Organic arsenic in patients (pts) with advanced solid tumors: Phase-1 results of zio-101 (s-dimethylarsino-glutathione)

3554 Background: ZIO-101(S-dimethylarsino-glutathione), a novel organic arsenic, is active against multiple cancers in vitro and in animal models. Anti-cancer activity is multifaceted and is mediated by disrupted mitochondrial function, increased reactive oxygen species (ROS) production, modified signal transduction and anti-angiogenesis. Methods: Phase-1 dose finding study to determine maximum tolerated dose (MTD), dose-limiting toxicity (DLT), pharmacokinetics (PK), and toxicities of ZIO-101 in patients with advanced solid tumors. Results: 34 pts (18 M/16 F) received 78–588 mg/m2/d IV for 5 consecutive days every 4 weeks. Median age was 61 (range, 42–79 y). Median N prior regimens was 3 (1–5). Pts had colorectal (N=17; 12 evaluable), renal (N=4), lung (N=3), melanoma (N=2), pancreas (N=2) and others (N=6). Median N of cycles was 2 (range, 1–12). MTD is 420 mg/m2/d and DLT was transient confusion, and ataxia. Fatigue, nausea and emesis were = grade-2. ZIO-101 was otherwise well-tolerated: There are no he...