The
anti-malarial drug artesunate has shown anticancer activity in vitro and in preliminary animal experiments, but experience in patients with
cancer is very limited. Pre-clinical studies in dogs indicated morbidity at high dosage levels. This study evaluated the effects of
artesunate in canine
cancer cell lines and in canine
cancer patients. Four canine cell lines were tested in vitro for sensitivity towards
artesunate and
dihydroartemisinin (DHA; active metabolite of
artesunate). The half-maximal inhibitory concentration (IC50) values for
artesunate or DHA were 2-60 μM in three cell lines, while one cell line was much less sensitive to
artesunate (IC50 337 μM) than to DHA (IC50 50 μM). A safety/efficacy field study with
artesunate was conducted in 23 dogs with non-resectable tumours.
Artesunate was administered for 7-385 days at a dosage of 651-1178 (median 922) mg/m(2). No neurological or
cardiac toxicity was observed and seven dogs exhibited no adverse effects at all.
Fever and haematological/gastrointestinal toxicity, mostly transient, occurred in 16 dogs. One dog died from
pneumonia. Plasma
artesunate and DHA levels fell below the limit of detection within 8-12 h after
artesunate administration, while levels after two hours were close to 1 μM.
Artesunate produced a long-lasting complete remission in one case of
cancer and short-term stabilization of another seven cases.