Randomized phase iii study of 5-fluorouracil continuous infusion vs. sequential methotrexate and 5-fluorouracil therapy in far advanced gastric cancer with peritoneal metastasis (jcog0106)

Kuniaki Shirao, Narikazu Boku, Yasuhide Yamada, Kensei Yamaguchi, Toshihiko Doi, Masahiro Goto, Junichiro Nasu, Tadamichi Denda, Yasuo Hamamoto, Atsuo Takashima, Haruhiko Fukuda, Atsushi Ohtsu

Research output: Contribution to journalArticle

41 Citations (Scopus)

Abstract

Objective: Owing to the risks of serious and sustained toxicity, anticancer drugs such as cisplatin and irinotecan cannot be readily administered to patients with gastric cancer and severe peritoneal metastasis. Therefore, a standard chemotherapy regimen has yet to be established for these types of patients. This randomized study investigated the utility of sequential methotrexate and 5-fluorouracil therapy vs. 5-fluorouracil continuous infusion for gastric cancer with peritoneal metastasis. Methods: Eligible patients had radiologically confirmed peritoneal metastasis with intestinal stenosis, peritoneal tumor or ascites. Treatment with 5-fluorouracil continuous infusion (800 mg/m2/day, ci, d1-5, q4w) or methotrexate and 5-fluorouracil therapy (methotrexate, 100 mg/m2, bolus infusion, followed 3 h later by 5-fluorouracil, 600 mg/m2, bolus infusion, with leucovorin rescue, q1w) was continued until disease progression or unacceptable toxicity. The projected sample size was 236, providing 80% power to detect a 40% increase in median overall survival in methotrexate and 5-fluorouracil therapy with a one-sided a of 0.05. Results: All 237 randomized patients were included in the primary analysis. The methotrexate and 5-fluorouracil therapy arm was not superior to the 5-fluorouracil continuous infusion arm (median survival time, 9.4 months in the 5-fluorouracil continuous infusion arm, 10.6 months in the methotrexate and 5-fluorouracil therapy arm; hazard ratio, 0.94; 95% confidence interval, 0.72-1.22; one-sided P = 0.31). Frequencies of Grade 3 or higher neutropenia, Grade 3 or higher anorexia and treatment-related deaths were 0.9, 27.4 and 1.7%, respectively, in the 5-fluorouracil continuous infusion arm, and 31.9, 33.6 and 0.9%, respectively, in the methotrexate and 5-fluorouracil therapy arm. Conclusions: Methotrexate and 5-fluorouracil therapy is not suitable for use as standard therapy for advanced gastric cancer with peritoneal metastasis.

Original languageEnglish
Article numberhyt114
Pages (from-to)972-980
Number of pages9
JournalJapanese Journal of Clinical Oncology
Volume43
Issue number10
DOIs
Publication statusPublished - 2013 Oct 1
Externally publishedYes

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Methotrexate
Fluorouracil
Stomach Neoplasms
Neoplasm Metastasis
Therapeutics
irinotecan
Survival
Leucovorin
Anorexia
Neutropenia
Drug-Related Side Effects and Adverse Reactions
Ascites
Sample Size
Cisplatin
Disease Progression
Pathologic Constriction
Confidence Intervals
Drug Therapy

Keywords

  • Chemotherapy
  • Gastric cancer
  • Peritoneal metastasis
  • Phase III study

ASJC Scopus subject areas

  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Cancer Research

Cite this

Randomized phase iii study of 5-fluorouracil continuous infusion vs. sequential methotrexate and 5-fluorouracil therapy in far advanced gastric cancer with peritoneal metastasis (jcog0106). / Shirao, Kuniaki; Boku, Narikazu; Yamada, Yasuhide; Yamaguchi, Kensei; Doi, Toshihiko; Goto, Masahiro; Nasu, Junichiro; Denda, Tadamichi; Hamamoto, Yasuo; Takashima, Atsuo; Fukuda, Haruhiko; Ohtsu, Atsushi.

