her metastases were controlled for about 7 months, hepatic arterial infusion of mitomycin C and degradable starch microspheres appears to be useful for treating liver metastasis of pancreatic cancer, but careful attention should be paid to the risk of severe complications such as bile duct necrosis.

Topics: Antineoplastic Combined Chemotherapy Protocols; Bile Duct Diseases; Carcinoma, Hepatocellular; Chemoembolization, Therapeutic; Chemotherapy, Adjuvant; Combined Modality Therapy; Doxorubicin; Fatal Outcome; Female; Humans; Infusions, Intra-Arterial; Liver Neoplasms; Middle Aged; Mitomycin; Necrosis; Neoplasm Staging; Pancreatic Neoplasms; Pancreaticoduodenectomy; Risk Assessment; Starch; Tomography, X-Ray Computed

There is no well-defined curative treatment for advanced and unresectable hepatocellular carcinoma. The widely used transarterial chemoembolization (TACE) with a doxorubicin-Lipiodol emulsion has not been shown to improve survival in randomized studies. Further, obstruction of the hepatic artery used in the procedure is badly tolerated in patients with cirrhosis. Drugs with a more rapid penetration into the cancer cells are likely to eliminate the need for obstruction of the hepatic artery. We therefore compared the cytotoxicity of another anthracycline pirarubicin with that of the commonly used doxorubicin. In this report, we show that pirarubicin has a greater in vitro cytotoxic effect than doxorubicin on the HepG2 and Hu-H7 human hepatoma cell lines. Pirarubicin emulsion with Lipiodol is more stable at 37 degrees C than doxorubicin-Lipiodol. Moreover, pirarubicin accumulates at a greater extent in the oil phase, permitting Lipiodol to act as a slow-releasing vector for the anthracycline. Further, amiodarone, a multidrug resistance inhibitor, was shown to decrease the intrinsic resistance of HepG2 and Hu-H7 cells to both anthracyclines, and the presence of polysorbate 80 in the amiodarone preparation increased the stability of the anthracycline-Lipiodol emulsions. We therefore conclude that pirarubicin is a better candidate for TACE than doxorubicin. The rapid and increased cytotoxicity of pirarubicin on hepatoma cancer cells and the stability of the pirarubicin-Lipiodol amiodarone emulsion could avoid the complete obstruction of the hepatic artery by Gelfoam sponges, and provide a better tolerated method of TACE in patients with latent liver insufficiency.

Topics: Amiodarone; Antibiotics, Antineoplastic; Carcinoma, Hepatocellular; Chemoembolization, Therapeutic; Chromatography, High Pressure Liquid; Doxorubicin; Drug Resistance, Multiple; Drug Stability; Emulsions; Enzyme Inhibitors; Humans; Iodized Oil; Liver Neoplasms; Tetrazolium Salts; Thiazoles; Tumor Cells, Cultured

The current study was conducted to evaluate retrospectively the effects of three kinds of regimens used in transcatheter arterial chemoembolization (TACE) in patients with unresectable hepatocellular carcinoma (HCC) and patients' prognosis, and to analyze their prognostic factors.. The study population was comprised of 152 patients who were treated by TACE alone. Three kinds of regimens were used successively: doxorubicin hydrochloride (ADM) and mitomycin C mixed with iodized oil in 26 patients (ADMOS group), a combination of cisplatin (CDDP) solution and ADMOS in 70 patients (CDDP-ADMOS group), and CDDP powder and pirarubicin hydrochloride mixed with iodized oil in 56 patients (CTLS group). The CTLS group was comprised of patients with significantly worse background factors than the other two groups.. The initial tumor response rate with a > 50% reduction was 12%, 23%, and 30%, respectively, in the ADMOS, CDDP-ADMOS, and CTLS groups. CTLS was significantly more effective than ADMOS (P < 0.05), and slightly but not significantly better than CDDP-ADMOS (P <0.1). The cumulative survival rates for the ADMOS, CDDP-ADMOS, and CTLS groups were 59.0%, 70.1%, and 72.0%, respectively, at 1 year; 0%, 16. 3%, and 29.8%, respectively, at 3 years; and 0%, 4.1%, and 16.8%, respectively, at 5 years, with median survival times of 448 days, 574 days, and 758 days, respectively. The CTLS group showed a slightly but not significantly better survival than the ADMOS and CDDP-ADMOS groups (P <0.1). Multivariate analysis indicated that the significantly important prognostic factors (in order) were extrahepatic metastasis followed by the TACE regimen, serum alpha-fetoprotein levels, and portal vein involvement and that CTLS was the best of the three regimens.. Although TACE, using an effective regimen, improves clinical results, tumor factors appear to be more important when determining prognosis.

