Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0019204 (hepatocellular carcinoma)
 71,386 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Twenty children with recurrent or unresponsive tumours (10 Wilms', 3 rhabdomyosarcoma, 4 Ewings's, 1 osteosarcoma, 1 hepatoblastoma, 1 hepatoma) and one untreated patient with renal carcinoma were given ifosfamide as a 24-h infusion (5 mg/m2), with mesna as uroprotective. The number of courses ranged from 1 to 13 (median 3), and the interval between them was 2-3 weeks. Sixteen of these patients had previously received cyclophosphamide. Complete clinical responses were seen in 3 cases (2 Wilms' and 1 Ewing's) and lasted 5, 7, and 9 months. Partial responses were seen in 3 instances, mixed response or stable disease in 4, and progressive disease in 11. Treatment was well tolerated in most patients, with no cystitis or severe myelosuppression, but 2 children developed transient neurological symptoms and 1 became hypertensive. Nausea and vomiting were controlled by high-dose dexamethasone in most children. Plasma ifosfamide levels were estimated by means of gas-liquid chromatography in 10 patients. Peak concentrations ranged from 38 to 125 micrograms/ml (median 80). The elimination half-life, at 2.5-5.2 h (median 3.2) was shorter than previously reported in adults. Future studies should test the possibility that ifosfamide-containing combination chemotherapy may be more effective than the regimens, usually including cyclophosphamide, that are currently used as front-line treatment of embryonal and Ewing's sarcoma.
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PMID:A phase II study of ifosfamide in children with recurrent solid tumours. 405 69

The patient was a 60-year-old Japanese male. He complained of epigastralgia and right chest pain of 4 month's duration, and general malaise, nausea and vomiting of 2 month's duration. Physical examination revealed on the right third rib a tender mass with a diameter of 2 cm and hepatomegaly with a multi-nodular surface and red palms. There were no signs of carcinoid syndrome, such as cutaneous flushing. Laboratory examinations disclosed certain biochemical alterations; alkaline phosphatase 810 IU/l, gamma-glutamyl transpeptidase (gamma-GTP) 2090 IU/l, carcinoembryonic antigen (CEA) 23.5 ng/ml and alpha-fetoprotein (AFP) 6,800 ng/ml. Both HBs-Ag and HBs-Ab were negative. The patient died in a uremic state, with rapid increases of jaundice and ascites. Autopsy revealed gastric carcinoid with extensive metastases to the liver and the bone marrow. Tumor cells showed argyrophilia but not argentaffinity. Immunofluorescence specific for AFP was positive in the hepatocytes, particularly those adjacent to the metastatic tumor cells but not in the tumor cells, either primary or secondary. 79 cases reported in Japan of serum AFP-positive malignant tumor other than hepatocellular carcinoma and certain other malignancies of germ cell origin are reviewed and discussed.
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PMID:Serum alpha-fetoprotein-positive gastric carcinoid with liver metastasis. 616 67

9,10-Anthracenedicarboxaldehyde bis[(4,5-dihydro-1 H-imidazol-2-yl)hydrazone] dihydrochloride (CL216,942) is a new anthracene bishydrazone derivative that was evaluated in a Phase I clinical trial. The schedule of administration consisted of a single i.v. injection repeated at 4-week intervals. Twenty-eight patients received a total of 61 courses of the drug in a dose range of 20 to 280 mg/sq m. Leukopenia was the dose-limiting toxicity. It was of short duration and reversible. A drug-induced hypotension was noted at higher doses in three patients. The hypotension was not dose limiting, it was reversible, and it could largely be avoided by prolonging the drug infusion time to 1 hr. One patient with unsuspected severe coronary artery disease died of complications of myocardial infarction subsequent to a hypotensive episode. Significant phlebitis was also noted at higher doses of drug. This degree of phlebitis could be lessened by diluting the drug in larger volumes of fluid. Three patients experienced diaphoresis, nausea, palpitations, and chest discomfort at the conclusion of the infusions. None of the patients had electrocardiographic changes. Mild fever, alopecia, and nausea and vomiting were noted occasionally. One patient with a hypernephroma and one patient with hepatocellular carcinoma experienced partial responses of their tumors secondary to the drug. Phase II studies of CL216,942 are planned at a starting dose of 260 mg/sq m as a single dose repeated at 21- to 28-day intervals.
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PMID:Phase I clinical investigation of 9,10-anthracenedicarboxaldehyde bis[(4,5-dihydro-1 H-imidazol-2-yl)hydrazone] dihydrochloride (CL216,942). 626 75

