s-1-(combination) and Carcinoma--Non-Small-Cell-Lung

Lung cancer is the leading cause of cancer-related deaths in the world, and non-small cell lung cancer accounts for > 75% of all lung cancer cases. Cisplatin-based concurrent chemoradiotherapy has become the standard treatment for locally advanced non-small cell lung cancer (NSCLC). Third-generation chemotherapy agents plus cisplatin have been most commonly used in concurrent chemoradiotherapy, which is also associated with more adverse effects and acute toxicities. S-1 as an oral chemotherapeutic agent exhibits higher antitumor activity, less adverse effects, and better biological availability. Recently, studies illustrated S-1-based concurrent chemoradiotherapy also had excellent effects in the treatment of locally advanced NSCLC.. A systematic literature search will be performed through February 2018 using MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, and Google Scholar for relevant articles published in any language. Randomized controlled trials and prospective comparative studies will be included. All meta-analyses will be performed using Review Manager software. The quality of the studies will be evaluated using the guidelines listed in the Cochrane Handbook. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses statements will be followed until the findings of the systematic review and meta-analysis are reported.. The results of this systematic review and meta-analysis will be published in a peer-reviewed journal.. Our study will draw an objective conclusion of the efficacy and safety of S-1-based chemoradiotherapy in the treatment of locally advanced unresectable NSCLC and provides level I evidence for clinical decision makings.

Topics: Antimetabolites, Antineoplastic; Carcinoma, Non-Small-Cell Lung; Chemoradiotherapy; Combined Modality Therapy; Disease-Free Survival; Drug Combinations; Humans; Lung Neoplasms; Neoplasm Staging; Oxonic Acid; Pneumonectomy; Randomized Controlled Trials as Topic; Systematic Reviews as Topic; Tegafur

The present study aims to assess the efficacy and safety of S-1 plus cisplatin as concurrent chemoradiation (experimental group [EG]) compared with standard concurrent chemoradiation regimens (control group[CG]) in patients with local advanced non-small cell lung cancer.. The Cochrane library, pubmed, and Ovid (elsevier) were retrieved. The included randomized controlled trials (RCT) were evaluated, and the statistical analysis was performed using RevMan 5.3 software. Cochrane handbook was applied to evaluate the methodological quality. Statistical significance was considered as P <.05.. There were 5 randomized control trials identified eligible for the meta-analysis. Meta-analysis of the pooled date suggested that overall survival (OS) (HR, 0.81; 95% CI, 0.58-1.13; P = .21, heterogeneity P = 1.00, I = 0%), progressives free survival (PFS) (HR, 0.82; 95% CI, 0.62-1.09; P = .18, heterogeneity P = .83, I = 0%) and 1,2,3-year OS (1-year OS: RR 1.03; 95% CI: 0.92-1.15, p = 0.59), (2-year OS: RR 1.14; 95% CI: 0.98-1.34, P = .09), (3 -year OS: RR 1.14; 95% CI: 0.90-1.44, P = .29) were not significantly different. The combination of S-1 and cisplatin had lower grade 3 or 4 leukocytopenia, neutropenia, (RR = 0.54, 95% CI: 0.38-0.75, P = .0003; RR = 0.23,95% CI: 0.14-0.36, P <.00001;, respectively). The rates of nausea, diarrhea, thrombocytopenia, pneumonitis, anorexia, anemia, febrile neutropenia were much the same in the 2 groups (RR = 1.35, 95% CI: 0.68-2.68, P = .38; RR = 1.85, 95% CI: 0.61-5.60, P = .28; RR = 1.67, 95% CI: 0.88-3.17, P = .12; RR = 1.19, 95% CI: 0.44-3.21, P = .73; RR = 1.35, 95% CI: 0.68-2.68, P = .38; RR = 0.86, 95% CI:0.55-1.34, P = .50; RR = 0.63, 95% CI:0.35-1.14, P = .13;, respectively).. This meta-analysis of 5 randomized control trails demonstrates that EG results similar OS, PFS, and 1,2,3-year OS, compared with CG, with lower risk of leukocytopenia, neutropenia.

Topics: Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Non-Small-Cell Lung; Cisplatin; Drug Combinations; Humans; Oxonic Acid; Radiotherapy; Randomized Controlled Trials as Topic; Tegafur

We performed a meta-analysis to evaluate the efficacy and safety for S-1-based regimens as the first-line treatment in Asian chemotherapy-naive patients with advanced non-small-cell lung cancer.. Eligible randomized clinical trials (RCTs) were included, of which data were extracted by inclusion criteria and exclusion one. Odds ratio and hazard ratio (HR) of outcomes including objective response rate (ORR), progression-free survival (PFS), overall survival (OS) and adverse effects (AEs) were explored for the final analysis.. Twenty-one RCTs including 3263 patients were fit into the analysis. Pooled HR for PFS was 1.01 (95% CI: 0.92-1.10; p = 0.88), the pooled HR for OS was 0.95 (95% CI: 0.85-1.06; p = 0.33) and the pooled odds ratio for ORR was 0.74 (95% CI: 0.61-0.90; p = 0.003). S-1-based regimens showed milder AEs in high-grade nausea/vomit, anorexia, leukopenia, neutropenia and febrile neutropenia (all p < 0.05).. The present study has revealed that S-1-based regimens are accompanied by the similar efficacy and slighter AEs compared with standard regimens as the first-line treatment in Asian chemotherapy-naive patients with advanced non-small-cell lung cancer.

Topics: Antineoplastic Combined Chemotherapy Protocols; Asian People; Carcinoma, Non-Small-Cell Lung; Clinical Trials as Topic; Drug Combinations; Humans; Lung Neoplasms; Neoplasm Metastasis; Neoplasm Staging; Odds Ratio; Oxonic Acid; Randomized Controlled Trials as Topic; Tegafur; Treatment Outcome

S-1 is a new oral fluoropyrimidine formulation that comprises tegafur, 5-chloro-2,4-dihydroxypyridine, and potassium oxonate. S-1 is designed to enhance antitumor activity and to reduce gastrointestinal toxicity. Several studies have demonstrated that both S-1 monotherapy and S-1 combination regimens showed encouraging efficacies and mild toxicities in the treatment of lung squamous cell carcinoma and adenocarcinoma. However, it is unclear whether S-1 can be used as standard care in advanced non-small cell lung cancer (NSCLC). The purpose of this meta-analysis was to assess the efficacy and safety of S-1-based chemotherapy, compared with standard chemotherapy, in patients with locally advanced or metastatic NSCLC. Thirteen randomized controlled trials (RCTs) involving 2,134 patients with a similar ratio of different pathological types were included. In first-line or second-line chemotherapy, compared with standard chemotherapy, S-1-based chemotherapy showed similar efficacy in terms of median overall survival (mOS), median progression free survival (mPFS), and objective response rate (ORR) (all P > 0.1), and significantly reduced the incidence of grade ≥ 3 hematological toxicities. In patients with locally advanced NSCLC receiving concurrent chemoradiotherapy, compared with standard chemoradiotherapy, significantly improved survival in the S-1-based chemotherapy was noted in terms of mOS and mPFS (risk radio [RR] = 1.289, P = 0.009; RR = 1.289, P = 0.000, respectively) with lower incidence of grade ≥ 3 neutropenia (RR = 0.453, P = 0.000). The present meta-analysis demonstrates that S-1-based chemotherapy shows similar benefits in advanced NSCLC and improves survival in locally advanced NSCLC, compared with standard treatment.

Topics: Antineoplastic Agents; Carcinoma, Non-Small-Cell Lung; Chemoradiotherapy; Drug Combinations; Humans; Lung Neoplasms; Oxonic Acid; Publication Bias; Tegafur; Treatment Outcome

We performed a meta-analysis of S-1-containing regimens versus control in the management of locally advanced/metastatic non-small-cell lung cancer.. Eligible studies included randomized studies evaluating S-1-containing regimens in the settings of locally advanced, first-line metastatic or second-line metastatic non-small-cell lung cancer.. Pooled odds ratio for overall response rate was 1.09 (95% CI: 0.85-1.38; p = 0.2), the pooled hazard ratio for progression-free survival was 0.98 (95% CI: 0.88-1.09; p = 0.69) and the pooled hazard ratio for overall survival was 0.98 (95% CI: 0.88-1.10; p = 0.75) for S-1-based regimens versus control. Moreover, the relative risk of febrile neutropenia was 0.34 (95% CI: 0.20-0.59; p = 0.0001).. Our meta-analysis has demonstrated that S-1-based regimens are associated with similar efficacy outcomes and better hematological tolerability.

Topics: Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Non-Small-Cell Lung; Drug Combinations; Humans; Lung Neoplasms; Neoplasm Metastasis; Neoplasm Staging; Odds Ratio; Oxonic Acid; Tegafur; Treatment Outcome

S-1 is an oral fluoropyrimidine derivative, including three pharmacological compounds: tegafur, gimeracil and oteracil, in a molar ratio of 1: 0.4: 1.. This review addresses the clinical evidence of S-1 in NSCLC in various clinical settings. Currently, S-1 for NSCLC is approved only in Japan. Prospective studies of S-1 as front-line and second-line chemotherapy with or without other agents and concurrent chemoradiotherapy are mainly reviewed. Only two Phase III clinical trials were published or presented for advanced NSCLC. S-1 and cisplatin is an active first-line chemotherapy regimen for advanced NSCLC and S-1 and carboplatin is noninferior to a carboplatin and paclitaexel regimen. The combination of S-1 and a platinum agent is active against NSCLC, regardless of tumor histology.. It is becoming possible to design effective regimens with S-1 against NSCLC in various clinical settings considering the ethnic differences in pharmacokinetics and a greater understanding of the underlying molecular pathways or biomarkers of NSCLC. Further Phase III studies with S-1 for both early and advanced NSCLC are warranted worldwide.