In: Japanese Journal of Clinical Oncology, Vol. 43, No. 10, hyt114, 01.10.2013, p. 972-980.

Research output: Contribution to journalArticle

Shirao, Kuniaki ; Boku, Narikazu ; Yamada, Yasuhide ; Yamaguchi, Kensei ; Doi, Toshihiko ; Goto, Masahiro ; Nasu, Junichiro ; Denda, Tadamichi ; Hamamoto, Yasuo ; Takashima, Atsuo ; Fukuda, Haruhiko ; Ohtsu, Atsushi. / Randomized phase iii study of 5-fluorouracil continuous infusion vs. sequential methotrexate and 5-fluorouracil therapy in far advanced gastric cancer with peritoneal metastasis (jcog0106). In: Japanese Journal of Clinical Oncology. 2013 ; Vol. 43, No. 10. pp. 972-980.
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abstract = "Objective: Owing to the risks of serious and sustained toxicity, anticancer drugs such as cisplatin and irinotecan cannot be readily administered to patients with gastric cancer and severe peritoneal metastasis. Therefore, a standard chemotherapy regimen has yet to be established for these types of patients. This randomized study investigated the utility of sequential methotrexate and 5-fluorouracil therapy vs. 5-fluorouracil continuous infusion for gastric cancer with peritoneal metastasis. Methods: Eligible patients had radiologically confirmed peritoneal metastasis with intestinal stenosis, peritoneal tumor or ascites. Treatment with 5-fluorouracil continuous infusion (800 mg/m2/day, ci, d1-5, q4w) or methotrexate and 5-fluorouracil therapy (methotrexate, 100 mg/m2, bolus infusion, followed 3 h later by 5-fluorouracil, 600 mg/m2, bolus infusion, with leucovorin rescue, q1w) was continued until disease progression or unacceptable toxicity. The projected sample size was 236, providing 80{\%} power to detect a 40{\%} increase in median overall survival in methotrexate and 5-fluorouracil therapy with a one-sided a of 0.05. Results: All 237 randomized patients were included in the primary analysis. The methotrexate and 5-fluorouracil therapy arm was not superior to the 5-fluorouracil continuous infusion arm (median survival time, 9.4 months in the 5-fluorouracil continuous infusion arm, 10.6 months in the methotrexate and 5-fluorouracil therapy arm; hazard ratio, 0.94; 95{\%} confidence interval, 0.72-1.22; one-sided P = 0.31). Frequencies of Grade 3 or higher neutropenia, Grade 3 or higher anorexia and treatment-related deaths were 0.9, 27.4 and 1.7{\%}, respectively, in the 5-fluorouracil continuous infusion arm, and 31.9, 33.6 and 0.9{\%}, respectively, in the methotrexate and 5-fluorouracil therapy arm. Conclusions: Methotrexate and 5-fluorouracil therapy is not suitable for use as standard therapy for advanced gastric cancer with peritoneal metastasis.",
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T1 - Randomized phase iii study of 5-fluorouracil continuous infusion vs. sequential methotrexate and 5-fluorouracil therapy in far advanced gastric cancer with peritoneal metastasis (jcog0106)

