title: A Randomised, Double Blind, Placebo-Controlled Pilot Study of Oral Artesunate Therapy for Colorectal Cancer.
abstract: BACKGROUND
  Artesunate is an antimalarial agent with broad anti-cancer activity in in vitro and animal experiments and case reports. Artesunate has not been studied in rigorous clinical trials for anticancer effects.
  
  
  OBJECTIVE
  To determine the anticancer effect and tolerability of oral artesunate in colorectal cancer (CRC).
  
  
  METHODS
  This was a single centre, randomised, double-blind, placebo-controlled trial. Patients planned for curative resection of biopsy confirmed single primary site CRC were randomised (n = 23) by computer-generated code supplied in opaque envelopes to receive preoperatively either 14 daily doses of oral artesunate (200 mg; n = 12) or placebo (n = 11). The primary outcome measure was the proportion of tumour cells undergoing apoptosis (significant if > 7% showed Tunel staining). Secondary immunohistochemical outcomes assessed these tumour markers: VEGF, EGFR, c-MYC, CD31, Ki67 and p53, and clinical responses.
  
  
  RESULTS
  20 patients (artesunate = 9, placebo = 11) completed the trial per protocol. Randomization groups were comparable clinically and for tumour characteristics. Apoptosis in > 7% of cells was seen in 67% and 55% of patients in artesunate and placebo groups, respectively. Using Bayesian analysis, the probabilities of an artesunate treatment effect reducing Ki67 and increasing CD31 expression were 0.89 and 0.79, respectively. During a median follow up of 42 months 1 patient in the artesunate and 6 patients in the placebo group developed recurrent CRC.
  
  
  CONCLUSIONS
  Artesunate has anti-proliferative properties in CRC and is generally well tolerated.
authors.affiliation: Institute of Infection and Immunity, Department of Pathology, United Kingdom.
authors.forename: Sanjeev
authors.initials: S
authors.lastname: Krishna
authors.affiliation: Department of Surgery, St. George's, University of London, Cranmer Terrace, SW17 0RE, United Kingdom.
authors.forename: Senthil
authors.initials: S
authors.lastname: Ganapathi
authors.affiliation: Institute of Infection and Immunity, Department of Pathology, United Kingdom.
authors.forename: Irina Chis
authors.initials: IC
authors.lastname: Ster
authors.affiliation: Department of Pharmaceutical Biology, Johannes Gutenberg-University, Staudinger Weg 5, 55128 Mainz, Germany.
authors.forename: Mohamed E M
authors.initials: ME
authors.lastname: Saeed
authors.affiliation: Department of Gastroenterology, Surrey and Sussex Healthcare NHS Trust, East Surrey Hospital, Canada Avenue, Redhill, Sussex RH1 5RH, United Kingdom.
authors.forename: Matt
authors.initials: M
authors.lastname: Cowan
authors.affiliation: Institute of Infection and Immunity, Department of Pathology, United Kingdom.
authors.forename: Caroline
authors.initials: C
authors.lastname: Finlayson
authors.affiliation: Institute of Infection and Immunity, Department of Pathology, United Kingdom.
authors.forename: Hajnalka
authors.initials: H
authors.lastname: Kovacsevics
authors.affiliation: Dafra Pharma nv, 2300 Turnhout, Belgium.
authors.forename: Herwig
authors.initials: H
authors.lastname: Jansen
authors.affiliation: Institut für Tropenmedizin, Universitätsklinikum Tübingen, Wilhelmstraße 27, D-72074 Tübingen, Germany.
authors.forename: Peter G
authors.initials: PG
authors.lastname: Kremsner
authors.affiliation: Department of Pharmaceutical Biology, Johannes Gutenberg-University, Staudinger Weg 5, 55128 Mainz, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Efferth
authors.affiliation: Department of Surgery, St. George's, University of London, Cranmer Terrace, SW17 0RE, United Kingdom.
authors.forename: Devinder
authors.initials: D
authors.lastname: Kumar
mesh_terms: D000284:Administration, Oral; D000368:Aged; D037621:Artemisinins / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use*; D000077332:Artesunate; D014408:Biomarkers, Tumor / Q000378:metabolism; D002272:Carcinoembryonic Antigen / Q000378:metabolism; D015179:Colorectal Neoplasms / Q000188:drug therapy*; D003710:Demography; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000378:metabolism; D008297:Male; D010865:Pilot Projects; D010919:Placebos; D013194:Staining and Labeling; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D037621:Artemisinins; D014408:Biomarkers, Tumor; D002272:Carcinoembryonic Antigen; D019394:Ki-67 Antigen; D010919:Placebos; D000077332:Artesunate
keywords: Artesunate; Colorectal cancer; Dihydroartemisinin; Ki67; Neutropaenia