Topics: Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Carboplatin; Carcinoma, Non-Small-Cell Lung; Chemoradiotherapy; Cisplatin; Clinical Trials as Topic; Combined Modality Therapy; Drug Combinations; Humans; Lung Neoplasms; Oxonic Acid; Tegafur

UFT and S-1 are oral 5-fluorouracil (5-FU) derivative drugs containing an inhibitor of dihydropyrimidine dehydrogenase (DPD); they are defined as DPD-inhibitory fluoropyrimidine (DIF). Because DPD is the key enzyme of 5-FU degradation, 5-FU is not active in primary lung cancers with high DPD activity, which causes rapid degradation of 5-FU. Thus, theoretically, a DIF can overcome a cancer's resistance to 5-FU through inhibiting the enzyme activity of DPD, with the result that 5-FU may be active in primary lung cancer. In fact, UFT has proved to be effective in a postoperative adjuvant setting for early non-small-cell lung cancer (NSCLC) in several randomized controlled studies (RCTs). S-1, in which a more potent DPD inhibitor is combined, is active in advanced NSCLC regardless of the histological cell subtype, and its clinical efficacy in first-line therapy for unresectable advanced disease as well as in postoperative adjuvant therapy for resected disease is now being examined in a variety of RCTs. In the present review, the mechanism of action of UFT and S-1 as well as clinical evidence regarding their use in the treatment of NSCLC are summarized.

Topics: Administration, Oral; Antineoplastic Agents; Carcinoma, Non-Small-Cell Lung; Chemotherapy, Adjuvant; Dihydrouracil Dehydrogenase (NADP); Drug Combinations; Drug Resistance, Neoplasm; Enzyme Inhibitors; Evidence-Based Medicine; Humans; Lung Neoplasms; Oxonic Acid; Radiotherapy, Adjuvant; Tegafur; Time Factors; Treatment Outcome; Uracil

S-1 (also known as TS-1; Taiho Pharmaceutical Co. Ltd.; Tokyo, Japan) is a new oral fluoropyrimidine formulation that combines tegafur, 5-chloro-2,4-dihydroxypyridine (CDHP), and potassium oxonate in a molar ratio of 1:0.4:1. Single-agent S-1 has demonstrated marked activity against non-small-cell lung cancer (NSCLC) as well as a broad array of other solid tumors, including gastric, colorectal, breast, cervical, and pancreatic cancers. This comprehensive review summarizes the results of previous clinical studies and describes ongoing clinical trials of S-1 in advanced NSCLC. S-1 combined with platinum compounds, irinotecan, and gemcitabine has produced promising results in terms of feasibility, safety, and effectiveness. Available data have stimulated further research, including phase III trials for the first-line treatment of advanced NSCLC.

Topics: Administration, Oral; Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Non-Small-Cell Lung; Clinical Trials as Topic; Drug Combinations; Humans; Japan; Lung Neoplasms; Oxonic Acid; Tegafur

S-1 is a newly developed oral anti-tumor agent, which contains 5-chloro-2, 4-dihydroxypyridine and potassium oxonate to strengthen biological activities of 5-fluorouracil. Response rate of S-1 for advanced non-small cell lung cancer was reported to be 12.5-22%. Response rate of combination chemotherapy with S-1 plus cisplatin (CDDP) was reported to be 47%, and the median survival time was 11 months. Adverse events of the combination chemotherapy were milder than other combination chemotherapy described before. Therefore, S-1 plus CDDP combination chemotherapy is a future candidate for phase III clinical study.

Topics: Administration, Oral; Anemia; Anorexia; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Non-Small-Cell Lung; Cisplatin; Drug Administration Schedule; Drug Combinations; Female; Humans; Lung Neoplasms; Male; Neutropenia; Oxonic Acid; Remission Induction; Tegafur

The present paper presents a review of the second-line treatment of non-small cell lung cancer (NSCLC) and reports a phase I study of the combination chemotherapy of docetaxel (DOC) and S-1 as second-line chemotherapy. Current options for the second-line treatment of NSCLC include cytotoxic drugs, such as DOC, pemetrexed, and targeted therapies. However, single-agent chemotherapy has shown limited activities. A new treatment approach is needed for this patient population. We hypothesized that combination chemotherapy of DOC and S-1 would be effective through the additive and synergistic activities. We performed a phase I clinical trial of this combination chemotherapy. S-1 was administered orally at a dose of 80 mg/m2 for 14 days, followed by a drug-free interval of a week (one cycle). The starting dose level (level 1) of DOC was set to 40 mg/m2, until a dose of 60 mg/m2 was reached at level 3. Three patients were treated with level 2, in which the dose of DOC was increased up to 50 mg/m2. Two of 3 patients had grade 4 neutropenia, which was determined as dose-limiting toxicity. The dose level of DOC 40 mg/m2 on day 1 in combination with S-1 80 mg/m2 for 14 days of a three week cycle was recommended for a phase II study. Partial response was achieved in 4 of the 9 patients. This combined chemotherapy consisting of S-1 and DOC may prove effective for treating recurrent cases of NSCLC. A phase II study is ongoing.

Topics: Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Non-Small-Cell Lung; Clinical Trials, Phase I as Topic; Clinical Trials, Phase II as Topic; Clinical Trials, Phase III as Topic; Docetaxel; Drug Administration Schedule; Drug Combinations; Humans; Lung Neoplasms; Maximum Tolerated Dose; Oxonic Acid; Randomized Controlled Trials as Topic; Taxoids; Tegafur

Lung cancer is the leading cause of cancer-related death throughout the world including Japan. During the 1990s, new cytotoxic agents such as irinotecan, paclitaxel, docetaxel, vinorelbine, gemcitabine, and amrubicin showed impressive single-agent activity in patients with lung cancer. To date, clinical research has defined the current standard chemotherapy for advanced non-small cell lung cancer (NSCLC) as modern platinum-based doublets considered more efficacious than any single regimen and with no added benefit to triplet therapies. However, we have reached an efficacy plateau with these agents. Rearrangement of the drug combination or change of the drug doses and schedules will not result in significant further progress. New, less toxic agents that improve survival and quality of life are clearly needed. In the last three decades, we have gained a growing understanding of the molecular biologic changes and the complex series of cellular signals that allow cancer cells to manifest behavior. This provides an opportunity to develop novel therapies aimed at inhibiting some of these changes and signals. Targeted agents, primarily the epidermal growth factor receptor inhibitors, have led to a new era in the treatment of NSCLC. This paper will review the current status of cytotoxic agents and molecular targeted therapy in lung cancer potential useful in the treatment of the patients.

Topics: Anthracyclines; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antineoplastic Agents; Bevacizumab; Boronic Acids; Bortezomib; Camptothecin; Carcinoma, Non-Small-Cell Lung; Cetuximab; Clinical Trials as Topic; Deoxycytidine; Drug Combinations; Erlotinib Hydrochloride; Furans; Gefitinib; Gemcitabine; Glutamates; Guanine; Humans; Irinotecan; Lung Neoplasms; Oxonic Acid; Pemetrexed; Pyrazines; Pyridines; Quinazolines; Tegafur; Vinblastine; Vinorelbine

Cisplatin-based chemoradiotherapy is considered standard treatment for unresectable locally advanced non-small-cell lung cancer (LA-NSCLC). This study examined two regimens of chemotherapy in concurrent chemoradiation. Eligible patients with unresectable, radically irradible LA-NSCLC were randomized to either the SP (S-1 and cisplatin) or DP (docetaxel and cisplatin) arms with concurrent thoracic radiotherapy of 60 Gy, comprising 2 Gy per daily fraction. The primary endpoint was the overall survival (OS) rate at 2 years (the 2-year OS rate). From May 2011 to August 2014, 110 patients were enrolled. Of 106 eligible patients, the 2-year OS rates were 79% (95% CI: 66%-88%) and 69% (95% CI: 55%-80%) the SP and DP arms, respectively. The median progression-free survival was 11.6 months for the SP arm and 19.9 months for the DP arm, while the median survival time was 55.2 months for the SP arm and 50.8 months for the DP arm. Grade 3/4 leukopenia were more frequent in DP arm. The incidences of febrile neutropenia and pneumonitis tended to be higher in DP arm. There were no treatment-related deaths in either arm. The primary endpoint was met in both arms. The SP arm as a future reference regimen will be chosen due to fewer toxicities and better OS.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Non-Small-Cell Lung; Chemoradiotherapy; Cisplatin; Docetaxel; Drug Combinations; Female; Follow-Up Studies; Humans; Lung Neoplasms; Male; Middle Aged; Neoplasm Recurrence, Local; Oxonic Acid; Prognosis; Survival Rate; Tegafur; Thoracic Neoplasms

Combination carboplatin and S-1 is active in the treatment of non-small cell lung cancer (NSCLC). However, data on this combination for elderly patients with NSCLC are insufficient.

