Objective—To determine the acute and short-term
adverse effects of a liposome-encapsulated form of
cisplatin at increasing dosages of up to twice the
known maximally tolerated dose (MTD) of unencapsulated
cisplatin in clinically normal dogs.
Procedure—4 dosages (70, 100, 125, and 150 mg/m2)
were evaluated, and the 4 dogs received a total of 9
infusions (1 to 3 infusions/dog). Dogs were monitored
to detect changes in clinical and clinicopathologic status.
Evaluations consisting of a physical examination,
CBC, serum biochemical analysis, and urinalysis were
performed before and 7 and 21 days after each infusion.
Results—Acute anaphylactic-like reactions to liposome-
encapsulated cisplatin were common but clinically
manageable. Nephrotoxicosis and substantial
myelosuppression, toxic effects commonly associated
with unencapsulated cisplatin, were not observed
in dogs treated with liposome-encapsulated cisplatin
at dosages equivalent to twice the known MTD of
Conclusions and Clinical Relevance—Liposome-encapsulated
cisplatin can be safely administered to
clinically normal dogs at dosages of up to 150 mg/m2
without the need for concurrent hydration protocols.
This was a necessary prerequisite to enable phase I
clinical trials in dogs with naturally developing cancers
that could theoretically benefit from escalation in the
dosage of cisplatin. Determination of an MTD, cumulative
and long-term toxic effects, and efficacy can now
be conducted in the context of phase I trials in tumorbearing
dogs. (Am J Vet Res 2004;65:1474–1478)