J Gastric Cancer.  2010 Dec;10(4):155-161.

In Vitro Adenosine Triphosphate Based Chemotherapy Response Assay in Gastric Cancer

• Park S
• Woo Y
• Kim H
• Lee YC
• Choi S
• Hyung WJ
• Noh SH

Abstract

PURPOSE
The purpose of this study was to investigate the reliability and the clinical applicability of the adenosine-triphosphate-based chemotherapy response assay (ATP-CRA) as a method of determining in vitro chemosensitivity in patients with gastric cancer.
MATERIALS AND METHODS
A total of 243 gastric cancer tissue samples were obtained from gastrectomies performed between February 2007 and January 2010. We evaluated the effectiveness of the ATP-CRA assay in determining the chemosensitivity of gastric cancer specimens using eleven chemotherapeutic agents - etoposide, doxorubicin, epirubicin, mytomicin, 5-fluorouracil, oxaliplatin, irinotecan, docetaxel, paclitaxel, methotraxate, and cisplatin - for chemosensitivity studies using ATP-CRA. We assessed the failure rate, the cell death rate, and the chemosensitivity index.
RESULTS
The failure rate of ATP-CRA was 1.6% (4/243). The mean coefficient of variation for triplicate ATP measurements was 6.5%. Etoposide showed the highest cell death rate (35.9%) while methotrexate showed the lowest (16.6%). The most active chemotherapeutic agent was etoposide, which most frequently ranked highest in the chemosensitivity test: 31.9% (51/160). Oxaliplatin was more active against early gastric cancers than advanced gastric cancers, whereas docetaxel was more active against advanced cancers. The lymph node negative group showed a significantly higher cell death rate than the lymph node positive group when treated with doxorubicin, epirubicin, and mitomycin.
CONCLUSIONS
ATP-CRA is a stable and clinically applicable in vitro chemosensitivity test with a low failure rate. The clinical usefulness of ATP-CRA should be evaluated by prospective studies comparing the regimen guided by ATP-CRA with an empirical regimen.

Keyword

Stomach neoplasms; Chemosensitivity assay; ATP based chemoresponse

MeSH Terms

Adenosine
Adenosine Triphosphate
Camptothecin
Cell Death
Cisplatin
Doxorubicin
Epirubicin
Etoposide
Fluorouracil
Gastrectomy
Humans
Lymph Nodes
Methotrexate
Organoplatinum Compounds
Paclitaxel
Polyphosphates
Stomach Neoplasms
Taxoids
Adenosine
Adenosine Triphosphate
Camptothecin
Cisplatin
Doxorubicin
Epirubicin
Etoposide
Fluorouracil
Methotrexate
Organoplatinum Compounds
Paclitaxel
Polyphosphates
Taxoids

Reference

1. Bosetti C, Bertuccio P, Levi F, Lucchini F, Negri E, La Vecchia C. Cancer mortality in the European Union, 1970-2003, with a joinpoint analysis. Ann Oncol. 2008. 19:631–640.

2. Accessed January 4, 2010. http://www.nhic.or.kr/.

3. Yoo CH, Noh SH, Shin DW, Choi SH, Min JS. Recurrence following curative resection for gastric carcinoma. Br J Surg. 2000. 87:236–242.

4. Macdonald JS, Smalley SR, Benedetti J, Hundahl SA, Estes NC, Stemmermann GN, et al. Chemoradiotherapy after surgery compared with surgery alone for adenocarcinoma of the stomach or gastroesophageal junction. N Engl J Med. 2001. 345:725–730.

5. Macdonald JS, Fleming TR, Peterson RF, Berenberg JL, Mc-Clure S, Chapman RA, et al. Adjuvant chemotherapy with 5-FU, adriamycin, and mitomycin-C (FAM) versus surgery alone for patients with locally advanced gastric adenocarcinoma: A Southwest Oncology Group study. Ann Surg Oncol. 1995. 2:488–494.

6. Höhler T, Möhler M. New chemotherapeutic options in advanced gastric cancer. Onkologie. 2003. 26:Suppl 7. 54–59.

7. Neale MH, Myatt NE, Khoury GG, Weaver P, Lamont A, Hungerford JL, et al. Comparison of the ex vivo chemosensitivity of uveal and cutaneous melanoma. Melanoma Res. 2001. 11:601–609.

8. Kang SM, Park MS, Chang J, Kim SK, Kim H, Shin DH, et al. A feasibility study of adenosine triphosphate-based chemotherapy response assay (ATP-CRA) as a chemosensitivity test for lung cancer. Cancer Res Treat. 2005. 37:223–227.

9. Cree IA, Kurbacher CM, Untch M, Sutherland LA, Hunter EM, Subedi AM, et al. Correlation of the clinical response to chemotherapy in breast cancer with ex vivo chemosensitivity. Anticancer Drugs. 1996. 7:630–635.

