indication

Used in combination with infusional 5-FU/LV, is indicated for the treatment of advanced carcinoma of the colon or rectum and for adjuvant treatment of stage III colon cancer patients who have undergone complete resection of the primary tumor.

pharmacology

Oxaliplatin selectively inhibits the synthesis of deoxyribonucleic acid (DNA). The guanine and cytosine content correlates with the degree of Oxaliplatin-induced cross-linking. At high concentrations of the drug, cellular RNA and protein synthesis are also suppressed.

mechanism of action

After activation, oxaliplatin binds preferentially to the guanine and cytosine moieties of DNA, leading to cross-linking of DNA, thus inhibiting DNA synthesis and function.

toxicity

There have been five cases of oxaliplatin overdose reported. One patient received two 130 mg/m2 doses of oxaliplatin (cumulative dose of 260 mg/m²) within a 24-hour period. The patient experienced Grade 4 thrombocytopenia (<25,000/mm³) without any bleeding, which resolved. Two other patients were mistakenly administered oxaliplatin instead of carboplatin. One patient received a total oxaliplatin dose of 500 mg and the other received 650 mg. The first patient experienced dyspnea, wheezing, paresthesia, profuse vomiting and chest pain on the day of administration. She developed respiratory failure and severe bradycardia, and subsequently did not respond to resuscitation efforts. The other patient also experienced dyspnea, wheezing, paresthesia, and vomiting.

biotransformation

Oxaliplatin undergoes nonenzymatic conversion in physiologic solutions to active derivatives via displacement of the labile oxalate ligand. Several transient reactive species are formed, including monoaquo and diaquo DACH platinum, which covalently bind with macromolecules. There is no evidence of cytochrome P450-mediated metabolism in vitro.

absorption

Bioavailability is complete following intravenous administration.

half life

Approximately 10 - 25 minutes

route of elimination

The major route of platinum elimination is renal excretion. At five days after a single 2-hour infusion of oxaliplatin, urinary elimination accounted for about 54% of the platinum eliminated, with fecal excretion accounting for only about 2%.

drug interactions

Topotecan: Administration of Topotecan after Oxaliplatin therapy may increase the risk of hematologic toxicity, such as neutropenia and/or thrombocytopenia. A dose adjustment may be required or the sequence of administration reversed.

Trastuzumab: Trastuzumab may increase the risk of neutropenia and anemia. Monitor closely for signs and symptoms of adverse events.