Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019158 (hepatitis)
 30,205 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hepatic regional treatment represents an attempt to improve tumor response by increasing drug concentration with low systemic toxicities. Recently in vitro and clinical studies have shown that the cytotoxicity of 5-fluorodeoxyuridine (FUDR) and 5-fluorouracil (5FU) can be potentiated by high doses of leucovorin (LCV). Two pilot studies with intraarterial FUDR, 5FU, and LCV were initiated. Since 1982, 221 patients with colorectal liver metastases were treated by various forms of long-term monthly continuous regional treatment using implantable ports or pumps. FUDR (0.05 to 1.7 mg/kg/d) was administered alone or combined with 5-FU and leucovorin. In 61 patients curative liver resection was possible and was followed by adjuvant arterial treatment. Overall median survival time (MST) was 15 months and increased to 36 months after liver resection. This was influenced by the following important factors: treatment, number of metastases, extent of infiltration, tumor volume, and minimal intraoperatively diagnosed extrahepatic disease. The response rate varied from 69% to 23%. Time of development of extrahepatic progression was not delayed by additional systemic treatment. Local side effects significantly depended on the duration of arterial infusion. The rate of biliary sclerosis ranged from 19% to 0%. Occurrence of chemical hepatitis was between 7% and 38%. In contrast, after combined intraarterial treatment with LCV, systemic side effects, mainly stomatitis and diarrhea, were dose limiting. Despite the improvement of survival after regional treatment, further randomized trials are mandatory to compare regional with relevant systemic treatment.
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PMID:Continuous regional treatment with fluoropyrimidines for metastases from colorectal carcinomas: influence of modulation with leucovorin. 153 72

To assess the feasibility and effectiveness of combined therapy on locally advanced cervical cancer, we entered 38 patients into a study. The patients were treated with mitomycin-C (10 mg/m2) on Days 1 and 30 and 5-FU (1000 mg/m2) on Days 1 to 4 and Days 30 to 33. In 5 weeks 4500-5000 cGy was given concurrently, followed by radioactive implants. Twenty-six patients had an early-stage disease (IB-IIB) and twelve had a late-stage disease (IIIB-IVA). Eighty-seven percent (33/38) of the patients had a tumor measuring 5 cm or more. The other 5 patients with a tumor size under 5 cm had biopsy-proven positive pelvic nodes; 2 of these 5 patients had a pretherapy hysterectomy. Tumor response, complete (CR) vs partial (PR), was assessed in 36 patients 3 months after completion of therapy. A CR was noted in 80% (29/36) of the patients. The PR status conferred a detrimental effect on the pelvic disease control (PDC), disease-free survival (DFS), and survival (S) while late stage correlated with the development of distant metastases (DM) and a poor DFS. PDC was obtained in 93% (27/29) of the patients who had a CR, as compared to only 43% (3/7) of those with a PR (P = 0.0228). The DFS and S rates were 59 and 77% for patients with a CR and 21 and 19% for those with a PR; respective P values were 0.0340 and 0.0002. Eleven percent (3/26) of the patients with an early stage developed DM, as compared to 50% (6/12) of those with late stage, (P = 0.0016). The DFS rates were 80 and 37% for patients with an early and late stage, respectively (P = 0.0141). Four patients developed transient neutropenia and one had transient thrombocytopenia. The second dose of mitomycin-C was omitted in 4 patients due to persistent neutropenia in 3 and to transfusion-related hepatitis in 1. Two percent (5/21) of the patients who had a staging laparotomy developed wound dehiscence. Three patients developed non-cancer-related small bowel obstruction requiring surgery. We concluded that this combined regimen was well tolerated. Although it was effective in controlling the cancer in the pelvis, this regimen failed to control DM in late-stage patients.
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PMID:Mitomycin-C/5-FU and radiation therapy for locally advanced uterine cervical cancer. 175 91

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.
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PMID:Intra-arterial hepatic chemotherapy with pirarubicin. Preclinical and clinical studies. 229 52

