Pegylated Liposomal Irinotecan, a novel formulation of irinotecan, is designed to enhance drug delivery and prolong its circulation in the body. Encapsulation within liposomes protects the active agent, allowing for controlled release and increased effectiveness against tumours. The U.S. Food and Drug Administration (FDA) granted approval for its use on October 22, 2015, for treating metastatic pancreatic cancer in patients previously treated with gemcitabine-based therapies. 

The approval followed the successful NAPOLI-1 clinical trial, which demonstrated improved overall survival and progression-free survival in patients receiving this formulation compared to standard treatment. Pegylation enhances stability and bioavailability, reducing premature metabolism and allowing sustained drug action at tumour sites.

Pegylated Liposomal Irinotecan is approved by the FDA for the following indications:

• Treatment of metastatic pancreatic adenocarcinoma in combination with fluorouracil (5-FU) and leucovorin, specifically in patients who have progressed after gemcitabine-based treatment.
• Used as part of second-line therapy in patients with advanced pancreatic cancer.

Pegylated Liposomal Irinotecan is administered intravenously (IV) over approximately 90 minutes, typically every 2 weeks. It is given under the supervision of an oncologist to ensure proper dosage and management of potential adverse effects. When used as a monotherapy, the recommended dose is 70 mg/m², administered once every 2 weeks. However, when combined with fluorouracil (5-FU) and leucovorin, the dosage is reduced to 50 mg/m² every 2 weeks. Dosage adjustments may be necessary for patients with hepatic impairment, and dose modifications may be required based on the severity of observed toxicities, including diarrhoea or neutropenia. Pre-medication with antiemetics is often recommended to manage nausea and vomiting. Close monitoring of liver function and blood counts during therapy helps optimise the safety and effectiveness of treatment.

Common Side Effects:

• Nausea and vomiting
• Diarrhea
• Fatigue
• Abdominal pain
• Anemia
• Loss of appetite

Serious Side Effects:

• Severe neutropenia
• Persistent or severe diarrhoea
• Severe allergic reactions
• Hepatic toxicity
• Pulmonary toxicity

• Severe Neutropenia: Increased risk of life-threatening neutropenia, especially in patients with poor bone marrow reserves.
• Severe Diarrhea: This can cause severe, prolonged diarrhoea that may lead to dehydration and electrolyte imbalance.
• Hepatic Impairment: Patients with liver dysfunction may experience increased toxicity and require dose adjustments.
• Hypersensitivity Reactions: Risk of severe allergic reactions, including anaphylaxis, during or after infusion.
• Pulmonary Toxicity: Rare but possible interstitial lung disease or pneumonitis.

Patients receiving this formulation should be monitored closely for signs of neutropenia and severe diarrhoea. Antidiarrheal agents should be administered promptly at the first sign of loose stools. It is important to assess liver function before and during treatment, with dose modifications considered for patients with hepatic impairment. Pre-medication with antiemetics is recommended to manage nausea and vomiting. Adequate hydration should be maintained to prevent dehydration, and patients should be advised to report any symptoms of infection or respiratory distress immediately.

Patients should maintain adequate hydration and follow their healthcare provider’s recommendations to manage potential side effects. Antidiarrheal medications, such as loperamide, should be kept on hand to manage diarrhoea early. Monitoring blood counts regularly can help detect neutropenia before it becomes severe. If any symptoms of infection, dehydration, or persistent vomiting occur, immediate medical attention should be sought. Avoiding grapefruit juice during treatment is recommended, as it may interfere with drug metabolism and increase toxicity.

1. Wang-Gillam A, Li CP, Bodoky G, et al. NAPOLI-1 Phase III Study of Liposomal Irinotecan in Metastatic Pancreatic Cancer: Final Overall Survival Analysis and Characteristics of Long-Term Survivors. European Journal of Cancer. 2019;108:78-87. https://pubmed.ncbi.nlm.nih.gov/30654298/
2. S. Food and Drug Administration. ONIVYDE (Irinotecan Liposome Injection) Prescribing Information. 2015. https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/207793lbl.pdf
3. European Medicines Agency. Onivyde Pegylated Liposomal: EPAR - Product Information. https://www.ema.europa.eu/en/medicines/human/EPAR/onivyde-pegylated-liposomal

The information provided here is for educational purposes only and is not intended to replace professional medical advice. Always consult your healthcare provider before starting or discontinuing any medication.