Quality of life with docetaxel plus cisplatin versus paclitaxel plus carboplatin in patients with completely resected non-small cell lung cancer: quality of life analysis of TORG 0503.

PURPOSE: The TORG0503 study was undertaken to select a preferred platinum-based third-generation regimen for patients with completely resected non-small cell lung cancer (NSCLC). This study aimed to describe the quality of life (QOL) analysis of that study. METHODS: Patients with completely resected NSCLC were randomized to receive three cycles of docetaxel plus cisplatin (DC) or paclitaxel plus carboplatin (PC) on day 1 every 3 weeks. QOL was assessed at three time points (baseline, after two cycles, and after three cycles) using the Functional Assessment of Cancer Therapy-taxane (FACT-Taxane). The adjusted odds ratio (OR) and 95% confidence interval (CI) were calculated by logistic regression analysis that was adjusted for the baseline score in the FACT-Taxane total score and each subscale to evaluate treatment (PC vs. DC) effectiveness. RESULTS: QOL data from 104 patients (DC, n = 56 patients; PC, n = 48) were analyzed. In the FACT-Taxane total score, the baseline-adjusted OR (95% CI) of not worse QOL for the DC group was 3.3 (1.4-8.3) compared with the PC group. In the taxane subscale, the baseline-adjusted OR (95% CI) was 6.2 (2.6-16.0). CONCLUSION: Total QOL was maintained better in the DC group than in the PC group, especially the taxane subscale that consists of neurotoxicity and taxane components in spite of no treatment-related death in both arms between DC and PC. We might recommend DC as the control regimen for the next clinical trial from the viewpoint of QOL, similar to the primary outcomes in TORG0503.

Randomized phase II trial of adjuvant chemotherapy with docetaxel plus cisplatin versus paclitaxel plus carboplatin in patients with completely resected non-small cell lung cancer: TORG 0503.

OBJECTIVE: Adjuvant chemotherapy is standard of care for patients with completely resected stage IB, II and IIIA NSCLC. However, optimum chemotherapy regimen has not been determined. TORG0503 was undertaken to select a preferred platinum-based 3rd generation regimen in this clinical setting. MATERIALS AND METHODS: Patients with completely resected stage IB, IIA, IIB or stage IIIA NSCLC were stratified by stage (IB/IIA vs. IIB/IIIA) and institutions, and randomized to receive 3 cycles of docetaxel (60 mg/m2) plus cisplatin (80 mg/m2) (arm A) or paclitaxel (200 mg/m2) plus carboplatin (AUC 6) (arm B) on day 1, every 3 weeks. The primary endpoint of the study was 2-year relapse free survival, and the key secondary endpoints included overall survival, feasibility and toxicity. RESULTS: 111 patients were randomized, 58 patients to arm A and 53 to arm B. Patient demographics were balanced between the two arms. 93 % (54/58) of patients on the arm A and 92 % (49/53) patients on the arm B completed the planned 3 cycles of chemotherapy. There was no treatment-related death in both arms. The 2 and 5 year relapse free survival was 74.5 % (95 %CI: 68.6-80.4) and 61.6 % in the arm A, and 72.0 % (95 %CI: 65.7-78.3) and 46.0 % in the arm B. The overall 2, 5-year survival was 89.7 %, 73.9 % in the arm A and 86.9 %, 67.5 % in the arm B. CONCLUSION: Both docetaxel plus cisplatin and paclitaxel plus carboplatin are safe and feasible regimens as adjuvant chemotherapy. We choose docetaxel plus cisplatin as the control regimen for the next clinical trial.

Phase II study of vinorelbine plus carboplatin with concurrent radiotherapy in elderly patients with non-small cell lung cancer.

