Gastric cancer remains the third leading cause of cancer-related death worldwide and is especially frequent in East Asia. Fluoropyrimidines are the backbone of first-line chemotherapy for advanced gastric cancer (AGC), and S-1 provides new option with its simplicity and convenience. 5-Fluorouracil (5-FU) was the only efficacious treatment for AGC before the nineties of the 20th century, and afterwards with the discovery of chemotherapy such as cisplatin, oxaliplatin, S-1 and capecitabine, response rate as well as survival had been improved greatly. Most of AGC will progress after first-line treatment; therefore, seeking an efficient and low toxic maintaining regimen to prolong progression-free survival (PFS) becomes a hot topic in oncologic field. Some clinical researches demonstrated maintenance treatment for advanced colorectal cancer (CRC) and lung cancer. The investigators had conducted a phase III clinical trial that demonstrated capecitabine maintenance versus observation prolonged PFS significantly after first-line chemotherapy with FOLFOX or XELOX regimens in advanced CRC. In AGC, several retrospective studies revealed patients receiving 5-FU/leucovorin(LV), capecitabine, or trastuzumab maintaining therapy experienced significantly longer PFS than that stopped chemotherapy after first-line chemotherapy. Some one-arm phase II clinical trials found 5-FU/LV, capecitabine, S-1, capecitabine plus bevacirumab, or capecitabine plus bevacirumab plus trastuzumab maintenance seemed to yield sound PFS and good tolerance. However, there were no randomized controlled clinical trials for maintenance treatment of these regimens in AGC, except that a phase II Chinese randomized controlled trial of Uracil and Tegafur (UFT) versus observation experienced early termination. Above all, so far, there is no data to demonstrate that regular 2-6 months of chemotherapy followed by maintenance treatment could prolong PFS and OS for AGC. S-1 is effective for gastric cancer, and was approved as palliative treatment for advanced gastric cancer and adjuvant treatment; in addition, with its relative less frequency of side effects and convenient oral administration, S-1 as maintenance regimen could be prone to be accepted by patients. Therefore, the current study is designed to investigate that S-1 as maintenance treatment after first-line palliative chemotherapy could improve PFS and OS for patients with advanced gastric cancer through a perspective randomized clinical study.
Patients with AGC who achieved objective response or stable disease after 2-6 months of first-line chemotherapy were randomly assigned to one of two groups, to receive either S-1 (40 mg for BSA\<1.25 m2, 50 mg for 1.25≤BSA\<1.50 m2 and 60 mg for BSA≥1.50 m2 b.i.d. on days 1-14, q3w) as maintenance therapy or observation. The treatment will continue until disease progression or unacceptable toxicity.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
200
S-1 maintenance till disease progression or untolerable toxicities, in oral doses of 40 mg (BSA\<1.25 m2), 50 mg (1.25≤BSA\<1.50 m2) and 60 mg (BSA≥1.50 m2) b.i.d. on days 1-14 for each 21-day cycle.
Observation without anti-tumor treatment
Sun Yat-sen University Cancer Center
Guangzhou, Guangdong, China
RECRUITINGmaintenance progression-free survival (PFS)
The Kaplan-Meier survival from randomization to maintenance or observation until the date of first documented progression or date of death from any cause, whichever came first.
Time frame: from date of randomization to maintenance or observation until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 2 years
progression-free survival from induction treatment (PFS2)
The Kaplan-Meier survival from induction treatment (the initiation date of first-line chemotherapy) until the date of first documented progression or date of death from any cause after maintenance treatment or observation, whichever came first
Time frame: from induction treatment (the initiation date of first-line chemotherapy) until the date of first documented progression or date of death from any cause after maintenance treatment or observation, whichever came first, assessed up to 2 years
overall survival (OS)
The Kaplan-Meier survival from induction treatment (the initiation date of first-line chemotherapy) until death from any cause or the last follow-up date.
Time frame: from induction treatment (the initiation date of first-line chemotherapy) until death from any cause or the last follow-up date, assessed up to 2 years.
toxicity relevant to S-1 maintenance/observation
any toxicities occurring during the treatment of S-1 maintenance/observation
Time frame: from date of randomization to maintenance or observation until the date of first documented progression or unaccepted toxicities, assessed up to 30 days after the last oral administration of S-1.
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