Topics: Adult; Aged; Aged, 80 and over; Antibiotics, Antineoplastic; Antineoplastic Agents; Carcinoma, Hepatocellular; Chemoembolization, Therapeutic; Cisplatin; Disease-Free Survival; Doxorubicin; Drug Combinations; Female; Humans; Infusions, Intra-Arterial; Iodized Oil; Liver Neoplasms; Male; Middle Aged; Mitomycin; Multivariate Analysis; Prognosis; Retrospective Studies; Time Factors

We report a case of far advanced breast cancer showing an excellent response to chemo-endocrine therapy. A 40-year-old female with a huge ulcerated tumor on her left anterior chest visited our hospital. Distant metastases were found in the lymph nodes, liver and bone. Therefore, endocrine therapy (toremifene and medroxyprogesterone acetate) and chemotherapy (cyclophosphamide, Therarubicin and 5-fluorouracil) were started as a combination treatment. As a result, the main tumor and metastatic lesion were remarkably reduced, and extended mastectomy with resection of right axillary lymph nodes was performed. Histologically, cancer cells in the primary lesion mostly disappeared, and only one lymph node in the left axillary lesion showed metastasis. No recurrence was found for 16 months after the surgical treatment. The combined therapy in the present case was extremely effective.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Bone Neoplasms; Breast Neoplasms; Combined Modality Therapy; Cyclophosphamide; Doxorubicin; Drug Administration Schedule; Female; Fluorouracil; Humans; Liver Neoplasms; Lymphatic Metastasis; Neoplasm Staging; Toremifene

We present a case of pulmonary embolism that occurred during the injection of lipiodol during transcatheter arterial chemoembolization under general anaesthesia. A 7-year-old child suffering from a large hepatoblastoma was admitted for arterial chemoembolization and carcinostatic administration. Pulmonary embolism due to lipiodol during arterial chemoembolization was evident by a sudden fall in oxyhaemoglobin saturation from 100 to 90%. This was associated with a spread of lipiodol into both lungs, particularly the middle lung zones and detected by chest fluoroscopy. Arterial blood gases returned to normal values 1 day later but pulmonary infiltration persisted for 7 days before final clearance. Pulmonary embolism caused by lipiodol during arterial chemoembolization is infrequent, but such a complication could prove fatal. Understanding the risk of pulmonary embolism in patients receiving lipiodol, during and after arterial chemoembolization, and late onset pulmonary injury is important and a close follow-up for several days after arterial chemoembolization is advisable.

Topics: Antibiotics, Antineoplastic; Antineoplastic Agents; Catheterization, Peripheral; Chemoembolization, Therapeutic; Child; Contrast Media; Critical Care; Doxorubicin; Fluoroscopy; Follow-Up Studies; Hepatoblastoma; Humans; Iodized Oil; Liver Neoplasms; Male; Oxygen; Oxyhemoglobins; Positive-Pressure Respiration; Pulmonary Embolism; Radiography, Interventional

Though the first choice of treatment for liver metastasis in colon cancer is surgical resection of liver, 30-60% of such patients experience a recurrence of liver metastasis. Even if reoperation is done optimally, the surgical resection of liver metastasis may not be a definitely curative treatment. For cases of liver metastasis from colon cancer that are non-resectable due to multiple liver metastases, other organ metastases (lung, bone, brain etc.), the advanced age of the patient, or other complications (cerebrovascular disease, diabetes mellitus, heart disease etc.), hepatic arterial infusion or systemic combination chemotherapies are selected. In the present paper, we report 3 cases of effective systemic chemotherapy utilizing CPT-11 for liver metastases from colon cancers. The method was UFT + irinotecan (CPT-11), cisplatin (CDDP) + tegafur + CPT-11, UFT + CPT-11 + etoposide (ETP) + pirarubicin (THP). The result obtained was a partial response (PR) in each case. As there were few adverse effects, we could provide treatment during a short-term admission or an outpatient basis. We thus obtained good post-chemotherapeutic QOL, and these regimens may be effective forms of chemotherapies in the future.

Topics: Adenocarcinoma; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Cisplatin; Colonic Neoplasms; Doxorubicin; Drug Administration Schedule; Drug Evaluation; Etoposide; Female; Humans; Irinotecan; Liver Neoplasms; Male; Tegafur; Uracil

A 59-year-old female complaining of breast tumor with suppurative discharge was diagnosed as having advanced breast cancer (T4cN3M1-StIV), with giant liver metastasis. Seven courses of combined chemoendocrine therapy (CTF + MPA) were used. Following the chemoendocrine therapy, primary tumor, lung, pleural, supraclavicular and parasternal metastasis disappeared, and the liver metastasis was obviously diminished. These effects continued for 1 year 7 months. Although CTF + MPA chemoendocrine therapy is widely used with advanced or recurrent breast cancer, a clearly effective case has almost never been reported. The reason for the remarkable effect in this case was the consistent immunity to breast cancer.

