Pegylated liposomal Doxorubicin: a review of its use in the treatment of relapsed or refractory multiple myeloma.
Pegylated liposomal doxorubicin (Doxil, Caelyx) is associated with less frequent neutropenia, alopecia and cardiotoxicity than conventional doxorubicin and has an improved pharmacokinetic profile, allowing for intravenous administration over 1 hour. In the US and EU (as well as a number of other countries), pegylated liposomal doxorubicin is approved for use in combination with the proteasome inhibitor bortezomib for the treatment of patients with relapsed or refractory multiple myeloma. Results of the primary efficacy analysis of a large phase III trial in bortezomib-naive patients with relapsed or refractory multiple myeloma demonstrated that the combination of pegylated liposomal doxorubicin plus bortezomib significantly prolonged the time to progression (TTP) compared with bortezomib alone. In addition, pegylated liposomal doxorubicin plus bortezomib significantly increased TTP in most subgroup analyses, including in patients with or without previous anthracycline exposure. A number of secondary outcomes, including progression-free survival and overall survival at 15 months, were also improved with the combination compared with bortezomib alone in the overall study population. Pegylated liposomal doxorubicin plus bortezomib was associated with a higher incidence of grade 3 or 4 adverse events than bortezomib alone, which was mainly attributed to an increase in myelosuppression and gastrointestinal events with the combination. These events were predictable and often managed by dosage modifications and supportive therapy. The addition of pegylated liposomal doxorubicin to bortezomib treatment did not increase the incidence of cardiotoxicity or peripheral neuropathy, but did induce hand-foot syndrome in a proportion of patients. Pegylated liposomal doxorubicin plus bortezomib is now established as an additional standard of care in the treatment of patients with relapsed or refractory multiple myeloma who have received at least one prior therapy.
Plosker
Greg L
GL
Wolters Kluwer Health | Adis, Auckland, New Zealand. demail@adis.co.nz
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001897:Boronic Acids / Q000627:therapeutic use; D000069286:Bortezomib; D004317:Doxorubicin / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D019008:Drug Resistance, Neoplasm; D006801:Humans; D009101:Multiple Myeloma / Q000188:drug therapy*; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy*; D011092:Polyethylene Glycols / Q000494:pharmacology / Q000627:therapeutic use; D011719:Pyrazines / Q000627:therapeutic use
D001897:Boronic Acids; D011719:Pyrazines; C506643:liposomal doxorubicin; D011092:Polyethylene Glycols; D000069286:Bortezomib; D004317:Doxorubicin