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

Sridhar Mani, Thomas Schiano, Juan C. Garcia, Rafat H. Ansari, Brian Samuels, David F. Sciortino, Shrunali Tembe, Keith L. Shulman, Alfred Baker, Steven E. Benner, Everett E. Vokes

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

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 ≥ 60%, platelet count ≥ 75,000/μL, total bilirubin ≤ 2.0x 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 1 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.

Original languageEnglish (US)
Pages (from-to)279-283
Number of pages5
JournalInvestigational New Drugs
Volume16
Issue number3
DOIs
StatePublished - 1998
Externally publishedYes

Fingerprint

Tegafur
Uracil
Leucovorin
Hepatocellular Carcinoma
Fluorouracil
Dyspnea
Nausea
Diarrhea
Fever of Unknown Origin
Hyperbilirubinemia
Survival
Poisons
Liver
Anorexia
Therapeutics
Platelet Count
Bilirubin
Vomiting
Fatigue
Anemia

Keywords

  • Alpha-fetoprotein
  • Hepatocellular cancer
  • Hepatoma
  • Leucovorin
  • Tegafur
  • Uracil

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology

Cite this

Mani, S., Schiano, T., Garcia, J. C., Ansari, R. H., Samuels, B., Sciortino, D. F., ... Vokes, E. E. (1998). Phase II trial of uracil/tegafur (UFT) plus leucovorin in patients with advanced hepatocellular carcinoma. Investigational New Drugs, 16(3), 279-283. https://doi.org/10.1023/A:1006104217137

Phase II trial of uracil/tegafur (UFT) plus leucovorin in patients with advanced hepatocellular carcinoma. / Mani, Sridhar; Schiano, Thomas; Garcia, Juan C.; Ansari, Rafat H.; Samuels, Brian; Sciortino, David F.; Tembe, Shrunali; Shulman, Keith L.; Baker, Alfred; Benner, Steven E.; Vokes, Everett E.

In: Investigational New Drugs, Vol. 16, No. 3, 1998, p. 279-283.

Research output: Contribution to journalArticle

Mani, S, Schiano, T, Garcia, JC, Ansari, RH, Samuels, B, Sciortino, DF, Tembe, S, Shulman, KL, Baker, A, Benner, SE & Vokes, EE 1998, 'Phase II trial of uracil/tegafur (UFT) plus leucovorin in patients with advanced hepatocellular carcinoma', Investigational New Drugs, vol. 16, no. 3, pp. 279-283. https://doi.org/10.1023/A:1006104217137
Mani, Sridhar ; Schiano, Thomas ; Garcia, Juan C. ; Ansari, Rafat H. ; Samuels, Brian ; Sciortino, David F. ; Tembe, Shrunali ; Shulman, Keith L. ; Baker, Alfred ; Benner, Steven E. ; Vokes, Everett E. / Phase II trial of uracil/tegafur (UFT) plus leucovorin in patients with advanced hepatocellular carcinoma. In: Investigational New Drugs. 1998 ; Vol. 16, No. 3. pp. 279-283.
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abstract = "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 ≥ 60{\%}, platelet count ≥ 75,000/μL, total bilirubin ≤ 2.0x 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 1 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.",
keywords = "Alpha-fetoprotein, Hepatocellular cancer, Hepatoma, Leucovorin, Tegafur, Uracil",
author = "Sridhar Mani and Thomas Schiano and Garcia, {Juan C.} and Ansari, {Rafat H.} and Brian Samuels and Sciortino, {David F.} and Shrunali Tembe and Shulman, {Keith L.} and Alfred Baker and Benner, {Steven E.} and Vokes, {Everett E.}",
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T1 - Phase II trial of uracil/tegafur (UFT) plus leucovorin in patients with advanced hepatocellular carcinoma

AU - Mani, Sridhar

AU - Schiano, Thomas

AU - Garcia, Juan C.

AU - Ansari, Rafat H.

AU - Samuels, Brian

AU - Sciortino, David F.

AU - Tembe, Shrunali

AU - Shulman, Keith L.

AU - Baker, Alfred

AU - Benner, Steven E.

AU - Vokes, Everett E.

PY - 1998

Y1 - 1998

N2 - 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 ≥ 60%, platelet count ≥ 75,000/μL, total bilirubin ≤ 2.0x 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 1 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.

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KW - Alpha-fetoprotein

KW - Hepatocellular cancer

KW - Hepatoma

KW - Leucovorin

KW - Tegafur

KW - Uracil

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