Impact of in vitro chemosensitivity test‑guided platinum‑based adjuvant chemotherapy on the surgical outcomes of patients with p‑stage IIIA non‑small cell lung cancer that underwent complete resection

Akazawa,Yuki; Higashiyama,Masahiko; Nishino,Kazumi; Uchida,Jyunji; Kumagai,Toru; Inoue,Takako; Fujiwara,Ayako; Tokunaga,Toshiteru; Okami,Jiro; Imamura,Fumio; Kodama,Ken; Kobayashi,Hisayuki

doi:10.3892/mco.2017.1340

Impact of in vitro chemosensitivity test‑guided platinum‑based adjuvant chemotherapy on the surgical outcomes of patients with p‑stage IIIA non‑small cell lung cancer that underwent complete resection

Authors:
- Yuki Akazawa
- Masahiko Higashiyama
- Kazumi Nishino
- Jyunji Uchida
- Toru Kumagai
- Takako Inoue
- Ayako Fujiwara
- Toshiteru Tokunaga
- Jiro Okami
- Fumio Imamura
- Ken Kodama
- Hisayuki Kobayashi
View Affiliations

Affiliations: Department of Thoracic Oncology, Osaka International Cancer Institute (formerly, Osaka Medical Center for Cancer and Cardiovascular Diseases), Osaka 541‑8567, Japan, Department of General Thoracic Surgery, Osaka International Cancer Institute (formerly, Osaka Medical Center for Cancer and Cardiovascular Diseases), Osaka 541‑8567, Japan, Department of Surgery, Yao Municipal Hospital, Osaka 581‑0069, Japan, Technical Research Laboratory, Kurabo Industries Ltd., Osaka 541‑8581, Japan
Published online on: July 24, 2017 https://doi.org/10.3892/mco.2017.1340
Pages: 327-335
Copyright: © Akazawa et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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

The impact of in vitro chemosensitivity test‑guided platinum‑based adjuvant chemotherapy on the surgical outcomes of patients undergoing complete resection for locally advanced non‑small cell lung cancer (NSCLC) has yet to be elucidated. In the present study, the utility of adjuvant chemotherapy based on the collagen gel droplet embedded culture drug sensitivity test (CD‑DST) in patients with p (pathology)‑stage IIIA NSCLC was retrospectively analyzed. A series of 39 patients that had received platinum‑based adjuvant chemotherapy following complete resection between 2007 and 2012 were enrolled. Their surgical specimens were subjected to the CD‑DST. The patients were subsequently classified into two groups on the basis of in vitro anti‑cancer drug sensitivity data obtained using the CD‑DST: The sensitive group (25 patients) were treated with regimens including one or two of the anti‑cancer drug(s) that were indicated to be effective by the CD‑DST, whereas the non‑sensitive group (14 patients) were treated with chemotherapy regimens that did not include any CD‑DST‑selected anti‑cancer drugs. There were no significant differences in the background characteristics of the two groups [including in respect of the pathological TN (tumor‑lymph node) stage, tumor histology, epidermal growth factor receptor mutation status, the frequency of each chemotherapy regimen, and the number of administered cycles]. The 5‑year disease‑free survival (DFS) rate of the sensitive group was 32.3%, whereas that of the non‑sensitive group was 14.3% (P=0.037). In contrast, no difference in overall survival (OS) was observed (P=0.76). Multivariate analysis revealed that adjuvant chemotherapy based on the CD‑DST had a significant favorable effect on the DFS (P=0.01). Therefore, the present study has demonstrated that CD‑DST data obtained from surgical specimens aid the selection of effective platinum‑based adjuvant chemotherapy regimens for patients undergoing complete resection for p‑stage IIIA NSCLC. The use of CD‑DST‑guided platinum‑based regimens may have a beneficial impact on the DFS of such patients.

