Clinical predictive value of in vitro anticancer drug sensitivity test for the therapeutic effect of adjuvant chemotherapy in patients with stage II-III colorectal cancer

Mekata,Eiji; Sonoda,Hiromichi; Shimizu,Tomoharu; Tatsuta,Takeshi; Yamaguchi,Tomohiro; Endo,Yoshihiro; Tani,Tohru

doi:10.3892/mco.2013.102

Clinical predictive value of in vitro anticancer drug sensitivity test for the therapeutic effect of adjuvant chemotherapy in patients with stage II-III colorectal cancer

Authors:
- Eiji Mekata
- Hiromichi Sonoda
- Tomoharu Shimizu
- Takeshi Tatsuta
- Tomohiro Yamaguchi
- Yoshihiro Endo
- Tohru Tani
View Affiliations

Affiliations: Department of Surgery, Shiga University of Medical Science, Otsu, Shiga 520-2192, Japan
Published online on: April 11, 2013 https://doi.org/10.3892/mco.2013.102
Pages: 763-767

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Clinically useful predictors of the efficacy of adjuvant chemotherapy following curative colorectal surgery remain to be determined. In the present study, we investigated the clinical utility of the collagen gel droplet‑embedded culture drug sensitivity test (CD‑DST) as a predictor of the therapeutic response to 5‑fluorouracil (5‑FU)‑based adjuvant chemotherapy in patients with stage II‑III colorectal cancer. CD‑DST was conducted using tumor samples surgically obtained from 189 patients. The therapeutic effect of 5‑FU‑based regimens between high (high‑group) and low (low‑group) sensitivity groups and a group that did not receive chemotherapy [CTx(-) group] was compared. CD‑DST was successfully performed in 151 out of the 189 patients (79.9%), 87 of whom received 5‑FU‑based adjuvant chemotherapy after surgery. Twenty‑seven of these 87 patients (31.0%) were classified as the high‑group and the remaining 60 (69.0%) as the low‑group. The 5‑year recurrence‑free survival (RFS) in the high‑group was significantly higher compared to that in the low‑ and the CTx(-) groups. No differences in the 5‑year RFS were observed between the low‑ and CTx(-) groups. In conclusion, CD‑DST appears to be useful for predicting the therapeutic response to 5‑FU‑based adjuvant chemotherapy in patients with stage II‑III colorectal cancer.

