Dataset Information

New in vitro system 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 samples in vitro via 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.

Conclusion

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.

SUBMITTER: Kischkel FC

PROVIDER: S-EPMC5337084 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

New <i>in vitro</i> system to predict chemotherapeutic efficacy of drug combinations in fresh tumor samples.

Kischkel Frank Christian FC Eich Julia J Meyer Carina I CI Weidemüller Paula P Krapfl Jens J Yassin-Kelepir Rauaa R Job Laura L Fraefel Marius M Braicu Ioana I Kopp-Schneider Annette A Sehouli Jalid J De Wilde Rudy Leon RL

PeerJ 20170302

<h4>Background</h4>To find the best individual chemotherapy for cancer patients, the efficacy of different chemotherapeutic drugs can be predicted by pretesting tumor samples <i>in vitro</i> via the chemotherapy-resistance (CTR)-Test<sup>®</sup>. 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 combin ...[more]

PMID: 28265509

Similar Datasets

Project description:Recent WHO guidelines recommend dual therapy with ceftriaxone or cefixime plus azithromycin for gonorrhea. Azithromycin in combination with gentamicin or spectinomycin has been recommended in treatment failure cases. Due to emergence of multi-drug resistant (MDR) and extensively-drug resistant (XDR) Neisseria gonorrhoeae strains, it is important to look for efficacy of these combinations and also of others that might be used in future. Therefore, we aimed to evaluate in vitro synergy of 21 dual combinations including current and alternative WHO recommended treatment regimens and other dual combinations.The potential utility of in-vitro interactions of 21 combinations was investigated against 95 N. gonorrhoeae strains including 79 MDR and one XDR strain collected during March 2013 to July 2017 and fractional inhibitory concentration index (FICI) was calculated. These 21 combinations comprised of two WHO currently recommended (cefixime+azithromycin, ceftriaxone+azithromycin); two WHO recommended in treatment failure cases (azithromycin+gentamicin, spectinomycin+azithromycin) and other 17 combinations.FICI of the four WHO recommended antimicrobial combinations were higher (>1.0) than the five novel combinationbreeds (FICI range 0.603-0.951) in the study i.e. gentamicin+ertapenem, moxifloxacin+ertapenem, spectinomycin+ertapenem, azithromycin+ moxifloxacin, cefixime+gentamicin. No antagonistic effect of the above four WHO recommended combinations except spectinomycin+azithromycin (FICI = 4.25) was observed for the XDR strain. Out of above five novel combinations, four combinations produced high synergistic effects in overall 95 strains and also for the XDR strain with FICI of 0.13 to 0.38. Antagonistic effects varying from 3.2 to 12.6% were observed for 10 out of 21 tested combinations (azithromycin in combination with gentamicin and spectinomycin; ceftriaxone with moxifloxacin, gentamicin, spectinomycin and ertapenem; spectinomycin with moxifloxacin and gentamicin; cefixime and gentamicin combination with moxifloxacin).WHO recommended cefixime+azithromycin, ceftriaxone+azithromycin combinations having no antagonism indicates their continuing clinical utility. Highest antagonism without any synergistic effect for the WHO recommended spectinomycin+azithromycin in treatment failure cases suggests that this combination should be evaluated further both in vitro and in vivo. Highest synergistic or additive effect without any antagonistic effect of the above five novel combinations suggests that these may be recommended for treatment in future.