Oxaliplatin, in combination with infusional 5-fluorouracil and folinic acid, is indicated for:

• Adjuvant therapy of stage III colon cancer in patients who have undergone complete resection of the primary tumor
• Treatment of advanced colorectal cancer

Oxaliplatin undergoes non-enzymatic conversion in physiologic solutions and forms active derivatives through displacement of the unstable oxalate ligand. During this process, several short-lived reactive species are produced, including monoaquo and diaquo DACH platinum, which bind covalently to macromolecules. Oxaliplatin forms both interstrand and intrastrand platinum-DNA crosslinks. These crosslinks occur between the N7 positions of two adjacent guanines (GG), adjacent adenine-guanines (AG), and guanines separated by another nucleotide (GNG). As a result, DNA replication and transcription are inhibited. Its cytotoxic effect is cell-cycle non-specific. In vivo studies have demonstrated antitumor activity of oxaliplatin against colon carcinoma. When combined with 5-fluorouracil, oxaliplatin shows greater antiproliferative activity in both in vitro and in vivo tumor models than either drug used alone.

Administer oxaliplatin in combination with 5-fluorouracil/folinic acid every 2 weeks. For advanced disease, treatment is recommended until disease progression or unacceptable toxicity. For adjuvant use, treatment is recommended for a total of 6 months (12 cycles).

Day 1: Oxaliplatin 85 mg/m² intravenous infusion in 250–500 mL 5% Dextrose injection, USP and folinic acid 200 mg/m² intravenous infusion in 5% Dextrose Injection, USP both given over 120 minutes at the same time in separate bags using a Y-line, followed by 5-fluorouracil 400 mg/m² intravenous bolus given over 2–4 minutes, followed by 5-fluorouracil 600 mg/m² intravenous infusion in 500 mL 5% Dextrose Injection, USP (recommended) as a 22-hour continuous infusion.

Day 2: Folinic acid 200 mg/m² intravenous infusion over 120 minutes, followed by 5-fluorouracil 400 mg/m² intravenous bolus given over 2–4 minutes, followed by 5-fluorouracil 600 mg/m² intravenous infusion in 500 mL 5% Dextrose Injection, USP (recommended) as a 22-hour continuous infusion.

No specific cytochrome P450-based drug interaction studies have been carried out for Oxaliplatin. In patients receiving Oxaliplatin 85 mg/m² every 2 weeks together with 5-fluorouracil and folinic acid, no significant pharmacokinetic interaction was observed. However, when Oxaliplatin was given at a dose of 130 mg/m² every 3 weeks, about a 20% increase in plasma concentrations of 5-fluorouracil was reported. Since platinum-containing compounds are mainly eliminated through the kidneys, the clearance of these compounds may be reduced when Oxaliplatin is used together with potentially nephrotoxic medicines, although this has not been specifically studied.

Oxaliplatin is contraindicated in patients with a known allergy to Oxaliplatin or to other platinum-containing compounds.

The most commonly reported adverse reactions with Oxaliplatin include peripheral sensory neuropathy, neutropenia, thrombocytopenia, anaemia, nausea, increased transaminases and alkaline phosphatase, diarrhoea, vomiting, fatigue, and stomatitis. Other adverse reactions, including serious ones, have also been reported.

Oxaliplatin is classified as Pregnancy Category D and may cause fetal harm if used during pregnancy. There are no adequate and well-controlled studies in pregnant women. Women of childbearing potential should avoid becoming pregnant during Oxaliplatin treatment. It is not known whether Oxaliplatin or its derivatives are excreted into human milk. Because of the possibility of serious adverse reactions in nursing infants, a decision should be made either to stop breastfeeding or to discontinue the drug, depending on the importance of treatment to the mother.

Allergic Reactions: Grade 3/4 hypersensitivity reactions, including anaphylactic or anaphylactoid responses, have been reported in 2–3% of patients receiving oxaliplatin for colon cancer. These potentially fatal reactions may occur within minutes of administration and at any treatment cycle. Management typically involves standard therapy with epinephrine, corticosteroids, and antihistamines, and treatment should be discontinued. Rechallenge is contraindicated in affected patients.

Neurological Toxicity: Neurological adverse effects should be closely monitored, particularly when oxaliplatin is used with other neurotoxic agents. A neurological assessment is recommended before each administration and periodically thereafter. It is unclear whether patients with pre-existing peripheral nerve damage have increased susceptibility to oxaliplatin-induced neuropathy. In patients who develop acute laryngopharyngeal dysesthesia during or within 48 hours after a two-hour infusion, subsequent infusions should be administered over six hours. To reduce the risk of dysesthesia, patients should avoid exposure to cold and refrain from consuming cold food or beverages during and for 48 hours after treatment.

Pulmonary Toxicity: Oxaliplatin has been associated with pulmonary fibrosis (reported in <1% of patients), which may be fatal. If unexplained respiratory symptoms such as dry cough, dyspnea, crackles, or pulmonary infiltrates appear, oxaliplatin should be withheld until further evaluation rules out interstitial lung disease or pulmonary fibrosis.

Hepatotoxicity: Liver-related adverse effects, including sinusoidal obstruction syndrome and nodular regenerative hyperplasia, have been reported. In cases of abnormal liver function tests or portal hypertension not explained by hepatic metastases, further evaluation for sinusoidal obstruction syndrome is warranted. Rare cases of drug-induced hepatic vascular disorders should also be considered.

Cardiovascular Toxicity: QT interval prolongation and ventricular arrhythmias, including fatal Torsade de Pointes, have been reported following oxaliplatin use. ECG monitoring is recommended in patients with congestive heart failure, bradyarrhythmias, electrolyte imbalances, or those receiving QT-prolonging medications such as Class Ia and III antiarrhythmics. Correct hypokalemia and hypomagnesemia prior to treatment and monitor electrolytes periodically. Avoid use in patients with congenital long QT syndrome.

There is no known antidote for Oxaliplatin overdose. Expected complications include thrombocytopenia, hypersensitivity reactions, myelosuppression, nausea, vomiting, diarrhoea, and neurotoxicity. Reported overdose effects have included severe thrombocytopenia without bleeding, anaemia, sensory neuropathy, paresthesia, dysesthesia, laryngospasm, facial muscle spasms, gastrointestinal problems, severe dehydration, dyspnoea, wheezing, chest pain, respiratory failure, severe bradycardia, and even death. Patients suspected of overdose should be closely monitored and treated supportively. The maximum single infusion dose reported for Oxaliplatin is 825 mg.

Cytotoxic Chemotherapy.

Store in a cool and dry place, protected from light and moisture. Keep out of the reach of children.