Phase I Clinical Trial of High Doses of Seleno-L-methionine in Combination with Axitinib in Patients with Previously Treated Metastatic Clear Cell Renal Cell Carcinoma
Abstract
Background: Data in clear cell renal cell carcinoma (ccRCC) xenografts defined the seleno-Lmethionine (SLM) dose and the plasma selenium concentrations associated with the enhancement of HIF1α/2α degradation, stabilization of tumor vasculature, enhanced drug delivery, and efficacy of axitinib. The data provided the rationale for the development of this phase I clinical trial of SLM and axitinib in advanced or metastatic relapsed ccRCC. Patients and Methods: Patients were ≥18 years with histologically and radiologically confirmed advanced or metastatic ccRCC who had received at least one prior systemic therapy, which could include axitinib (last dose ≥6 months prior to enrollment). Escalating dose levels of SLM (2500, 3000 and 4000 μg) were administered orally twice daily for 14 days, then once daily concurrently with axitinib 5 mg twice daily using a 3+3 design in Phase I. Patients were treated at the 4000 μg dose level in the expansion cohort to obtain preliminary estimates of efficacy. Results: No dose limiting toxicities occurred at the 4000 μg SLM dose level. Among the 27 patients treated with 4000 μg of SLM, the overall response rate was 55.6%, median duration of response was 18.4 months, median progression-free survival was 14.8 months, and median overall survival was 19.6 months. Preliminary results have shown that plasma selenium concentrations, inhibition of TGF-β1 and stabilization of tumor vasculature by SLM are time dependent. Conclusions: SLM (4000 μg) in…
How strong is the evidence?
Evidence Hub reads this as a cohort study, done in people. Its evidence level is 3 of 5 (Moderate · trial / cohort / secondary analysis). Trials without a large randomized design, cohorts and secondary analyses give moderate evidence. Reported size: 27 participants or records.
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