View Figures

View References

1	Le Chevalier T, Arriagada R, Pignon JP and Scagliotti GV: Should adjuvant chemotherapy become standard treatment in all patients with resected non-small-cell lung cancer? Lancet Oncol. 6:182–184. 2005. View Article : Google Scholar : PubMed/NCBI
2	Sugimura H, Nichols FC, Yang P, Allen MS, Cassivi SD, Deschamps C, Williams BA and Pairolero PC: Survival after recurrent nonsmall-cell lung cancer after complete pulmonary resection. Ann Thorac Surg. 83:409–418. 2007. View Article : Google Scholar : PubMed/NCBI
3	Xie Y and Minna JD: Non-small-cell lung cancer mRNA expression signature predicting response to adjuvant chemotherapy. J Clin Oncol. 28:4404–4407. 2010. View Article : Google Scholar : PubMed/NCBI
4	Leong D, Rai R, Nguyen B, Lee A and Yip D: Advances in adjuvant systemic therapy for non-small-cell lung cancer. World J Clin Oncol. 5:633–645. 2014. View Article : Google Scholar : PubMed/NCBI
5	Arriagada R, Bergman B, Dunant A, Le Chevalier T, Pignon JP and Vansteenkiste J: International Adjuvant Lung Cancer Trial Collaborative Group: Cisplatin-based adjuvant chemotherapy in patients with completely resected non-small-cell lung cancer. N Engl J Med. 350:351–360. 2004. View Article : Google Scholar : PubMed/NCBI
6	Winton T, Livingston R, Johnson D, Rigas J, Johnston M, Butts C, Cormier Y, Goss G, Inculet R, Vallieres E, et al: Vinorelbine plus cisplatin vs. observation in resected non-small-cell lung cancer. N Engl J Med. 352:2589–2597. 2005. View Article : Google Scholar : PubMed/NCBI
7	Douillard JY, Rosell R, De Lena M, Carpagnano F, Ramlau R, Gonzáles-Larriba JL, Grodzki T, Pereira JR, Le Groumellec A, Lorusso V, et al: Adjuvant vinorelbine plus cisplatin versus observation in patients with completely resected stage IB-IIIA non-small-cell lung cancer (Adjuvant Navelbine International Trialist Association [ANITA)]: A randomised controlled trial. Lancet Oncol. 7:719–727. 2006. View Article : Google Scholar : PubMed/NCBI
8	Pignon JP, Tribodet H, Scagliotti GV, Douillard JY, Shepherd FA, Stephens RJ, Dunant A, Torri V, Rosell R, Seymour L, et al: Lung adjuvant cisplatin evaluation: A pooled analysis by the LACE Collaborative Group. J Clin Oncol. 26:3552–3559. 2008. View Article : Google Scholar : PubMed/NCBI
9	Fukuoka M, Wu YL, Thongprasert S, Sunpaweravong P, Leong SS, Sriuranpong V, Chao TY, Nakagawa K, Chu DT, Saijo N, et al: Biomarker analyses and final overall survival results from a phase III, randomized, open-label, first-line study of gefitinib versus carboplatin/paclitaxel in clinically selected patients with advanced non-small-cell lung cancer in Asia (IPASS). J Clin Oncol. 29:2866–2874. 2011. View Article : Google Scholar : PubMed/NCBI
10	Cameron L and Solomon B: New treatment options for ALK-rearranged non-small cell lung cancer. Curr Treat Options Oncol. 16:492015. View Article : Google Scholar : PubMed/NCBI
11	Lord RV, Brabender J, Gandara D, Alberola V, Camps C, Domine M, Cardenal F, Sánchez JM, Gumerlock PH, Tarón M, et al: Low ERCC1 expression correlates with prolonged survival after cisplatin plus gemcitabine chemotherapy in non-small cell lung cancer. Clin Cancer Res. 8:2286–2291. 2002.PubMed/NCBI
12	Gong W, Zhang X, Wu J, Chen L, Li L, Sun J, Lv Y, Wei X, Du Y, Jin H and Dong J: RRM1 expression and clinical outcome of gemcitabine-containing chemotherapy for advanced non-small-cell lung cancer: A meta-analysis. Lung Cancer. 75:374–380. 2012. View Article : Google Scholar : PubMed/NCBI
13	Sève P and Dumontet C: Is class III beta-tubulin a predictive factor in patients receiving tubulin-binding agents? Lancet Oncol. 9:168–175. 2008. View Article : Google Scholar : PubMed/NCBI
14	Hirai Y, Yoshimasu T, Oura S, Ota F, Naito K, Nishiguchi H, Hashimoto S and Okamura Y: Is class III beta-tubulin a true predictive marker of sensitivity to vinorelbine in non-small cell lung cancer? Chemosensitivity data evidence. Anticancer Res. 31:999–1005. 2011.PubMed/NCBI
15	Wallerek S and Sørensen JB: Biomarkers for efficacy of adjuvant chemotherapy following complete resection in NSCLC stages I–IIIA. Eur Respir Rev. 24:340–355. 2015. View Article : Google Scholar : PubMed/NCBI
