CLEVELANDHospitalizations due to adverse events were less likely to
occur among newly diagnosed multiple myeloma patients who received DVd (pegylated
liposomal doxorubicin [Doxil]/vincristine/dexamethasone (than those who
received VAd (vincristine/doxorubicin [Adriamycin]/reduced-dose
dexamethasone). Early results from a randomized phase III trial were
reported by Mohamad A. Hussein, MD, of the Cleveland Clinic. The data are
very preliminary, as safety data could be collected on only 94 of 135
patients who are enrolled at 22 sites in the study (ASCO abstract 1107).
Hospitalizations relating to adverse events occurred in 17 of 50 DVd
patients and 16 of 44 VAd patients. Adverse events related to the regimen
caused more extended hospitalizations in the VAd patients: 7 compared to 3
in the DVd arm of the study. Only 3% of DVd treatment cycles were associated
with unscheduled hospital admissions compared to 42% of VAd cycles.
Dr. Hussein said efficacy results are not available because outcomes had
been blinded in the phase III trial, which is still recruiting patients. He
reported that a phase II pilot trial showed DVd to produce an overall
response rate of 88% in newly diagnosed multiple myeloma patients. The
median time to failure was 23.1 months, and 1-year and 2-year
progression-free survival rates were 42% and 23%, respectively.
Patients on the DVd regimen receive 40 mg/m² of pegylated liposomal
doxorubicin and 1.4 mg/m² (to a maximum of 2.0 mg) of vincristine
intravenously on day 1 and 40 mg of dexamethasone by mouth on days 1 to 4.
Patients on the VAd regimen receive 0.4 mg/day of vincristine and 9 mg/m²/day of conventional doxorubicin by continuous infusion plus 40 mg of
dexamethasone by mouth for 4 days.
Both regimens are delivered in cycles repeated every 4 weeks until the
patient has disease progression, toxicity becomes unacceptable, or a plateau
phase is reached. Dr. Hussein said toxicity has not been a problem in the
DVd regimen, which appears to be well tolerated. Ten DVd patients (20%) were
reported to have gone on to transplantation after responding to therapy
compared to four VAd patients (9%).
Dr. Hussein said the investigators believe myeloma is a perfect target
for pegylated liposomal doxorubicin because the pegylated liposomal
formulation of doxorubicin has high vascular activity and can attack the
disease in the bone marrow where it grows. Another advantage is that
pegylated liposomal doxorubicin can be delivered intravenously on an
"Myeloma cells are slow to grow, and you want to expose them for a
longer time to the drug," Dr. Hussein told ONI. "VAd is usually
delivered by continuous infusion for 4 days, but with the Doxil you can have
active drug for 90 days."