Oxaliplatin

Oxaliplatin (Eloxatin) is similar to other platinum analogs (cisplatin) in that it binds to the N-7 position of guanine that results in cross-linking of DNA and double-stranded

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DNA breaks. ' ' Oxaliplatin differs from cisplatin in that the DNA damage induced by oxaliplatin may not be as easily recognized by DNA repair genes, often seen in colorectal cancer. Oxaliplatin, in combination with 5-fluorouracil-based regimens, is indicated for the first- and second-line treatment of metastatic colorectal cancer as well as the adjuvant treatment of colorectal cancer.

The dose-limiting toxicity of oxaliplatin is acute and chronic neuropathy.49 Acute neuropathies occur within 1 to 2 days of dosing, resolve within 2 weeks, and usually occur peripherally. These acute neuropathies occur in almost all patients to some degree and are exacerbated by exposure to cold temperature or cold objects. Health care providers should instruct patients to avoid cold drinks, use of ice, and to cover skin before exposure to cold or cold objects. In addition, carbamazepine, gabapentin, ami-fostine, and calcium and magnesium infusions have been used to both prevent and treat oxaliplatin-induced neuropathies, although use of these agents is not widely accepted.43 Persistent neuropathies generally occur after eight cycles of oxaliplatin and are characterized by defects that can interfere with daily activities (e.g., writing, buttoning, swallowing, and walking). Patients may receive predefined breaks from oxaliplatin to decrease the onset of these toxicities with reinitiation of therapy.36 This strategy varies among protocols, but involves administering a certain number of predefined oxaliplatin cycles and then stopping. Maintenance therapy with another agent is usually administered and then the oxaliplatin-based regimen is restarted based on the protocol. These neuropathies occur in up to half of patients receiving oxaliplatin but usually resolve with dosage reductions or after oxaliplatin is stopped.33,49 Oxaliplatin has minimal renal, myelosuppressive effects, and nausea/vomiting when compared to other platinum drugs. Oxaliplatin is given IV in a variety of dosing schedules with a typical dose of 85 mg/m2 IV every 2 weeks.

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