Phase II trial of uracil/tegafur (UFT) plus leucovorin in patients with advanced hepatocellular carcinoma.

Abstract:

UNLABELLED:Although UFT 300 mg/m2/day and leucovorin 90 mg/day administered orally in divided doses administered every 8 hours for 28 days repeated every 35 days could be administered safely to patients with advanced hepatomas and good performance status, this combination and schedule has limited activity in treating advanced hepatoma. BACKGROUND/PURPOSE:Biochemical modulation of 5-fluorouracil has yielded higher response rates in hepatoma when compared to treatment with 5-fluorouracil as a single agent, although the impact on survival has been negligible. This study was conducted to determine the activity and evaluate the toxicity of uracil and tegafur in a 4:1 molar concentration ratio (UFT; Bristol-Myers Squibb, Wallingford, CT) plus oral calcium leucovorin in the treatment of patients with advanced hepatocellular carcinoma (hepatoma). PATIENTS AND METHODS:Sixteen patients with advanced measurable hepatocellular carcinoma were enrolled onto the trial. All patients had a Karnofski performance status > or = 60%, platelet count > or = 75,000/micro L, total bilirubin < or = 2.0 x institutional upper limit of normal but otherwise normal liver and kidney function profile and bidimensionally measurable disease by CT or ultrasound examination. None of these patients received prior cytotoxic chemotherapy or radiation therapy for advanced disease. Fourteen patients received 300 mg/m2/d UFT plus 90 mg/d leucovorin administered orally in divided daily doses every 8 hours for 28 days repeated every 35 days. Two patients registered for the trial but did not receive study medication. Objective tumor response, the primary purpose of this trial, was evaluated after two courses of therapy. Other end-points included toxicity, time to progression, and overall survival. RESULTS:Fourteen patients were evaluable for response and toxicity, respectively. No complete or partial responders were observed in this trial. Three patients had stable disease lasting 17 to 22 weeks. Toxicity was mild with severe (grade 3 or 4) liver pain, diarrhea, anorexia/nausea, fatigue, dyspnea, hyperbilirubinemia, anemia, and edema seen in 3 (21%), 2 (14%), 3 (21%), 2 (14%), 1 (7%), 1 (7%), 1 (7%) and 1 (7%) patients, respectively. The most frequent grade I and 2 toxic effects included fever of unknown origin, dyspnea, nausea, vomiting and diarrhea. CONCLUSION:UFT 300 mg/m2/d plus oral leucovorin 90 mg/d administered for 28 days did not demonstrate antitumor activity against advanced hepatomas. Further treatment using this regimen is not recommended for this disease.

journal_name

Invest New Drugs

authors

Mani S,Schiano T,Garcia JC,Ansari RH,Samuels B,Sciortino DF,Tembe S,Shulman KL,Baker A,Benner SE,Vokes EE

doi

10.1023/a:1006104217137

subject

Has Abstract

pub_date

1998-01-01 00:00:00

pages

279-83

issue

3

eissn

0167-6997

issn

1573-0646

journal_volume

16

pub_type

临床试验,杂志文章
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    pub_type: 杂志文章

    doi:10.1007/BF00175291

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  • Riccardin D, a novel macrocyclic bisbibenzyl, induces apoptosis of human leukemia cells by targeting DNA topoisomerase II.

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    pub_type: 杂志文章

    doi:10.1007/s10637-010-9554-8

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    pub_type: 杂志文章

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    pub_type: 杂志文章,多中心研究,随机对照试验

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    pub_type: 临床试验,杂志文章

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    pub_type: 杂志文章

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    pub_type: 杂志文章

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    更新日期:2004-04-01 00:00:00

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    pub_type: 杂志文章,随机对照试验

    doi:10.1007/s10637-013-0055-4

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    更新日期:2014-06-01 00:00:00

  • Anticancer activities of vitamin K3 analogues.

    abstract::In a previous study we reported on the synthesis of 1,4-naphthoquinone-sulfides by thiolation of 1,4-naphthohydroquinones with primary aryl and alkyl thiols using laccase as catalyst. These compounds were synthesized as Vitamin K3 analogues. Vitamin K3 (VK3; 2-methyl-1,4-naphthoquinone; menadione) is known to have pot...

    journal_title:Investigational new drugs

    pub_type: 杂志文章

    doi:10.1007/s10637-019-00855-8

    authors: Wellington KW,Hlatshwayo V,Kolesnikova NI,Saha ST,Kaur M,Motadi LR

    更新日期:2020-04-01 00:00:00

  • A novel N-myristylated synthetic octapeptide inhibits protein kinase C activity and partially reverses murine fibrosarcoma cell resistance to adriamycin.

    abstract::This report shows that N-acylation of the protein kinase C (PKC) substrate Arg-Lys-Arg-Thr-Leu-Arg-Arg-Leu (RKRTLRRL) provides it with a potent inhibitory activity against PKC. N-myristoyl-RKRTLRRL inhibited Ca2(+)- and phosphatidylserine (PS)-dependent histone phosphorylation catalyzed by PKC with a 50% inhibitory co...

    journal_title:Investigational new drugs

    pub_type: 杂志文章

    doi:10.1007/BF00175084

    authors: O'Brian CA,Ward NE,Liskamp RM,de Bont DB,Earnest LE,van Boom JH,Fan D

    更新日期:1991-05-01 00:00:00