357
Review
www.expert-reviews.com ISSN 1473-7140 © 2009 Expert Reviews Ltd 10.1586/14737140.9.3.357
Anthracyclines are a highly efficacious treatment
for hematological malignancies, including acute
myeloid leukemia, acute lymphoblastic leukemia,
multiple myeloma, Hodgkin’s disease and non-
Hodgkin’s lymphoma (NHL). Doxorubicin-
based combination chemotherapy continues to
be a cornerstone of chemotherapy for NHL.
The cyclophosphamide, doxorubicin, vinc-
ristine and prednisolone (CHOP) regimen is
the gold-standard treatment for patients with
aggressive NHL [1] . This first-generation com-
bination chemotherapy is associated with a
complete remission (CR) rate of approximately
50%, with 30% of patients being alive and dis-
ease free 5 years after chemotherapy [1] . Many
attempts have been made to improve the clini-
cal outcome with second- and third-generation
schedules, without any significant improvement
in terms of CR rate, disease-free survival (DFS)
or overall survival (OS) [2–4] . The addition of
rituximab (MabThera
®
, Roche, Switzerland;
Rituxan
®
, Genentech-Biogen IDEC, USA),
a monoclonal antibody against the CD20
antigen expressed on the vast majority of B-cell
lymphomas, to the CHOP regimen has been
shown to improve outcome in elderly patients
with advanced disease, without any significant
increase in toxicity [5] . Subsequent studies have
also confirmed the efficacy of this approach in
younger patients [6] .
However, multiple relapses are common
for patients with NHL, resulting in second-,
third-, fourth- or possibly even fifth-line treat-
ment during a period of 12–15 years. The main
problem is that salvage therapy may well be with
an anthracycline-based regimen, which could
lead to cumulative doses of doxorubicin of
more than 450 mg/m
2
. Cardiotoxicity is still
a key medical concern because the cumulative
toxicity of anthracyclines is dose limiting and
irreversible [7–9] .
Liposomal formulations have been developed
with the aim of improving the therapeutic index
of doxorubicin by reducing the drug’s cardio-
toxicity but maintaining its anti-tumor effi-
cacy. Two liposomal formulations are currently
Giuseppe Visani
†
and
Alessandro Isidori
†
Author for correspondence
Hematology and Hematopoietic
Stem Cell Transplant Center,
San Salvatore Hospital,
Via Lombroso 1, 61100 Pesaro,
Italy
Tel.: +39 072 136 4039
Fax: +39 072 136 4036
g.visani@ospedalesansalvatore.it
Anthracyclines, including doxorubicin, are widely used in the treatment of B-cell non-Hodgkin’s
lymphoma (NHL). However, their clinical potential is limited by their cardiotoxic adverse effects,
which include cardiomyopathy and congestive heart failure. Anthracycline-induced cardiotoxicity
is cumulative and irreversible. Liposomal doxorubicin has been developed with the aim of
improving the therapeutic index of doxorubicin by reducing the drug’s cardiotoxicity.
Nevertheless, liposomal conjugation of doxorubicin results in preferential distribution of the
drug in the tumor compared with normal tissue, maintaining its anti-tumor efficacy. Nonpegylated
liposomal doxorubicin produced a promising response rate when substituted for conventional
doxorubicin in the cyclophosphamide, doxorubicin, vincristine and prednisolone regimen in the
treatment of patients with NHL either at diagnosis or at relapse. The ability of nonpegylated
liposomal doxorubicin to overcome excessive drug efflux due to P-glycoprotein (MDR-1)
overexpression in NHL might confer on this drug a curative potential for patients with a bad
prognosis (e.g., MDR-1 overexpressing, the elderly or frail).
KEYWORDS:anthracycline•B-cellnon-Hodgkin’slymphoma•cardiotoxicity•eficacy•nonpegylatedliposomal
doxorubicin•safety
Nonpegylated liposomal
doxorubicin in the treatment
of B-cell non-Hodgkin’s
lymphoma: where we stand
Expert Rev. Anticancer. Ther. 9(3), 357–363 (2009)
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