View Figures

View References

1.	André T, Boni C, Mounedji-Boudiaf L, et al: Oxaliplatin, fluorouracil, and leucovorin as adjuvant treatment for colon cancer. N Engl J Med. 350:2343–2351. 2004.
2.	Kuebler JP, Wieand HS, O’Connell MJ, et al: Oxaliplatin combined with weekly bolus fluorouracil and leucovorin as surgical adjuvant chemotherapy for stage II and III colon cancer: results from NSABP C-07. J Clin Oncol. 25:2198–2204. 2007. View Article : Google Scholar
3.	Japanese Society for Cancer of the Colon and Rectum: JSCCR Guidelines 2010 for the Treatment of Colorectal Cancer. Kanehara & Co, Ltd.; Tokyo: 2010
4.	Watanabe T, Wu TT, Catalano PJ, et al: Molecular predictors of survival after adjuvant chemotherapy for colon cancer. N Engl J Med. 344:1196–1206. 2001. View Article : Google Scholar : PubMed/NCBI
5.	Sargent DJ, Marsoni S, Monges G, et al: Defective mismatch repair as a predictive marker for lack of efficacy of fluorouracil-based adjuvant therapy in colon cancer. J Clin Oncol. 28:3219–3226. 2010. View Article : Google Scholar : PubMed/NCBI
6.	Sinicrope FA, Foster NR, Thibodeau SN, et al: DNA mismatch repair status and colon cancer recurrence and survival in clinical trials of 5-fluorouracil-based adjuvant therapy. J Natl Cancer Inst. 103:863–875. 2011. View Article : Google Scholar : PubMed/NCBI
7.	Tsuji S, Midorikawa Y, Takahashi T, Yagi K, Takayama T, Yoshida K, Sugiyama Y and Aburatani H: Potential responders to FOLFOX therapy for colorectal cancer by Random Forests analysis. Br J Cancer. 106:126–132. 2012. View Article : Google Scholar : PubMed/NCBI
8.	Kobayashi H: Collagen gel droplet culture method to examine in vitro chemosensitivity. Methods Mol Med. 110:59–67. 2005.PubMed/NCBI
9.	Yabushita H, Ohnishi M, Komiyama M, et al: Usefulness of collagen gel droplet embedded culture drug sensitivity testing in ovarian cancer. Oncol Rep. 12:307–311. 2004.PubMed/NCBI
10.	Mori S, Kunieda K, Sugiyama Y and Saji S: Prediction of 5-fluorouracil and cisplatin synergism for advanced gastrointestinal cancers using a collagen gel droplet embedded culture. Surg Today. 33:577–583. 2003. View Article : Google Scholar : PubMed/NCBI
11.	Okumura K, Shiomi H, Mekata E, et al: Correlation between chemosensitivity and mRNA expression level of 5-fluorouracil-related metabolic enzymes during liver metastases of colorectal cancer. Oncol Rep. 15:875–882. 2006.
12.	Shimizu T, Murata S, Mekata E, et al: Clinical potential of an antitumor drug sensitivity test and diffusion-weighted MRI in a patient with a recurrent solid pseudopapillary tumor of the pancreas. J Gastroenterol. 42:918–922. 2007. View Article : Google Scholar : PubMed/NCBI
13.	Japanese Society for Cancer of the Colon and Rectum: General Rules for Clinical and Pathological Studies on Cancer of the Colon, Rectum and Anus. 7th edition. Kanehara & Co; Tokyo: 2006
14.	Kobayashi H, Higashiyama M, Minamigawa K, et al: Examination of in vitro chemosensitivity test using collagen gel droplet culture method with colorimetric endpoint quantification. Jpn J Cancer Res. 92:203–210. 2001. View Article : Google Scholar : PubMed/NCBI
15.	Kobayashi H: Development of a new in vitro chemosensitivity test using collagen gel droplet embedded culture and image analysis for clinical usefulness. Recent Results Cancer Res. 161:48–61. 2003. View Article : Google Scholar : PubMed/NCBI
16.	Higashiyama M, Oda K, Okami J, et al: In vitro-chemosensitivity test using the collagen gel droplet embedded culture drug test (CD-DST) for malignant pleural mesothelioma: possibility of clinical application. Ann Thorac Cardiovasc Surg. 14:355–362. 2008.
17.	Shimada Y, Hamaguchi T, Moriya Y, et al: Randomized phase III study of adjuvant chemotherapy with oral uracil and tegafur plus leucovorin versus intravenous fluorouracil and levofolinate in patients (pts) with stage III colon cancer (CC): Final results of Japan Clinical Oncology Group study (JCOG0205). J Clin Oncol. 30:(Suppl; abs. 3524),. 2012.
18.	Benson AB III, Schrag D, Somerfield MR, et al: American Society of Clinical Oncology recommendations on adjuvant chemotherapy for stage II colon cancer. J Clin Oncol. 22:3408–3419. 2004. View Article : Google Scholar : PubMed/NCBI
19.	Isogai A, Nagaya M, Matsumoto H, et al: An anticancer drug sensitivity test to determine the effectiveness of UFT as postoperative adjuvant chemotherapy for patients with stage III colorectal cancer. Surgery. 142:741–748. 2007. View Article : Google Scholar : PubMed/NCBI
20.	Hoffman RM: In vitro sensitivity assays in cancer: a review, analysis, and prognosis. J Clin Lab Anal. 5:133–143. 1991. View Article : Google Scholar : PubMed/NCBI
21.	Kondo T, Imamura T and Ichihashi H: In vitro test for sensitivity of tumor to carcinostatic agents. Gann. 57:113–121. 1966.PubMed/NCBI
22.	Mosmann T: Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods. 65:55–63. 1983. View Article : Google Scholar : PubMed/NCBI