Topics: Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Area Under Curve; Carboplatin; Carcinoma, Non-Small-Cell Lung; Drug Combinations; Female; Humans; Lung Neoplasms; Male; Neutropenia; Oxonic Acid; Survival Rate; Tegafur; Thrombocytopenia; Treatment Outcome

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carboplatin; Carcinoma, Non-Small-Cell Lung; Chemotherapy, Adjuvant; Disease-Free Survival; Drug Combinations; Feasibility Studies; Female; Humans; Lung Neoplasms; Male; Middle Aged; Oxonic Acid; Tegafur

A proportion of patients with stage IV non-small-cell lung cancer (NSCLC) is predicted to receive third-line treatment. However, currently no standard third-line treatment for NSCLC is available. Anlotinib is an oral, multi-targeted tyrosine kinase (TK) receptor inhibitor, which was approved as a third-line treatment for stage IV NSCLC in China on May 9, 2018. Nevertheless, The objective response rate of patients treated with anlotinib was merely 9.2% and the overall survival was only 3 months compared with the patients treated with placebo. Previous studies have shown that cancer treatment with a combination of chemotherapy with TK receptor inhibitors is effective and safe well tolerated. Therefore, the combination of anlotinib with other chemotherapeutic agents may be an effective treatment strategy for patients with stage IV NSCLC. Oral S-1 is a third-generation fluorouracil derivative; it showed good efficacy and caused relatively low toxicity in patients with NSCLC.. The purpose of this trial is to evaluate the efficacy and safety of anlotinib combined with S-1 as the third-line treatment for patients with stage IV NSCLC. This is a prospective, phase II clinical trial. We will enroll29 patients with stage IV NSCLC treated with anlotinib plus S-1. Tumors will be assessed using computed tomography prior to treatment, after two, four, and six cycles of treatment, and during follow-up every 3 months until disease progression or death. The primary endpoint is the objective response rate (ORR). The secondary endpoints are progression-free survival, duration of response, proportion of disease control, and safety.. The expected outcome of this study is that anlotinib combined with S-1 has tolerable toxicity and better ORR than anlotinibmonotherapy. The results may indicate additional treatment options for patients with stage IV NSCLC.
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Topics: Adolescent; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Non-Small-Cell Lung; Drug Combinations; Female; Follow-Up Studies; Humans; Indoles; Lung Neoplasms; Male; Middle Aged; Oxonic Acid; Prognosis; Prospective Studies; Quinolines; Randomized Controlled Trials as Topic; Research Design; Survival Rate; Tegafur; Young Adult

Several recent studies have shown that salvage chemotherapy following PD-1 blockade produces high antitumor activity in some patients with non-small lung cancer (NSCLC). However, the underlying synergistic mechanisms remain uncertain. The blood neutrophil-to-lymphocyte ratio (NLR) and absolute neutrophil count (ANC) can reflect the number of circulating myeloid-derived suppressor cells and tumor-associated neutrophils. The immunosuppressive status of the tumor microenvironment could be monitored by the time-series patterns of NLR and ANC. The dynamics of NLR and ANC during nivolumab treatment were retrospectively explored in 15 patients: 8 patients receiving subsequent salvage chemotherapy (2 groups: 3 non-responders and 5 responders), and 7 responders to nivolumab alone (2 groups: 4 partial response and 3 complete response). The dynamics of NLR and ANC during nivolumab differed among these four groups (NLR P = 0.045, ANC P = 0.067). NLR and ANC during nivolumab treatment increased over time in non-responders to salvage chemotherapy, with an inverse relationship between drug response and NLR or ANC at four to six weeks among the four groups. We hypothesize that the early dynamics of NLR and ANC during nivolumab may be associated with the late efficacy of subsequent salvage chemotherapy. Further studies involving a large cohort are needed to confirm these findings, which could provide insight into the role of myeloid immunosuppressor cells in combination PD-1 blockade and chemotherapy.

Topics: Adenocarcinoma; Aged; Albumins; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Carboplatin; Carcinoma, Non-Small-Cell Lung; Carcinoma, Squamous Cell; Case-Control Studies; Docetaxel; Drug Combinations; Female; Follow-Up Studies; Humans; Lung Neoplasms; Lymphocytes; Male; Middle Aged; Neutrophils; Nivolumab; Oxonic Acid; Paclitaxel; Prognosis; Ramucirumab; Retrospective Studies; Salvage Therapy; Survival Rate; Tegafur

Because chemoradiotherapy using cisplatin and S-1, an oral fluoropyrimidine, is effective for unresectable non-small cell lung cancer (NSCLC), an induction setting was used in a multicenter phase II study (Clinical trial number: UMIN000008205). The correlations of relapse and clinicopathological factors were analyzed.. We defined locally advanced NSCLC as pathologically proven chest wall invasion or hilar and/or mediastinal lymph node metastases by endobronchial ultrasound-guided transbronchial needle aspiration. The patients received two courses of S-1 administration for 14 days and intravenous cisplatin injection on day 8. A total dose of 40 Gy radiotherapy was concurrently received. Surgical resection was performed after completion of the treatment.. Of the 23 eligible patients, 18 had stage IIIA and 5 had stage IIB NSCLC. Twenty of the eligible patients (87.0%) completed the regimen. Six (26.1%) complete responses were identified and 12 cases (52.2%) were histopathologically downstaged by induction chemoradiotherapy (ICRT). The 3-year overall survival rate was 58.1% and relapse-free survival (RFS) rate was 52.0%, respectively. Among several clinicopathological parameters, univariate RFS analysis identified that only downstaging was significantly associated with longer RFS times (p = 0.003). The radiological response did not reflect pathological response. When the variables of preoperative pathologically proven N2 metastasis, pathological ICRT effectiveness, and downstaging were included in the Cox proportional hazard modes, only the parameter of downstaging displayed significant hazard ratio (hazard ratio 0.13, p = 0.010).. This protocol is considered an option among preoperative therapies and has obvious benefits for pathologically downstaged cases.. UMIN000008205.. June 19, 2012.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Non-Small-Cell Lung; Chemoradiotherapy; Cisplatin; Drug Combinations; Female; Humans; Lung Neoplasms; Lymphatic Metastasis; Male; Middle Aged; Neoplasm Recurrence, Local; Neoplasm Staging; Oxonic Acid; Survival Rate; Tegafur

Background Optimal maintenance therapy for lung squamous cell carcinoma (SCC) has not been established. The aim of this study was to evaluate the efficacy and safety of switch maintenance therapy with S-1, an oral fluoropyrimidine, after induction therapy with carboplatin and nanoparticle albumin-bound paclitaxel (nab-paclitaxel) in chemotherapy-naïve patients with advanced SCC. Methods Chemotherapy-naïve patients with advanced SCC received induction therapy with four cycles of carboplatin (at an area under the curve of 6, day 1 of a 28-day cycle) and nab-paclitaxel (100 mg/kg, days 1, 8, and 15). Patients who achieved disease control after induction therapy received maintenance therapy with S-1 (80 mg/m

Topics: Adult; Aged; Aged, 80 and over; Albumins; Antineoplastic Combined Chemotherapy Protocols; Bone Neoplasms; Brain Neoplasms; Carboplatin; Carcinoma, Non-Small-Cell Lung; Carcinoma, Squamous Cell; Drug Combinations; Female; Follow-Up Studies; Humans; Liver Neoplasms; Lung Neoplasms; Lymphatic Metastasis; Maintenance Chemotherapy; Male; Middle Aged; Nanoparticles; Oxonic Acid; Paclitaxel; Prognosis; Survival Rate; Tegafur

The East Asia S-1 Trial in Lung Cancer (EAST-LC) was a randomized phase III study conducted in East Asia that demonstrated the non-inferiority of S-1 to docetaxel in previously treated patients with advanced non-small cell lung cancer (NSCLC). Here, we reported the results of the Japanese subgroup treated with docetaxel 60 mg/m. Patients were randomized 1:1 to receive either S-1 or docetaxel. The primary endpoint was overall survival (OS); the secondary endpoints included progression-free survival (PFS), response rate (RR), quality of life (QOL), and safety.. Patient characteristics in the Japanese subgroup (n = 724) were similar to those in the overall EAST-LC population. Median OS was 13.4 months in the S-1 group and 12.6 months in the docetaxel group. In pemetrexed-pretreated patients, OS with S-1 was similar to that with docetaxel. Median PFS was 2.9 and 3.0 months in the S-1 and docetaxel groups, respectively. RR was 9.4% and 10.3% in the S-1 and docetaxel groups, respectively. The QOL of patients treated with S-1 was better compared with that of patients treated with docetaxel. Decreased appetite and diarrhea were more common in the S-1 group, whereas the frequency of neutropenia and febrile neutropenia was markedly higher in the docetaxel group.. This Japanese subgroup analysis showed that S-1 had similar efficacy to docetaxel in patients with previously treated advanced NSCLC. These results are similar to those of the overall EAST-LC population.

