Zolon

Oxaliplatin, a cell cycle-phase-nonspecific antineoplastic drug, belongs to a new class of platinum agent that contains a platinum atom complexed with oxalate and diaminocyclohexane (DACH).

Chemically, oxaliplatin is

trans-I-diaminocyclohexane oxalatoplatinum

or

cis-(oxalate(trans-1,2-diaminocyclohexane)platinum(II))

The empirical formula of oxaliplatin is

C₈H₁₄N₂O₄Pt

The molecular weight of Oxaliplatin is 397.30.

Oxaliplatin is slightly soluble in water and methanol and insoluble in ethanol.

Oxaliplatin is indicated in the treatment of metastatic colorectal cancers after failure of treatment with fluoropyrimidines, alone by monochemotherapy or along with fluoropyrimidines.

Usage

As directed by the oncologist.

The 18% objective response rate obtained with first-line therapy confirms that the activity of single-agent oxaliplatin is comparable to other anticancer therapies considered active against colorectal cancer.

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.

Both inter- and intrastrand Pt-DNA crosslinks are formed.

Crosslinks are formed between

• The N7 positions of two adjacent guanines (GG)
• Adjacent adenine-guanines (AG)
• Guanines separated by an intervening nucleotide (GNG)

These crosslinks inhibit DNA replication and transcription.

Cytotoxicity is cell-cycle non-specific.

• Read the label carefully before use.

• Store in a cool and dry place below 25°C and protect from light.

• Do not freeze.

• Keep out of the reach of children.

Colorectal Cancer In Adults

As Single Agent

When used alone, the recommended dose of oxaliplatin is 130 mg/m² as a continuous intravenous infusion over 2 to 6 hours.

The dose may be repeated at an interval of 3 weeks.

In Combination Therapy

IV: On Day 1

• Administer oxaliplatin 85 mg/m² concurrently with leucovorin 200 mg/m² (in separate containers using a Y line) by IV infusion over 2 hours.

• Then administer fluorouracil 400 mg/m² by IV injection over 2 to 4 minutes.

• Followed by fluorouracil 500 mg/m² by IV infusion over 22 hours.

On Day 2

• Administer leucovorin 200 mg/m² by IV infusion over 2 hours.

• Then administer fluorouracil 400 mg/m² by IV injection over 2 to 4 minutes.

• Followed by fluorouracil 600 mg/m² by IV infusion over 22 hours.

Repeat regimen at intervals of 2 weeks.

Dosage Adjustment In Toxicity

Peripheral Neuropathy

• Administer oxaliplatin over 6 hours.
• No adjustment required for fluorouracil and leucovorin.

Persistent Grade 2 Neurosensory Effect

• Reduce oxaliplatin dose by 25% (i.e., 65 mg/m²).
• No adjustment required for fluorouracil and leucovorin.

In Patients Who Recover From

• Grade 3 or 4 GI toxicity
• Grade 4 neutropenia
• Grade 3 or 4 thrombocytopenia

Dose Modifications

• Reduce oxaliplatin dose by 25% (i.e., 65 mg/m²).
• Reduce fluorouracil dose by 20% (i.e., to 300 mg/m² by IV injection over 2 to 4 minutes and 500 mg/m² by IV infusion over 22 hours).

Renal Impairment

In patients with impaired renal function, observe caution.

Monitoring Parameters

Assess the patients for

• Differential WBC count
• Haemoglobin
• Platelet count
• ALT
• AST
• Bilirubin
• Creatinine levels

before each oxaliplatin cycle.