Abstract
3670 Background:Neurotoxicity is dose-limiting in high proportion of patients (Pts) with metastatic colorectal cancer (CRC) treated with Ox. Two categories of neuropathy (NP) have been described: 1) acute dysesthesia/paresthesia (85–90%) and 2) cumulative sensory NP increasing in intensity with higher cumulative doses. NP has a significant negative impact on patients, limiting duration of Ox treatments. GB is used as neuroprotective agent in neurodegenerative diseases. Potential mechanisms of action include the prevention of uncoupling of oxidative phophorylation and protection of cell membrane through free radical scavenging. Pre-clinical data support anti-cancer benefit of GB through targeted inhibition of peripheral-type benzodiazepine receptors over-expressed on mitochondrial membranes in many tumors including colon cancer. Data suggests that GB synergizes with chemotherapy in addition to potential prevention of neurotoxicity. Methods:We conducted a retrospective analysis of 17 CRC pts treated with either FOLFOX (13) or CAPEOX (4) in either the adjuvant (2) or metastatic (15) setting. GB 120 mg orally bid was added to chemotherapy. No Ca or Mg was given. The Ox-specific neurotoxicity grading scale was used to monitor NP. Results:11/17 pts initiated GB at cycle 1or 2 of treatment, only reporting grade 1 acute NP limited to less than 6 days(d), and 9/11 lasting only 2–3 d. The other 6 pts initiated GB after cycle 2, and 5/6 pts reported decreased intensity and duration in NP from GB. No laryngospasm was observed in any patient. The data on the cumulative sensory NP will be mature and reported at the meeting. No GB related side effects have been observed. Conclusions: GB appears to decrease the intensity and duration of acute dysesthesias caused by Ox and may yield synergistic anti-tumor activity. A phase II trial is underway testing the impact of GB on Ox-induced neurotoxicity and potential additional clinical efficacy. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Sanofi-Synthelabo Roche; Sanofi-Synthelabo Institute Henri Beaufour-IPSEN; Sanofi-Synthelabo
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