10. Huh JW, Park YA, Lee KY, Sohn SK. Heterogeneity of adenosine triphosphate-based chemotherapy response assay in colorectal cancer-secondary publication. Yonsei Med J. 2009. 50:697–703.

11. Konecny G, Crohns C, Pegram M, Felber M, Lude S, Kurbacher C, et al. Correlation of drug response with the ATP tumorchemosensitivity assay in primary FIGO stage III ovarian cancer. Gynecol Oncol. 2000. 77:258–263.

12. Weisenthal LM, Dill PL, Finklestein JZ, Duarte TE, Baker JA, Moran EM. Laboratory detection of primary and acquired drug resistance in human lymphatic neoplasms. Cancer Treat Rep. 1986. 70:1283–1295.

13. Bird MC, Bosanquet AG, Gilby ED. In vitro determination of tumour chemosensitivity in haematological malignancies. Hematol Oncol. 1985. 3:1–10.

14. Bogden AE, Griffin W, Reich SD, Costanza ME, Cobb WR. Predictive testing with the subrenal capsule assay. Cancer Treat Rev. 1984. 11:Suppl A. 113–124.

15. Rozencweig M, Hofmann V, Sanders C, Rombaut W, Früh U, Martz G. In vitro growth of human malignancies in a cloning assay. Recent Results Cancer Res. 1984. 94:1–7.

16. Tanigawa N, Kern DH, Hikasa Y, Morton DL. Rapid assay for evaluating the chemosensitivity of human tumors in soft agar culture. Cancer Res. 1982. 42:2159–2164.

17. Carmichael J, DeGraff WG, Gazdar AF, Minna JD, Mitchell JB. Evaluation of a tetrazolium-based semiautomated colorimetric assay: assessment of chemosensitivity testing. Cancer Res. 1987. 47:936–942.

18. Vescio RA, Redfern CH, Nelson TJ, Ugoretz S, Stern PH, Hoffman RM. In vivo-like drug responses of human tumors growing in three-dimensional gel-supported primary culture. Proc Natl Acad Sci USA. 1987. 84:5029–5033.

19. Freeman AE, Hoffman RM. In vivo-like growth of human tumors in vitro. Proc Natl Acad Sci USA. 1986. 83:2694–2698.

20. Von Hoff DD, Clark GM, Stogdill BJ, Sarosdy MF, O'Brien MT, Casper JT, et al. Prospective clinical trial of a human tumor cloning system. Cancer Res. 1983. 43:1926–1931.

21. Von Hoff DD, Kronmal R, Salmon SE, Turner J, Green JB, Bonorris JS, et al. A Southwest Oncology Group study on the use of a human tumor cloning assay for predicting response in patients with ovarian cancer. Cancer. 1991. 67:20–27.

22. Xu JM, Song ST, Tang ZM, Jiang ZF, Liu XQ, Zhou L, et al. Predictive chemotherapy of advanced breast cancer directed by MTT assay in vitro. Breast Cancer Res Treat. 1999. 53:77–85.

23. Schrag D, Garewal HS, Burstein HJ, Samson DJ, Von Hoff DD, Somerfield MR. American Society of Clinical Oncology Technology Assessment: chemotherapy sensitivity and resistance assays. J Clin Oncol. 2004. 22:3631–3638.

24. Cunningham D, Allum WH, Stenning SP, Thompson JN, Van de Velde CJ, Nicolson M, et al. Perioperative chemotherapy versus surgery alone for resectable gastroesophageal cancer. N Engl J Med. 2006. 355:11–20.

25. Neri B, Cini G, Andreoli F, Boffi B, Francesconi D, Mazzanti R, et al. Randomized trial of adjuvant chemotherapy versus control after curative resection for gastric cancer: 5-year follow-up. Br J Cancer. 2001. 84:878–880.

26. Sakuramoto S, Sasako M, Yamaguchi T, Kinoshita T, Fujii M, Nashimoto A, et al. ACTS-GC Group. Adjuvant chemotherapy for gastric cancer with S-1, an oral fluoropyrimidine. N Engl J Med. 2007. 357:1810–1820.

27. Kodera Y, Ito S, Fujiwara M, Mochizuki Y, Ohashi N, Ito Y, et al. In vitro chemosensitivity test to predict chemosensitivity for paclitaxel, using human gastric carcinoma tissues. Int J Clin Oncol. 2006. 11:449–453.

28. Iwahashi M, Nakamori M, Nakamura M, Noguchi K, Ueda K, Nakatani Y, et al. Individualized adjuvant chemotherapy guided by chemosensitivity test sequential to extended surgery for advanced gastric cancer. Anticancer Res. 2005. 25:3453–3459.

29. Park JY, Kim YS, Bang S, Hyung WJ, Noh SH, Choi SH, et al. ATP-based chemotherapy response assay in patients with unresectable gastric cancer. Oncology. 2007. 73:439–440.

30. Lee JH. The results of the ATP Based chemotherapy response assay in gastric cancer tissues. J Korean Gastric Cancer Assoc. 2007. 7:160–166.