Journal
GASTRIC CANCER
Volume 20, Issue 6, Pages 1004-1009Publisher
SPRINGER
DOI: 10.1007/s10120-017-0720-y
Keywords
Cancer stem cell; CD44v-positive; Gastric cancer; Sulfasalazine; xCT
Categories
Funding
- Ministry of Health, Labor, and Welfare of Japan
- Renovation Project of Early and Exploratory Clinical Trial Center, National Cancer Center, Research and Development Fund [24-A-1]
- Grants-in-Aid for Scientific Research [17J02923, 17H01401] Funding Source: KAKEN
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A previous dose-escalation study of sulfasalazine (SSZ), an inhibitor of cystine-glutamate exchange transporter xc (-), in the variant form of CD44 (CD44v)-positive cancer stem cells (CSCs) suggested that administration of SSZ induces the reduction of CD44v-positive cells and intracellular reduced glutathione (GSH) levels in patients with advanced gastric cancer (AGC). Here we report a study to evaluate SSZ in combination with cisplatin in patients with CD44v-expressing AGC refractory to cisplatin. SSZ was given by oral administration four times daily with 2 weeks on and 1 week off. Cisplatin at 60 mg/m(2) was administered every 3 weeks. Of the 15 patients who underwent prescreening of CD44v expression, 8 patients were positive, and 7 patients were treated with the dose level of SSZ at 6 g/day. One patient experienced dose-limiting toxicity (DLT) as grade 3 anorexia. Although no other patients experienced DLT, 4 patients required dose interruption or reduction of SSZ; thus, we terminated further dose escalation. No patient achieved objective response, but 1 patient completed six cycles with stable disease for more than 4 months as well as reduction of intratumoral GSH level. The combination of SSZ plus cisplatin was manageable, although dose modification was frequently required during a short observational period.
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