16	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
17	Higashiyama M, Oda K, Okami J, Maeda J, Kodama K, Imamura F, Minamikawa K, Takano T and Kobayashi H: Prediction of chemotherapeutic effect on postoperative recurrence by in vitro anticancer drug sensitivity testing in non-small cell lung cancer patients. Lung Cancer. 68:472–477. 2010. View Article : Google Scholar : PubMed/NCBI
18	Takebayashi K, Mekata E, Sonoda H, Shimizu T, Endo Y and Tani T: Clinical potential of the anticancer drug sensitivity test for patients with synchronous stage IV colorectal cancer. Cancer Chemother Pharmacol. 72:217–222. 2013. View Article : Google Scholar : PubMed/NCBI
19	Naitoh H, Yamamoto H, Murata S, Kobayashi H, Inoue K and Tani T: Stratified phase II trial to establish the usefulness of the collagen gel droplet embedded culture-drug sensitivity test (CD-DST) for advanced gastric cancer. Gastric Cancer. 17:630–637. 2014. View Article : Google Scholar : PubMed/NCBI
20	Ochiai T, Nishimura K, Watanabe T, Kitajima M, Nakatani A, Inou T, Washio M, Sakuyama N, Sato T, Kishine K, et al: Individualized chemotherapy for colorectal cancer based on the collagen gel droplet-embedded drug sensitivity test. Oncol Lett. 4:621–624. 2012.PubMed/NCBI
21	Higashiyama M, Kodama K, Yokouchi H, Takami K, Nakagawa H, Imamura F, Minamigawa K and Kobayashi H: Cisplatin-based chemotherapy for postoperative recurrence in non-small cell lung cancer patients: Relation of the in vitro chemosensitive test to clinical response. Oncol Rep. 8:279–283. 2001.PubMed/NCBI
22	Kawamura M, Gika M, Abiko T, Inoue Y, Oyama T, Izumi Y, Kobayashi H and Kobayashi K: Clinical evaluation of chemosensitivity testing for patients with unresectable non-small cell lung cancer (NSCLC) using collagen gel droplet embedded culture drug sensitivity test (CD-DST). Cancer Chemother Pharmacol. 59:507–513. 2007. View Article : Google Scholar : PubMed/NCBI
23	Maejima K, Tokunaga A, Kiyama T, Kanno H, Bou H, Watanabe M, Suzuki H and Uchida E: Chemosensitivity test for 5-fluorouracil and 5-chloro-2, 4-dihydroxypyridine predicts outcome of gastric cancer patients receiving S-1 postoperatively. Gastric Cancer. 13:231–237. 2010. View Article : Google Scholar : PubMed/NCBI
24	Tanahashi M, Niwa H, Yukiue H, Suzuki E, Haneda H and Yoshii N: Adjuvant chemotherapy based on the in vitro histoculture drug response assay for non-small cell lung cancer improves survival. J Thorac Oncol. 5:1376–1381. 2010. View Article : Google Scholar
25	Chang WJ, Sun JM, Lee JY, Ahn JS, Ahn MJ and Park K: A retrospective comparison of adjuvant chemotherapeutic regimens for non-small cell lung cancer (NSCLC): Paclitaxel plus carboplatin versus vinorelbine plus cisplatin. Lung Cancer. 84:51–55. 2014. View Article : Google Scholar : PubMed/NCBI
26	Kubota K, Watanabe K, Kunitoh H, Noda K, Ichinose Y, Katakami N, Sugiura T, Kawahara M, Yokoyama A, Yokota S, et al: Phase III randomized trial of docetaxel plus cisplatin versus vindesine plus cisplatin in patients with stage IV non-small-cell lung cancer: The Japanese Taxotere lung cancer study group. J Clin Oncol. 22:254–261. 2004. View Article : Google Scholar : PubMed/NCBI
27	Uramoto H, Nakanishi R, Nagashima A, Uchiyama A, Inoue M, Osaki T, Yoshimatsu T, Sakata H, Nakanishi K and Yasumoto K: A randomized phase II trial of adjuvant chemotherapy with bi-weekly carboplatin plus paclitaxel versus carboplatin plus gemcitabine in patients with completely resected non-small cell lung cancer. Anticancer Res. 30:4695–4699. 2010.PubMed/NCBI
28	Scagliotti GV, Parikh P, von Pawel J, Biesma B, Vansteenkiste J, Manegold C, Serwatowski P, Gatzemeier U, Digumarti R, Zukin M, et al: Phase III study comparing cisplatin plus gemcitabine with cisplatin plus pemetrexed in chemotherapy-naive patients with advanced-stage non-small-cell lung cancer. J Clin Oncol. 26:3543–3551. 2008. View Article : Google Scholar : PubMed/NCBI
29	Aoki T, Ebihara A, Yogo Y, Suemasu K and Sakamaki F: Analysis of continuous first-line treatment with docetaxel and carboplatin for advanced non-small cell lung cancer. Oncol Lett. 7:1771–1777. 2014.PubMed/NCBI