OBJECTIVE: Concurrent chemoradiotherapy is the standard treatment for locally advanced non-small cell lung cancer. In the current aging society, the establishment of an ideal treatment strategy for locally advanced non-small cell lung cancer in the elderly is warranted. To assess the efficacy of concurrent chemoradiotherapy with carboplatin and vinorelbine in elderly patients with locally advanced non-small cell lung cancer. PURPOSE: To assess the efficacy of concurrent chemoradiotherapy with carboplatin and vinorelbine in elderly patients with locally advanced non-small cell lung cancer. METHODS: This multicenter, phase II study included patients with physiologically or medically unresectable stage I-III NSCLC, who were ≥70 years old. The patients received carboplatin (AUC 2) and vinorelbine (15 mg/m2) both on day 1, 8, 22 and 29 concurrently with radiotherapy (2.0 Gy/day, 30 fractions, total 60 Gy). The primary endpoint was the objective response rate. The secondary endpoints were the progression-free survival, overall survival and the incidence of adverse events. RESULTS: 50 patients were accrued (42 men and 8 women). The median age was 77 years (range, 70-89 years) and the clinical stage was I/II/III in 3/7/40, respectively. Forty-seven patients completed the planned treatment. The response was complete remission in 4, partial response in 31, stable disease in 12 and progressive disease in 3, giving an objective response rate of 70% (95% confidence interval: 55.4-82.1). Frequent high Grade 3 or higher adverse events were hematologic, but no treatment deaths were noted. The median and 2-year progression-free survival were 8.4 months and 21.1% (95% confidence interval: 9.5-32.7%), respectively, and the median and 2-year overall survival were 15.4 months and 41.1% (95% confidence interval: 27.0-55.2), respectively. CONCLUSION: Concurrent chemoradiotherapy with carboplatin and vinorelbine showed an acceptable objective response rate and safety in elderly patients.

Randomized phase II study of pemetrexed or pemetrexed plus bevacizumab for elderly patients with previously untreated non-squamous non-small cell lung cancer: Results of the Lung Oncology Group in Kyushu (LOGIK1201).

OBJECTIVES: To evaluate the efficacy and safety, we conducted a randomized phase II study of pemetrexed (Pem) versus Pem + bevacizumab (Bev) for elderly patients with non-squamous non-small cell lung cancer (NSqNSCLC). PATIENTS AND METHODS: The eligibility criteria were as follows: NSqNSCLC, no prior therapy, stage IIIB/IV disease or postoperative recurrence, age: ≥75 years, performance status (PS): 0-1, and adequate bone marrow function. The patients were randomly assigned (1:1 ratio) to receive Pem or Pem + Bev. The primary endpoint was progression-free survival (PFS). The secondary endpoints were the response rate, OS, toxicities, and cost-effectiveness. RESULTS: Forty-one patients were enrolled and 40 (20 from each group) were assessable. Their characteristics were as follows: male/female = 23/17; median age (range) = 78 (75-83); stage IIIB/IV/postoperative recurrence = 1/30/9; PS 0/1 = 11/29. All cases involved adenocarcinoma. There was no significant intergroup difference in PFS and the median PFS (95% confidence interval) values of the Pem and Pem + Bev groups were 5.4 (3.0-7.4) and 5.5 (3.6-9.9) months, respectively (p = 0.66). The response rate was significantly higher in the Pem + Bev group (15% vs. 55%, p = 0.0146), and there was no significant difference in OS (median: 16.0 vs. 16.4 months, p = 0.58). Grade 3 and 4 leukopenia, neutropenia, and thrombocytopenia were seen in 10 and 30, 20 and 55, and 5 and 5 cases, respectively. Drug costs were higher in the Pem + Bev group (median: 1,522,008 vs. 3,368,428 JPY, p = 0.01). No treatment-related deaths occurred. CONCLUSIONS: Adding Bev to Pem did not result in improved survival in the elderly NSqNSCLC patients. Compared with Pem + Bev, Pem monotherapy had similar effects on survival, a more favorable toxicity profile, and was more cost-effective in elderly NSqNSCLC patients. Pem monotherapy might be one of the optional regimen for NSqNSCLC patients aged ≥75 years.

Anticoagulant Therapy for Disseminated Intravascular Coagulation After Gastrointestinal Surgery.

Many studies about anticoagulant therapy for disseminated intravascular coagulation (DIC) confused gastrointestinal surgery-related DIC with DIC unrelated to a prior operation. Furthermore, the potentially increased risk of bleeding by anticoagulants complicates their use. We carried out a systematic review to describe the efficacy and safety of anticoagulant agents for DIC after gastrointestinal surgery. Several studies have indicated that gabexate mesylate improves DIC score without increasing bleeding events, and that antithrombin is associated with lower mortality of DIC after gastrointestinal surgery. Recombinant thrombomodulin has been the most frequently analyzed anticoagulant agent in this field. DIC score and survival rate were better in patients treated with recombinant thrombomodulin, without increasing bleeding events. In conclusion, anticoagulant therapy may be effective and safe in DIC after gastrointestinal surgery.

Detection of ALK rearrangement in an octogenarian patient with pleomorphic carcinoma of the lung.

