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      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

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          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.

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          Cisplatin-based adjuvant chemotherapy in patients with completely resected non-small-cell lung cancer.

          On the basis of a previous meta-analysis, the International Adjuvant Lung Cancer Trial was designed to evaluate the effect of cisplatin-based adjuvant chemotherapy on survival after complete resection of non-small-cell lung cancer. We randomly assigned patients either to three or four cycles of cisplatin-based chemotherapy or to observation. Before randomization, each center determined the pathological stages to include, its policy for chemotherapy (the dose of cisplatin and the drug to be combined with cisplatin), and its postoperative radiotherapy policy. The main end point was overall survival. A total of 1867 patients underwent randomization; 36.5 percent had pathological stage I disease, 24.2 percent stage II, and 39.3 percent stage III. The drug allocated with cisplatin was etoposide in 56.5 percent of patients, vinorelbine in 26.8 percent, vinblastine in 11.0 percent, and vindesine in 5.8 percent. Of the 932 patients assigned to chemotherapy, 73.8 percent received at least 240 mg of cisplatin per square meter of body-surface area. The median duration of follow-up was 56 months. Patients assigned to chemotherapy had a significantly higher survival rate than those assigned to observation (44.5 percent vs. 40.4 percent at five years [469 deaths vs. 504]; hazard ratio for death, 0.86; 95 percent confidence interval, 0.76 to 0.98; P<0.03). Patients assigned to chemotherapy also had a significantly higher disease-free survival rate than those assigned to observation (39.4 percent vs. 34.3 percent at five years [518 events vs. 577]; hazard ratio, 0.83; 95 percent confidence interval, 0.74 to 0.94; P<0.003). There were no significant interactions with prespecified factors. Seven patients (0.8 percent) died of chemotherapy-induced toxic effects. Cisplatin-based adjuvant chemotherapy improves survival among patients with completely resected non-small-cell lung cancer. Copyright 2004 Massachusetts Medical Society
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            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

            Whether adjuvant chemotherapy improves survival of patients with non-small-cell lung cancer (NSCLC) is not known. We aimed to compare the effect of adjuvant vinorelbine plus cisplatin versus observation on survival in patients with completely resected NSCLC. 840 patients with stage IB-IIIA NSCLC from 101 centres in 14 countries were randomly assigned to observation (n=433) or to 30 mg/m(2) vinorelbine plus 100 mg/m(2) cisplatin (n=407). Postoperative radiotherapy was not mandatory and was undertaken according to every centre's policy. The primary endpoint was overall survival. Analysis was by intention to treat. This trial is registered as an International Standard Randomised Controlled Trial, number ISRCTN95053737. 367 patients in the chemotherapy group and 431 in the control group received their assigned treatment. 301 (36%) patients had stage IB disease, 203 (24%) had stage II disease, and 325 (39%) had stage IIIA disease. Tolerance to chemotherapy mainly included neutropenia in 335 (92%) patients and febrile neutropenia in 34 (9%); seven (2%) toxic deaths were also recorded. Compliance was greater with cisplatin than with vinorelbine (median dose intensity 89% [range 17-108] vs 59% [17-100]). After a median follow-up of 76 months (range 43-116), median survival was 65.7 months (95% CI 47.9-88.5) in the chemotherapy group and 43.7 (35.7-52.3) months in the observation group. Adjusted risk for death was significantly reduced in patients assigned chemotherapy compared with controls (hazard ratio 0.80 [95% CI 0.66-0.96]; p=0.017). Overall survival at 5 years with chemotherapy improved by 8.6%, which was maintained at 7 years (8.4%). Adjuvant vinorelbine plus cisplatin extends survival in patients with completely resected NSCLC, better defining indication of adjuvant chemotherapy.
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              Vinorelbine plus cisplatin vs. observation in resected non-small-cell lung cancer.

              We undertook to determine whether adjuvant vinorelbine plus cisplatin prolongs overall survival among patients with completely resected early-stage non-small-cell lung cancer. We randomly assigned patients with completely resected stage IB or stage II non-small-cell lung cancer to vinorelbine plus cisplatin or to observation. The primary end point was overall survival; principal secondary end points were recurrence-free survival and the toxicity and safety of the regimen. A total of 482 patients underwent randomization to vinorelbine plus cisplatin (242 patients) or observation (240); 45 percent of the patients had pathological stage IB disease and 55 percent had stage II, and all had an Eastern Cooperative Oncology Group performance status score of 0 or 1. In both groups, the median age was 61 years, 65 percent were men, and 53 percent had adenocarcinomas. Chemotherapy caused neutropenia in 88 percent of patients (including grade 3 febrile neutropenia in 7 percent) and death from toxic effects in two patients (0.8 percent). Nonhematologic toxic effects of chemotherapy were fatigue (81 percent of patients), nausea (80 percent), anorexia (55 percent), vomiting (48 percent), neuropathy (48 percent), and constipation (47 percent), but severe (grade 3 or greater) toxic effects were uncommon (<10 percent). Overall survival was significantly prolonged in the chemotherapy group as compared with the observation group (94 vs. 73 months; hazard ratio for death, 0.69; P=0.04), as was relapse-free survival (not reached vs. 46.7 months; hazard ratio for recurrence, 0.60; P<0.001). Five-year survival rates were 69 percent and 54 percent, respectively (P=0.03). Adjuvant vinorelbine plus cisplatin has an acceptable level of toxicity and prolongs disease-free and overall survival among patients with completely resected early-stage non-small-cell lung cancer. Copyright 2005 Massachusetts Medical Society.
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                Author and article information

                Journal
                Mol Clin Oncol
                Mol Clin Oncol
                MCO
                Molecular and Clinical Oncology
                D.A. Spandidos
                2049-9450
                2049-9469
                September 2017
                24 July 2017
                24 July 2017
                : 7
                : 3
                : 327-335
                Affiliations
                [1 ]Department of Thoracic Oncology, Osaka International Cancer Institute (formerly, Osaka Medical Center for Cancer and Cardiovascular Diseases), Osaka 541-8567, Japan
                [2 ]Department of Respiratory Medicine, Osaka General Medical Center, Osaka 558-8585, Japan
                [3 ]Department of General Thoracic Surgery, Osaka International Cancer Institute (formerly, Osaka Medical Center for Cancer and Cardiovascular Diseases), Osaka 541-8567, Japan
                [4 ]Department of Surgery, Yao Municipal Hospital, Osaka 581-0069, Japan
                [5 ]Technical Research Laboratory, Kurabo Industries Ltd., Osaka 541-8581, Japan
                Author notes
                Correspondence to: Professor Masahiko Higashiyama, Department of General Thoracic Surgery, Osaka International Cancer Institute (formerly, Osaka Medical Center for Cancer and Cardiovascular Diseases), 3-1-69 Otemae, Chuo-ku, Osaka 541-8567, Japan, E-mail: higasiyama-ma@ 123456mc.pref.osaka.jp
                Article
                MCO-0-0-1340
                10.3892/mco.2017.1340
                5547765
                b56f0555-ee4a-4c66-983f-69b50d2f6d36
                Copyright: © Akazawa et al.

                This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

                History
                : 10 March 2016
                : 22 July 2017
                Categories
                Articles

                adjuvant chemotherapy,stage iiia,non-small cell lung cancer,collagen gel droplet embedded culture drug sensitivity test,chemosensitivity test,platinum-based regimen,disease-free survival

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