30	Janjigian YY, Park BJ, Zakowski MF, Ladanyi M, Pao W, D'Angelo SP, Kris MG, Shen R, Zheng J and Azzoli CG: Impact on disease-free survival of adjuvant erlotinib or gefitinib in patients with resected lung adenocarcinomas that harbor EGFR mutations. J Thorac Oncol. 6:569–575. 2011. View Article : Google Scholar : PubMed/NCBI
31	D'Angelo SP, Janjigian YY, Ahye N, Riely GJ, Chaft JE, Sima CS, Shen R, Zheng J, Dycoco J, Kris MG, et al: Distinct clinical course of EGFR-mutant resected lung cancers: Results of testing of 1118 surgical specimens and effects of adjuvant gefitinib and erlotinib. J Thorac Oncol. 7:1815–1822. 2012. View Article : Google Scholar : PubMed/NCBI
32	Goss GD, O'Callaghan C, Lorimer I, Tsao MS, Masters GA, Jett J, Edelman MJ, Lilenbaum R, Choy H, Khuri F, et al: Gefitinib versus placebo in completely resected non-small-cell lung cancer: Results of the NCIC CTG BR19 study. J Clin Oncol. 31:3320–3326. 2013. View Article : Google Scholar : PubMed/NCBI
33	Lv C, An C, Feng Q, Ma Y, Li S, Wang J, Zhang J, Wang X, Yan S, Fang J, et al: A retrospective study of stage I to IIIa lung adenocarcinoma after resection: What is the optimal adjuvant modality for patients with an EGFR mutation? Clin Lung Cancer. 16:e173–e181. 2015. View Article : Google Scholar : PubMed/NCBI
34	Olaussen KA, Dunant A, Fouret P, Brambilla E, André F, Haddad V, Taranchon E, Filipits M, Pirker R, Popper HH, et al: DNA repair by ERCC1 in non-small-cell lung cancer and cisplatin-based adjuvant chemotherapy. N Engl J Med. 355:983–991. 2006. View Article : Google Scholar : PubMed/NCBI
35	Friboulet L, Olaussen KA, Pignon JP, Shepherd FA, Tsao MS, Graziano S, Kratzke R, Douillard JY, Seymour L, Pirker R, et al: ERCC1 isoform expression and DNA repair in non-small-cell lung cancer. N Engl J Med. 368:1101–1110. 2013. View Article : Google Scholar : PubMed/NCBI
36	Kurbacher CM and Cree IA: Chemosensitivity testing using microplate adenosine triphosphate-based luminescence measurements. Methods Mol Med. 110:101–120. 2005.PubMed/NCBI
37	Moon YW, Choi SH, Kim YT, Sohn JH, Chang J, Kim SK, Park MS, Chung KY, Lee HJ and Kim JH: Adenosine triphosphate-based chemotherapy response assay (ATP-CRA)-guided platinum-based 2-drug chemotherapy for unresectable nonsmall-cell lung cancer. Cancer. 109:1829–1835. 2007. View Article : Google Scholar : PubMed/NCBI
38	Yoshimasu T, Oura S, Hirai I, Tamaki T, Kokawa Y, Hata K, Ohta F, Nakamura R, Kawago M, Tanino H, et al: Data acquisition for the histoculture drug response assay in lung cancer. J Thorac Cardiovasc Surg. 133:303–308. 2007. View Article : Google Scholar : PubMed/NCBI
39	Tanigawa N, Yamaue H, Ohyama S, Sakuramoto S, Inada T, Kodera Y, Kitagawa Y, Omura K, Terashima M, Sakata Y, et al: Exploratory phase II trial in a multicenter setting to evaluate the clinical value of a chemosensitivity test in patients with gastric cancer (JACCRO-GC 04, Kubota memorial trial). Gastric Cancer. 19:350–360. 2016. View Article : Google Scholar : PubMed/NCBI
40	Nakamura R, Saikawa Y, Kubota T, Kumagai A, Kiyota T, Ohashi M, Yoshida M, Otani Y, Kumai K and Kitajima M: Role of the MTT chemosensitivity test in the prognosis of gastric cancer patients after postoperative adjuvant chemotherapy. Anticancer Res. 26:1433–1437. 2006.PubMed/NCBI
41	Fujita Y, Hiramatsu M, Kawai M, Nishimura H, Miyamoto A and Tanigawa N: Histoculture drug response assay predicts the postoperative prognosis of patients with esophageal cancer. Oncol Rep. 21:499–505. 2009.PubMed/NCBI
42	Higashiyama M, Okami J, Maeda J, Tokunaga T, Fujiwara A, Kodama K, Imamura F and Kobayashi H: Differences in chemosensitivity between primary and paired metastatic lung cancer tissues: In vitro analysis based on the collagen gel droplet embedded culture drug test (CD-DST). J Thorac Dis. 4:40–47. 2012.PubMed/NCBI
43	Maniwa Y, Yoshimura M, Hashimoto S, Takata M and Nishio W: Chemosensitivity of lung cancer: Differences between the primary lesion and lymph node metastasis. Oncol Lett. 1:345–349. 2010. View Article : Google Scholar : PubMed/NCBI