title: Doxil (Caelyx): an exploratory study with pharmacokinetics in patients with hormone-refractory prostate cancer.
abstract: Doxil, a doxorubicin formulation of polyethylene glycol-coated liposomes, has 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 prostate cancer (HRPC) with considerable toxicity. A pilot study of Doxil was conducted in 15 patients with HRPC. Doxil was administered i.v. using two regimes of equal dose intensity, either 45 mg/m2 every 3 weeks or 60 mg/m2 every 4 weeks. Plasma levels of doxorubicin were analyzed in 10 patients. The most common side effect was stomatitis with a higher incidence at the 60 mg/m2 dose level. In contrast, hand-foot syndrome was more frequent and severe in patients treated with the 3 week schedule of 45 mg/m2. Three patients responded to treatment (based on objective response in one patient and reduction of PSA level greater than 50% in the other two) and two patients had stable disease, all of them receiving 60 mg/m2. Pharmacokinetic analysis shows a proportional increase of plasma drug levels with dose and the characteristic long circulation time of Doxil with half-lives in the range of 3 days, somewhat longer than previously reported. In conclusion, Doxil at 60 mg/m2 every 4 weeks appears to be active against HRPC, but severe mucocutaneous toxicities prevented further investigation of this regime.
authors.affiliation: Sharet Institute of Oncology, Hadassah Hebrew University Medical Center, Jerusalem, Israel.
authors.forename: A
authors.initials: A
authors.lastname: Hubert
authors.forename: O
authors.initials: O
authors.lastname: Lyass
authors.forename: D
authors.initials: D
authors.lastname: Pode
authors.forename: A
authors.initials: A
authors.lastname: Gabizon
mesh_terms: D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics*; D019540:Area Under Curve; D018572:Disease-Free Survival; D004317:Doxorubicin / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics*; D004337:Drug Carriers; D006728:Hormones / Q000627:therapeutic use; D006801:Humans; D007262:Infusions, Intravenous; D008081:Liposomes; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000517:prevention & control*; D012867:Skin / Q000187:drug effects; D013280:Stomatitis / Q000139:chemically induced; D017211:Treatment Failure
chemical_list: D000970:Antineoplastic Agents; D004337:Drug Carriers; D006728:Hormones; D008081:Liposomes; D004317:Doxorubicin