Topics: Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Bone Neoplasms; Breast Neoplasms; Carcinoma, Ductal, Breast; Cyclophosphamide; Doxorubicin; Drug Administration Schedule; Female; Fluorouracil; Humans; Liver Neoplasms; Lung Neoplasms; Lymphatic Metastasis; Medroxyprogesterone Acetate; Middle Aged

An 11-month-old infant with a huge hepatoblastoma occupying almost the entire liver was admitted to the hospital. Serum alpha fetoprotein (AFP) level was elevated to 685,120 ng/mL. Combination chemotherapy with continuous arterial infusion of tetrahydropyranyl Adriamycin (THP-Adriamycin) and cisplatin based on the 91B1 protocol of the Japanese Study Group For Pediatric Liver Tumor (JPLT) was administered as the adjuvant chemotherapy. The tumor responded to three courses of chemotherapy and shrank in size, although venocavography showed that the inferior vena cava (IVC) was completely occluded below the entry of the hepatic veins. Right hepatic trisegmentectomy was performed with an IVC-atrial venovenous bypass that prevented massive bleeding. In this case, it was recognized that the IVC-atrial venovenous bypass was advantageous in an infant. The procedure is very simple and the blood flow obtained by the bypass was sufficient. Two weeks postoperatively, three courses of chemotherapy were initiated after the protocol. The patient remains well without signs of recurrence 39 months postoperatively, and the AFP value has remained within 10 ng/mL.

Topics: Antibiotics, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Combined Modality Therapy; Doxorubicin; Female; Hepatectomy; Hepatoblastoma; Humans; Infant; Infusions, Intra-Arterial; Liver Neoplasms; Vena Cava, Inferior

The patient was a 71-year-old man who had been diagnosed as having a left renal pelvic cancer with liver metastasis. We performed total left nephroureterectomy with lymphnode cleaning and partial resection of the liver. Because abdominal CT 5 months after the operation revealed multiple metastasis of the liver, we performed chemotherapy with a regimen consisting of methotrexate 50 mg (intravenous injection), cisplatin 30 mg and pirarubicin 20 mg (intraarterial infusion), and leucovorin 3 mg (intramuscular injection), three times at intervals of 6 hours. Ten days after chemotherapy, CT revealed the disappearance of most of the liver metastatic lesions, and a partial response was obtained. We are now performing the regimen at an interval of a month to a month and one-half to control the metastatic lesions.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Transitional Cell; Cisplatin; Doxorubicin; Hepatic Artery; Humans; Infusions, Intra-Arterial; Infusions, Intravenous; Injections, Intramuscular; Kidney Neoplasms; Kidney Pelvis; Leucovorin; Liver Neoplasms; Lymph Node Excision; Lymphatic Metastasis; Male; Methotrexate

We experienced a case of multiple liver metastasis from postoperative gastric cancer who showed long-term survival with hepatic arterial infusion chemotherapy (HAI) of MMC and pirarubicin. A catheter was inserted into the hepatic artery, and 4 mg of MMC and 20 mg of pirarubicin were administered through an implantable port catheter every two to four weeks. The total dose of MMC and pirarubicin by the time of this report was 164 mg and 820 mg, respectively. The follow-up CT scan 2 months after the beginning of HAI showed a decrement of the liver tumors. The decrease rate at 12 and 17 months was 50% and 70%, respectively, which was diagnosed as partial response (PR). The therapeutic effect at 49 months is still PR without any sign of tumor enlargement of extra hepatic lesion.

Topics: Antineoplastic Combined Chemotherapy Protocols; Doxorubicin; Gastrectomy; Hepatic Artery; Humans; Infusion Pumps, Implantable; Infusions, Intra-Arterial; Liver Neoplasms; Male; Middle Aged; Mitomycin; Stomach Neoplasms; Survivors

The prognosis of hepatoblastoma is poor unless the tumor is completely resected. Various types of chemotherapy have been developed to increase its resectability. Recently, transcatheter arterial chemoembolization (TACE) has been developed for the treatment of unresectable adult hepatoma with favorable results. The authors applied this procedure to hepatoblastoma in infants and children.. TACE was performed in eight hepatoblastoma cases. After an intraarterial catheter was inserted into the main feeding artery of the tumor, injection of adriamycin or THP-adriamycin (20 to 30 mg/m2) dispersed in lipiodol and cisplatin (40 to 60 mg/m2) followed by embolization using Gelfoam pieces was performed. Effects of TACE were evaluated according to shrinkage of tumor mass on imaging examinations, alpha-fetoprotein (AFP) levels, and pathological findings of the surgical specimens 4 weeks after TACE.. A marked reduction in tumor size associated with a decrease in AFP level occurred 1 month after the treatment. Tumor shrinkage ranged from 0.9% to 45.0% with a mean value of 25.8%. AFP levels decreased by 0.2% to 11.9% with a mean level of 4.6% from initial levels. In addition, there was no marked chemotherapeutic agent-induced toxicity noted during the observation period. Resection of the tumors was performed safely after TACE in all cases. Pathological examination showed massive necrosis in the surgical specimens, and the mean percentage of necrotic area within the tumor was 71.1%. Two patients died of extensive lung metastasis 2 months and 3 years after the operation, respectively. The remaining six were doing well and free of disease at a mean follow-up period of 50 months.. TACE is an effective, safe, and useful method for the initial treatment of hepatoblastoma.