Topics: Adult; Aged; Aged, 80 and over; Antimetabolites, Antineoplastic; Carcinoma, Non-Small-Cell Lung; Disease-Free Survival; Docetaxel; Drug Combinations; Female; Humans; Japan; Lung Neoplasms; Male; Middle Aged; Neutropenia; Oxonic Acid; Quality of Life; Tegafur; Treatment Outcome

We conducted a Phase I/II study of carboplatin, S-1 and concurrent thoracic radiotherapy (TRT) for elderly patients (71 years or older) with unresectable stage III non-small cell lung cancer (NSCLC).. Patients received carboplatin (AUC 3-5) on Day 1 and S-1 (30-40 mg/m2 two times daily) on Days 1-14, every 2 weeks, for up to four cycles, plus concurrent TRT at a total dose of 60 Gy. The primary endpoint for the Phase II study was the 1-year progression-free survival (PFS) rate.. Eighteen patients were enrolled in the Phase I study. Febrile neutropenia, a decreased platelet count and esophagitis were dose-limiting toxicities. The recommended doses for the Phase II study were determined to be an AUC of 3 for carboplatin, 40 mg/m2 twice daily for S-1. Twenty-eight patients were evaluated in the Phase II study. The 1-year PFS rate was 57.1% (90% CI 41.6-71.4%), and the median PFS was 16.8 months (95% CI 7.8-not assessable [NA]). The lower limit of the 90% CI for 1-year PFS exceeded the prespecified threshold value of 30%; therefore, the primary endpoint was met. Grades 3-4 toxicities included thrombocytopenia (21%) and hyponatremia (11%). Grade 3 radiation pneumonitis was observed in 18% of patients. No treatment-related deaths were observed.. Combination chemotherapy consisting of carboplatin plus S-1 and concurrent TRT had a promising efficacy in elderly patients with locally advanced NSCLC; however, radiation pneumonitis was frequently observed.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Carboplatin; Carcinoma, Non-Small-Cell Lung; Chemoradiotherapy; Drug Combinations; Female; Humans; Leukopenia; Lung Neoplasms; Male; Neoplasm Staging; Oxonic Acid; Paclitaxel; Progression-Free Survival; Radiation Pneumonitis; Tegafur; Treatment Outcome

S-1 plus cisplatin is a standard chemotherapy regimen for advanced non-small cell lung cancer (NSCLC). The addition of bevacizumab has been shown to significantly improve overall survival (OS) in patients with advanced non-squamous (NSq) NSCLC who received carboplatin plus paclitaxel, however, failed to show an OS advantage in patients who received cisplatin plus gemcitabine.. Chemotherapy-naive patients with Stage IIIB, IV or recurrent non-SQ NSCLC were treated with a 3-week cycle of S-1 80 mg/m2 on days 1-14, cisplatin 60 mg/m2 on day 8 and bevacizumab 15 mg/kg on day 8 for 4-6 cycles. Patients without progressive disease (PD) received maintenance bevacizumab 15 mg/kg on day 1 with a 3-week cycle and S-1 80 mg/m2 every other day. The primary endpoint was progression-free survival (PFS). Secondary endpoints were objective response rate (ORR), OS, toxicity profile and Quality of life (QOL).. From June 2013 to January 2015, 39 eligible patients were enrolled from eight institutions. Thirty-one patients (79%) completed four cycles of induction chemotherapy, and maintenance chemotherapy was initiated in 23 patients (59%). Median PFS, OS and ORR were 7.3 months (95% CI: 5.9-8.7), 21.4 months (95% CI: 14.7-not reached) and 64%, respectively. The most common grade 3/4 toxicities were leukopenia (12.8%), neutropenia (23.0%) and hypertension (28.2%). QOL analyses showed detrimental effects after initiation of the regimen.. S-1 plus cisplatin in combination with bevacizumab met the primary endpoint in patients with advanced NSq-NSCLC. RR was anticipated to be high with acceptable toxicities.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Carcinoma, Non-Small-Cell Lung; Cisplatin; Drug Combinations; Female; Humans; Kaplan-Meier Estimate; Lung Neoplasms; Male; Middle Aged; Neoplasm Staging; Oxonic Acid; Patient Compliance; Quality of Life; Survival Analysis; Tegafur

S-1 is an oral fluoropyrimidine that is active in the treatment of non-small cell lung cancer (NSCLC); however, an optimal treatment schedule and appropriate dose adjustments of S-1 in elderly patients have not yet been established.. We conducted a phase II trial to evaluate the efficacy and safety of a 2-week S-1 monotherapy treatment followed by a 1-week interval as a first-line treatment of elderly NSCLC patients, by adjusting the dose based on the individual creatinine clearance (Ccr) and body surface area (BSA). The primary endpoint was the disease control rate.. Forty patients were enrolled. The disease control and response rates were 89.5% (95% confidence interval [CI] = 79.8-99.2) and 7.9% (95% CI = 0.0-16.4), respectively. The median progression-free survival and overall survival times were 4.4 months (95% CI = 4.2-8.5) and 17.0 months (95% CI = 11.2-18.7), respectively. Neutropenia, anorexia, hyponatremia, hypokalemia, and pneumonia of grade ≥ 3 occurred in 5.0%, 7.5%, 5.0%, 2.5%, and 2.5% of patients, respectively. Among the patient-reported outcomes, most of the individual factors in the patients' quality of life, including upper intestine-related symptoms improved with the treatment, except for dyspnea, which slightly albeit continuously worsened throughout the study.. In elderly patients with previously untreated advanced NSCLC, a 2-week S-1 monotherapy treatment, tailored to both the Ccr and BSA, with a 1-week interval was well tolerated and demonstrated promising efficacy. This study was registered at the University Hospital Medical Information Network (UMIN) Center (ID: UMIN000002035), Japan.

Topics: Administration, Oral; Aged; Aged, 80 and over; Antimetabolites, Antineoplastic; Body Surface Area; Carcinoma, Non-Small-Cell Lung; Creatinine; Drug Administration Schedule; Drug Combinations; Female; Humans; Lung Neoplasms; Male; Metabolic Clearance Rate; Oxonic Acid; Precision Medicine; Survival Rate; Tegafur; Treatment Outcome

EGFR-tyrosine kinase inhibitors (TKIs) combined with TS-1 might overcome EGFR-TKI resistance, which has been indicated by several preclinical studies. We investigated the synergistic efficacy and safety of the combination therapy of EGFR-TKIs and TS-1 in non-small cell lung cancer (NSCLC) patients with acquired resistance to previous EGFR-TKI therapy.. This was a phase II, single-arm and single-center prospective study. Stage IIIB-IV NSCLC patients with acquired resistance to prior EGFR-TKI treatment were enrolled. All patients were administered combination therapy of TS-1 and continuing EGFR-TKIs in this study. The primary endpoints were progression-free survival (PFS), while overall survival (OS), disease control rate (DCR), and safety were secondary endpoints.. A total of 42 patients with acquired resistance to EGFR-TKIs were eligible for this study. The median PFS for all patients was five months (95% confidence interval [CI] 3.6-5.4). The OS and DCR were 31.9 (95% CI 17.8-46.0) months and 69.0% (29/42), respectively. No grade 4 toxicity or grade 3 hematologic toxicity was observed in this study. One patient (2%) experienced grade 3 elevated total serum bilirubin.. The combination treatment of TS-1 and EGFR-TKIs was effective and well tolerated by patients who had experienced prior EGFR-TKI treatment failure. Our results need to be validated by larger prospective clinical trials.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Non-Small-Cell Lung; Disease-Free Survival; Drug Combinations; Drug Resistance, Neoplasm; ErbB Receptors; Humans; Lung Neoplasms; Middle Aged; Oxonic Acid; Protein Kinase Inhibitors; Tegafur; Treatment Outcome

Cisplatin-based chemoradiotherapy is the standard treatment for unresectable, locally advanced non-small-cell lung cancer (NSCLC). This trial evaluated two experimental regimens that combine chemotherapy with concurrent radiotherapy.. Eligible patients with unresectable stage III NSCLC were randomised to either the SP arm (S-1 and cisplatin) or VP arm (vinorelbine and cisplatin), with early concurrent thoracic radiotherapy of 60 Gy, comprising 2 Gy per daily fraction. The primary endpoint was the overall survival rate at 2 years (2-year overall survival (OS)) (Study ID: UMIN000002420).. From September 2009 to September 2012, 112 patients were enroled. Of the 108 eligible patients, the 2-year OS was 75.6% (80% confidence interval (CI), 67-82%) in the SP arm and 68.5% (80% CI: 60-76%) in the VP arm. The hazard ratio (HR) for death between the two arms was 0.85 (0.48-1.49). The median progression-free survival was 14.8 months for the SP arm and 12.3 months for the VP arm with an HR of 0.92 (0.58-1.44). There were four treatment-related deaths in the SP arm and five in the VP arm.. The null hypotheses for 2-year OS were rejected in both arms. The West Japan Oncology Group will employ the SP arm as the investigational arm in a future phase III study.

