Takako Eguchi Nakajima1, Kensei Yamaguchi2, Narikazu Boku3, Ichinosuke Hyodo4, Junki Mizusawa5, Hiroki Hara6, Tomohiro Nishina7, Takeshi Sakamoto8, Kohei Shitara9, Katsunori Shinozaki10, Hiroshi Katayama5, Shinichiro Nakamura11, Kei Muro12, Masanori Terashima13. 1. Department of Clinical Oncology, St. Marianna University School of Medicine, 2-16-1 Sugao, Miyamae-ku, Kawasaki, Kanagawa, 216-8511, Japan. tnakajima@marianna-u.ac.jp. 2. Department of Gastroenterology, The Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan. 3. Department of Gastrointestinal Medical Oncology, National Cancer Center Hospital, Tokyo, Japan. 4. Department of Gastroenterology, University of Tsukuba, Tsukuba, Japan. 5. Japan Clinical Oncology Group (JCOG) Data Center/Operations Office, National Cancer Center Hospital, Tokyo, Japan. 6. Department of Gastroenterology, Saitama Cancer Center, Saitama, Japan. 7. Department of Gastrointestinal Medical Oncology, National Hospital Organization Shikoku Cancer Center, Matsuyama, Japan. 8. Department of Gastroenterology, Hyogo Cancer Center, Akashi, Japan. 9. Gastroenterology and Gastrointestinal Oncology, National Cancer Center Hospital East, Kashiwa, Japan. 10. Division of Clinical Oncology, Hiroshima Prefectural Hospital, Hiroshima, Japan. 11. West Japan Oncology Group (WJOG) Data Center Division, Yokohama, Japan. 12. Department of Clinical Oncology, Aichi Cancer Center, Nagoya, Japan. 13. Department of Gastrointestinal Oncology, Shizuoka Cancer Center, Nagaizumi, Japan.
Abstract
BACKGROUND:Oral fluoropyrimidine plus cisplatin is often not tolerated by patients with severe peritoneal metastases of gastric cancer. Combination of 5-fluorouracil (5-FU), l-leucovorin (l-LV), and paclitaxel (FLTAX) has promising activity for such patients. We conducted a phase II/III study comparing FLTAX with 5-FU/l-LV. METHODS:Eligibility criteria included: unresectable or recurrent gastric adenocarcinoma; 20-75 years; performance status (PS) 0-2; peritoneal metastases + ; massive ascites and/or inadequate oral intake; no prior chemotherapy. Patients were randomly assigned to receive 5-FU/l-LV or FLTAX. The primary endpoint of phase III was overall survival: UMIN000010949. RESULTS:We enrolled 101 patients. Early deaths occurred in patients with PS 2 having massive ascites and inadequate oral intake simultaneously; the protocol was amended to exclude such patients. Median survival times were 6.1 and 7.3 months for the 5-FU/l-LV and the FLTAX arms, respectively (HR 0.792; 80% CI 0.596-1.053; one-sided p = 0.1445). FLTAX arm had longer progression-free survival (PFS) [1.9 vs 5.4 months (HR 0.64; 95% CI, 0.43-0.96; p = 0.029)]. Grade 3/4 adverse events such as leucopenia and anorexia were more frequently observed in the 5-FU/l-LV arm. In the 5-FU/l-LV arm, two deaths were treatment-related. In the 5-FU/l-LV and FLTAX arms, 12 and 3 deaths occurred within 30 days after the last protocol treatment, respectively. CONCLUSIONS:Chemotherapy was indicated for patients with severe peritoneal metastases excluding patients with PS 2 having massive ascites and inadequate oral intake simultaneously. FLTAX did not confer a significant survival benefit but may be preferred because of longer PFS and acceptable toxicity.
RCT Entities:
BACKGROUND: Oral fluoropyrimidine plus cisplatin is often not tolerated by patients with severe peritoneal metastases of gastric cancer. Combination of 5-fluorouracil (5-FU), l-leucovorin (l-LV), and paclitaxel (FLTAX) has promising activity for such patients. We conducted a phase II/III study comparing FLTAX with 5-FU/l-LV. METHODS: Eligibility criteria included: unresectable or recurrent gastric adenocarcinoma; 20-75 years; performance status (PS) 0-2; peritoneal metastases + ; massive ascites and/or inadequate oral intake; no prior chemotherapy. Patients were randomly assigned to receive 5-FU/l-LV or FLTAX. The primary endpoint of phase III was overall survival: UMIN000010949. RESULTS: We enrolled 101 patients. Early deaths occurred in patients with PS 2 having massive ascites and inadequate oral intake simultaneously; the protocol was amended to exclude such patients. Median survival times were 6.1 and 7.3 months for the 5-FU/l-LV and the FLTAX arms, respectively (HR 0.792; 80% CI 0.596-1.053; one-sided p = 0.1445). FLTAX arm had longer progression-free survival (PFS) [1.9 vs 5.4 months (HR 0.64; 95% CI, 0.43-0.96; p = 0.029)]. Grade 3/4 adverse events such as leucopenia and anorexia were more frequently observed in the 5-FU/l-LV arm. In the 5-FU/l-LV arm, two deaths were treatment-related. In the 5-FU/l-LV and FLTAX arms, 12 and 3 deaths occurred within 30 days after the last protocol treatment, respectively. CONCLUSIONS: Chemotherapy was indicated for patients with severe peritoneal metastases excluding patients with PS 2 having massive ascites and inadequate oral intake simultaneously. FLTAX did not confer a significant survival benefit but may be preferred because of longer PFS and acceptable toxicity.