Xaloplat

Approved Indications:

• Stage III Colon Cancer (Adjuvant Setting)
• In combination with fluorouracil and leucovorin following complete resection of the primary tumor.
• Advanced or Metastatic Colorectal Cancer
• First-line and subsequent treatment as part of the FOLFOX regimen (fluorouracil + leucovorin + oxaliplatin).

Clinically Accepted Off-label Uses:

• Gastric and Gastroesophageal Junction Cancers – as part of combination chemotherapy.
• Esophageal Cancer – in advanced stages.
• Pancreatic Cancer – investigational protocols.
• Ovarian Cancer (Platinum-Sensitive Relapse) – alternative to cisplatin/carboplatin.
• Non-Hodgkin Lymphoma – in certain salvage regimens.

Route of Administration: Intravenous (IV) infusion only.
Diluent: Use only 5% Dextrose. Do not use saline solutions.

Adult Dosage:

• Adjuvant Colon Cancer:
• Oxaliplatin 85 mg/m² IV over 2 hours on Day 1, every 2 weeks for 12 cycles, in combination with fluorouracil and leucovorin.
• Metastatic Colorectal Cancer:
• Oxaliplatin 85 mg/m² IV every 2 weeks, typically in combination with fluorouracil and leucovorin, continued until disease progression or unacceptable toxicity.

Special Populations:

• Renal Impairment:
• Mild to Moderate (CrCl ≥30 mL/min): No initial dose adjustment required.
• Severe (CrCl <30 mL/min): Use with caution; limited data.
• Hepatic Impairment:
• No dosage adjustment generally needed; monitor liver function closely.
• Elderly:
• No specific adjustment, but increased vigilance for neurotoxicity is recommended.
• Pediatric Use:
• Safety and efficacy not established; not approved in pediatric populations.

Administration Notes:

• Infuse oxaliplatin over 2 to 6 hours, depending on regimen.
• Use non-aluminum IV sets and bags.
• Do not administer with other agents in the same infusion line.

Oxaliplatin is a third-generation platinum-based antineoplastic agent. After administration, it is converted into reactive platinum complexes that form inter- and intrastrand DNA crosslinks. These crosslinks inhibit DNA replication and transcription, leading to cell cycle arrest and apoptotic cell death. Oxaliplatin-DNA adducts are bulky and escape recognition by the mismatch repair system, which gives it activity even in some cisplatin-resistant tumors.

• Absorption: Not applicable (IV use only).
• Distribution: Rapid distribution; plasma protein binding 85%–88%.
• Metabolism: Non-enzymatic conversion to active derivatives; not CYP450 dependent.
• Half-life: Triphasic elimination:
• Alpha: ~0.3 hours
• Beta: ~16 hours
• Terminal (gamma): ~273 hours (due to tissue binding)
• Excretion: Primarily renal; ~50% of dose eliminated in urine within 5 days.

• Pregnancy: Category D – Positive evidence of human fetal risk. Use only if clearly needed.
• Lactation: Unknown if excreted in breast milk. Due to potential for serious adverse effects, breastfeeding is not recommended during treatment and for at least 3 months after final dose.
• Fertility Warning: May cause irreversible infertility in men and women.

• Primary Class: Antineoplastic Agent
• Subclass: Platinum-based Chemotherapy (3rd Generation)

• Known hypersensitivity to oxaliplatin or other platinum-containing compounds.
• History of severe allergic reactions to platinum agents.
• Pre-existing severe peripheral neuropathy.
• Concurrent use with live vaccines (e.g., yellow fever).
• Myelosuppression (severe neutropenia or thrombocytopenia) not yet recovered.

• Peripheral Neuropathy:
• Acute: Triggered by cold; often reversible.
• Chronic: Dose-dependent; may become permanent.
• Myelosuppression:
• Monitor CBC before each cycle; risk of neutropenia, anemia, thrombocytopenia.
• Hypersensitivity Reactions:
• May occur during any cycle, including anaphylaxis. Premedication may be needed.
• Pulmonary Toxicity:
• Rare interstitial lung disease or pulmonary fibrosis may occur.
• Hepatotoxicity:
• Liver function abnormalities and sinusoidal injury reported.
• Cardiac Concerns:
• Rare QT prolongation; monitor ECG in high-risk patients.
• Vaccination Risk:
• Avoid live vaccines due to immunosuppression.
• Fertility Effects:
• Potential gonadal toxicity; sperm banking may be advised.

Very Common (>10%):

• Hematologic: Neutropenia, thrombocytopenia, anemia
• Gastrointestinal: Nausea, vomiting, diarrhea, stomatitis
• Nervous System: Peripheral sensory neuropathy (cold-induced or chronic)
• General: Fatigue, pyrexia, appetite loss

Common (1%–10%):

• Liver: Elevated liver enzymes (ALT, AST, bilirubin)
• Skin: Rash, pruritus
• Allergic Reactions: Urticaria, bronchospasm

Serious/Rare:

• Anaphylaxis
• Interstitial lung disease
• Rhabdomyolysis
• QT interval prolongation
• Renal impairment
• Severe colitis

• Nephrotoxic Agents (e.g., aminoglycosides): May worsen renal toxicity.
• Live Vaccines: Risk of disseminated infection in immunocompromised state.
• Other Myelosuppressive Agents: Additive bone marrow suppression.
• Anticoagulants or Antiplatelet Drugs: Increased bleeding risk due to thrombocytopenia.
• CYP450 Interactions: Not significant; oxaliplatin is not metabolized by CYP enzymes.

• NCCN and ESMO Guidelines continue to recommend FOLFOX (including oxaliplatin) as a first-line and adjuvant therapy in colorectal cancer.
• Reduced duration (3 vs. 6 months) of adjuvant therapy is recommended in certain low-risk colon cancer patients to minimize cumulative neuropathy.
• Ongoing clinical trials are evaluating oxaliplatin-containing regimens in gastric, pancreatic, and esophageal cancers.
• Research into liposomal or nanoparticle formulations is underway to reduce toxicity and improve delivery.

• Unopened Vials (Concentrate):
• Store at 20°C to 25°C (68°F to 77°F).
• Allowable temperature range: 15°C to 30°C.
• Keep away from light; store in the original packaging.
• Diluted Solution in 5% Dextrose:
• Stable for 24 hours under refrigeration (2°C–8°C).
• Stable for 6 hours at room temperature (20°C–25°C).
• Do not freeze.
• Do not use sodium chloride or chloride-containing solutions.