Thirty-three patients with liver metastases of colorectal cancer were treated by intra-arterial 5-FU chemotherapy. The median survival time of all patients was 14 months. A partial remission could be observed in nine patients, and a further 15 patients had stable disease. Patients were treated on an outpatient basis and the toxicity of treatment was mild. We observed no case of sclerosing cholangitis or chemical hepatitis. Intra-arterial 5-FU chemotherapy provided treatment results similar to those reported for FUdR but with less hepatobiliary toxicity.
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PMID:Hepatic arterial infusion (HAI) chemotherapy for liver metastases of colorectal cancer using 5-FU. 232 13

Fifty-nine colorectal cancer patients with metastatic liver cancer who underwent intra-arterial infusion chemotherapy (IAIC) at the National Cancer Center Hospital from May 1986 to February 1989 were reviewed. Excisions of metastatic liver cancer were performed in 36 patients and 23 had nonresectable metastatic liver cancer. Catheter troubles, including severe infection (8), extravasations (3), obstruction (1) and other problems (1) occurred in 13 (22.0%) patients, and 6 patients (10.2%) were unable to receive IAIC. Three patients did not undergo IAIC because of hepatitis or other reasons. Serious complications following IAIC, including sclerosing cholangitis (6), extravasations (6) and obstructions (3) were observed in 15 patients (30.0%). Results of IAIC were discussed in 21 patients undergoing hepatic resection and 17 patients with nonresectable metastatic liver cancer. 5-Fluorouracil (5-FU) (700 mg/m2) and mitomycin C (MMC) (7 mg/m2) were infused through implantable pumps every week or every two weeks. Total infused doses of 5-FU ranged from 500 to 15,000 mg (mean: 8,300 +/- 3,400 mg) and those of MMC were from 26 to 144 mg (mean: 58.8 +/- 32.7 mg) in 21 patients undergoing hepatic resections, whereas 1,500-26,250 mg (mean: 11,000 +/- 7,800 mg) of 5-FU and 0-130 mg of MMC (mean: 57.3 +/- 33.3) were infused in 17 patients with nonresectable liver cancer. Seven patients (33.3%) had recurrent liver cancer during 7-31 months (mean: 16.2 +/- 6.0 m) follow-up after hepatic resections, whilst only 3 of 13 patients (23.1%) with solitary liver metastasis had recurrent liver cancer. Three of these recurrent liver cancer patients (37.5%) underwent hepatic re-excision. Seven of 17 nonresectable patients (41.2%) were responders. Three patients completely responded (CR) and 4 responded partially (PR). Another study is needed to clarify the effect of IAIC in survival. IAIC should be undertaken as a treatment not only for patients with nonresectable metastatic liver cancer, but also for those with resectable metastatic liver cancer in order to prevent hepatic recurrence.
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PMID:[Results of intra-arterial infusion chemotherapy of colorectal cancer in patients with metastatic liver cancer]. 250 27

Fifty-two (52) patients with nonresectable hepatic-only metastases from colorectal carcinoma (tumor volume less than 75%) were treated by intraarterial FUdR, 0.2 mg/kg/d x 14 days/month (IA) using implantable pumps (Infusaid). They were randomized either for IA or for IA + systemic 5-FU 700 mg/m2/d x 3 days/month (IA/IV). Forty-six (46) patients were evaluable (26 IA; 20 IA/IV). Both groups were comparable in respect to primary tumor stage, age, liver function tests, tumor markers and extent of tumor infiltration. Twenty-six (26) patients (56%) demonstrated a complete (CR) or partial response (PR) with at least a 50% decrease in CEA levels and a significant tumor volume reduction (IA 50%; IA/IV 65%). Quality of response was significantly correlated with median survival (MS) time of 25 months for CR and PR. Approximate MS for IA and IA/IV was 16 and 19.5 months, respectively, and approximate median survival time to extra- and/or intrahepatic progression was 9 months (IA) and 11 months (IA/IV). Incidence of extrahepatic recurrence was not influenced by any treatment (IA 62%; IA/IV 60%). Overall approximate median time to occurrence of extrahepatic disease was 12.5 months (IA 13; IA/IV 10). Liver disease progression was observed in 38 patients (IA 85%; IA/IV 80%). A median time of 8 months to diagnosis of liver disease progression was calculated for IA, and IA/IV was 11.5 months. Incidence of chemical hepatitis for IA and IA/IV was 54 and 45%, while biliary sclerosis occurred in 15% and 10% of the cases, respectively, and did not correlate with response rates. Systemic side effects (25%) were only observed in the IA/IV group and induced significantly more interruptions of therapy than in the IA group. It is concluded from this study that additional systemic 5-FU treatment does not prevent the occurrence of extrahepatic disease under local chemotherapy of the liver.
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PMID:Prevention of extrahepatic disease during intraarterial floxuridine of colorectal liver metastases by simultaneous systemic 5-fluorouracil treatment? A prospective multicenter study. 253 92

