Phase II Trial of S-1 as Second-Line Therapy in Patients with Advanced Non-small Cell Lung Cancer

Division of Oncology, Department of Medicine, Washington University School of Medicine, St Louis, Missouri 63110, USA.
Journal of thoracic oncology: official publication of the International Association for the Study of Lung Cancer (Impact Factor: 5.28). 02/2011; 6(4):790-5. DOI: 10.1097/JTO.0b013e3182103b51
Source: PubMed


Currently available agents for the treatment of advanced stage non-small cell lung cancer (NSCLC) have limited efficacy. S-1 is a novel formulation of oral fluoropyrimidine shown to be tolerable and active in patients with NSCLC in Japan. We conducted a multicenter phase II study in previously treated patients with NSCLC to evaluate the efficacy of single-agent S-1 in a predominantly non-Asian population.
Patients with advanced NSCLC and previously treated with only one line of chemotherapy received oral S-1 at 30 mg/m every 12 hours for 14 consecutive days followed by a 7-day rest until meeting discontinuation criteria. The primary end point was to evaluate the overall response rate.
Fifty-seven patients were accrued from 21 centers across the United States. Overall response rates and stable disease according to independent review were 7.1% and 48.2%, respectively, with a disease control rate of 55.3%. Progression-free survival was 2.9 months, median overall survival 7.3 months, and 1-year survival 31.6%. There were no significant differences in survival according to histologic subtype. The treatment was well tolerated, with the most common treatment-related side effects being nausea (54%) and diarrhea (49%).
Single-agent S-1 is well tolerated and has activity comparable with the other agents approved for use in recurrent/relapsed NSCLC.

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    • "Switch maintenance chemotherapy is considered to enhance the efficacy of adjuvant chemotherapy. Previous phase II trials have demonstrated that S-1 monotherapy produced a response rate of 7–14%, a median progression-free survival (PFS) of 3–4 months, and a median OS of 7–16 months as a second-line treatment for advanced NSCLC (Totani et al, 2009; Govindan et al, 2011; Shiroyama et al, 2011). Pemetrexed is effective against nonsquamous NSCLC; on the other hand, S-1 is effective against both non-squamous and squamous NSCLC. "
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    ABSTRACT: Background: We conducted a multicentre feasibility study for single agent long-term S-1 chemotherapy following docetaxel plus cisplatin in patients with curatively resected stage II–IIIA non-small cell lung cancer. Methods: Patients received three cycles of docetaxel (60 mg m−2) plus cisplatin (80 mg m−2) and then received S-1 (40 mg m−2 twice daily) for 14 consecutive days with a 1-week rest for >6 months (maximum, 1 year). The primary end point was feasibility, which was defined as the proportion of patients who completed eight or more cycles of S-1 chemotherapy. If the lower 95% confidence interval (CI) of this proportion was 50% or more, then the treatment was considered as feasible. The sample size was set at 125 patients. Results: One hundred and thirty-one patients were enrolled, of whom 129 patients were eligible and assessable. In all, 109 patients (84.5%) completed 3 cycles of docetaxel plus cisplatin and 66 patients (51.2%, 95% CI: 42.5–59.8) completed 8 or more cycles of S-1 treatment. Grade 3/4 toxicities during the S-1 chemotherapy included anaemia (7.3%), neutropaenia (3.7%), and anorexia (3.7%). Conclusion: The toxicity level was acceptable, although the results did not meet our criterion for feasibility. Modification of the treatment schedule for S-1 chemotherapy might improve the treatment compliance.
    Full-text · Article · Jul 2013 · British Journal of Cancer
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    • "S-1 showed activity in a second-line setting as well [10]. Of more interest, single agent S-1 showed modest activity as a third-line or further-line treatment [11,12]. On the other hand, capecitabine, which is another oral 5-FU agent, showed clinically meaningful results in NSCLC when combined with irinotecan and docetaxel in both first-line and second-line settings [13-16]. "
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    ABSTRACT: This study was designed to evaluate the efficacy of a combination treatment of S-1 plus either irinotecan or docetaxel for advanced/metastatic non-small cell lung cancer (NSCLC) patients who have already failed 3 or more lines of treatment. This was a prospective single center phase II study. The eligible patients received S-1 40 mg/m(2) twice a day orally on days 1 though 14 combined with irinotecan 150 mg/m(2)on D1 only or docetaxel 35 mg/m(2) on D1 and D8. The treatment was repeated every 3 weeks until disease progression, unacceptable toxicity, or patient refusal. The choice between the two regimens was made at the discretion of the treating physician. A total of 14 patients participated in the study. There were 3 patients with squamous cell carcinoma, 9 with adenocarcinoma, and 2 with NSCLC, NOS. Eight of the patients were male. There were 8 patients with an Eastern Cooperative Oncology Group (ECOG) of 1, and 6 patients with an ECOG of 2. All the patients had already been treated with platinum-based chemotherapy and epidermal growth factor receptor tyrosine kinase inhibitor therapy. Out of the 14 patients, 10 received irinotecan and S-1 and the other 4 received docetaxel and S-1. Twelve patients had also received pemetrexed. Disappointingly, there were no response from 2 patients with a stable disease, and therefore, as per the protocol, we stopped the study early. With a median follow-up time of 49 months, the median survival time was 5.6 months (95% confidence interval, 4.3 to 6.9 months). S-1 containing doublets did not show activity in this population as a salvage treatment and further investigation cannot be recommended.
    Full-text · Article · Dec 2011 · Cancer Research and Treatment
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    ABSTRACT: In this phase II clinical trial, we evaluated the efficacy and safety of S-1 monotherapy in patients with previously treated advanced non-small-cell lung cancer (NSCLC). We also measured plasma concentrations of 5-fluorouracil (5-FU) and 5-chloro-2,4-dihydroxypyridine components of S-1 and examined correlation with effectiveness and toxicity. S-1 was given orally at a dose of 80 mg/m(2)/day for 14 consecutive days, followed by a 7-day rest period. This treatment course was repeated until disease progression or intolerable toxicity. We enrolled 30 patients. The response rate was 26.7% (8/30), and the disease control rate was 70% (21/30). Median progression-free survival (PFS) was 3.1 months, and median overall survival (OS) was 11.2 months. Mutations in the epidermal growth factor receptor (EGFR) gene were analyzed in 27 patients. The response rate was higher in patients with mutant EGFR (50.0%) than in those with wild-type EGFR (11.8%, P = 0.0288). Median PFS was 4.8 and 2.5 months (P = 0.038), and median OS was 22.4 and 8.4 months (P = 0.071). There was no grade 4 toxicity in this study. Five patients had grade 3 non-hematologic toxicity, and there was a trend toward higher plasma concentrations of 5-FU in those patients than in another patients. S-1 monotherapy is effective and well-tolerated treatment for previously treated advanced NSCLC.
    No preview · Article · Dec 2011 · Cancer Chemotherapy and Pharmacology
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