Topics: Antibiotics, Antineoplastic; Antineoplastic Agents; Chemoembolization, Therapeutic; Child, Preschool; Contrast Media; Doxorubicin; Female; Gelatin Sponge, Absorbable; Hepatoblastoma; Humans; Infant; Iodized Oil; Liver Neoplasms; Male; Treatment Outcome

A 75-year-old male was admitted one year after surgery for advanced gastric cancer. He was diagnosed as having multiple liver metastases with elevated serum CEA level. Combination chemotherapy consisting of THP-ADM, MMC and 5'-DFUR was done in the outpatient clinic. As a result, both multiple metastatic liver tumors and serum CEA level showed a remarkable response.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoembryonic Antigen; Combined Modality Therapy; Doxorubicin; Floxuridine; Gastrectomy; Humans; Liver Neoplasms; Male; Mitomycin; Remission Induction; Stomach Neoplasms

A 46-year-old male with unresectable hepatocellular carcinoma (HCC) comprised of severe liver dysfunction was treated by intra-arterial infusion chemotherapy through an implantable reservoir. During 39 months, a total amount of THP-ADR 420 mg, ADR 70 mg and CDDP 350 mg was infused. Through the therapy, the tumor size on the lateral segment was well controlled, and serum AFP and PIVKA-II levels were also lowered. No severe side effect was observed. The patient was treated on an outpatient basis, and a good quality of life during therapy was maintained. This case suggests that THP-ADR may play an important role in a combined intraarterial chemotherapy for advanced HCC.

Topics: Antibiotics, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Hepatocellular; Cisplatin; Doxorubicin; Humans; Infusion Pumps, Implantable; Infusions, Intra-Arterial; Liver Neoplasms; Male; Middle Aged

The role of biological response modifiers (BRM) in locoregional therapy for liver metastases of colorectal cancer was studied clinically and experimentally. Seven patients with numerous metastases to both lobes of liver were given intraarterial administration of BRM in combination with anticancer drugs. A partial response was observed in 1 patient. The response rate was 14.3%. Alternatively, intraarterial administration of both OK-432 and IL-2 into the rabbit with liver metastases of VX-2 tumors could bring about the infiltration of cytotoxic T lymphocytes around the tumors, followed by a significant decrease of the metastatic nodules. In addition, the same anti-tumor effect was observed when PSK was administered intraperitoneally into the BALB/c mouse with liver metastases of colon 26 tumors. Moreover, the therapeutic effect of water in oil type emulsion encapsulating both OK-432 and IL-2 was greater than that of the solution of BRM in BALB/c mouse with liver metastases of colon 26 tumors. These results indicated that BRM could be one of the promising agents in locoregional therapy against liver metastases of colorectal cancer.

Topics: Adult; Aged; Animals; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Colorectal Neoplasms; Doxorubicin; Female; Fluorouracil; Hepatic Artery; Humans; Infusions, Intra-Arterial; Interleukin-2; Leucovorin; Liver Neoplasms; Liver Neoplasms, Experimental; Male; Mice; Middle Aged; Picibanil; Rabbits

We reported a patient with advanced gastric cancer and a liver metastasis, who responded remarkably to combination chemotherapy using THP, 5'-DFUR and CDDP. The patient was administered four courses of THP (15 mg/m2/day, on day 1, iv), 5'-DFUR (1400 mg/m2/day, on days 1-4 and 15-18, orally), and CDDP (80 mg/m2/day, on day 5, iv) every 4 weeks. As a result, both the primary and metastatic tumors decreased remarkably in size at more than 19 weeks (PR) and we performed curative total resection of the stomach and partial resection of the liver. Histologically, the effects of chemotherapy on gastric focus were evaluated as grade 1a and the liver metastasis completely disappeared. This combination therapy proved useful to treat advanced gastric cancer in this patient.

Topics: Adenocarcinoma; Aged; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Doxorubicin; Drug Administration Schedule; Floxuridine; Gastrectomy; Humans; Liver Neoplasms; Male; Stomach Neoplasms

The patient was a 2-year-old who was admitted with the diagnosis of liver tumor. The diagnosis at admission was stage III A hepatoblastoma complicated with tumor thrombosis of portal vein. Soon after the admission, the patient's general condition became deteriorated with increased ascites and severer jaundice. As the patient was considered to be in oncogenic emergency, chemotherapy with systemic administration of ADR and CDDP was started. Despite decreases in tumor marker and tumor shrinkage on imaging examinations, tachycardia and arrythmia occurred from the end of the second course of chemotherapy, suggesting ADR-induced cardiomyopathy, when the systemic administration of ADR was switched to less cardiotoxic hepatic arterial infusion of THP-ADR. Following 13 courses of intra-arterial infusion with the total dose of THP-ADR of 200 mg/m2, the tumor was found to have reduced markably in size and thus surgical resection of the tumor was performed. Our experience of this case indicates that, considering the pharmacokinetics and side effects, THP-ADR should be a very effective anti-tumor agent for intra-arterial hepatic infusion. The patient died 10 months after surgery because of multiple metastases into the brain and lungs.

