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 language | English |
|---|---|
| Article number | hyt114 |
| Pages (from-to) | 972-980 |
| Number of pages | 9 |
| Journal | Japanese Journal of Clinical Oncology |
| Volume | 43 |
| Issue number | 10 |
| DOIs | |
| Publication status | Published - 2013 Oct 1 |
| Externally published | Yes |
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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 journal › Article
}
TY - JOUR
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
UR - http://www.scopus.com/inward/record.url?scp=84885149501&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84885149501&partnerID=8YFLogxK
U2 - 10.1093/jjco/hyt114
DO - 10.1093/jjco/hyt114
M3 - Article
C2 - 24014884
AN - SCOPUS:84885149501
VL - 43
SP - 972
EP - 980
JO - Japanese Journal of Clinical Oncology
JF - Japanese Journal of Clinical Oncology
SN - 0368-2811
IS - 10
M1 - hyt114
ER -