title: Drug cocktail optimization in chemotherapy of cancer.
abstract: BACKGROUND
  In general, drug metabolism has to be considered to avoid adverse effects and ineffective therapy. In particular, chemotherapeutic drug cocktails strain drug metabolizing enzymes especially the cytochrome P450 family (CYP). Furthermore, a number of important chemotherapeutic drugs such as cyclophosphamide, ifosfamide, tamoxifen or procarbazine are administered as prodrugs and have to be activated by CYP. Therefore, the genetic variability of these enzymes should be taken into account to design appropriate therapeutic regimens to avoid inadequate drug administration, toxicity and inefficiency.
  
  
  OBJECTIVE
  The aim of this work was to find drug interactions and to avoid side effects or ineffective therapy in chemotherapy.
  
  
  METHODS
  Information on drug administration in the therapy of leukemia and their drug metabolism was collected from scientific literature and various web resources. We carried out an automated textmining approach. Abstracts of PubMed were filtered for relevant articles using specific keywords. Abstracts were automatically screened for antineoplastic drugs and their synonyms in combination with a set of human CYPs in title or abstract.
  
  
  RESULTS
  We present a comprehensive analysis of over 100 common cancer treatment regimens regarding drug-drug interactions and present alternatives avoiding CYP overload. Typical concomitant medication, e.g. antiemetics or antibiotics is a preferred subject to improvement. A webtool, which allows drug cocktail optimization was developed and is publicly available on http://bioinformatics.charite.de/chemotherapy.
authors.affiliation: Charité - Universitätsmedizin Berlin, Dental, Oral and Maxillary Medicine, CC3, Department of Operative and Preventive Dentistry, Berlin, Germany.
authors.forename: Saskia
authors.initials: S
authors.lastname: Preissner
authors.forename: Mathias
authors.initials: M
authors.lastname: Dunkel
authors.forename: Michael F
authors.initials: MF
authors.lastname: Hoffmann
authors.forename: Sarah C
authors.initials: SC
authors.lastname: Preissner
authors.forename: Nikolai
authors.initials: N
authors.lastname: Genov
authors.forename: Wen Wei
authors.initials: WW
authors.lastname: Rong
authors.forename: Robert
authors.initials: R
authors.lastname: Preissner
authors.forename: Karlheinz
authors.initials: K
authors.lastname: Seeger
mesh_terms: D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use*; D004347:Drug Interactions; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy*
chemical_list: D000970:Antineoplastic Agents