Improving the therapeutic index of anthracycline chemotherapy: focus on liposomal doxorubicin (Myocet).
Anthracyclines are valuable cytotoxic agents in cancer treatment. However, their usefulness is limited by cumulative dose-dependent cardiotoxicity that may manifest as life-threatening congestive heart failure. To avoid cardiotoxicity, the use of doxorubicin is typically capped at a safe cumulative dose. Liposomal formulations may reduce cardiac risks whilst maintaining anti-cancer efficacy. Efficacy and safety studies of non-pegylated liposomal doxorubicin (NPLD) in metastatic breast cancer (MBC) are reviewed, along with studies that examine efficacy and cardiac tolerability in combination with newer agents such as paclitaxel and trastuzumab. These show that cardiac safety of liposomal doxorubicin is similar to that of epirubicin in cumulative dose, but that the formulation, unlike epirubicin, has similar anti-cancer efficacy to doxorubicin at equimolar doses. Liposomal doxorubicin may have a better therapeutic index than non-liposomal anthracyclines. This justifies further studies in patients where cumulative cardiotoxicity is a concern, as does study of its use with other potentially cardiotoxic agents.
Leonard
R C F
RC
Imperial College NHS Trust, Hammersmith Hospital, Du Cane Road, London W12 OHS, UK. rleonard@imperial.ac.uk
Williams
S
S
Tulpule
A
A
Levine
A M
AM
Oliveros
S
S
D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000494:pharmacology; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D003520:Cyclophosphamide / Q000008:administration & dosage; D004317:Doxorubicin / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D015251:Epirubicin / Q000008:administration & dosage; D006321:Heart / Q000187:drug effects; D006333:Heart Failure / Q000139:chemically induced; D006801:Humans; D008081:Liposomes; D053475:Receptor-Interacting Protein Serine-Threonine Kinase 2; D000068878:Trastuzumab; D016276:Ventricular Function / Q000187:drug effects
D000903:Antibiotics, Antineoplastic; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D008081:Liposomes; D015251:Epirubicin; D004317:Doxorubicin; D003520:Cyclophosphamide; D053475:Receptor-Interacting Protein Serine-Threonine Kinase 2; D000068878:Trastuzumab