title: Newin vitrosystem to predict chemotherapeutic efficacy of drug combinations in fresh tumor samples.
abstract: BACKGROUND
  To find the best individual chemotherapy for cancer patients, the efficacy of different chemotherapeutic drugs can be predicted by pretesting tumor samplesin vitrovia the chemotherapy-resistance (CTR)-Test®. Although drug combinations are widely used among cancer therapy, so far only single drugs are tested by this and other tests. However, several first line chemotherapies are combining two or more chemotherapeutics, leading to the necessity of drug combination testing methods.
  
  
  METHODS
  We established a system to measure and predict the efficacy of chemotherapeutic drug combinations with the help of the Loewe additivity concept in combination with the CTR-test. A combination is measured by using half of the monotherapy's concentration of both drugs simultaneously. With this method, the efficacy of a combination can also be calculated based on single drug measurements.
  
  
  RESULTS
  The established system was tested on a data set of ovarian carcinoma samples using the combination carboplatin and paclitaxel and confirmed by using other tumor species and chemotherapeutics. Comparing the measured and the calculated values of the combination testings revealed a high correlation. Additionally, in 70% of the cases the measured and the calculated values lead to the same chemotherapeutic resistance category of the tumor.
  
  
  CONCLUSIONS
  Our data suggest that the best drug combination consists of the most efficient single drugs and the worst drug combination of the least efficient single drugs. Our results showed that single measurements are sufficient to predict combinations in specific cases but there are exceptions in which it is necessary to measure combinations, which is possible with the presented system.
authors.affiliation: TherapySelect, Heidelberg, Germany.
authors.forename: Frank Christian
authors.initials: FC
authors.lastname: Kischkel
authors.affiliation: TherapySelect, Heidelberg, Germany.
authors.forename: Julia
authors.initials: J
authors.lastname: Eich
authors.affiliation: TherapySelect, Heidelberg, Germany.
authors.forename: Carina I
authors.initials: CI
authors.lastname: Meyer
authors.affiliation: TherapySelect, Heidelberg, Germany.
authors.forename: Paula
authors.initials: P
authors.lastname: Weidemüller
authors.affiliation: TherapySelect, Heidelberg, Germany.
authors.forename: Jens
authors.initials: J
authors.lastname: Krapfl
authors.affiliation: TherapySelect, Heidelberg, Germany.
authors.forename: Rauaa
authors.initials: R
authors.lastname: Yassin-Kelepir
authors.affiliation: TherapySelect, Heidelberg, Germany.
authors.forename: Laura
authors.initials: L
authors.lastname: Job
authors.affiliation: TherapySelect, Heidelberg, Germany.
authors.forename: Marius
authors.initials: M
authors.lastname: Fraefel
authors.affiliation: Gynecology Department, Charité Berlin, Virchow Campus Berlin, Germany.
authors.forename: Ioana
authors.initials: I
authors.lastname: Braicu
authors.affiliation: Division of Biostatistics, German Cancer Research Center, Heidelberg, Germany.
authors.forename: Annette
authors.initials: A
authors.lastname: Kopp-Schneider
authors.affiliation: Gynecology Department, Charité Berlin, Virchow Campus Berlin, Germany.
authors.forename: Jalid
authors.initials: J
authors.lastname: Sehouli
authors.affiliation: University Hospital for Gynecology, Carl von Ossietzky University Oldenburg, Germany.
authors.forename: Rudy Leon
authors.initials: RL
authors.lastname: De Wilde
keywords: Additive effect; Chemotherapy-resistance-test; Drug combination; Drug combination testing; Drug sensitivity testing; Individualized cancer therapy; Ovarian carcinoma