Topics: Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Non-Small-Cell Lung; Chemoradiotherapy; Cisplatin; Dose Fractionation, Radiation; Drug Combinations; Female; Humans; Japan; Lung Neoplasms; Male; Neoplasm Staging; Oxonic Acid; Survival Analysis; Tegafur; Treatment Outcome; Vinorelbine

Platinum-based combination chemotherapy is the standard postoperative adjuvant treatment for pathological stage II/III non-small cell lung cancer (NSCLC). Oral S-1 therapy has good efficacy and relatively low toxicity for the treatment of advanced NSCLC. We investigated whether long-term S-1 monotherapy is also useful as an adjuvant therapy after surgery in patients with NSCLC.. We conducted a phase II randomized open-label multi-institutional study in patients with pathological stage II/IIIA NSCLC (7. A total of 70 and 71 patients were enrolled in S-1 arm and S-1 plus cisplatin arm, respectively. The 2-year DFS rates were 52% (95% confidence interval [CI], 0.40-0.63) and 61% (95% CI, 0.48-0.70) for S-1 arm and S-1 plus cisplatin arm, respectively. Both arms met the primary endpoint. Neither DFS nor OS was significantly different between the arms (log-rank test: P =  0.1695 and P =  0.8684, respectively). The main G3/4 adverse events were loss of appetite and anemia (S-1 vs. S-1 plus cisplatin: 4.3% vs. 11.6% and 0% vs. 5.8%, respectively). The treatment completion rate did not differ between the two arms (S-1 vs. S-1 plus cisplatin: 45.7%, 95% CI, 41.9-66.3% vs. 43.5% 95% CI, 44.0-68.4%).. Long-term adjuvant chemotherapy with S-1 was a feasible and promising treatment for patients with completely resected NSCLC, regardless of cisplatin addition. S-1 monotherapy should be investigated further, based on its low toxicity and practical convenience.

Topics: Aged; Antineoplastic Agents; Carcinoma, Non-Small-Cell Lung; Chemotherapy, Adjuvant; Cisplatin; Drug Combinations; Female; Follow-Up Studies; Humans; Lung Neoplasms; Male; Middle Aged; Neoplasm Staging; Oxonic Acid; Pneumonectomy; Postoperative Period; Tegafur

The clinical benefit of chemotherapy and the appropriate regimen for non-small-cell lung cancer (NSCLC) patients with interstitial lung disease (ILD) remain unclear. To fulfill this unmet medical need, we conducted a phase II study to elucidate the efficacy of S-1 in combination with carboplatin (CBDCA) in NSCLC patients with ILD.. A total of 33 advanced or recurrent NSCLC patients with ILD were prospectively enrolled in this multicenter, open-label, phase II study. Every 4 weeks, CBDCA at a dose of AUC 5 on day 1 and S-1 at a dose of 80 mg/m. The median age at initiating chemotherapy was 70. Sixteen patients (48.5%) had squamous cell carcinoma histology. With respect to the types of ILD, the usual interstitial pneumonia pattern was dominant (66.7%). The median number of cycles administered was 3, and the overall response rate and disease control rate were 33.3% and 78.8%, respectively. The median progression-free survival, the median survival time and the 1-year survival rate were 4.8 months, 12.8 months and 51.4%, respectively. Acute exacerbation of ILD caused by chemotherapy was noted in 2 patients (6.1%).. This is the first prospective study designed to evaluate the efficacy of a specific chemotherapeutic regimen as the primary endpoint in patients with advanced NSCLC with ILD. The combination of S-1 with CBDCA may be a treatment option for advanced NSCLC patients with ILD (The clinical trial registration number: UMIN000011046).

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Carboplatin; Carcinoma, Non-Small-Cell Lung; Carcinoma, Squamous Cell; Disease-Free Survival; Drug Combinations; Female; Humans; Lung Diseases, Interstitial; Lung Neoplasms; Male; Middle Aged; Neoplasm Recurrence, Local; Oxonic Acid; Prospective Studies; Survival Rate; Tegafur

To assess the efficacy and toxicity of S-1 and bevacizumab combination therapy for patients previously treated for advanced non-squamous non-small cell lung cancer (NSCLC).. This was a prospective, multi-center, single-arm phase II study. Patients with non-squamous NSCLC who had experienced progression after cytotoxic chemotherapy were enrolled. Oral S-1 was administered on days 1-14 of a 21-day cycle, and bevacizumab (15 mg/kg) was given intravenously on day 1. Patients received S-1 adjusted on the basis of their creatinine clearance and body surface area. The primary endpoint was response rate (RR); secondary endpoints were progression-free survival (PFS), overall survival (OS), and safety.. We enrolled 30 patients. One patient had never received platinum-based therapy. Five patients had activating mutations of the epidermal growth factor receptor gene, of whom four had received tyrosine kinase inhibitors before this study. The RR was 6.7% [95% confidence interval (CI) 1.8-21.3%], and the disease control rate (DCR) was 80% (95% CI 62.7-90.5%). Median PFS was 4.8 months (95% CI 2.7-6.4 months], and median OS was 13.8 months (95% CI 8.4 months-not applicable). Patients did not experience any Grade 4 toxicity or treatment-related death. Grade 3 hematologic toxicity (anemia) occurred in one patient (3.3%). The main Grade 3 non-hematologic toxicities were anorexia (10%), infection (10%), and diarrhea (6.7%).. The addition of bevacizumab to S-1 was tolerable, but not beneficial for patients with previously treated non-squamous NSCLC. We do not recommend further study of this regimen.

Topics: Adult; Aged; Angiogenesis Inhibitors; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Carcinoma, Non-Small-Cell Lung; Disease-Free Survival; Drug Combinations; Female; Humans; Lung Neoplasms; Male; Middle Aged; Oxonic Acid; Prospective Studies; Tegafur; Treatment Outcome

We conducted this single-institute; prospective, non-randomized parallel two-arm phase II study to evaluate the efficacy and safety of switch maintenance chemotherapy with S-1 after induction therapy with a platinum-based regimen in patients with advanced non-small cell lung cancer (NSCLC).. Between July 2010 and January 2014, 79 patients were enrolled, of which 78 were found to be eligible for inclusion in this study. The treatment success rate at three months was 28.2% (90% confidence interval (CI), 7.1-17.1%) in the S-1 group and 64.1% (90% CI, 50.0-76.8%) in the S-1+Bev group. The primary endpoint was met in the S-1+Bev group. The median PFS and OS were 2.6 months and 11.0 months in the S-1 group, and 4.6 months and 19.9 months in the S-1+Bev group, respectively. The most common grade three toxicity was neutropenia (10% incidence in the S-1+Bev group). There were no cases of febrile neutropenia.. Switch maintenance chemotherapy with S-1 in combination with continuation maintenance chemotherapy with bevacizumab yielded modest efficacy with mild and acceptable toxicities.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Biomarkers, Tumor; Carcinoma, Non-Small-Cell Lung; Drug Combinations; Drug Substitution; Female; Humans; Lung Neoplasms; Maintenance Chemotherapy; Male; Middle Aged; Neoplasm Staging; Oxonic Acid; Retreatment; Survival Analysis; Tegafur; Treatment Outcome

We conducted a multicenter randomized study of adjuvant S-1 administration schedules for surgically treated pathological stage IB-IIIA non-small cell lung cancer patients.. Patients receiving curative surgical resection were centrally randomized to arm A (4 weeks of oral S-1 and a 2-week rest over 12 months) or arm B (2 weeks of S-1 and a 1-week rest over 12 months). The primary endpoints were completion of the scheduled adjuvant chemotherapy over 12 months, and the secondary endpoints were relative total administration dose, toxicity, and 3-year disease-free survival.. From April 2005 to January 2012, 80 patients were enrolled, of whom 78 patients were eligible and assessable. The planned S-1 administration over 12 months was accomplished to 28 patients in 38 arm A patients (73.7%) and to 18 patients in 40 arm B patients (45.0%, p = 0.01). The average relative dose intensity was 77.2% for arm A and 58.4% for arm B (p = 0.01). Drug-related grade 3 adverse events were recorded for 11% of arm A and 5% of arm B (p = 0.43). Grade 1-3 elevation of bilirubin, alkaline phosphatase, aspartate aminotransferase, and alanine transaminase were more frequently recorded in arm A than in arm B. The 3-year disease-free survival rate was 79.0% for arm A and 79.3% for arm B (p = 0.94).. The superiority of feasibility of the shorter schedule was not recognized in the present study. The conventional schedule showed higher completion rates over 12 months (p = 0.01) and relative dose intensity of S-1 (p = 0.01). Toxicity showed no significant difference among the shorter schedule and the conventional schedule, except for grade 1-3 elevation of bilirubin.. This randomized multicenter study was retrospectively registered with the UMIN-CTR (UMIN000016086, registration date December 30, 2014).

