title: Efficacy and safety of liposomal anthracyclines in phase I/II clinical trials.
abstract: Preclinical studies have established the pharmacologic advantages of liposomal anthracyclines, including pharmacokinetic profiles after bolus dosing that resemble continuous infusion of conventional anthracyclines, increased drug concentrations in tumor cells compared with the surrounding tissues, and reduced toxicity relative to conventional anthracycline treatment. Based on these studies, many phase I and phase II clinical trials were conducted to assess the safety and potential activity of liposomal anthracyclines in the management of both solid and hematologic tumors. These studies provided valuable insight into the safety of pegylated liposomal doxorubicin (Doxil/Caelyx [PLD]), nonpegylated liposomal doxorubicin (Myocet [NPLD]), and liposomal daunorubicin (DaunoXome [DNX]) over a range of doses, either as single-agent therapy or in combination with other cytotoxic agents. Other liposomal anthracyclines in development may be well tolerated but their activity remains to be elucidated by clinical trials. The available data also suggest that liposomal anthracyclines have activity not only against tumor types with known sensitivity to conventional anthracyclines, but also potentially for tumors that are typically anthracycline-resistant. Despite the availability of clinical data from a wide variety of tumor types and patient populations, further studies of liposomal anthracycline therapy are needed to fully establish their safety, efficacy, and dosing in the treatment of these patients.
authors.affiliation: The Arizona Cancer Center, Tucson, AZ, USA. dalberts@AZCC.Arizona.edu
authors.forename: David S
authors.initials: DS
authors.lastname: Alberts
authors.forename: Franco M
authors.initials: FM
authors.lastname: Muggia
authors.forename: James
authors.initials: J
authors.lastname: Carmichael
authors.forename: Eric P
authors.initials: EP
authors.lastname: Winer
authors.forename: Mohammad
authors.initials: M
authors.lastname: Jahanzeb
authors.forename: Alan P
authors.initials: AP
authors.lastname: Venook
authors.forename: Keith M
authors.initials: KM
authors.lastname: Skubitz
authors.forename: Edgardo
authors.initials: E
authors.lastname: Rivera
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Sparano
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: DiBella
authors.forename: Simon J
authors.initials: SJ
authors.lastname: Stewart
authors.forename: John J
authors.initials: JJ
authors.lastname: Kavanagh
authors.forename: Alberto A
authors.initials: AA
authors.lastname: Gabizon
mesh_terms: D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage* / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D017321:Clinical Trials, Phase I as Topic; D017322:Clinical Trials, Phase II as Topic; D003630:Daunorubicin / Q000008:administration & dosage* / Q000009:adverse effects; D004317:Doxorubicin / Q000008:administration & dosage* / Q000009:adverse effects; D006801:Humans; D008081:Liposomes
chemical_list: D000903:Antibiotics, Antineoplastic; D008081:Liposomes; D004317:Doxorubicin; D003630:Daunorubicin