Leucovorin and fluorouracil plus oxaliplatin or leucovorin and fluorouracil plus irinotecan as individualized first-line therapy based on a drug sensitivity test

Ochiai,Takumi; Nishimura,Kazuhiko; Watanabe,Tomoo; Kitajima,Masayuki; Hashiguchi,Tadasuke; Nakatani,Akinori; Marusasa,Takashi; Muraki,Akira; Nagaoka,Isao; Futagawa,Shunji

doi:10.3892/etm_00000050

March-April 2010 Volume 1 Issue 2

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March-April 2010 Volume 1 Issue 2

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Article

Leucovorin and fluorouracil plus oxaliplatin or leucovorin and fluorouracil plus irinotecan as individualized first-line therapy based on a drug sensitivity test

Authors:
- Takumi Ochiai
- Kazuhiko Nishimura
- Tomoo Watanabe
- Masayuki Kitajima
- Tadasuke Hashiguchi
- Akinori Nakatani
- Takashi Marusasa
- Akira Muraki
- Isao Nagaoka
- Shunji Futagawa
View Affiliations / Copyright

Affiliations: Department of Surgery, Tobu Chiiki Hospital Tokyo Metropolitan Health and Medical Treatment Corporation, Tokyo 125-8512, Japan
Pages: 325-329
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Published online on: March 1, 2010

https://doi.org/10.3892/etm_00000050
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Abstract

The purpose of this study was to determine the effect of the addition of oxaliplatin (l-OHP) or irinotecan (SN-38) to 5-fluorouracil (5-FU) using the collagen gel droplet embedded culture-drug sensitivity test (CD-DST) to establish whether leucovorin plus 5-FU should be administered in combination with l-OHP (FOLFOX) or SN-38 (FOLFIRI) in individualized first-line chemotherapy for the treatment of advanced colorectal cancer (CRC). Specimens of primary tumors were obtained from 24 CRC patients who had received no preoperative chemotherapy. CD-DST was performed, and the inhibition rate (IR) was obtained under multiple incubation conditions. The effects of addition of l-OHP or SN-38 were evaluated for the same area under the concentration curve (AUC) of 5-FU based on linear regression analysis. Approximate expression and correlation coefficients (5-FU vs. 5-FU + l-OHP, 5-FU vs. 5-FU + SN-38; AUC of 5-FU=72 and 5-FU vs. 5-FU + l-OHP, 5-FU vs. 5-FU + SN-38; AUC of 5-FU=144) were y=0.94x+8.53 (R2=0.95, p<0.0004), y=0.77x+26.18 (R2=0.76, p<0.0004) and y=0.91x+10.90 (R2=0.94, p<0.0004), y=0.52x+44.61 (R2=0.60, p<0.0004), respectively. Approximate expression of 5-FU vs. 5-FU + l-OHP almost fit the regression line (y=x+b1). This suggests that addition of l-OHP yields a constant additive effect, independent of the IR of 5-FU. However, approximate expression of 5-FU vs. 5-FU + SN-38 fit the regression line (y=ax+b2, a<1, b2≥b1). This suggests that addition of SN-38 yields a greater additive effect due to the lower IR of 5-FU. These results indicate that FOLFIRI should be selected as the first-line chemotherapy for the treatment of poor responders to 5-FU.

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Journals

International Journal of Molecular Medicine

International Journal of Oncology

Molecular Medicine Reports

Oncology Reports

Experimental and Therapeutic Medicine

Oncology Letters

Biomedical Reports

Molecular and Clinical Oncology

World Academy of Sciences Journal

International Journal of Functional Nutrition

International Journal of Epigenetics

Medicine International

Leucovorin and fluorouracil plus oxaliplatin or leucovorin and fluorouracil plus irinotecan as individualized first-line therapy based on a drug sensitivity test

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