We herein present a rare case of ALK-positive pulmonary pleomorphic carcinoma in an octogenarian patient. A computed tomography scan of the thorax indicated a pulmonary nodule in the right upper lobe of an asymptomatic 87-year-old female. The surgical resection revealed that the disease was pleomorphic carcinoma with pathological T2aN0M0, stage IB. EML4-ALK was evaluated using immunohistochemistry and fluorescence in situ hybridization, and EGFR mutations were analyzed using the Cycleave method. While there were no EGFR mutations detected, she was positive for the ALK rearrangement. This is the first report of ALK rearrangement in an octogenarian patient with pleomorphic carcinoma of the lung.

A feasibility trial of postoperative adjuvant chemotherapy with S-1, an oral fluoropyrimidine, for elderly patients with non-small cell lung cancer: a report of the Lung Oncology Group in Kyushu (LOGIK) protocol 0901.

BACKGROUND: The present study was designed to determine whether adjuvant chemotherapy with S-1 after surgical resection is feasible in elderly patients with non-small cell lung cancer (NSCLC), using a multi-institutional trial. METHODS: From July 2009 to July 2011, 25 patients received the following regimen: 2 weeks of administration and 1 week of withdrawal of S-1 at 50-100 mg/body per day in an outpatient setting. The primary endpoint of this trial was the completion rate of eight cycles. RESULTS: The completion rate of eight cycles was 70.8 % [95 % confidence interval (CI) 52.7-89.0 %]. The perfect completion rate of eight cycles on schedule with full doses without delays was 50 % (95 % CI 30.0-70.0 %). The reasons for incomplete cycles were: patient refusal in four cases, anorexia in two cases and thrombocytopenia in one case. As a consequence of delays and/or dose reductions, the relative dose intensity of S-1 was 76.3 %. CONCLUSIONS: Adjuvant chemotherapy with S-1 at a reduced dose and schedule was therefore found to be a feasible treatment for elderly Japanese patients who had undergone surgical resection for NSCLC (UMIN Clinical Trials Registry number UMIN000002383).

Localized biphasic type malignant mesothelioma arising in the peritoneum: Report of a case.

This report describes a rare case of localized malignant biphasic (mixed epithelioid and sarcomatoid) mesothelioma arising in the peritoneum. A 69-year-old male with a history of asbestos exposure, complaining of a painful mass in the left chest wall, was found via computed tomography (CT) to have a tumor in the left peritoneum. The resected tumor was histologically and immunohistochemically consistent with a malignant mesothelioma with mixed epithelioid and sarcomatoid type and no distant metastasis. The diagnosis of localized malignant biphasic mesothelioma arising in the peritoneum was appropriate because there was no evidence of any other primary tumor.

Differences in the expression of epithelial-mesenchymal transition related molecules between primary tumors and pulmonary metastatic tumors in colorectal cancer.

PURPOSE: Epithelial-mesenchymal transition (EMT) is a key event in cancer metastasis. This study immunohistochemically examined the expression of EMT-related molecules in both primary colorectal cancer and pulmonary metastases, and analyzed the expression pattern. METHODS: Ten patients with colorectal cancer that underwent surgical resections for both the primary tumor and metastatic pulmonary tumors were included. The expression status of EMT-related molecules was examined using immunohistochemical staining. RESULTS: Nine of the 10 cases maintained the expression of both E-cadherin and ß-catenin in the primary site. The expression of E-cadherin and ß-catenin in the pulmonary metastatic site was preserved in 10 and 12 out of 15 metastatic lesions, respectively. The EMT-related transcription factor, Twist, was positively expressed in all 10 cases, Smad interacting protein 1 (Sip1) in 9, Snail in 4 and Slug in 3 of the primary sites. On the other hand, staining for Twist, Sip1 and Snail at the metastatic pulmonary site, was negative in all 10 cases. CONCLUSION: The expression of EMT-related transcription factors in metastatic pulmonary tumors from colorectal cancer decreased in comparison to the primary tumors. These findings suggested that the expression status of EMT-related transcription factors might play an important role in the implantation of metastatic foci.

Serum antioxidant capacity and oxidative injury to pulmonary DNA in never-smokers with primary lung cancer.

