To determine the efficacy of oral 882C87 compared with oral acyclovir in the treatment of localized herpes zoster in immunocompromised patients. To assess the safety and tolerance of oral 882C87 in immunocompromised patients.

开始日期-

申办/合作机构

Glaxo Wellcome SA

100 项与奈替夫定相关的临床结果

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100 项与奈替夫定相关的转化医学

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100 项与奈替夫定相关的专利（医药）

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项与奈替夫定相关的文献（医药）

2014-05-01·Hepato-gastroenterology

Pilot Study of Hepatic Arterial Infusion Chemotherapy with Interferon-beta and 5-fluorouracil: A New Chemotherapy for Patients with Advanced Hepatocellular Carcinoma.

Article

作者: Kuno, Shizuka ; Yoshimitsu, Kengo ; Sakurai, Kunitoshi ; Takeyama, Yasuaki ; Iwata, Kaoru ; Morihara, Daisuke ; Hirano, Genryu ; Yokoyama, Keiji ; Kunimoto, Hideo ; Tanaka, Takashi ; Tsuchiya, Naoaki ; Sakisaka, Shotaro ; Shakado, Satoshi ; Fukunaga, Atsushi ; Irie, Makoto ; Nishizawa, Shinya ; Kora, Shin-ichi ; Sohda, Tetsuro ; Iwashita, Hideyuki ; Yotsumoto, Kaoru

BACKGROUND/AIMSThe present pilot study aimed to evaluate the safety and efficacy of hepatic arterial infusion chemotherapy (HAIC) with interferon-beta (IFN-β) and 5-fluorouracil (5-FU) in patients with advanced hepatocellular carcinoma (HCC).METHODOLOGYWe studied 10 patients with advanced HCC and who were unresponsive to previous HAIC using low-dose 5-FU and cisplatin. The median age was 67 years. Eight patients had portal vein tumor thrombosis and four patients had extrahepatic metastasis. Using a drug delivery system, patients were treated with HAIC of IFN-β (600 MIU/body, three times/week) and 5-FU (250 mg/body, five times/week). Chemotherapy was repeated consecutively for 2 weeks every 4 weeks.RESULTSSix (60%) patients had a decrease in tumor markers alpha-fetoprotein (APP) or des-gamma-carboxy prothrombin (DCP). The median overall survival was 108 days and the 1-year survival rate was 10.0%. Univariate analysis showed two significant prognostic factors related to long-term survival for more than 60 days: a decrease in APP or DCP 4 weeks after treatment (P = 0.035) and no extra hepatic metastasis (P = 0.035). Severe hepatic injury was not observed.CONCLUSIONSHAIC with IFN-β and 5-PU exerts modest antitumor effects and poses no particular safety concerns. This may be a new promising strategy for treatment of advanced HCC.

2005-01-01·Medicinal Research Reviews1区 · 医学

(E)-5-(2-bromovinyl)-2?-deoxyuridine (BVDU)

1区 · 医学

Review

作者: De Clercq, Erik

(E)-5-(2-bromovinyl)-2'-deoxyuridine (BVDU, Brivudin, Zostex, Zerpex, Zonavir), now more than 20 years after its discovery, still stands out as a highly potent and selective inhibitor of herpes simplex virus type 1 (HSV-1) and varicella-zoster virus (VZV) infections. It has been used in the topical treatment of herpetic keratitis and recurrent herpes labialis and the systemic (oral) treatment of herpes zoster (zona, shingles). The high selectivity of BVDU towards HSV-1 and VZV depends primarily on a specific phosphorylation of BVDU to its 5'-diphosphate (DP) by the virus-encoded thymidine kinase (TK). After further phosphorylation (by cellular enzymes), to the 5'-triphosphate (TP), the compound interferes as a competitive inhibitor/alternate substrate with the viral DNA polymerase. The specific phosphorylation by the HSV- and VZV-induced TK also explains the marked cytostatic activity of BVDU against tumor cells that have been transduced by the viral TK genes. This finding offers considerable potential in a combined gene therapy/chemotherapy approach for cancer. To the extent that BVDU or its analogues (i.e., BVaraU) are degraded (by thymidine phosphorylase) to (E)-5-(2-bromovinyl)uracil (BVU), they may potentiate the anticancer potency, as well as toxicity, of 5-fluorouracil. This ensues from the direct inactivating effect of BVU on dihydropyrimidine dehydrogenase, the enzyme that initiates the degradative pathway of 5-fluorouracil. The prime determinant in the unique behavior of BVDU is its (E)-5-(2-bromovinyl) substituent. Numerous BVDU analogues have been described that, when equipped with this particular pharmacophore, demonstrate an activity spectrum characteristic of BVDU, including selective anti-VZV activity.