Topics: Antibiotics, Antineoplastic; Brain Neoplasms; Child, Preschool; Doxorubicin; Drug Administration Schedule; Hepatic Artery; Hepatoblastoma; Humans; Infusions, Intra-Arterial; Liver Neoplasms; Lung Neoplasms; Male

A 67-year-old man with advanced gastric cancer with multiple liver metastases was treated by a new combination chemotherapy using 5-FU, THP and MMC (FTM). After the first course of FTM, both abnormal liver function and the elevated level of serum CA 19-9 were restored. After the second course of FTM, the primary lesion became a small ulcer around cardia. A partial response was recognized both in the primary lesion and in the liver metastases. No serious side effect was observed except for leukocytopenia, which was controlled by G-CSFS. This new combination chemotherapy (FTM) was suggested to be useful even for far advanced gastric cancer.

Topics: Adenocarcinoma; Aged; Antineoplastic Combined Chemotherapy Protocols; Doxorubicin; Drug Administration Schedule; Fluorouracil; Humans; Liver Neoplasms; Male; Mitomycin; Stomach Neoplasms

VX2 is a carcinoma established in rabbits and producing an autocrine growth factor, prostaglandin E2. Pirarubicin is a potent anti-VX2 agent. We investigated whether the oral intake of enprostil--a synthetic prostaglandin E2--or of diclofenac--a potent non-steroidal anti-inflammatory drug--increases the efficacy and decreases the hepatotoxicity of pirarubicin when injected in the portal trunk. Enprostil increased the number of hepatic tumoral nodules and induced hepatic alterations, especially venous dilatation. Paradoxically the combination of enprostil and pirarubicin was at least as effective as pirarubicin or diclofenac on VX2 cells. However, the toxicity was increased, especially with respect to sclerosing cholangitis. Diclofenac proved to be as effective as pirarubicin, and the addition of oral diclofenac to local pirarubicin injection increased its antitumoral effect (P < 0.02). However, the combination of diclofenac and pirarubicin was more toxic than pirarubicin alone and induced centrolobular necrosis and sclerosing cholangitis.

Topics: Administration, Oral; Animals; Antibiotics, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Diclofenac; Doxorubicin; Enprostil; Female; Liver; Liver Neoplasms; Portal System; Rabbits

An advanced esophageal cancer patient with multiple liver metastases was treated with a combination of CDDP, 5-FU and THP-ADM. Complete response was obtained against esophageal primary lesion endoscopically, and partial response was obtained against liver metastases observed by computed tomography. Bone marrow suppression of grade 3 was observed, but resolved within 2 weeks.

Topics: Antibiotics, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Squamous Cell; Cisplatin; Doxorubicin; Drug Administration Schedule; Esophageal Neoplasms; Fluorouracil; Humans; Liver Neoplasms; Male; Middle Aged

Early liver metastases have a predominant portal blood supply. Intraportal (i.port.) vein administration of cytotoxics could theoretically achieve enhanced drug concentrations in tumour cells and be effective as adjuvant therapy after resection of colorectal carcinoma. Pirarubicin (which has a higher hepatic extraction than doxorubicin) was investigated on liver metastases of the VX2 rabbit tumour, which were of less than 2 mm in diameter 7 days after cells injection into the portal vein. To evaluate antitumour activity, 24 rabbits were randomised into three groups 7 days after implantation: (a) control, (b) i.v. pirarubicin, (c) i.port. pirarubicin at doses of 2 mg kg-1 in both groups. Portal infusions led to no hematological or hepatic toxicity. Pharmacokinetic parameters showed a significantly reduced systemic exposure after i.port. administration. Fourteen days after treatment, livers and lungs were analysed. The mean number (+/- s.d.) of tumour foci was (a) 8.62 (+/- 5.4), (b) 4.62 (+/- 3.2), (c) 2.25 (+/- 1.4) (P < 0.05 a vs c). The mean tumour area was (a) 6.31 (+/- 6.1), (b) 1.31 (+/- 2.2), (c) 0.43 (+/- 0.4 cm2) (P < 0.05 a vs c) and the percentage (95% C.I.) of rabbits with lung metastasis was: (a) 87.5% (47-99%), (b) 75% (35-97%), (c) 12.5% (3-52%) (P < 0.02 b vs c). Intraportal pirarubicin seems to be well tolerated and more efficient than i.v. administration, particularly in preventing extrahepatic dissemination.

