What it's for (Indications)
- Oxaliplatin, a platinum-based antineoplastic agent (Example brand: Oxaliplatin AHP), is primarily indicated for the treatment of colorectal cancer.
- Its approved uses encompass both the adjuvant setting and advanced metastatic disease.
- For patients with Stage III (Duke's C) colon cancer who have undergone complete resection of the primary tumor, oxaliplatin is indicated as an adjuvant treatment.
- In this context, it is typically administered in combination with fluorouracil and leucovorin, forming regimens such as FOLFOX, which aim to reduce the risk of disease recurrence following surgery.
- Furthermore, oxaliplatin is a critical component in the management of metastatic colorectal cancer.
- It is indicated for use in the first-line treatment of patients with advanced or metastatic disease, commonly in combination with fluorouracil and leucovorin.
- It is also utilized in patients whose metastatic colorectal cancer has progressed following prior treatment regimens, often as part of combination chemotherapy.
- These indications are supported by significant clinical trial evidence demonstrating improved disease-free survival, progression-free survival, and overall survival in the respective patient populations, underscoring its role as a foundational chemotherapeutic agent for this malignancy.
Dosage Information
| Type | Guideline |
|---|---|
| Standard | Oxaliplatin for injection should be administered under the supervision of a qualified physician experienced in the use of cancer chemotherapeutic agents. It is administered in combination with 5-fluorouracil/leucovorin every 2 weeks. On Day 1: Oxaliplatin for injection 85 mg/m² intravenous infusion in 250 to 500 mL 5% Dextrose Injection, USP, and leucovorin 200 mg/m² intravenous infusion in 5% Dextrose Injection, USP, both given over 120 minutes concurrently in separate bags using a Y-line. This is followed by 5-fluorouracil 400 mg/m² intravenous bolus over 2 to 4 minutes, then 5-fluorouracil 600 mg/m² intravenous infusion in 500 mL 5% Dextrose Injection, USP (recommended) as a 22-hour continuous infusion. On Day 2: Leucovorin 200 mg/m² intravenous infusion over 120 minutes, followed by 5-fluorouracil as per regimen. |
Safety & Warnings
Common Side Effects
- Common adverse reactions (incidence ≥ 40%) include peripheral sensory neuropathy, neutropenia, thrombocytopenia, anemia, nausea, increase in transaminases and alkaline phosphatase, diarrhea, emesis, fatigue, and stomatitis.
- Serious adverse reactions include anaphylaxis and allergic reactions, neuropathy, severe neutropenia, pulmonary toxicities, hepatotoxicity, cardiovascular toxicities, and rhabdomyolysis.
Serious Warnings
- Black Box Warning: WARNING: ANAPHYLACTIC REACTIONS. Anaphylactic reactions to oxaliplatin for injection have been reported, and may occur within minutes of oxaliplatin for injection administration. Epinephrine, corticosteroids, and antihistamines have been employed to alleviate symptoms of anaphylaxis.
- Patients may experience severe anaphylactic and allergic reactions, which can occur within minutes of administration and may necessitate epinephrine, corticosteroids, and antihistamines.
- Other serious warnings and precautions include neuropathy (peripheral sensory neuropathy), severe neutropenia, pulmonary toxicities (e.
- g.
- , acute interstitial lung disease), hepatotoxicity (e.
- g.
- , sinusoidal obstruction syndrome), cardiovascular toxicities (e.
- g.
- , QT prolongation), and rhabdomyolysis.
- Appropriate management of therapy and complications requires adequate diagnostic and treatment facilities.
How it Works (Mechanism of Action)
Oxaliplatin undergoes nonenzymatic conversion in physiologic solutions to active derivatives via displacement of the labile oxalate ligand, forming transient reactive species like monoaquo and diaquo DACH platinum, which covalently bind with macromolecules. It forms both inter- and intrastrand Pt-DNA crosslinks, specifically between the N7 positions of two adjacent guanines (GG), adjacent adenine-guanines (AG), and guanines separated by an intervening nucleotide (GNG). These crosslinks inhibit DNA replication and transcription. Cytotoxicity is cell-cycle nonspecific. In vivo studies have shown antitumor activity against colon carcinoma. In combination with 5-fluorouracil, oxaliplatin exhibits greater in vitro and in vivo antiproliferative activity than either compound alone in several tumor models (HT29 colon, GR mammary, and L1210 leukemia).