Randomized phase II study of second-line chemotherapy with the best available 5-fluorouracil regimen versus weekly administration of paclitaxel in far advanced gastric cancer with severe peritoneal metastases refractory to 5-fluorouracil-containing regimens (JCOG0407)

Tomohiro Nishina, Narikazu Boku, Masahiro Gotoh, Yasuhiro Shimada, Yasuo Hamamoto, Hirofumi Yasui, Kensei Yamaguchi, Hiroki Kawai, Norisuke Nakayama, Kenji Amagai, Junki Mizusawa, Kenichi Nakamura, Kuniaki Shirao, Atsushi Ohtsu

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Background: This randomized phase II study compared weekly administration of paclitaxel (wPTX) with the best available 5-fluorouracil (5-FU) regimen as second-line treatment for advanced gastric cancer patients with severe peritoneal metastasis refractory to fluoropyrimidine. Methods: In the best available 5-FU arm, continuous infusion of 5-FU (800 mg/m2/day, days 1–5, every 4 weeks) was given to patients with prior chemotherapy including bolus 5-FU, and methotrexate and 5-FU sequential bolus injection (methotrexate at 100 mg/m2 followed by bolus 5-FU at 600 mg/m2 with leucovorin, weekly) was given to those who had previously received continuous infusion of 5-FU or oral administration of fluoropyrimidine. In the wPTX arm, paclitaxel (80 mg/m2) was administered on days 1, 8, and 15, every 4 weeks. This study adopted a screening design (one-sided α = 30 %) with the primary end point of overall survival. Results: One hundred patients were randomized to the 5-FU arm (n = 49) or the wPTX arm (n = 51). Although the median survival time was 7.7 months in both arms, the 2-year survival rates were 2.9 % in the 5-FU arm and 9.1 % in the wPTX arm [hazard ratio 0.89 (95 % confidence interval 0.57–1.38), one-sided p = 0.298}. The median progression-free survival was longer with wPTX than with 5-FU [3.7 months vs 2.4 months; hazard ratio 0.58 (95 % confidence interval 0.38–0.88), one-sided p = 0.005]. The incidences of grade 4 neutropenia, grade 3/4 febrile neutropenia, diarrhea, and treatment-related death were 6 %, 4 %, 10 %, and 2 %, respectively, in the 5-FU arm and 2 %, 0 %, 0 %, and 0 %, respectively, in the wPTX arm. Conclusions: As second-line chemotherapy, wPTX appears feasible and promising. This regimen can be included in a test arm in future phase III trials for treatment of advanced gastric cancer with severe peritoneal metastasis.

Original languageEnglish
Pages (from-to)902-910
Number of pages9
JournalGastric Cancer
Issue number3
Publication statusPublished - 2016 Jul 1
Externally publishedYes



  • 5-Fluorouracil
  • Gastric cancer
  • Paclitaxel
  • Peritoneal metastasis
  • Phase II study

ASJC Scopus subject areas

  • Oncology
  • Gastroenterology
  • Cancer Research

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