If liver metastases are diffuse and spread out in the two lobes of the liver, the question remains as to which treatment should be given. Experimental studies showed that when a tumor grows, its vascular pattern becomes mainly arterial. However, if the tumor is still increasing, its center becomes progressively necrotic. After hepatic artery ligation the blood flow of the liver metastases decreases by 90% in the tumor but depriving the arterial circulation of the tumor is not sufficient to achieve a complete cure since the portal blood supply always saves a rim of neoplastic cells around the necrotic area. On the other hand, local infusion of chemotherapy for liver metastases by the arterial route showed a response rate varying between 34 and 70% and the median survival varying between 8 and 17 months. When FUdR chemotherapy was administered using a totally implantable drug infusion pump no improvement in the survival was observed and moreover a high level of toxicity was described including hepatitis and biliary sclerosis. A combined therapy seems a rational approach to treat tumor cells in surviving to the arterial ligation by perfusing the liver with cytotoxic drugs via the portal vein. Taylor's study was very promising but a randomized phase III clinical trial led by the gastrointestinal cancer group of the EORTC with the aim to evaluate the effectiveness of hepatic artery ligation and portal infusion of 5-FU did not show any difference in the survival of the treated patients when compared with patients treated by hepatic artery ligation alone. 77 patients were registered. Data are now available for 55 patients, respectively 30 and 25 patients in the treated group and in the control group. In both groups the median time to progression was 6 months and the median survival time was 12 months. 20% of the patients treated by hepatic artery ligation and portal chemotherapy had a response, one of them with a complete response, 5 with partial response and 14 patients without significant change in the size of their metastases. On the contrary, in the group treated by hepatic artery ligation alone, only one patient had a partial response with 13 patients having no change in the size of their metastases.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Hepatic artery ligation or embolization and locoregional chemotherapy of liver metastases from colorectal cancer. 313 73

From 1980 to 1984, forty-five patients suffering gastric cancer were irradiated with curative intent. Twenty-three were considered at high risk of recurrence after complete surgical resection (invasion of the serosa, lymph nodes and/or surgical margins); eleven were treated after partial resection, and for eleven others, the local extension precluded surgery. Radiotherapy combined two lateral fields (usually with wedge filters) and an anterior field. The planned dose was 40 to 50 Gy, according to the amount of residual disease and doses delivered to the major part of the liver and the right and left kidneys did not exceed 30, 5, and 18 Gy, respectively. For patients aged less than 71 and whose general condition was acceptable, one cycle of chemotherapy (FAM for 20 patients and 5-FU for 10) preceded irradiation, followed if possible by 6 other cycles. Adverse effects, essentially anorexia, vomiting, and weight loss, led to definitively stopping irradiation in 8 cases, and were present in 21 other patients. Mean weight loss was 2.5 kg. Apart from one patient who developed a subphrenic abcess and died after reoperation, there was neither chronic complication, nor radiation hepatitis or nephritis. For 34 patients, the observation time was superior to 3 years: 23 died of their cancer, 1 of a subphrenic abcess, and 2 of an intercurrent disease. Eight were disease-free at 3 years (three of these were irradiated for macroscopic disease). For the overall series, the 4-year survival rate is 23%. There is a significant survival advantage for females versus males (p less than 0.01), a non-significant tendency in favor of microscopic residual disease versus macroscopic, and no advantage for the combination with FAM compared with no chemotherapy (non-randomized). This technique appears feasible with an acceptable tolerance and can control local tumor in a few cases. The planned dose of 40 Gy was probably too small and we are now testing 45 Gy delivered over the large initial volume, and boosts of 10-15 Gy to residual disease.
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PMID:Radiotherapy of gastric cancer with a three field combination: feasibility, tolerance, and survival. 367 19