1999-01-01·Drugs1区 · 医学

Current Pharmacological Approaches to the Therapy of Varicella Zoster Virus Infections

1区 · 医学

Review

作者: Robert Snoeck ; Erik De Clercq ; Graciela Andrei

Varicella zoster virus (VZV), a member of the herpesvirus family, is responsible for both primary (varicella, chickenpox) as well as reactivation (zoster, shingles) infections. In immunocompetent patients, the course of varicella is generally benign. For varicella zoster, post-herpetic neuralgia is the most common complication. In immunocompromised patients (particularly those with AIDS), transplant recipients and cancer patients, VZV infections can be life-threatening. For these patients and also for immunocompetent patients at risk such as pregnant women or premature infants, the current treatment of choice is based on either intravenous or oral aciclovir (acyclovir). The low oral bioavailability of aciclovir, as well as the emergence of drug-resistant virus strains, have stimulated efforts towards the development of new compounds for the treatment of individuals with VZV infections. Among these new compounds, penciclovir, its oral prodrug form famciclovir and the oral pro-drug form of aciclovir (valaciclovir), rank among the most promising. As with aciclovir itself, all of these drugs are dependent on the virus-encoded thymidine kinase (TK) for their intracellular activation (phosphorylation), and, upon conversion to their triphosphate form, they act as inhibitors/alternative substrate of the viral DNA polymerase. Therefore, cross-resistance to these drugs may be expected for those virus mutants that are TK-deficient and thus resistant to aciclovir. Other classes of nucleoside analogues dependent for their phosphorylation on the viral TK that have been pursued for the treatment of VZV infections include sorivudine, brivudine, fialuridine, fiacitabine and netivudine. Among oxetanocins, which are partially dependent on viral TK, lobucavir is now under clinical evaluation. Foscarnet, which does not require any previous metabolism to interact with the viral DNA polymerase, is used in the clinic when TK-deficient VZV mutants emerge during aciclovir treatment. TK-deficient mutants are also sensitive to the acyclic nucleoside phosphonates (i.e. [s]-1-[3-hydroxy-2-phosphonylmethoxypropyl]cytosine; HPMPC); these agents do not depend on the virus-encoded TK for their phosphorylation but depend on cellular enzymes for conversion to their diphosphoryl derivatives which then inhibit viral DNA synthesis. Vaccination for VZV has now come of age. It is recommended for healthy children, patients with leukaemia, and patients receiving immunosuppressive therapy or those with chronic diseases. The protection induced by the vaccine seems, to some extent, to include zoster and associated neuralgia. Passive immuniatin based on specific immunoglobulins does not effectively prevent VZV infection and is therefore restricted to high risk individuals (i.e. immunocompromised children and pregnant women).

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外链

KEGG	Wiki	ATC	Drug Bank
-	-	-	DB12606

研发状态

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适应症	最高研发状态	国家/地区	公司	日期
水痘	临床3期	美国	Glaxo Wellcome SA	2001-08-31
带状疱疹	临床3期	美国	Glaxo Wellcome SA	2001-08-31
HIV感染	临床3期	美国	Glaxo Wellcome SA	2001-08-31