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of 50 mg/m
2
is approximately 300-fold greater than that with free
drug. Clearance and volume of distribution are drastically reduced
(at least 250-fold and 60-fold, respectively). These studies indicate
the importance of utilizing the distinct pharmacokinetic parameters
of pegylated liposomal doxorubicin in dose scheduling.
12.5.2 Doxil Tolerability
It was already demonstrated in our
Cancer Research
publication
(Gabizon et al., 1994a) that, overall, Doxil is well tolerated and
shows a distinct superiority over free DOX in most evaluated side
eff ects. However, two side eff ects not typical of what is observed
for conventional doxorubicin treatment were observed. The first of
these shows up as flushing and shortness of breath; it is also referred
to as acute infusion reaction or pseudo-allergy (Gabizon et al., 2008;
Szebeni and Barenholz, 2012, this topic) and is reduced by reducing
rate of infusion. This side eff ect was recently reviewed by Szebeni
and Barenholz (2012) (this topic). The second eff ect that results is
grade 2 or 3 of desquamating dermatitis and is referred to as Palmar
Plantar Erythrodysthesia (PPE) or “foot and hand syndrome.” The
second eff ect increased with dose and was more pronounced for
3-week intervals than 4-week intervals between treatments (for
more details, see Solomon and Gabizon, 2008). For more details on
Doxil tolerability and side eff ects, see Doxil homepage (www.doxil.
com) and drugs online (www.drugs.com/pro/doxil.html).
12.5.3
Doxil Therapeutic Indications
In this review, I will not discuss in detail Doxil clinical performance,
which is covered in many scientific papers, reviews, and reports.
As of today (April 4, 2011), Doxil has more than 171,000 Google
citations, and most of them are related to clinical aspects.
A good starting point is a recent review by Solomon and Gabizon
(2008) entitled “Clinical Pharmacology of Liposomal Anthracyclines:
Focus on Pegylated Liposomal Doxorubicin”. Current relevant
websites are Wikipedia, Doxil homepage (www.doxil.com) and drugs
online (www.drugs.com/pro/doxil.html). A summary of indications
approved by the U.S. FDA and/or European Medicines Evaluation
Agency (EMA) and approval year for Doxil
is described as follows:
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