Doxil (Caelyx): an exploratory study with pharmacokinetics in patients with hormone-refractory prostate cancer

Doxil, a doxorubicin formulation of polyethylene glycol-coated liposomes, h as anti-tumor activity against Kaposi's sarcoma and other solid tumors with mild myelosuppression, minimal hair loss and a low risk of cardiotoxicity. Non-liposomal doxorubicin has modest activity in hormone-refractory prosta te cancer (HRPC) with considerable toxicity. A pilot study of Doxil was con ducted in 15 patients with HRPC. Doxil was administered i.v, using two regi mes of equal dose intensity, either 45 mg/m(2) every 3 weeks or 60 mg/m(2) every 4 weeks, Plasma levels of doxorubicin were analyzed in 10 patients, T he most common side effect was stomatitis with a higher incidence at the 60 mg/m(2) dose level. In contrast, hand-foot syndrome was more frequent and severe in patients treated with the 3 week schedule of 45 mg/m(2). Three pa tients responded to treatment (based on objective response in one patient a nd reduction of PSA level greater than 50% in the other two) and two patien ts had stable disease, all of them receiving 60 mg/m(2). Pharmacokinetic an alysis shows a proportional increase of plasma drug levels with dose and th e characteristic long circulation time of Doxil with half-lives in the rang e of 3 days, somewhat longer than previously reported, In conclusion, Doxil at 60 mg/m(2) every 4 weeks appears to be active against HRPC, but severe mucocutaneous toxicities prevented further investigation of this regime. [( C) 2000 Lippincott Williams & Wilkins.].