title: Safety and efficacy field study of artesunate for dogs with non-resectable tumours.
abstract: 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.
authors: Department of Clinical Sciences of Companion Animals, Faculty of Veterinary Medicine, PO Box 80.154, University of Utrecht, 3508 TD Utrecht, The Netherlands. G.R.Rutteman@uu.nl
authors: Gerard R
authors: GR
authors: Rutteman
authors: Suzanne A
authors: SA
authors: Erich
authors: Jan A
authors: JA
authors: Mol
authors: Bart
authors: B
authors: Spee
authors: Guy C M
authors: GC
authors: Grinwis
authors: Lawrence
authors: L
authors: Fleckenstein
authors: Cheryl A
authors: CA
authors: London
authors: Thomas
authors: T
authors: Efferth
mesh_terms: D000818:Animals; D000962:Antimalarials / Q000627:therapeutic use*; D037621:Artemisinins / Q000627:therapeutic use*; D000077332:Artesunate; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000662:veterinary*; D049109:Cell Proliferation / Q000187:drug effects; D004283:Dog Diseases / Q000188:drug therapy*; D004285:Dogs; D008223:Lymphoma / Q000188:drug therapy / Q000662:veterinary*; D009062:Mouth Neoplasms / Q000188:drug therapy / Q000662:veterinary*; D016896:Treatment Outcome; D014407:Tumor Cells, Cultured
chemical_list: D000962:Antimalarials; D037621:Artemisinins; D000077332:Artesunate; C039060:artenimol
keywords: Artesunate; cancer; comparative oncology; dog; safety study