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- Title
Phase 1 study of sulfasalazine and cisplatin for patients with CD44v-positive gastric cancer refractory to cisplatin (EPOC1407).
- Authors
Shitara, Kohei; Doi, Toshihiko; Nagano, Osamu; Fukutani, Miki; Hasegawa, Hiromi; Nomura, Shogo; Sato, Akihiro; Kuwata, Takeshi; Asai, Kai; Einaga, Yasuaki; Tsuchihashi, Kenji; Suina, Kentaro; Maeda, Yusuke; Saya, Hideyuki; Ohtsu, Atsushi
- Abstract
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 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.
- Subjects
STOMACH cancer patients; STOMACH cancer treatment; CISPLATIN; CANCER stem cells; MEDICAL screening
- Publication
Gastric Cancer, 2017, Vol 20, Issue 6, p1004
- ISSN
1436-3291
- Publication type
Article
- DOI
10.1007/s10120-017-0720-y