VP-16-213 (etoposide) is an orally and parenterally active antineoplastic agent synthesized from podophyllum extracts of a common North American plant, the May apple or mandrake. The drug delays and kills cells in the G2 phase of the cell cycle and is active in a variety of animal tumors and leukemias. Major therapeutic activity for the drug has been found in small cell bronchogenic carcinoma, germ cell malignancies, acute non-lymphocytic leukemia, Hodgkin's disease and non-HOdgkin's lymphoma. Minor therapeutic activity of the drug occurs in non-small cell bronchogenic carcinoma, pediatric neoplasms, hepatocellular carcinoma and gastric cancer. Toxicity is primarily hematologic, with alopecia, nausea and vomiting occurring less frequently.
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PMID:VP-16-213 (etoposide): the mandrake root from Issyk-Kul. 627 88

A phase II study of MCNU tablets in gastrointestinal cancer was carried out by the Hanshin MCNU cooperative study group involving 21 institutions. The selection of patients and evaluation of tumor response were based on the Criteria for the Evaluation of tumor Response by Chemotherapy in Solid Tumor Patients by Koyama and Saito. Of 67 patients who were entered into the study, 46 patients were evaluable, and comprised of 27 cases of gastric cancer, 13 of colorectal cancer, 2 hepatoma, and 4 patients suffering from other typas of gastrointestinal cancer. MCNU was administered orally at a dose of 50 mg/body/day for 4-6 days consecutive every 6-8 weeks. Only one partial response was obtained among the rectal cancer patients, with a response rate of 2.3% (1/43) in evaluable patients. Minor responses were obtained in 3 patients including 2 of gastric cancer with liver metastasis and 1 colon cancer with liver metastasis. Major side effects were marrow suppression and gastrointestinal symptoms. The former consisted of mainly leukopenia (15 patients, 30.0%), thrombocytopenia (20 patients, 40.0%), and oligochromaemia (10 patients, 20.0%). The latter consisted of mainly nausea and vomiting (5 patients, 10.0%).
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PMID:[A phase II study of ranomustine (MCNU) tablets in patients with gastrointestinal cancer--by cooperative study group]. 649

Patients with unresectable liver cancer (primary and metastatic) were treated with a newly-devised arterial infusion chemotherapy using Cis-DDP and its antidote Sodium thiosulfate (STS). The patients consisted of 4 with primary hepatoma and 1 with metastatic liver cancer originated from intestinal cancer. For the purpose of reducing unfavourable side effects without changing anticancer effect, Cis-DDP was infused into hepatic artery through the catheter while STS being administered systemically. According to Koyama and Saito's criteria, 2 of 5 patients showed partial response (PR) and the others showed no change (NC). The median survival time after onset of therapy was 6.6 months ranging from 2 to 11 months in all the patients. The myelosuppression and renal toxicity, which were considered to be the most serious side effects of Cis-DDP, were not found and liver function was not affected in all the patients. However, all the patients complained of nausea and vomiting. Thus, our experience has indicated that this newly devised infusion chemotherapy is a promising method for treating unresectable liver cancer, although further efforts are necessary for reducing the gastrointestinal toxicity.
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PMID:[Intra-arterial infusion through 2 routes in liver (primary and metastatic cancer]. 668 85

Cyclic intra-arterial infusion chemotherapy using Mitoxantrone via reservoir system was prescribed for 8 patients with advanced hepatocellular carcinoma. According to the clinical staging system, two patients were in Stage III and the other six patients in Stage IV-A. Vp-3 portal invasion was observed in six out of the eight patients. Mitoxantrone (5-8 mg/body) was administered intra-arterially via port-a-cath device every 4 weeks. For tumor response, there were two PR cases, four NC cases, and two PD cases. Thus, the response rate was 25%. The mean survival period was 6.5 months, and 1-year survival rate was 13%. In one of two PR cases, the survival time has been more than two years so far. Gastrointestinal toxicities such as nausea and vomiting were not severe. Critical myelosuppression requiring medication was not observed. Although a temporary increase of serum bilirubin was found in two cases, no severe damage to hepatic function was observed. From our preliminary data, this arterial infusion chemotherapy using Mitoxantrone via reservoir system can be safely performed on non-hospitalized patients with advanced hepatocellular carcinoma, and may be a useful treatment modality.
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PMID:[Clinical study of cyclic intra-arterial chemotherapy using mitoxantrone for advanced hepatocellular carcinoma]. 808 50

