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.