Oxaliplatin

Indications

Oxaliplatin is used for: Colorectal cancer, Colon cancer

Adult Dose

Intravenous Advanced colorectal cancer Adult: Day 1: Oxaliplatin 85 mg/m² IV + leucovorin 200 mg/m² IV infused over 2 hr, THEN 5-FU 400 mg/m² IV bolus over 2-4 minutes, THEN 5-FU 600 mg/m² IV infusion in D5W (500 mL) over 22 hr Day 2: Same regimen WITHOUT oxaliplatin Repeat every 2 weeks Adjuvant therapy in stage III colon cancer Adult: Day 1: Oxaliplatin 85 mg/m² IV + leucovorin 200 mg/m² IV infused over 2 hr, THEN 5-FU 400 mg/m² IV bolus over 2-4 minutes, THEN 5-FU 600 mg/m² IV infusion in D5W (500 mL) over 22 hr Day 2: Same regimen WITHOUT oxaliplatin Every 2 wk; given for 12 cycles, for a total of 6 months Dose Modification If persistent Grade 2 neuropathy, decrease dose to 75 mg/m² If persistent Grade 3 neuropathy, consider discontinuing oxaliplatin After recovery from grade 3/4 GI or grade 3/4 hematological toxicity: Decrease dose to 75 mg/m² , AND decrease 5-FU by 20% (300 mg/m² bolus, 500 mg/m² infusion)

Child Dose

Safety and efficacy not established

Renal Dose

Renal Impairment Exposure of unbound platinum tends to increase in renally impaired patients Mild (CrCl 50-80 mL/min): No dosage adjustment required Moderate (CrCl 30-49 mL/min): No dosage adjustment required Severe (CrCl <30 mL/min): Reduce starting dose

Administration

IV Preparation Reconstitute by adding 10 mL (for 50 mg vial) or 20 mL (for 100 mg vial) of SWI or D5W. Dilute required amount of reconstituted solution in an infusion solution of 250-500 mL of D5W. Do NOT use NS or chloride-containing solutions Do not use aluminum-containing needles or IV administration sets that may come in contact with carboplatin (aluminum can react causing precipitate formation and loss of potency) IV Administration Flush infusion line with D5W prior to administration of oxaliplatin or any concomitant drug Use separate bags for oxaliplatin and leucovorin (administered through Y-site)

Contra Indications

Pregnancy. Peripheral neuropathy with functional impairment. Severe renal impairment.

Precautions

Should be administered under the supervision of an experienced cancer chemotherapy physician. Use appropriate precautions for handling and disposal. Monitor neurological status and dose should be reduced if symptoms are prolonged or severe. Monitor blood counts during treatment and courses should not be repeated until blood counts have recovered. Caution in elderly, moderate degrees of renal impairment. Avoid using aluminum-containing needles or IV admin sets that may come into contact with oxaliplatin as aluminum has been reported to cause degradation of platinum compounds. Lactation. Lactation: not known if excreted in milk

Pregnancy-Lactation

Interactions

May decrease plasma levels of digoxin. May increase risk of toxicity with nephrotoxic drugs. When administered as sequential infusions, taxane derivatives (docetaxel, paclitaxel) should be administered before oxaliplatin to limit myelosuppression and enhance efficacy.

Adverse Effects

Side effects of Oxaliplatin : >10% Peripheral neuropathy (76%), Anemia (64%), Nausea (64%), Fatigue (61%), Diarrhea (46%), Vomiting (37%), Abdominal pain (31%), Constipation (31%), Thrombocytopenia (30%), Fever (25%), Anorexia (20%), Leukopenia (13%), Dyspnea (13%), Cough (11%) 1-10% Edema (10%), Neutropenia (7%), Pharyngolaryngeal dysesthesia (1-2%) <1% Pulmonary fibrosis, Posterior leukoencephalopathy syndrome Frequency Not Defined Anaphylactic-like reaction (uncommon), Pulmonary fibrosis (uncommon) Potentially Fatal: Anaphylaxis, pulmonary fibrosis.

Mechanism of Action

Oxaliplatin, a platinum-containing complex similar to cisplatin, is an alkylating agent. After intracellular hydrolysis, the platinum compound binds to DNA forming cross-links which inhibit DNA replication and transcription, resulting in cell death.