Morphine hydrochloride 10 mg suppository was given every 6 hours in a patient with hepatoma and hepatic cirrhosis. The serum morphine concentration increased continuously until 4 hours after the second administration, and peak level showed 17 ng.ml-1. Morphine-6-glucuronide and morphine-3-glucuronide in the serum persisted at low levels of 32.4 ng.ml-1 and 169 ng.ml-1 respectively. Three days after the administration, morphine suppository had to be discontinued because of severe nausea and vomiting. It should be noticed that a remarkable reduction in morphine metabolism may occur and this may lead to unexpected high serum concentration of morphine in a patient with hepatic dysfunction.
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PMID:[A patient with hepatoma and hepatic cirrhosis showing abnormally high blood morphine concentration after periodical suppository administration]. 830 46

We developed a Hotwire for use in percutaneous transcatheter thermotherapy (PTCT) for local tumor control. The Hotwire has a temperature sensor and a heater, and is inserted into the hepatic artery through a Y-connector and an angiocatheter. It can then warm fluid from the Y-connector to 45 degrees C under electorical control PTCT was performed on liver tumors using 4 mg of MMC and 10 mg Epirubicin. The antitumor effects and indications for PTCT were investigated in patients with unresectable liver tumors, including 3 patients who had hepatocellular carcinoma (HCC) with intraportal invasion and collateral vessels, one patient with liver metastasis of rectal cancer, and two gastric cancer patients. In all patients, tumor marker levels decreased (PIVKA-II; 8.5-->0.9, 2.9-->0.9, AFP; 1154-->753, CEA; 300-->226, TPA; 6319-->4227, 3312-->943), and CRP levels were markedly elevated with tumor fever. The only adverse reaction to PTCT was nausea and vomiting in one female patient. We repeated PTCT 6 times for giant HCC, and performance status was improved (2-->0). In conclusion, PTCT using the Hotwire is useful for treating hypervascular tumors limited to the liver, especially HCC with intraportal invasion and collateral vessels.
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PMID:[Percutaneous transcatheter thermotherapy (PTCT): use of hotwire for local tumor control]. 938 95

GI147211 is a novel, totally synthetic camptothecin with promising preclinical and early clinical activity. This study was designed to determine the maximum tolerated dose of Gl147211 as a 72-h infusion and to describe its pharmacokinetics and pharmacodynamics on this schedule. In a single-arm, rising-dose study in patients with advanced cancer, eight cohorts of three or more patients received 72-h infusions of Gl147211 at doses ranging from 0.25 to 2.5 mg m(-2) day(-1). Forty-four patients received a total of 124 cycles. All patients had refractory tumours and 40 had received prior chemotherapy and/or radiotherapy. Whole-blood Gl147211 lactone, total blood and total concentrations were measured during and over the 12 h following the infusion. Myelosuppression was observed at all dose levels. Neutropenia was dose limiting at 2.0 mg m(-2) day(-1) in minimally pretreated patients, while both neutropenia and thrombocytopenia were limiting at 1.5 mg m(-2) day(-1) in those more heavily pretreated. Phlebitis occurred with infusions through peripheral veins early in this study, necessitating the use of central venous access. Other toxicities included mild nausea and vomiting, fatigue, headache, central venous catheter infections and alopecia. Three partial and two minor responses lasting 8-34+ weeks were noted in patients with ovarian, colon and breast carcinomas and hepatoma. Mean steady-state concentrations of Gl147211 increased with dose over a range of 0.25-1.24 ng ml(-1). The mean terminal elimination half-life was 7.5 h, and the clearance averaged 1074 ml min(-1) m(-2) over the doses studied. The mean fractional excretion of unchanged drug in urine was 0.114. Gl147211 lactone exposure correlated with haematological toxicity. The recommended phase II doses for this regimen are 1.75 mg m(-2) day(-1) and 1.2 mg m(-2) day(-1) for minimally pretreated and heavily pretreated patients respectively. At these doses, steady-state Gl147211 concentrations within the range of those effective in vitro were achieved. Extensive phase II evaluation of this compound and further phase I trials evaluating more prolonged infusions are ongoing.
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PMID:A phase I clinical and pharmacokinetic study of the new topoisomerase inhibitor GI147211 given as a 72-h continuous infusion. 982 74


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