Topics: Animals; Antibiotics, Antineoplastic; Carcinoma; Doxorubicin; Infusions, Intravenous; Liver Neoplasms; Portal Vein; Rabbits

Topics: Antibodies; Carcinoma, Hepatocellular; Combined Modality Therapy; Doxorubicin; Epirubicin; Ferritins; Humans; Iodine Radioisotopes; Liver Neoplasms; Radioimmunotherapy; Tumor Cells, Cultured

We studied the effect of adjuvant hepatic arterial chemotherapy with THP-adriamycin (THP) and carboplatin (CBDCA) in patients with hepatocellular carcinoma (HCC). Fifteen patients were treated by intraarterial infusion of THP 30 mg on the second and third week after hepatectomy. CBDCA 450 mg was further injected on the fourth week (group A). Intrahepatic arterial administration of the drug was carried out through the subcutaneously implanted reservoir; one to five courses of the protocol were performed (average 2 times). Transient leukocytopenia occurred in six cases, liver dysfunction in one case, duodenal ulcer in one case and occlusion of the catheter connected reservoir in three cases. Forty-two patients not treated with this protocol postoperatively were employed as historical control (group B). There were no significant differences between group A and B in operative procedures, tumor stage, clinical stage, tumor size and other histopathological findings including nuclear DNA ploidy pattern. The two-year cumulative disease-free survival rate was 78% in group A, which was significantly better than the 55% of group B (p < 0.05). It may be concluded that intrahepatic arterial chemotherapy using THP and CBDCA plays an important role to prevent recurrences of the tumor after hepatectomy in patients with HCC.

Topics: Antibiotics, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Carboplatin; Carcinoma, Hepatocellular; Doxorubicin; Drug Administration Schedule; Female; Hepatic Artery; Humans; Infusion Pumps, Implantable; Infusions, Intra-Arterial; Liver Neoplasms; Male; Middle Aged; Survival Rate

Intraarterial chemotherapy with Adriamycin (ADM) has shown limited advantages over i.v. administration, with no reduction in systemic toxicities and modest decrease in peripheral plasma levels. In an effort to improve the selectivity of i.a. anthracycline chemotherapy, we compared pirarubicin (4'-O-tetrahydropyranyladriamycin, THP) and ADM in the surgically implanted VX2 rabbit tumor model. Both drugs were administered at the same dose (0.5 mg/kg) either by the intraarterial hepatic route (i.a.h.) or by the i.v. route. Anthracycline plasma and tissue levels were determined by high-performance liquid chromatography with fluorescence detection. ADM peak plasma concentration and area under the curve were not significantly reduced after i.a.h. administration compared to the i.v. route; however, ADM tumor concentration was 1.9-fold higher following i.a.h. administration compared to the i.v. infusion. After THP administration by the i.a.h. route, systemic exposure (area under the curve) was markedly reduced (8-fold) compared to the same dose administered i.v. These findings correlated well with the very low concentration of the drug in heart tissue following i.a.h. infusion. After i.a.h. administration, tumor THP concentrations were 10.5 times higher compared to the i.v. route. The pharmacokinetic advantage of i.a.h. administration of THP also led to a better antitumoral effect, as shown by a significantly lower tumor growth rate [3 +/- 2% (SD)] in the i.a.h.-treated animals compared to the i.v.-treated groups (58 +/- 9%). Administration of ADM by the i.a.h. route was also inferior to i.a.h. THP. Taken together, our results suggest a clear-cut advantage of THP over ADM for i.a.h. locoregional chemotherapy, because of higher local tumor concentrations, greater antitumoral effect, and lower systemic exposure following the i.a.h. administration of THP. This anthracycline analogue could also be of therapeutic advantage in tumors partially resistant to anthracyclines that would become vulnerable to the high local concentrations achieved with i.a.h. administration. Based on these encouraging results, clinical trials using THP administered by the i.a.h. route were initiated.

Topics: Animals; Cell Division; Doxorubicin; Female; Hepatic Artery; Injections, Intra-Arterial; Injections, Intravenous; Liver Neoplasms; Neoplasm Transplantation; Rabbits; Tumor Cells, Cultured

Seventeen patients with hepatocellular carcinoma were treated by intraarterial injection of CTL suspension. The doses of CTL suspension, CDDP and THP(mean +/- SD)/injection were 4.1 +/- 1.6 ml, 81.9 +/- 31.6 mg and 13.5 +/- 5.2 mg, respectively. The therapy was given once in 10 patients, twice in 6 and 4 times in one. Over 50 per cent reduction in tumor size was obtained in 5 patients (30%). Fifty or more % decrease in serum alpha-feto-protein (AFP) levels was observed in 3 of 7 patients (43%) with the initial serum AFP level of more than 200 ng/ml, Fever, abdominal pain, nausea and vomiting were noted in most cases. However, they disappeared within 2 weeks after therapy was completed. No severe complications were encountered except one case of a liver abscess which healed by administration of antibiotics. No severe changes in laboratory data were observed. This study suggests that a new method of intraarterial injection must be developed to enhance the therapeutic effect even more, in addition to an increased injection dose of CDDP/THP-LPD and higher concentration of CDDP and THP in LPD.