Natural history of patients with colorectal liver metastases is not significantly changed even by curative resection. The majority unfortunately relapse. The results of adjuvant treatment after resection were evaluated by analysis of 17 publications as well as by own data (60 patients). 340 patients were either treated by intraarterial (n = 201), systemic (n = 82), intraportal (n = 29) or intraperitoneal (n = 28) chemoinfusion (5-Fluorouracil or Floxuridine). An alternative approach was the treatment with specific immunotherapy using tumor vaccination (n = 35) or monoclonal antibodies (n = 20). Morbidity of adjuvant treatment includes local (chemical hepatitis, biliary sclerosis) and systemic (diarrhea, stomatitis) side effects. Technical complications could reach a level of up to 50% in case of local administration. With exception of 6 studies no comparison with a resection only group was performed. Despite postulated increase of survival and recurrence free time with historical controls the results of current ongoing studies are needed before general use of adjuvant treatment can be recommended.
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PMID:[Results of resection and adjuvant therapy of liver metastases of primary colorectal tumors--a review of the literature]. 750 91

Discovered by Isaac and Lindemann as a substance able to induce a biological interference among viruses and host cells, interferon appeared to include three main antigenic classes: alpha, beta and gamma. There is a large variety of actions exhibited by different types of interferon and among them it is possible to distinguish an antiviral, antineoplastic, immunomodulatory or hormonal activity. Many years ago, the antiviral action seemed to be relative to some cellular membrane disorders, but later other mechanisms were stressed. Among them, it is worth describing the transcription and transduction of antiviral proteins like the oligoadenilsinthetase and proteinphosphokinase, able to cause the viral RNA breackage. The antineoplastic action is exerted by direct and indirect mechanisms. Direct mechanisms include an antiproliferative activity and the induction to cellular differentiation whereas the indirect ones involve the enhancement on tumor cell surfaces of some tumor associated antigens included in the I class of MHC system. The immunomodulatory action is exerted by the stimulation of macrophages, T cells and Killer cells cytotoxic activity. The list of viral diseases sensitive to interferon treatment includes condiloma acuminata, herpes zoster, chronic B and C hepatitis and Kaposi sarcoma AIDS-related. High proportions of overall response rate were observed among interferon treated patients with condiloma acuminata (80-100%). The use of interferon in the treatment of herpes zoster achieved good results regarding a shorter duration of the time spent to induce the chest pains and cutaneous symptoms disappearance when compared with that relative to other antiviral drugs. Results obtained in the treatment of chronic B and C hepatitis regard the disappearance of viral replication serological markers and the improvement of histological and enzymatic pattern. The effectiveness of interferon in the therapy of Kaposi sarcoma is demonstrated by the reduction of cutaneous symptoms and recurrent infectious diseases incidence. The use of interferon in treatment of solid tumors seems to play secondary role and, at any rate, to be adjuvant to chemotherapy. The administration of beta interferon as therapy of breast cancer seems to increase the estrogens and progesterone concentration in the neoplastic tissue and so it aims to improve the sensitivity to the tamoxifen treatment. The addition of interferon alpha both to 5-FU and cis-platinum seems to improve the proportion of overall response rate respectively in the treatment of colon cancer and head and neck cancer.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:[Update on the use of interferons in clinical practice]. 758 95


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