Phase III randomized controlled trial comparing the survival of patients with unresectable hepatocellular carcinoma treated with nolatrexed or doxorubicin

Robert G. Gish, Camillo Porta, Lucian Lazar, Paul Ruff, Ronald Feld, Adina Croitoru, Lynn G Feun, Krzysztof Jeziorski, John Leighton, José Gallo, Gerard T. Kennealey

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Abstract

Purpose: The study objective was to compare the overall survival (OS) of patients with unresectable or metastatic hepatocellular carcinoma (HCC) treated with nolatrexed (NOL) or doxorubicin (DOX). Patients and Methods: Patients from North America, Europe, and South Africa (N = 445) with HCC were randomly assigned to receive NOL or DOX. Eligible patients had Kamofsky performance status (KPS) ≥ 60%, Cancer of the Liver Italian Program (CLIP) score ≤ 3, and adequate organ function. Primary end point was OS. Secondary end points included progression-free survival (PFS), objective response rates, and safety. The treatment groups were well-balanced with regards to age, sex, ethnic origin, and underlying liver disease. Randomization was stratified according to KPS and CLIP score. Results: At the time of the final analysis, 377 patients had died. Median OS was 22.3 weeks for NOL and 32.3 weeks for DOX (P = .0068). The hazard ratio was 0.753 in favor of DOX. Objective response rate (complete response [CR] plus partial response [PR]) was 1.4% for NOL and 4.0% for DOX. Median PFS was 12 weeks for NOL and 10 weeks for DOX (P = .7091). Median time to treatment failure was 8.4 weeks for NOL and 9.1 weeks for DOX (P = .0969). Grade 3 and 4 stomatitis, vomiting, diarrhea, and thrombocytopenia were more common in the NOL arm. Alopecia was more common in the DOX arm. More patients were withdrawn from study for toxicity in the NOL arm than in the DOX arm. Conclusion: NOL showed minimal activity in this phase III trial. Further exploration at this dose and schedule in HCC is not warranted.

Original languageEnglish
Pages (from-to)3068-3075
Number of pages8
JournalJournal of Clinical Oncology
Volume25
Issue number21
DOIs
StatePublished - Jul 20 2007

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Doxorubicin
Hepatocellular Carcinoma
Randomized Controlled Trials
Survival
Liver Neoplasms
Disease-Free Survival
nolatrexed
Stomatitis
Alopecia
Random Allocation
North America
South Africa
Treatment Failure
Thrombocytopenia
Vomiting
Liver Diseases
Diarrhea
Appointments and Schedules
Safety

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Medicine(all)

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Phase III randomized controlled trial comparing the survival of patients with unresectable hepatocellular carcinoma treated with nolatrexed or doxorubicin. / Gish, Robert G.; Porta, Camillo; Lazar, Lucian; Ruff, Paul; Feld, Ronald; Croitoru, Adina; Feun, Lynn G; Jeziorski, Krzysztof; Leighton, John; Gallo, José; Kennealey, Gerard T.

In: Journal of Clinical Oncology, Vol. 25, No. 21, 20.07.2007, p. 3068-3075.

Research output: Contribution to journalArticle

Gish, RG, Porta, C, Lazar, L, Ruff, P, Feld, R, Croitoru, A, Feun, LG, Jeziorski, K, Leighton, J, Gallo, J & Kennealey, GT 2007, 'Phase III randomized controlled trial comparing the survival of patients with unresectable hepatocellular carcinoma treated with nolatrexed or doxorubicin', Journal of Clinical Oncology, vol. 25, no. 21, pp. 3068-3075. https://doi.org/10.1200/JCO.2006.08.4046
Gish, Robert G. ; Porta, Camillo ; Lazar, Lucian ; Ruff, Paul ; Feld, Ronald ; Croitoru, Adina ; Feun, Lynn G ; Jeziorski, Krzysztof ; Leighton, John ; Gallo, José ; Kennealey, Gerard T. / Phase III randomized controlled trial comparing the survival of patients with unresectable hepatocellular carcinoma treated with nolatrexed or doxorubicin. In: Journal of Clinical Oncology. 2007 ; Vol. 25, No. 21. pp. 3068-3075.
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abstract = "Purpose: The study objective was to compare the overall survival (OS) of patients with unresectable or metastatic hepatocellular carcinoma (HCC) treated with nolatrexed (NOL) or doxorubicin (DOX). Patients and Methods: Patients from North America, Europe, and South Africa (N = 445) with HCC were randomly assigned to receive NOL or DOX. Eligible patients had Kamofsky performance status (KPS) ≥ 60{\%}, Cancer of the Liver Italian Program (CLIP) score ≤ 3, and adequate organ function. Primary end point was OS. Secondary end points included progression-free survival (PFS), objective response rates, and safety. The treatment groups were well-balanced with regards to age, sex, ethnic origin, and underlying liver disease. Randomization was stratified according to KPS and CLIP score. Results: At the time of the final analysis, 377 patients had died. Median OS was 22.3 weeks for NOL and 32.3 weeks for DOX (P = .0068). The hazard ratio was 0.753 in favor of DOX. Objective response rate (complete response [CR] plus partial response [PR]) was 1.4{\%} for NOL and 4.0{\%} for DOX. Median PFS was 12 weeks for NOL and 10 weeks for DOX (P = .7091). Median time to treatment failure was 8.4 weeks for NOL and 9.1 weeks for DOX (P = .0969). Grade 3 and 4 stomatitis, vomiting, diarrhea, and thrombocytopenia were more common in the NOL arm. Alopecia was more common in the DOX arm. More patients were withdrawn from study for toxicity in the NOL arm than in the DOX arm. Conclusion: NOL showed minimal activity in this phase III trial. Further exploration at this dose and schedule in HCC is not warranted.",
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T1 - Phase III randomized controlled trial comparing the survival of patients with unresectable hepatocellular carcinoma treated with nolatrexed or doxorubicin