Topics: Adult; Aged; alpha-Fetoproteins; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Hepatocellular; Chemoembolization, Therapeutic; Cisplatin; Doxorubicin; Female; Hepatic Artery; Humans; Iodized Oil; Liver Neoplasms; Male; Middle Aged

A 63-year-old Japanese woman who was being treated for liver cirrhosis was diagnosed as having hepatocellular carcinoma in the caudate lobe of the liver. Transcatheter hepatic arterial chemoembolization was performed for this lesion, but severe neutropenia occurred. To restore white blood cell (WBC) counts, recombinant human granulocyte colony-stimulating factor (rhG-CSF) was administered (250 micrograms per day during 10 days, intravenously). Subsequently, WBC counts recovered immediately without side effects. This suggests that rhG-CSF could be useful for the treatment of neutropenia after chemoembolization, even in cirrhotic patients.

Topics: Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Hepatocellular; Chemoembolization, Therapeutic; Doxorubicin; Etoposide; Female; Granulocyte Colony-Stimulating Factor; Humans; Liver Cirrhosis; Liver Neoplasms; Middle Aged; Neutropenia; Recombinant Proteins

Surgery was attempted in a case of stage IV ovarian cancer with a hepatic metastatic lesion measuring 119 x 96 mm. However, radical surgery was impossible and the operation ended up as no more than exploratory laparotomy. Before closing, Cisplatin 100 mg and Etoposide 200 mg were instilled into the intraperitoneal cavity. Two courses of systemic chemotherapy with PAC (Cisplatin 50 mg, Pirarubicin 40 mg, Cyclophosphamide 400 mg) were instituted. To examine shrinkage of the hepatic metastasis and the peritoneal tumors, A "Second look" operation was conducted. Abdominal simple total hysterectomy, bilateral salpingo-oophorectomy, omentectomy and partial sigmoidectomy resulted in no residual lesions in the peritoneal cavity with the exception of the hepatic metastatic lesion (69 x 57 mm). Two additional courses of PAC therapy were administered after the "Second look" operation. The hepatic metastatic lesion shrank to 45 x 41 mm; a decrease of 83.8% compared to the pre-therapy in size. Liver function tests and tumor chemical markers (TPA, CA 125, SLX) revealed decreased values that were consistent with a tumor size reduction. Good PR was achieved with only a systemic chemotherapy; i.e., without resorting to local injections of chemotherapeutic agents into the liver.

Topics: Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Cyclophosphamide; Cystadenocarcinoma; Doxorubicin; Female; Humans; Liver Neoplasms; Middle Aged; Ovarian Neoplasms; Remission Induction

This report describes a 55-year-old man who had a curative operation for leiomyosarcoma of the stomach 6 years ago. Unresectable liver metastases was discovered during the second laparotomy and successfully treated by intra hepato-arterial chemotherapy, which included MMC, ADM and Therarubicin with Infuse-A-Port. He remains well presently with a decrease in the size of the liver metastases and no metastasis to any other organs upon investigation by an abdominal CT 2 years and 2 months after the second laparotomy.

Topics: Antineoplastic Combined Chemotherapy Protocols; Doxorubicin; Fluorouracil; Hepatic Artery; Humans; Infusion Pumps, Implantable; Infusions, Intra-Arterial; Leiomyosarcoma; Liver Neoplasms; Male; Middle Aged; Mitomycin; Mitomycins; Picibanil; Stomach Neoplasms

Fourteen cases of malignant liver tumor in childhood were experienced in our department during past 14 years. Since 1984 we have performed preoperative targeting anticancer chemotherapy using oily anticancer agents such as THP-adriamycin 30 mg/m2. These oil emulsion was making with 20 mg amounts of THP-adriamycin dissolved in 5 ml urographin and 15 ml volume of lipiodol. These mixture were administered by catheterizing the hepatic artery under X-ray monitoring in 6 cases with hepatoblastoma. Remarkable anticancer effects of this targeting chemotherapy were achieved, the serum AFP level and tumor size both showing a decrease in all cases, and the resectability of tumor showing a increase in 5 among 6 cases in comparison with 50% resectability before 1983.

Topics: Adolescent; Age Factors; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Hepatocellular; Contrast Media; Doxorubicin; Drug Carriers; Female; Humans; Infant; Iodized Oil; Liver Neoplasms; Male

A 30-month-old boy was investigated because of a huge abdominal mass in the right upper abdomen. A computed tomography scan and celiac angiography showed that the tumor involved bilateral lobes of the liver. At first, for this disseminated and "unresectable" tumor we did liver biopsy and hepatic arterial catheterization. Through this catheter we started chemotherapy using THP-Adriamycin and cis-platinum. After three courses of chemotherapy, a second-look operation was performed and trisegmentectomy was done to remove the main tumor and metastases, including the left lobe and the right anterior segment. The trisegmentectomy was performed with success, and the boy's serum alpha-fetoprotein (AFP) remains normal 37 months after the start of treatment, indicating a probable permanent cure. Such cases have rarely been reported in the literature. Our experience in treating this patient would seem to encourage aggressive management of advanced hepatoblastoma in other patients.

