A phase I trial of scutellaria barbata (BZL101) for metastatic breast cancer.
1099 Background: BZL101 is an aqueous extract from herba Scutellaria Barbata. BZL101 demonstrates in vitro growth inhibitory effects on human breast cancer cell lines and does not inhibit the growth of normal human mammary epithelium. In a murine xenograft model, oral and intraperitoneal administration of BZL101 inhibited tumor formation without any observed toxicity. Treatment of breast cancer cells with BZL101 leads to sustained inhibition of glycolysis, as evident from the decreased enzymatic activities within the glycolytic pathway and inhibition of lactate production. Because tumor cells primarily rely on glycolysis for energy production (Warburg effect), targeting this pathway may lead to novel cytotoxic agents with less toxicity than the currently available treatments. We are conducting an open-label, dose escalation, phase I trial of BZL101 for MBC to determine the MTD. METHODS: Eligible patients have histologically confirmed MBC and measurable disease. Patients can not receive any other anticancer treatment on trial. Three patients are enrolled at each dose level and treated for 28 days. If toxicity is acceptable, 3 additional patients are enrolled to a higher dose until the MTD is reached. The primary endpoints are safety and toxicity and tumor response defined by RECIST. RESULTS: 14 patients have been enrolled. The mean number of prior treatments for metastatic disease was 3.6. There have been no SAEs attributable to BZL101. There was one grade 4 AE for AST elevation attributed to BZL101. All other BZL101 related AEs were grade 1 and 2 of which the most frequent were: diarrhea (29%), nausea (14%), headache (14%) and ALT increase (14%). 5 patients were evaluable for response and one patient had stable disease for 8 months with radiographic evidence of tumor shrinkage. CONCLUSIONS: BZL101 has a favorable tolerability profile and encouraging clinical activity for the treatment of MBC. [Table: see text].
Perez, AT; Shaw, HS; Fleming, GF; Hershman, DL; Franco, S; Shapiro, CL; Neal, K; Cohen, I; Tagliaferri, M; Tripathy, D
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