Indications Colorectal Cancer (USA and Non-US) Ovarian CA (Non-US) Mechanisms A third generation platinum compound. Cell cycle-nonspecific with activity is all phases of the cell cycle. Covalently binds to DNA with preferential binding to the N-7 position of guanine and adenine. Produces DNA cross-links, both intrastrand (>90%) and interstrand (< 5%) that leads to the inhibition of of DNA synthesis and function as well as inhibition of transcription. DNA mismatch repair enzymes are unable to recognize oxaliplatin DNA adducts Binding to nuclear or cytoplasmic proteins may results in additional cytotoxic effects Toxicity Neurotoxicity: Peripheral sensory neuropathy with distal paresthesias, often triggered or exacerbated by cold. Acute dysthesias in the upper extremities and laryngopharyngeal region with episodes of difficulty breathing or swallowing usually observed within hours or 1-3 days after therapy. Nausea and Vommiting Diarrhea Myelosuppression (mild thrombocytopenia, anemia more common than neutropenia) Severe allergic reactions with facial flushing, rash, urticaria, bronchospasm, hypotension. Renal toxicity: Rare Ototoxicity: Rare Resistance Decreased drug accumulation Increased DNA repair enzyme activity