title: A dose-escalating pilot study of sterically stabilized, pegylated liposomal doxorubicin (Lipo-Dox) in patients with metastatic breast cancer.
abstract: Doxorubicin is considered among the most active single agents used against advanced breast cancer. Recent advances in the design of liposomes as carriers of cytotoxic drugs have resulted in a new formulation of doxorubicin with improved pharmacokinetic and tumor-localizing properties. The objectives of this dose-escalating pilot study were to evaluate the efficacy and safety of the sterically stabilized, pegylated liposomal doxorubicin (Lipo-Dox) for the treatment of metastatic breast cancer. Lipo-Dox was given at the dosage of 45 mg/m2 over 1 hr of intravenous infusion every 4 weeks initially and could be escalated up to a maximum of 60 mg/m2. Response was assessable in 17 of 19 intent-to-treat patients. An objective response was achieved in 41.2% (95% confidence interval: 17.8%-64.6%) of patients (5.9% complete response and 35.3% partial response), and 23.5% had stable disease. Median time to disease progression was 163 days. Major treatment-related toxicities included neutropenia, stomatitis, and skin toxicity in this dose-escalation program. Impressively, no grade 4 toxicities have ever been observed. The only grade 3 nonhematological toxicity ever to occur was reversible skin toxicity, presented as palmar-plantar erythrodysthesia. No severe nausea/vomiting, wig-necessary alopecia, or significant cardiac function change were encountered. In conclusion, Lipo-Dox is shown by this first reported pilot study to be an active agent for treatment of advanced breast cancer with a safety profile that differs markedly from free doxorubicin. The dosage of 45-60 mg/m2 every 4 weeks was well tolerated. Because myelosuppression and other nonhematological toxicities associated with Lipo-Dox were generally mild and acceptable, further assessment of this drug particularly in combination with other chemotherapeutic drugs in the management of early or advanced breast cancer is suggested.
authors.affiliation: Division of Medical Oncology, Department of Medicine, Taipei Veterans General Hospital, National Yang-Ming University, School of Medicine, Taipei, Taiwan, ROC.
authors.forename: Ta-Chung
authors.initials: TC
authors.lastname: Chao
authors.forename: Wei-Shu
authors.initials: WS
authors.lastname: Wang
authors.forename: Chueh-Chuan
authors.initials: CC
authors.lastname: Yen
authors.forename: Tzeon-Jye
authors.initials: TJ
authors.lastname: Chiou
authors.forename: Jin-Hwang
authors.initials: JH
authors.lastname: Liu
authors.forename: Po-Min
authors.initials: PM
authors.lastname: Chen
mesh_terms: D000328:Adult; D000368:Aged; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage* / Q000009:adverse effects*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D018450:Disease Progression; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000008:administration & dosage* / Q000009:adverse effects*; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D008081:Liposomes; D008875:Middle Aged; D009362:Neoplasm Metastasis
chemical_list: D000903:Antibiotics, Antineoplastic; D008081:Liposomes; D004317:Doxorubicin