Pegylated Liposomal Doxorubicin: Metamorphosis of an Old Drug into a New Form of Chemotherapy

The document from 2001 examines pegylated liposomal doxorubicin (Doxil), a modified form of the chemotherapy drug doxorubicin, which uses poly(ethylene glycol)-coated liposomes to enhance its circulation time and modify its toxicity profile. Doxil is characterized by a unique toxicity profile that includes mucocutaneous toxicities, mild myelosuppression, minimal alopecia, and no significant cardiac toxicity. It has a lower maximum tolerated dose (MTD) than conventional doxorubicin, but allows for a higher cumulative MTD. Clinically, Doxil has proven particularly effective in treating AIDS-related Kaposi's sarcoma and recurrent ovarian cancer. It exhibits a plasma half-life of 2-3 days, with most of the drug remaining encapsulated in liposomes during circulation. The document also reviews Doxil's pharmacokinetics, noting a trend towards saturation of clearance at doses between 10-60 mg/m², and its accumulation in malignant effusions and tumors. Doxil's recommended dose is 50 mg/m² every 4 weeks, based on Phase II studies. The document concludes that Doxil's unique pharmacokinetics may inform optimal dosing schedules and that further research is needed to explore its pharmacokinetic/pharmacodynamic relationship. Additionally, Doxil has shown promise in Phase III studies for recurrent epithelial ovarian cancer and Phase II studies for breast cancer, with a 31% overall response rate in the latter. The document suggests future research directions, including optimizing combination chemotherapy protocols and investigating Doxil's role with other therapeutic agents and as a radiosensitizer.