Evaluation of menogaril in renal cell carcinoma

The Southwest Oncology Group (SWOG) studied the response rate and toxicity of menogaril (200 mg/m 2 i.v. q 28 days) in patients with advanced metastatic renal cell carcinoma. During the early stage of the trial two partial responses were seen in the first 20 treated patients, and an additional 36 evaluable patients were studied. Three of 56 (5%) evaluable patients achieved partial responses. Significant white cell toxicity was observed. Mild or moderate degrees of thrombocytopenia, gastrointestinal side effects, alopecia and phlebitis occurred. No cardiac toxicity was noted. The low response rate suggests that menogaril in this dose schedule has no role in the treatment of patients with advanced metastatic renal cancer.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/45344/1/10637_2004_Article_BF00171987.pd

O2⋅- and H2O2-Mediated Disruption of Fe Metabolism Causes the Differential Susceptibility of NSCLC and GBM Cancer Cells to Pharmacological Ascorbate

Pharmacological ascorbate has been proposed as a potential anti-cancer agent when combined with radiation and chemotherapy. The anti-cancer effects of ascorbate are hypothesized to involve the autoxidation of ascorbate leading to increased steady-state levels of H2O2; however, the mechanism(s) for cancer cell-selective toxicity remain unknown. The current study shows that alterations in cancer cell mitochondrial oxidative metabolism resulting in increased levels of O2⋅- and H2O2 are capable of disrupting intracellular iron metabolism, thereby selectively sensitizing non-small-cell lung cancer (NSCLC) and glioblastoma (GBM) cells to ascorbate through pro-oxidant chemistry involving redox-active labile iron and H2O2. In addition, preclinical studies and clinical trials demonstrate the feasibility, selective toxicity, tolerability, and potential efficacy of pharmacological ascorbate in GBM and NSCLC therapy