BACKGROUND/AIM: Recently, in spite of the decrease in smoking in developed nations, the prevalence of primary lung cancer has been increasing in never-smokers. In the present study, we examined the status of oxidative stress and attempted to clarify the influence of oxidative stress in non-smoking patients with lung cancer. PATIENTS AND METHODS: Sixty-one lung cancer patients who underwent a surgical resection, including 27 never-smokers and 34 ever-smokers with a history of more than 20 pack-years, were included. In addition, 18 surgical patients with benign lung diseases treated during the same period were also included as non-malignant controls. Using blood samples, both serum oxidative stress (OS) and anti-oxidant capacity (AOC) were examined with the derivatives of reactive oxygen metabolites (D-Roms) test and the biological antioxidant power (BAP) test, respectively. To assess the oxidative damage of the DNA in lung tissues, the non-lesion site tissues of the lung were immunohistochemically examined for the accumulation of thymidine glycol (TG). RESULTS: There was no significant relationship between the serum OS level and various clinicopathological factors including the patient age, sex, body mass index, pathologic stage, and smoking status. On the other hand, the mean level of AOC was significantly lower in never-smokers than in ever-smokers. Although the mean TG-positive rate in ever-smokers was significantly higher than that in never-smokers, the mean TG-positive rate of the latter was significantly higher than that of patients with benign diseases. CONCLUSION: The present study first demonstrated the low AOC in never-smokers with NSCLC, which may be a factor contributing to excessive oxidative DNA damage in the lung tissues.

BioKnife, a uPA activity-dependent oncolytic Sendai virus, eliminates pleural spread of malignant mesothelioma via simultaneous stimulation of uPA expression.

Malignant pleural mesothelioma (MPM) is highly intractable and readily spreads throughout the surface of the pleural cavity, and these cells have been shown to express urokinase-type plasminogen activator receptor (uPAR). We here examined the potential of our new and powerful recombinant Sendai virus (rSeV), which shows uPAR-specific cell-to-cell fusion activity (rSeV/dMFct14 (uPA2), named "BioKnife"), for tumor cell killing in two independent orthotopic xenograft models of human. Multicycle treatment using BioKnife resulted in the efficient rescue of these models, in association with tumor-specific fusion and apoptosis. Such an effect was also seen on both MSTO-211H and H226 cells in vitro; however, we confirmed that the latter expressed uPAR but not uPA. Of interest, infection with BioKnife strongly facilitated the uPA release from H226 cells, and this effect was completely abolished by use of either pyrrolidine dithiocarbamate (PDTC) or BioKnife expressing the C-terminus-deleted dominant negative inhibitor for retinoic acid-inducible gene-I (RIG-IC), indicating that BioKnife-dependent expression of uPA was mediated by the RIG-I/nuclear factor-κB (NF-κB) axis, detecting RNA viral genome replication. Therefore, these results suggest a proof of concept that the tumor cell-killing mechanism via BioKnife may have significant potential to treat patients with MPM that is characterized by frequent uPAR expression in a clinical setting.

Localized pleural amyloidosis: report of a case.

We herein describe an asymptomatic 31-year-old male who was admitted for an investigation of an abnormal pleural tumor detected by chest radiography. We performed various preoperative investigations including fluorodeoxyglucose-positron emission tomography. The maximum standardized uptake value (SUVmax) was 2.2, and malignancy could not be ruled out. We therefore carried out a thoracoscopy-assisted partial resection of the right upper lobe combined with a parietal pleurectomy. The pathological examination showed that there was a tumor localized with pleural amyloidosis.

A unique method for repairing intraoperative pulmonary air leakage with both polyglycolic acid sheets and fibrin glue.

BACKGROUND: In the present study we present a unique maneuver, using both fibrin glue and polyglycolic acid (PGA) sheets, for repairing intraoperative pulmonary air leakage, and report our clinical results. METHODS: Based on the results from in vitro experiments, we retrospectively investigated the clinical effects of our method for repairing intraoperative pulmonary air leakage in 377 consecutive patients, who underwent a pulmonary resection for primary lung cancer or metastatic lung tumors from 2004 to 2009. From April 2004 through September 2007, repair of intraoperative pulmonary air leakage was performed in 204 patients using only fibrin glue. From October 2007 through December 2009, the repair was performed in 173 patients with a unique application of both fibrin glue and PGA sheets, i.e., (1) rubbing fibrin glue A solution, (2) applying a PGA sheet cut to an appropriate size, (3) rubbing fibrin glue B solution on the PGA sheet, and (4) reapplying fibrin glue A solution and rubbing. RESULTS: The mean duration of postoperative pleural drainage was significantly shorter in the latter time period when both fibrin glue and PGA sheets were used than in the former period when fibrin glue was used alone. The incidence of prolonged air leakage longer than 1 week was also significantly lower in the latter era than in the former era. CONCLUSION: Our unique application of both fibrin glue and PGA sheets for the intraoperative repair of pulmonary air leakage effectively resulted in a shortening of the duration of postoperative pleural drainage.