Topics: Adult; Aged; Antimetabolites, Antineoplastic; Carcinoma, Adenosquamous; Carcinoma, Non-Small-Cell Lung; Carcinoma, Squamous Cell; Chemotherapy, Adjuvant; Disease-Free Survival; Drug Administration Schedule; Drug Combinations; Feasibility Studies; Female; Humans; Lung Neoplasms; Male; Middle Aged; Oxonic Acid; Patient Compliance; Prospective Studies; Tegafur; Treatment Outcome; Young Adult

Chemotherapy remains a viable option for the management of advanced non-small-cell lung cancer (NSCLC) despite recent advances in molecular targeted therapy and immunotherapy. We evaluated the efficacy of oral 5-fluorouracil-based S-1 as second- or third-line therapy compared with standard docetaxel therapy in patients with advanced NSCLC.. Patients with advanced NSCLC previously treated with ≥1 platinum-based therapy were randomized 1 : 1 to docetaxel (60 mg/m2 in Japan, 75 mg/m2 at all other study sites; day 1 in a 3-week cycle) or S-1 (80-120 mg/day, depending on body surface area; days 1-28 in a 6-week cycle). The primary endpoint was overall survival. The non-inferiority margin was a hazard ratio (HR) of 1.2.. A total of 1154 patients (577 in each arm) were enrolled, with balanced patient characteristics between the two arms. Median overall survival was 12.75 and 12.52 months in the S-1 and docetaxel arms, respectively [HR 0.945; 95% confidence interval (CI) 0.833-1.073; P = 0.3818]. The upper limit of 95% CI of HR fell below 1.2, confirming non-inferiority of S-1 to docetaxel. Difference in progression-free survival between treatments was not significant (HR 1.033; 95% CI 0.913-1.168; P = 0.6080). Response rate was 8.3% and 9.9% in the S-1 and docetaxel arms, respectively. Significant improvement was observed in the EORTC QLQ-C30 global health status over time points in the S-1 arm. The most common adverse drug reactions were decreased appetite (50.4%), nausea (36.4%), and diarrhea (35.9%) in the S-1 arm, and neutropenia (54.8%), leukocytopenia (43.9%), and alopecia (46.6%) in the docetaxel arm.. S-1 is equally as efficacious as docetaxel and offers a treatment option for patients with previously treated advanced NSCLC.. Japan Pharmaceutical Information Center, JapicCTI-101155.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Large Cell; Carcinoma, Non-Small-Cell Lung; Carcinoma, Squamous Cell; Docetaxel; Drug Combinations; Drug Resistance, Neoplasm; Female; Follow-Up Studies; Humans; Lung Neoplasms; Male; Middle Aged; Oxonic Acid; Prognosis; Salvage Therapy; Survival Rate; Taxoids; Tegafur; Young Adult

Postoperative 1-year administration of S-1, an oral derivative of 5-fluorouracil (5-FU), was shown to be feasible in lung cancer. The 5-year survival rates of postoperative patients treated with S-1 adjuvant chemotherapy and the prognostic impact of clinicopathological factors were examined.. The data of 50 patients with curatively resected pathological stage IB to IIIA non-small cell lung cancer, who were treated with S-1 postoperatively, were analyzed. The prognostic impacts of 22 clinicopathological factors including expressions of the 5-FU pathway enzymes were evaluated. A single-nucleotide polymorphism (SNP), i.e. 538G>A (rs17822931), of ABCC11/MRP8, which encodes a 5-FU excretion enzyme that is known as an earwax type determinant, was also evaluated.. The 5-year overall and relapse-free survival rates were 72.5 and 67.5%, respectively. A performance status ≥ 1, lymphatic vessel invasion, blood vessel invasion, and the A/A type of SNP538, which is responsible for the dry earwax type, were significantly associated with shorter relapse-free survivals. In 34 patients who showed a relative performance of 70% or more for chemotherapy, multivariate survival analysis indicated significant hazard ratios only for the A/A type of SNP538 (p = 0.007).. S-1 has sufficient power as adjuvant chemotherapy. However, its effect might be small in the dry earwax type patient group in an adjuvant setting.

Topics: Administration, Oral; Adult; Aged; Aged, 80 and over; Antimetabolites, Antineoplastic; ATP-Binding Cassette Transporters; Carcinoma, Non-Small-Cell Lung; Chemotherapy, Adjuvant; Disease-Free Survival; Drug Combinations; Female; Humans; Lung Neoplasms; Male; Middle Aged; Oxonic Acid; Polymorphism, Single Nucleotide; Prognosis; Survival Analysis; Tegafur

S-1, a novel oral fluoropyrimidine, is active in the treatment of non-small cell lung cancer (NSCLC). However, data on S-1 for elderly patients with NSCLC are insufficient.. Eligibility criteria were no prior chemotherapy, stage IIIB or IV NSCLC, performance status 0-1, age >70 years, and adequate hematological, hepatic, and renal functions. Patients received S-1 (40 mg/m(2) twice a day) for 28 consecutive days. This schedule was repeated every 6 weeks. The primary end point was the tumor response rate.. Thirty-two patients were enrolled and 31 patients were evaluable for response. The patients' median age was 80 years (range: 71-88). The response rate was 22.6% (95% CI: 11-38). Neutropenia, anemia, thrombocytopenia, febrile neutropenia, and diarrhea of grade ≥ 3 occurred in 6, 6, 10, 3, and 3%, respectively.. In elderly patients with previously untreated advanced NSCLC, S-1 appears to be well tolerated and demonstrates encouraging activity.

Topics: Aged; Aged, 80 and over; Anemia; Antimetabolites, Antineoplastic; Carcinoma, Non-Small-Cell Lung; Drug Administration Schedule; Drug Combinations; Female; Humans; Lung Neoplasms; Male; Nausea; Neutropenia; Oxonic Acid; Tegafur; Treatment Outcome; Vomiting

In the CATS (Cisplatin And TS-1) randomized trial comparing cisplatin plus either docetaxel (DP arm) or TS-1 (SP arm) in lung cancer, efficacy was found to be equivalent but the global quality of life (QOL) score was higher in the SP arm. The purpose of the current study was to identify which of the adverse events (AEs) contributed to the deterioration of QOL.. QOL and AE data from the CATS trial were used to quantitatively analyze the relationship between deterioration of QOL score and occurrence of AEs. Subtracted values of the QOL score from post-chemotherapy to pre-chemotherapy were fully compared between patients with or without each AE (Student's t test, significance level = 0.001). Multivariate linear regression analysis was also performed. Analysis of variance was performed to identify whether grade of AE(s) might be significantly correlated with the deterioration of the QOL score (significance level of 0.05).. As expected, gastrointestinal (GI) toxicities were associated with worsening of a variety of QOL items in both trial arms, detected by both univariate and multivariate analysis (p < 0.001 and p < 0.0001, respectively). Multivariate analysis unpredictably indicated that an increase in serum bilirubin level was the only AE that was uniquely associated with worsening of physical functioning (p = 0.0002), cognitive functioning (p < 0.0001), and financial problems (p = 0.0005) in the DP arm, although not in the SP arm. GI toxicities tended to be prolonged in the SP arm.. An increase in serum bilirubin level may contribute to the worse global QOL of subjects in the DP arm in the CATS trial. The method we used here may be a unique approach to identify unpredictable AE(s) that worsen the QOL of patients treated by chemotherapy.

Topics: Antineoplastic Combined Chemotherapy Protocols; Bilirubin; Carcinoma, Non-Small-Cell Lung; Cisplatin; Cognition Disorders; Docetaxel; Drug Combinations; Gastrointestinal Diseases; Humans; Lung Neoplasms; Oxonic Acid; Quality of Life; Taxoids; Tegafur

This phase II trial investigated the efficacy and safety of S-1 plus bevacizumab (SB) after failure of platinum-based chemotherapy in patients with non-squamous non-small cell lung cancer (non-sq NSCLC).. Patients with non-sq NSCLC who had undergone prior platinum-based chemotherapy, regardless of the use of bevacizumab, were eligible. S-1 (80 mg/m(2)) was administered orally twice daily for 14 days, and bevacizumab (15 mg/kg) on day 1 every 3 weeks until disease progression or unacceptable toxicity occurred. The primary endpoint was progression-free survival (PFS).. Twenty-eight patients (14 males and 14 females; median age 62 years; performance status 0/1/2: 21/7/0) were accrued from 4 centers. Almost half (n = 15, 53.6 %) of these had received prior bevacizumab therapy. The median PFS and overall survival were 3.2 months [95 % confidence interval (CI) 2.2-4.0 months] and 11.4 months (95 % CI 8.9-13.9 months), respectively. Prior exposure to bevacizumab did not affect the PFS. An objective response was observed in 4 patients, the response rate and disease control rate being 14.3 and 85.7 %, respectively. The treatment was well tolerated, the most common treatment-related side effects being anorexia (75 %) and fatigue (68 %).. Although SB was well tolerated, this combination did not provide any additional benefit in terms of PFS for patients with non-sq NSCLC after failure of platinum-based chemotherapy. It will be important to clarify the most suitable agent for use with bevacizumab, and the optimal timing of bevacizumab therapy for lung cancer.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Carcinoma, Non-Small-Cell Lung; Disease-Free Survival; Drug Combinations; Female; Humans; Lung Neoplasms; Male; Middle Aged; Oxonic Acid; Platinum Compounds; Survival Rate; Tegafur; Treatment Failure; Treatment Outcome

The aim of this study was to investigate the efficacy and safety of S-1 plus cisplatin combined with concurrent radiotherapy (SCCCR) versus cisplatin alone combined with concurrent radiotherapy (CCCR) in Chinese patients with unresectable stage III nonsmall-cell lung cancer (NSCLC).. Between January 2012 and December 2014, 72 eligible Chinese patients with NSCLC were included and randomly divided into 2 groups, each having 36 patients. Patients in the SCCCR group received S-1 plus cisplatin with concurrent, radiotherapy. The other 36 patients in the CCCR group were administered cisplatin with concurrent radiotherapy. The primary outcome was the overall response rate. The secondary outcomes were overall survival (OS), progression-free survival (PFS), and adverse events.. The 3-year overall response rates for the SCCCR and CCCR groups were 60.1% and 53.3%, respectively (P = 0.041). The median OS was 35.1 (range, 6.5-47.2) months and 24.6 (range, 2.8-24.3) months for the SCCCR and CCCR groups, respectively (P = 0.016). The median PFS for the SCCCR and CCCR groups was 31.4 (range, 5.6-39.3) months and 22.3 (range, 2.4-36.5) months, respectively (P = 0.023). The toxicity profiles were similar for both groups.. The efficacy and safety of SCCCR was more encouraging compared to those of CCCR in Chinese NSCLC patients. In addition, the toxicities in both groups were tolerable.