Topics: Antineoplastic Combined Chemotherapy Protocols; Child, Preschool; Cisplatin; Combined Modality Therapy; Doxorubicin; Hemangiosarcoma; Hepatectomy; Humans; Infusions, Intra-Arterial; Liver Neoplasms; Male

Antitumor drugs dispersed in a lipid lymphographic medium (Lipiodol, Laboratorie Guerbert, Rue Jean-Chaptal, France) were intraarterially administered in two infants with unresectable hepatoblastoma. The Lipiodol and antitumor drug complex was found to selectively accumulate in the tumor and was associated with a marked reduction in the tumor size and a 50% decrease in the alpha-fetoprotein (AFP) level after 4 days in one patient and 16 days in the other. The tumor was successfully resected by right trisegmentectomy in one patient, but surgery was not performed on the other because of evidence of pulmonary metastasis. The patients had moderate fever for 2 to 3 days after the intraarterial chemotherapy. It is believed that intraarterial chemotherapy with Lipiodol may be a useful preoperative chemotherapy for initially unresectable hepatoblastoma.

Topics: Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Hepatocellular; Cisplatin; Doxorubicin; Drug Carriers; Fluorouracil; Hepatic Artery; Humans; Infant; Injections, Intra-Arterial; Iodized Oil; Liver Neoplasms; Male

Intraarterial injection of anti-tumor drugs (THP-ADR, CDDP, 5-FU) dispersed in lipid contrast medium (Lipiodol, Laboratorie Guerbert, France) was used in an infant with initially unresectable hepatoblastoma. Lipiodol complex selectively accumulated in the tumor tissue and may keep the chemotherapeutic agents in the tumor tissue for a longer period of time, and a significant reduction of the tumor with a four-day half-life of alpha-fetoprotein (AFP) was followed immediately after the institution of chemotherapy. Successful resection of decreased tumor by extended right hepatectomy under more favorable conditions was performed 2 months after diagnosis. Intraarterial chemotherapy with Lipiodol was particularly useful in potentiating the cytoreduction of anti-tumor drugs and was also useful in reducing the toxicities of anti-tumor drugs to the host.

Topics: Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Hepatocellular; Cisplatin; Doxorubicin; Fluorouracil; Humans; Infant; Injections, Intra-Arterial; Iodized Oil; Liver Neoplasms; Male

Two patients with recurrent gastrointestinal carcinoma were treated with THP. Partial response was recognized in the local recurrent tumor of one patient and in liver metastasis of a second patient. THP was administered every three weeks at a dose of 60 mg per total body weight intravenously. The total dose of THP achieved was 720 mg in the first patient and 920 mg in the second. Despite the high dosage, neither cardiotoxicity nor alopecia was observed. These results suggest that the administration of THP may be efficacious and safe in the management of patients with recurrent gastrointestinal carcinoma.

Topics: Adenocarcinoma; Adult; Doxorubicin; Female; Humans; Injections, Intravenous; Liver Neoplasms; Male; Middle Aged; Neoplasm Recurrence, Local; Rectal Neoplasms; Stomach Neoplasms

A phase II study on THP((2''R)-4'-0-Tetrahydropyranyladriamycin) was performed in 47 patients with advanced or recurrent gastrointestinal cancer through the cooperation of nine institutions in Hiroshima Prefecture from April 1982 to November 1984. THP was given by means of intravenous infusion and/or intraaortic infusion and the 47 cases were divided into two groups according to the method of administration: (A) 40-60 mg/body every 3 or 4 weeks, or (B) 30 mg/body every week. Among 24 evaluable cases, partial response (PR) was observed in two cases of recurrent metastatic lymph nodes in gastric cancer patients. The (A) method of administration was more effective than (B). Subjective side effects observed were appetite loss, nausea, vomiting and general fatigue, but these were not so severe. Leukocyte nadir occurred at the 1st or 2nd week of THP administration, but thrombocytes were not appreciably decreased.

Topics: Antineoplastic Agents; Colonic Neoplasms; Doxorubicin; Drug Administration Schedule; Drug Evaluation; Humans; Infusions, Intra-Arterial; Infusions, Parenteral; Liver Neoplasms; Rectal Neoplasms; Stomach Neoplasms

THP-ADM is a new antitumor agent which belongs to the anthracycline family. This agent has shown a high therapeutic index compared with the mother compound, Adriamycin, in preclinical and clinical studies. This time, a pharmacokinetic study of THP-ADM was performed and the following characteristics of this agent were clarified. Short t1/2 was noted compared with that of Adriamycin in a 3-compartment open model. Leukocyte concentration of THP-ADM was much higher than that of plasma or red blood cells. Renal excretion over 48 hours was 9% and biliary excretion over the same period was 20%. Tissue concentration revealed high THP-ADM and low Adriamycin in all tissues excluding the liver. In liver tissue, a high concentration of Adriamycin and a low concentration of THP-ADM was observed. A small amount of Adriamycin was noted in the plasma following THP-ADM administration. The Adriamycin was most likely related to the small amount of existing Adriamycin in THP-ADM or conversion of THP-ADM to Adriamycin in the liver tissue or both. Poor penetration of THP-ADM was noted into the third space.

Topics: Doxorubicin; Humans; Kinetics; Liver; Liver Neoplasms; Neoplasms; Stomach Neoplasms