Oxaliplatin Dosage

Usual Adult Dose for Colorectal Cancer

Day 1:
Oxaliplatin 85 mg/m2 and leucovorin 200 mg/m2 intravenously over 120 minutes, followed by
fluorouracil 400 mg/m2 over 2 to 4 minutes, followed by
fluorouracil 600 mg/m2 as a 22 hour infusion.

Day 2:
Leucovorin 200 mg/m2 intravenously over 120 minutes, followed by
fluorouracil 400 mg/m2 over 2 to 4 minutes, followed by
fluorouracil 600 mg/m2 as a 22 hour infusion.

The cycle is repeated every 2 weeks.

Renal Dose Adjustments

Platinum AUCs increase as renal function decreases. Caution is recommended.

Pharmacokinetic data has suggested that dose reductions of single-agent oxaliplatin are not necessary in patients with mild to moderate renal impairment.

The initial recommended dose of oxaliplatin should be reduced to 65 mg/m2 in patients with severe renal impairment (creatinine clearance less than 30 ml/min).

Liver Dose Adjustments

Data on three cancer patients with severe hepatic dysfunction have been reported. The comparable platinum exposure early after administration in conjunction with the lack of acute toxicity do not support a dose reduction of oxaliplatin in patients with markedly elevated bilirubin concentrations. However, a larger number of patients must be examined before valid dose recommendations can be derived.

Dose Adjustments

White blood cell count with differential, hemoglobin, platelet count, and blood chemistries should be monitored before each treatment cycle. Patients should also be evaluated for clinical toxicity including neuropathy.

Acute toxicities may be mitigated by prolonging the oxaliplatin infusion time from 2 to 6 hours.

For patients who experience persistent Grade 2 neurosensory toxicity that does not resolve, a dose reduction of oxaliplatin to 65 mg/m2 is recommended.

For patients who have recovered from Grade 3/4 gastrointestinal or hematologic toxicity, dose reductions of oxaliplatin to 65 mg/m2, fluorouracil bolus to 300 mg/m2, and fluorouracil 22 hour infusion to 500 mg/m2 are recommended.

Precautions

Hypersensitivity and anaphylactic/anaphylactoid reactions have been reported and occur within minutes of administration. Other platinum compounds have been associated with fatal hypersensitivity reactions. Patients should be monitored during infusion and supportive therapy should be immediately available. Epinephrine, corticosteroids, and antihistamines have been used to manage symptoms.

Oxaliplatin should be administered under the supervision of a qualified physician experienced in the use of cancer chemotherapeutic agents. Appropriate management of therapy and complications is possible only when adequate diagnostic and treatment facilities are readily available.

Oxaliplatin has been associated with acute early onset and persistent peripheral sensory neuropathy. Ice should be avoided during infusion because the cold temperature may exacerbate acute neurological symptoms. Patients should be advised to avoid cold drinks, ice, and to cover exposed skin before exposure to cold temperatures.

Oxaliplatin has been associated with potentially fatal pulmonary fibrosis. If respiratory symptoms occur during treatment, oxaliplatin should be discontinued until interstitial lung disease and pulmonary fibrosis have been excluded.

Caution is advised in patients with renal impairment. Clearance of platinum decreases in patients with renal insufficiency.

Patients should be advised of the risk of low blood cell counts and instructed to notify their physician if they experience fever, diarrhea, evidence of infection, persistent vomiting, signs of dehydration, cough or breathing difficulties, or signs of allergic reaction.

The effectiveness of oxaliplatin in pediatric patients (less than 18 years of age) has not been established.

Dialysis

Data not available

Other Comments

A final dilution must never be performed with a sodium chloride solution or other chloride-containing solutions. Oxaliplatin should be diluted in an infusion solution of 250 to 500 mL D5W. Leucovorin should also be mixed in D5W, and D5W is the recommended diluent for the 22-hour fluorouracil infusion.

Aluminum-containing needles or intravenous administration sets should not be used to prepare or mix oxaliplatin because aluminum may cause degradation of platinum compounds.

The infusion line should be flushed with D5W before administration of other medications.