Topics: Adult; Aged; Aged, 80 and over; Antimetabolites, Antineoplastic; Carcinoma, Non-Small-Cell Lung; Cisplatin; Drug Combinations; Female; Humans; Lung Neoplasms; Male; Middle Aged; Oxonic Acid; Tegafur

Although cisplatin-based chemotherapy combined with thoracic irradiation (TRT) is a standard treatment for unresectable, locally advanced non-small cell lung cancer (NSCLC), this treatment outcome has remained unsatisfactory. We had previously conducted a phase I trial of cisplatin plus S-1, an oral 5-fluorouracil derivative, and TRT, which were safe and effective.. In this phase II trial, 48 patients with stage III NSCLC received cisplatin (40mg/m(2) on days 1, 8, 29 and 36) and S-1 (80mg/m(2) on days 1-14 and 29-42) and TRT (60Gy). The primary endpoint was the response rate.. A partial response was observed in 37 patients (77%; 95% confidence interval: 63-88%). At a median follow up of 54 months, the median progression-free survival and median survival time were 9.3 and 31.3 months, respectively. No difference in efficacy was observed when the patients were stratified by histology. Toxicities were generally mild except for grade 3 or worse febrile neutropenia and pneumonitis of 8% and 4%, respectively. No patient developed severe esophagitis. At the time of this analysis, 35 (73%) of the 48 patients recurred; 15 (31%) showed distant metastasis, 17 (35%) had loco-regional disease, and 2 (4%) showed both loco-regional disease and distant metastasis.. This chemoradiotherapy regimen yielded a relatively favorable efficacy with mild toxicities in patients with locally advanced NSCLC.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Non-Small-Cell Lung; Chemoradiotherapy; Cisplatin; Disease Progression; Drug Combinations; Female; Humans; Lung Neoplasms; Male; Middle Aged; Neoplasm Recurrence, Local; Neoplasm Staging; Oxonic Acid; Radiotherapy; Radiotherapy Dosage; Retreatment; Survival Analysis; Tegafur; Treatment Outcome

We investigated the efficacy and safety of S-1 and cisplatin with concurrent thoracic radiation (SCCR) over cisplatin alone plus concurrent thoracic radiation (CCR) for unresectable stage III non-small-cell lung cancer (NSCLC).. Between January 2009 and November 2011, 40 eligible patients with NSCLC were included and divided randomly into two groups. Twenty patients received SCCR with S-1 (orally at 40 mg/m(2) per dose, b.i.d.) on days 1 through 14, cisplatin (60 mg/m(2) on day 1) every 4 weeks for two cycles, and radiotherapy (60 Gy/30 fractions over 6 weeks) beginning on day 1. Twenty subjects received CCR (cisplatin and radiotherapy, the same as for SCCR).. The 3-year overall response rate was 59.3% and 52.4% for the SCCR and CCR groups, respectively, and the difference was statistically significant, while the median overall survival was 33 months (range, 4-41 months) and 24 months (range, 2-37 months), respectively (P = 0.048). The median progression-free survival was 31 months for SCCR (range, 5-39 months), whereas it was 20 months (range, 2-37 months) for CCR (P = 0.037). The toxicity profile was similar in both groups.. In summary, we demonstrated that S-1 and cisplatin with concurrent thoracic radiation was more effective than cisplatin plus radiotherapy in NSCLC patients with acceptable toxicity.. Chinese Clinical Trials Register: ChiCTR-TRC-13003997 .

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Large Cell; Carcinoma, Non-Small-Cell Lung; Carcinoma, Squamous Cell; Chemoradiotherapy; Cisplatin; Drug Combinations; Female; Follow-Up Studies; Humans; Lung Neoplasms; Male; Middle Aged; Neoplasm Staging; Oxonic Acid; Pilot Projects; Prognosis; Radiotherapy Dosage; Survival Rate; Tegafur; Young Adult

Although cytotoxic chemotherapy is essential in epidermal growth factor receptor (EGFR)‑mutated non‑small cell lung cancer (NSCLC), it is unclear which regimen is most effective. We retrospectively compared the efficacy of standard platinum‑based chemotherapy with that of combination chemotherapy using vinorelbine (VNR) plus dihydropyrimidine dehydrogenase‑inhibitory fluoropyrimidine (DIF) in EGFR‑mutated lung adenocarcinomas, and we investigated a potential mechanism by which the combination chemotherapy of VNR + DIF was favorable in the treatment of EGFR‑mutated lung adenocarcinoma in vitro. In our retrospective analysis, the response rate and disease control rate afforded by the VNR + DIF treatment tended to be better than those by platinum‑based chemotherapy, and the progression‑free survival of the 24 VNR + DIF‑treated patients was significantly longer than that of the 15 platinum‑based chemotherapy patients. In EGFR‑mutated PC9 cells, VNR induced EGFR dephosphorylation at a clinically achievable concentration. 1BR3‑LR cells, a line of fibroblast cells transfected with a mutant EGFR construct, were completely resistant to gefitinib in the medium containing 10% fetal bovine serum (FBS), whereas the sensitivity of these cells to gefitinib was increased in 0.5% FBS‑containing medium. Similarly, the sensitivity of 1BR3‑LR cells to VNR was increased when they were cultured in low‑serum condition. In addition, sodium orthovanadate (Na3VO4) inhibited the EGFR dephosphorylation induced by VNR or gefitinib and suppressed the cell growth inhibition by these agents in PC9 cells. VNR and gefitinib showed synergistic cell growth inhibition in combination with 5‑fluorouracil (5‑FU) in PC9 cells. We propose that the EGFR dephosphorylation induced by VNR is related to cell growth inhibitory activity of VNR, and that this is one of the mechanisms of the synergistic effect of VNR + 5‑FU in EGFR‑mutated lung cancer cells. In conclusion, the combination chemotherapy of VNR + DIF may be a promising treatment for NSCLC patients with EGFR mutations.

Topics: Adenocarcinoma; Adenocarcinoma of Lung; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Non-Small-Cell Lung; Cell Line, Tumor; Dihydrouracil Dehydrogenase (NADP); Drug Combinations; ErbB Receptors; Female; Fluorouracil; Gefitinib; Humans; Kaplan-Meier Estimate; Lung Neoplasms; Male; Middle Aged; Mutation; Oxonic Acid; Quinazolines; Retrospective Studies; Tegafur; Treatment Outcome; Vinblastine; Vinorelbine

This Phase II study was conducted to evaluate the efficacy and safety of S-1 and irinotecan combination therapy as a second-line treatment in patients with advanced non-small cell lung cancer.. Irinotecan was administered at 60 mg/m(2) on Days 1 and 8. Oral S-1 was administered on Days 1-14 every 3 weeks at 80 mg/day for patients with a body surface area of <1.25 m(2), 100 mg/day for patients with a body surface area of 1.25-1.5 m(2) and 120 mg/day for patients with a body surface area of >1.5 m(2). The primary endpoint was response rate, while the secondary endpoints were progression-free survival, overall survival and safety.. Thirty-one patients were enrolled in this study. The response and disease control rates were 6.5 and 58.1%, respectively. Progression-free survival and median survival time were 2.8 and 12.6 months, respectively. Grade 3-4 adverse events were reported for 29.0% of the patients. Hematological toxicities of Grade 3 or 4 included leukopenia (9.7%), neutropenia (9.7%), febrile neutropenia (3.2%), thrombopenia (3.2%) and anemia (6.5%). Non-hematological toxicities of Grade 3 or 4 included pneumonitis (6.5%), diarrhea, colitis, dyspnea, rash, oral mucositis, anorexia and pulmonary thromboembolism/deep vein thrombosis (3.2% each).. S-1 and irinotecan combination therapy at the present dose and schedule exhibited only modest efficacy with mild toxicities in previously treated patients with non-small cell lung cancer. No further clinical investigation with current dose and schedules is warranted for patients with non-small cell lung cancer who failed first-line platinum-based doublet chemotherapy.