[Interstitial pneumonitis].

The risk management of interstitial pneumonitis in cancer chemotherapy not only involves an adverse event by an anticancer drug, but there are four steps with the incidence of interstitial pneumonitis: 1 ) the time before chemotherapy treatment, selection of chemotherapy regimens and patients, 2 ) the time chemotherapy treatment is performed, 3 ) the time during following-up, 4 ) the time when interstitial pneumonitis occurs. It is necessary to decrease the risk of interstitial pneumonitis by several steps, cooperating with an entire medical staff.

Concurrent chemoradiotherapy using cisplatin plus S-1, an oral fluoropyrimidine, followed by surgery for selected patients with stage III non-small cell lung cancer: a single-center feasibility study.

PURPOSE: This single-institutional study was designed to determine whether S-1, an oral fluoropyrimidine, plus cisplatin with concurrent radiotherapy is feasible as an induction treatment for locally advanced non-small cell lung cancer (NSCLC). METHODS: Eighteen patients were analyzed in this study from July 2005 to March 2008. The patients received 40 mg/m(2) S-1 orally twice per day on days 1 through 14 and 22 through 35, and cisplatin (60 mg/m(2)) was injected intravenously on days 8 and 29. The patients also underwent radiotherapy, and received a total dose of 40 Gy in 20 fractions beginning on day 1. Surgical resection was performed from 3 to 6 weeks after completing the induction treatment. RESULTS: Nine (50%) of the 18 patients who received the induction treatment achieved a partial response. One patient refused to undergo surgery. The remaining 17 patients underwent a complete surgical resection. There were no deaths nor any major morbidities during the perioperative period. The recurrence-free survival and overall survival rate at 2 years for the patients who underwent resection were 63.3% and 88.2%, respectively. CONCLUSION: Induction treatment using S-1 plus cisplatin and concurrent radiotherapy and surgical resection for selected patients with stage III NSCLC is a feasible and promising new treatment modality.

Physical assessment immediately after lobectomy via miniposterolateral thoracotomy assisted by videothoracoscopy for non-small cell lung cancer.

PURPOSE: We evaluated the invasiveness of videothoracoscopy-assisted mini-posterolateral thoracotomy (VAmPLT) for non-small cell lung cancer (NSCLC). METHODS: This study prospectively analyzed 50 NSCLC patients who underwent VAmPLT lobectomy. We measured maximal negative inspiratory pressure (PImax), maximal positive expiratory pressure (PEmax), quadriceps strength (QS), 6-min walk test (6mWT), and postoperative pain during the perioperative period. We then compared the results of the 6mWT and the postoperative pain of the VAmPLT lobectomy patients with those of a control group of 50 NSCLC patients who underwent standard posterolateral thoracotomy (PLT) techniques just prior to implementation of the VAmPLT lobectomy. RESULTS: The PImax and PEmax at the baseline, then on postoperative days (PODs) 1, 7, and 14 were 125% ± 5% and 120% ± 4%, 69% ± 4% and 62% ± 4%, 115% ± 5% and 100% ± 4%, and 123% ± 4%, and 110% ± 4%, respectively. The QS at the baseline, then on PODs 7 and 14 was 138% ± 5%, 129% ± 6%, and 133% ± 5%, respectively. Improvement from the baseline was seen in PImax by POD 7, and in PEmax and QS by POD 14. The 6mWT results and the level of postoperative pain after VAmPLT lobectomy were superior to those after PLT. CONCLUSIONS: The advantages of VAmPLT lobectomy over PLT include less postoperative pain and earlier recovery of physical function.

Non-small cell lung cancer in never smokers as a representative 'non-smoking-associated lung cancer': epidemiology and clinical features.