AU - Shirao, Kuniaki

AU - Boku, Narikazu

AU - Yamada, Yasuhide

AU - Yamaguchi, Kensei

AU - Doi, Toshihiko

AU - Goto, Masahiro

AU - Nasu, Junichiro

AU - Denda, Tadamichi

AU - Hamamoto, Yasuo

AU - Takashima, Atsuo

AU - Fukuda, Haruhiko

AU - Ohtsu, Atsushi

PY - 2013/10/1

Y1 - 2013/10/1

N2 - Objective: Owing to the risks of serious and sustained toxicity, anticancer drugs such as cisplatin and irinotecan cannot be readily administered to patients with gastric cancer and severe peritoneal metastasis. Therefore, a standard chemotherapy regimen has yet to be established for these types of patients. This randomized study investigated the utility of sequential methotrexate and 5-fluorouracil therapy vs. 5-fluorouracil continuous infusion for gastric cancer with peritoneal metastasis. Methods: Eligible patients had radiologically confirmed peritoneal metastasis with intestinal stenosis, peritoneal tumor or ascites. Treatment with 5-fluorouracil continuous infusion (800 mg/m2/day, ci, d1-5, q4w) or methotrexate and 5-fluorouracil therapy (methotrexate, 100 mg/m2, bolus infusion, followed 3 h later by 5-fluorouracil, 600 mg/m2, bolus infusion, with leucovorin rescue, q1w) was continued until disease progression or unacceptable toxicity. The projected sample size was 236, providing 80% power to detect a 40% increase in median overall survival in methotrexate and 5-fluorouracil therapy with a one-sided a of 0.05. Results: All 237 randomized patients were included in the primary analysis. The methotrexate and 5-fluorouracil therapy arm was not superior to the 5-fluorouracil continuous infusion arm (median survival time, 9.4 months in the 5-fluorouracil continuous infusion arm, 10.6 months in the methotrexate and 5-fluorouracil therapy arm; hazard ratio, 0.94; 95% confidence interval, 0.72-1.22; one-sided P = 0.31). Frequencies of Grade 3 or higher neutropenia, Grade 3 or higher anorexia and treatment-related deaths were 0.9, 27.4 and 1.7%, respectively, in the 5-fluorouracil continuous infusion arm, and 31.9, 33.6 and 0.9%, respectively, in the methotrexate and 5-fluorouracil therapy arm. Conclusions: Methotrexate and 5-fluorouracil therapy is not suitable for use as standard therapy for advanced gastric cancer with peritoneal metastasis.

AB - Objective: Owing to the risks of serious and sustained toxicity, anticancer drugs such as cisplatin and irinotecan cannot be readily administered to patients with gastric cancer and severe peritoneal metastasis. Therefore, a standard chemotherapy regimen has yet to be established for these types of patients. This randomized study investigated the utility of sequential methotrexate and 5-fluorouracil therapy vs. 5-fluorouracil continuous infusion for gastric cancer with peritoneal metastasis. Methods: Eligible patients had radiologically confirmed peritoneal metastasis with intestinal stenosis, peritoneal tumor or ascites. Treatment with 5-fluorouracil continuous infusion (800 mg/m2/day, ci, d1-5, q4w) or methotrexate and 5-fluorouracil therapy (methotrexate, 100 mg/m2, bolus infusion, followed 3 h later by 5-fluorouracil, 600 mg/m2, bolus infusion, with leucovorin rescue, q1w) was continued until disease progression or unacceptable toxicity. The projected sample size was 236, providing 80% power to detect a 40% increase in median overall survival in methotrexate and 5-fluorouracil therapy with a one-sided a of 0.05. Results: All 237 randomized patients were included in the primary analysis. The methotrexate and 5-fluorouracil therapy arm was not superior to the 5-fluorouracil continuous infusion arm (median survival time, 9.4 months in the 5-fluorouracil continuous infusion arm, 10.6 months in the methotrexate and 5-fluorouracil therapy arm; hazard ratio, 0.94; 95% confidence interval, 0.72-1.22; one-sided P = 0.31). Frequencies of Grade 3 or higher neutropenia, Grade 3 or higher anorexia and treatment-related deaths were 0.9, 27.4 and 1.7%, respectively, in the 5-fluorouracil continuous infusion arm, and 31.9, 33.6 and 0.9%, respectively, in the methotrexate and 5-fluorouracil therapy arm. Conclusions: Methotrexate and 5-fluorouracil therapy is not suitable for use as standard therapy for advanced gastric cancer with peritoneal metastasis.

KW - Chemotherapy

KW - Gastric cancer

KW - Peritoneal metastasis

KW - Phase III study

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