AU - Gish, Robert G.

AU - Porta, Camillo

AU - Lazar, Lucian

AU - Ruff, Paul

AU - Feld, Ronald

AU - Croitoru, Adina

AU - Feun, Lynn G

AU - Jeziorski, Krzysztof

AU - Leighton, John

AU - Gallo, José

AU - Kennealey, Gerard T.

PY - 2007/7/20

Y1 - 2007/7/20

N2 - Purpose: The study objective was to compare the overall survival (OS) of patients with unresectable or metastatic hepatocellular carcinoma (HCC) treated with nolatrexed (NOL) or doxorubicin (DOX). Patients and Methods: Patients from North America, Europe, and South Africa (N = 445) with HCC were randomly assigned to receive NOL or DOX. Eligible patients had Kamofsky performance status (KPS) ≥ 60%, Cancer of the Liver Italian Program (CLIP) score ≤ 3, and adequate organ function. Primary end point was OS. Secondary end points included progression-free survival (PFS), objective response rates, and safety. The treatment groups were well-balanced with regards to age, sex, ethnic origin, and underlying liver disease. Randomization was stratified according to KPS and CLIP score. Results: At the time of the final analysis, 377 patients had died. Median OS was 22.3 weeks for NOL and 32.3 weeks for DOX (P = .0068). The hazard ratio was 0.753 in favor of DOX. Objective response rate (complete response [CR] plus partial response [PR]) was 1.4% for NOL and 4.0% for DOX. Median PFS was 12 weeks for NOL and 10 weeks for DOX (P = .7091). Median time to treatment failure was 8.4 weeks for NOL and 9.1 weeks for DOX (P = .0969). Grade 3 and 4 stomatitis, vomiting, diarrhea, and thrombocytopenia were more common in the NOL arm. Alopecia was more common in the DOX arm. More patients were withdrawn from study for toxicity in the NOL arm than in the DOX arm. Conclusion: NOL showed minimal activity in this phase III trial. Further exploration at this dose and schedule in HCC is not warranted.

AB - Purpose: The study objective was to compare the overall survival (OS) of patients with unresectable or metastatic hepatocellular carcinoma (HCC) treated with nolatrexed (NOL) or doxorubicin (DOX). Patients and Methods: Patients from North America, Europe, and South Africa (N = 445) with HCC were randomly assigned to receive NOL or DOX. Eligible patients had Kamofsky performance status (KPS) ≥ 60%, Cancer of the Liver Italian Program (CLIP) score ≤ 3, and adequate organ function. Primary end point was OS. Secondary end points included progression-free survival (PFS), objective response rates, and safety. The treatment groups were well-balanced with regards to age, sex, ethnic origin, and underlying liver disease. Randomization was stratified according to KPS and CLIP score. Results: At the time of the final analysis, 377 patients had died. Median OS was 22.3 weeks for NOL and 32.3 weeks for DOX (P = .0068). The hazard ratio was 0.753 in favor of DOX. Objective response rate (complete response [CR] plus partial response [PR]) was 1.4% for NOL and 4.0% for DOX. Median PFS was 12 weeks for NOL and 10 weeks for DOX (P = .7091). Median time to treatment failure was 8.4 weeks for NOL and 9.1 weeks for DOX (P = .0969). Grade 3 and 4 stomatitis, vomiting, diarrhea, and thrombocytopenia were more common in the NOL arm. Alopecia was more common in the DOX arm. More patients were withdrawn from study for toxicity in the NOL arm than in the DOX arm. Conclusion: NOL showed minimal activity in this phase III trial. Further exploration at this dose and schedule in HCC is not warranted.

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