Recent interest in lung cancer without a history of tobacco smoking has led to the classification of a distinct disease entity of 'non-smoking-associated lung cancer'. In this review article, we have made an overview of the recent literature concerning both the epidemiology and clinical features of lung cancer in never smokers, and have brought 'non-smoking-associated lung cancer' into relief. The etiology of lung cancer in never smokers remains indefinite although many putative risk factors have been described including secondhand smoking, occupational exposures, pre-existing lung diseases, diet, estrogen exposure, etc. Non-small cell lung cancer (NSCLC) in never smokers is clinically characterized by an increased incidence in females and a higher occurrence of adenocarcinoma in comparison to NSCLC in ever smokers in both surgical patients and non-resectable advanced-stage patients. Furthermore, the prognosis of never-smoking NSCLC is better than that of smoking-related NSCLC in both surgical patients and non-resectable advanced-stage patients. Recently recognized novel gene mutations such as EGFR (epidermal growth factor receptor) mutations are largely limited to never smokers or light smokers, and the expression of this gene is responsible for the clinical efficacy of gefitinib, an epidermal growth factor receptor-tyrosine kinase inhibitor. NSCLC with the EML4 (echinoderm microtubule-associated protein-like 4)-ALK (anaplastic lymphoma kinase) fusion gene is also more likely to occur in never smokers and in those with adenocarcinoma histology, and is expected to benefit from ALK inhibitors. In consideration of the future increase in never-smoking NSCLC or 'non-smoking-associated lung cancer', both clinical trials and investigations are needed.

Prognostic impact of local treatment against postoperative oligometastases in non-small cell lung cancer.

OBJECTIVES: In this study, we investigated prognostic factors associated with survival after distantly metastatic recurrence in surgically resected non-small cell lung cancer (NSCLC), and clarified the influence of local treatment on the prognosis for oligometastatic recurrence. METHODS: From 1994 through 2004, 418 consecutive patients with NSCLC underwent complete resection; 138 experienced a postoperative recurrence by December 2005. Of those, we reviewed 93 patients with only distant metastases for clinicopathological information, treatment modality, and survival. RESULTS: For the 93 patients with distant metastasis alone, the 2- and 5-year survival rates after recurrence were 43.9% and 38.7%, respectively. Of those patients, 44 first received local treatment, including radiotherapy in 31 and a surgical resection in 13. Their recurrent disease (oligometastases) was limited with the potential to be controlled with local treatment. The targeted metastatic organs were brain in 14 patients, bone in 14, lungs in 12, and other organs in 4. Significant prognostic factors for postrecurrence survival included adenocarcinoma histology, long disease-free interval (DFI) (1 year or longer), and the performance of local treatment for oligometastases. CONCLUSION: Local therapy such as radiotherapy and surgery, might be considered first-line treatment in patients with postoperative oligometastatic recurrence, especially those with a DFI ≥ 1 year.

Increased levels of platelet-associated immunoglobulin G in a patient with pulmonary adenocarcinoma.

This report describes a rare case of thrombocytopenia with high levels of platelet-associated immunoglobulin G (PA-IgG) in a patient with an adenocarcinoma of the lung. After surgical resection, the platelet count gradually increased and the serum PA-IgG levels decreased to within normal reference ranges. These findings suggest a relationship between pulmonary adenocarcinoma and PA-IgG.

Feasibility study of postoperative adjuvant chemotherapy with S-1 (tegaful, gimeracil, oteracil potassium) for non-small cell lung cancer-LOGIK 0601 study.

INTRODUCTION: The feasibility of using S-1, a novel oral dihydropyrimidine dehydrogenase (DPD)-inhibitory 5-fluorouracil, as postoperative adjuvant chemotherapy for completely resected non-small cell lung cancer (NSCLC) was analyzed. METHODS: Adjuvant chemotherapy consisted of eight courses (2-week administration and 1-week withdrawal) of S-1, at 80-120 mg/body per day in an outpatient setting. From July 2006 through March 2007, 30 patients were enrolled in this multi-institutional trial. RESULTS: The planned eight courses of S-1 administration were accomplished to 17 patients (56.7%; 95% confidence interval 37.4-74.5%). Two patients discontinued the treatment due to the disease recurrence, and therefore the completion rate was calculated to be 60.7%. The completion rate in patients younger than 70 years old was 78.6% while it was 42.9% in those of 70 years old or older. In seven patients including five elderly patients (> or =70 years old), S-1 administration was discontinued due to subjective symptoms, such as anorexia, during the early courses. The rate of patients with mild renal impairment (60< or =creatinine clearance<80 ml/min) tended to be higher in the elderly patients than that in the younger patients. Although grade 3 neutropenia (6.7%), anemia (6.7%), thrombocytopenia (3.3%) and digestive hemorrhage (3.3%) were observed, no grade 4 adverse events occurred. CONCLUSION: Postoperative long-term administration of S-1 seems feasible as adjuvant chemotherapy for NSCLC, with few adverse events except for the early development of anorexia, especially in the elderly patients.