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Updated: Mar 7, 2026
Diagonal Method to Measure Synergy Among Any Number of Drugs
Published on: June 21, 2018
Application of sequential factorial design and orthogonal array composite design (OACD) to study combination of 5
Xiaolong Jia1, Yiyang Li2, Alok Sharma2
1Department of Urology, Ningbo First Hospital, Ningbo Hospital of Zhejiang University, Ningbo, Zhejiang 315010, China; School of Biomedical Engineering, Institute for Personalized Medicine, Shanghai Jiao Tong University, Shanghai 200030, China.
Abstract:
Prostate cancer is one of the most common cancers among men in the United States. It is also a major leading cause of cancer death among men of all races. In order to treat prostate cancer, drug combinations are often applied. Drug combinations target at different pathways of cells can potentially lead to higher efficacy and lower toxicity due to drug synergy. In this paper, we sequentially applied a two-level design and a follow-up orthogonal array composite design (OACD) to investigate combinations of five anti-cancer drugs, namely, doxorubicin, docetaxel, paclitaxel, cis-dichlorodiamine platinum and dihydroartemisinin. Our initial screening using a two-level full factorial design identified doxorubicin and docetaxel as the most significant drugs. A follow-up experiment with an OACD revealed more complicated drug interactions among these 5 anti-cancer drugs. Quadratic effects of doxorubicin and paclitaxel appeared to be significant. A further investigation on contour plots of all the two-drug pairs indicated that combination of doxorubicin and docetaxel are the most effective companion, while the combination of cis-dichlorodiamine platinum and dihydroartemisinin showed unknown antagonistic effects which diminished the individual drug anti-cancer efficacy. These observations have significant practical implications in the understanding of anti-cancer drug mechanism that can facilitate clinical practice of better drug combinations.
Insights
Investigating five anti-cancer drugs for prostate cancer treatment, this study found doxorubicin and docetaxel combinations are most effective. Other drug interactions were complex, with some showing antagonistic effects, impacting treatment efficacy.
Area of Science:
- Oncology
- Pharmacology
- Biostatistics
Background:
- Prostate cancer is a leading cause of cancer death in US men.
- Drug combinations are utilized to improve efficacy and reduce toxicity in cancer therapy.
- Drug synergy can enhance anti-cancer effects by targeting multiple cellular pathways.
Purpose of the Study:
- To investigate the efficacy of combinations of five anti-cancer drugs for prostate cancer.
- To identify optimal drug combinations and understand their interactions.
- To provide insights for improved clinical drug combination strategies.
Main Methods:
- Sequential application of a two-level full factorial design and an orthogonal array composite design (OACD).
- Screening of five anti-cancer drugs: doxorubicin, docetaxel, paclitaxel, cis-dichlorodiamine platinum, and dihydroartemisinin.
- Analysis of drug interactions, including individual drug effects, quadratic effects, and two-drug pair interactions using contour plots.
Main Results:
- Initial screening identified doxorubicin and docetaxel as the most significant drugs.
- Orthogonal array composite design revealed complex interactions among the five drugs.
- Doxorubicin and docetaxel combination demonstrated the highest efficacy.
- Quadratic effects of doxorubicin and paclitaxel were significant.
- Cis-dichlorodiamine platinum and dihydroartemisinin combination exhibited antagonistic effects, reducing anti-cancer efficacy.
Conclusions:
- The combination of doxorubicin and docetaxel is a highly effective treatment strategy for prostate cancer.
- Understanding complex drug interactions, including synergistic and antagonistic effects, is crucial for optimizing cancer therapy.
- These findings have significant implications for developing better drug combinations in clinical practice.
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