Topics: Adult; Aged; Antineoplastic Agents, Phytogenic; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Carcinoma, Non-Small-Cell Lung; Drug Combinations; Female; Humans; Irinotecan; Lung Neoplasms; Male; Middle Aged; Oxonic Acid; Survival Analysis; Tegafur; Young Adult

Gefitinib, an epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI), is an effective treatment for advanced non-small cell lung cancer (NSCLC) in patients with activating EGFR mutations. However, there have been little evidence-based studies of gefitinib in combination with platinum-doublet therapy in these patients. We performed a phase II trial to determine the efficacy and safety of triplet chemotherapy with gefitinib, carboplatin, and S-1 as a first-line treatment. This was a multicentre, single-arm, phase II trial of carboplatin, S-1, and gefitinib in advanced NSCLC patients with activating EGFR mutations. Patients received four courses of these drugs in 3-4 week cycles. In each cycle, carboplatin (area under curve = 5) was administered on day 1, S-1 (80 mg/m(2)) on days 1-14, and gefitinib (250 mg) every day. Subsequently, the same regimen without carboplatin was administered until disease progression or unacceptable toxicity occurred. The 1-year progression-free survival (PFS) was the primary endpoint, while response rate (RR), PFS, overall survival (OS), and safety were secondary endpoints. Thirty-five patients were enrolled into this study. The 1-year PFS was 74.3% and the overall RR was 85.7%. The median PFS for all patients was 17.6 months (95% confidence interval 15.5-∞), but the median OS was not reached, because 28 patients were still alive after a median follow-up time of 21.4 months. Haematological adverse events (grade 3 or higher) included neutropaenia (17.1%), thrombocytopenia (14.3%), and anaemia (5.7%), while non-haematological adverse events (grade 3 or higher) included elevated aminotransferase (20.0%), diarrhoea (14.3%), and febrile neutropaenia (2.9%). No interstitial lung disease or treatment-related deaths occurred. Combination chemotherapy with carboplatin, S-1, and gefitinib is efficacious and well tolerated as a first-line treatment in advanced NSCLC patients with activating EGFR mutations.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Carboplatin; Carcinoma, Non-Small-Cell Lung; Disease-Free Survival; Drug Combinations; ErbB Receptors; Female; Gefitinib; Humans; Lung Neoplasms; Male; Middle Aged; Mutation; Oxonic Acid; Quinazolines; Tegafur; Treatment Outcome

Platinum-based two-drug combination chemotherapy has been standard of care for patients with advanced nonsmall-cell lung cancer (NSCLC). The primary aim was to compare overall survival (OS) of patients with advanced NSCLC between the two chemotherapy regimens. Secondary end points included progression-free survival (PFS), response, safety, and quality of life (QoL).. Patients with previously untreated stage IIIB or IV NSCLC, an Eastern Cooperative Oncology Group performance status of 0-1 and adequate organ function were randomized to receive either oral S-1 80 mg/m(2)/day on days 1-21 plus cisplatin 60 mg/m(2) on day 8 every 4-5 weeks, or docetaxel 60 mg/m(2) on day 1 plus cisplatin 80 mg/m(2) on day 1 every 3-4 weeks, both up to six cycles.. A total of 608 patients from 66 sites in Japan were randomized to S-1 plus cisplatin (n = 303) or docetaxel plus cisplatin (n = 305). OS for oral S-1 plus cisplatin was noninferior to docetaxel plus cisplatin [median survival, 16.1 versus 17.1 months, respectively; hazard ratio = 1.013; 96.4% confidence interval (CI) 0.837-1.227]. Significantly higher febrile neutropenia (7.4% versus 1.0%), grade 3/4 neutropenia (73.4% versus 22.9%), grade 3/4 infection (14.5% versus 5.3%), and grade 1/2 alopecia (59.3% versus 12.3%) were observed in the docetaxel plus cisplatin than in the S-1 plus cisplatin. There were no differences found in PFS or response between the two arms. QoL data investigated by EORTC QLQ-C30 and LC-13 favored the S-1 plus cisplatin.. Oral S-1 plus cisplatin is not inferior to docetaxel plus cisplatin and is better tolerated in Japanese patients with advanced NSCLC.. UMIN000000608.

Topics: Adenocarcinoma; Administration, Oral; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Large Cell; Carcinoma, Non-Small-Cell Lung; Carcinoma, Squamous Cell; Cisplatin; Docetaxel; Drug Combinations; Female; Follow-Up Studies; Humans; Lung Neoplasms; Male; Middle Aged; Neoplasm Staging; Oxonic Acid; Prognosis; Quality of Life; Survival Rate; Taxoids; Tegafur

This randomized phase II trial investigated the efficacy and safety of docetaxel plus bevacizumab and S-1 plus bevacizumab in the second-line treatment of non-squamous (non-Sq) non-small-cell lung cancer (NSCLC).. Patients with non-Sq NSCLC who experienced disease progression after prior platinum-based chemotherapy with or without bevacizumab were randomly assigned to receive docetaxel plus bevacizumab (DB) once every 3 weeks or S-1 orally twice daily on days 1-14 plus bevacizumab (SB) on day 1 every 3 weeks until disease progression.. Ninety patients were randomized. The median progression-free survival (PFS) was 3.9 months (95% confidence interval [CI]=3.0-6.5) in DB and 3.5 months (95% CI=2.9-5.9) in SB. The objective response rate was significantly higher in DB than in SB (22.2% vs. 2.2%; P=0.004), whereas the disease control rates of the arms were identical (62.2% vs. 62.2%; P=1.00). Patients receiving DB were more likely to have ≥grade 3 neutropenia (93.4% vs. 4.4%) and febrile neutropenia (33.3% vs. 0%) than SB. In DB, PFS and overall survival (OS) were significantly longer among bevacizumab-naïve patients than among bevacizumab-experienced patients (median PFS: 7.2 vs. 2.9 months; P=0.004; and median OS: 21.3 vs. 14.1 months; P=0.012).. DB and SB produced modest PFS benefits in the second-line treatment of patients with advanced non-Sq NSCLC. Because of the toxicity of DB and the low response rate of SB, neither regimen warrants further investigation, excluding DB in bevacizumab-naïve patients with advanced non-Sq NSCLC.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Carcinoma, Non-Small-Cell Lung; Docetaxel; Drug Combinations; Female; Humans; Kaplan-Meier Estimate; Lung Neoplasms; Male; Middle Aged; Neoplasm Metastasis; Neoplasm Staging; Oxonic Acid; Platinum; Retreatment; Taxoids; Tegafur; Treatment Outcome

The aims of this study were to evaluate the efficacy and safety of S-1 versus cisplatin (CDDP)+S-1 in patients with completely resected stage II and IIIA non-small cell lung cancer, and to identify predictive biomarkers whose expression in the tumors was significantly associated with patient outcome.. A total of 200 patients were randomly assigned to receive either S-1 (40 mg/m(2) twice per day) for 2 consecutive weeks repeated every 3 weeks for 1 year (S group) or CDDP (60 mg/m(2)) on day 1 plus oral S-1 (40 mg/m(2) twice per day) for 2 consecutive weeks repeated every 3 weeks for four cycles (CS group) within 8 weeks after surgery. The primary endpoints were relapse-free survival (RFS) at 2 years and identification of predictive biomarkers whose expressions have been reported to be associated with CDDP or fluoropyrimidine sensitivity.. The RFS rate at 2 years was 65.6% (95% confidence intervals; CI, 55.3-74.0%) in the S group and 58.1% (95% CI, 47.7-67.2%) in the CS group. The only gene with interaction of P < 0.05 was uridine monophosphate synthase (UMPS; P = 0.0348). The benefit that members of the S group had over members of the CS group was higher expression of UMPS. In vitro and in vivo experiments confirmed that overexpression of UMPS enhanced the antitumor effect of fluoropyrimidine.. Adjuvant S-1 monotherapy might be preferable to CDDP+S-1 for patients with completely resected NSCLC. UMPS expression may define a patient subset that would benefit from long-term postoperative S-1 monotherapy.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Biomarkers; Carcinoma, Non-Small-Cell Lung; Chemotherapy, Adjuvant; Cisplatin; Combined Modality Therapy; Drug Combinations; Drug Resistance, Neoplasm; Female; Humans; Lung Neoplasms; Male; Middle Aged; Neoplasm Staging; Oxonic Acid; Prognosis; Tegafur; Treatment Outcome; Young Adult

This study was conducted to evaluate the efficacy and safety of S-1 in patients with advanced non-small-cell lung cancer (NSCLC), receiving two or more prior chemotherapy regimens.. S-1 was administered orally for 14 consecutive days, followed by a 7-day rest period. This treatment course was repeated until disease progression or intolerable toxicity occurred.. From 2010 to 2012, 45 patients were enrolled in this study. Of the 45 patients, 4 patients [8.9 %, 95 % confidence interval (CI) 0.6-17.2 %] exhibited a partial response and 24 patients (53.3 %) exhibited stable disease. The disease control rate was 62.2 % (95 % CI 48.1-76.4 %). Median progression-free survival was 71 days, and median survival time was 205 days. Four patients had grade 3 hematological toxicities, but toxicities of grade 4 were not observed in this study.. Although S-1 monotherapy as third-line treatment or beyond was well tolerated, the response rate for this regimen did not demonstrate sufficient activity for patients with advanced NSCLC.

Topics: Adult; Aged; Aged, 80 and over; Antimetabolites, Antineoplastic; Carcinoma, Non-Small-Cell Lung; Disease-Free Survival; Drug Combinations; Female; Humans; Lung Neoplasms; Male; Middle Aged; Oxonic Acid; Tegafur

Archival formalin-fixed, paraffin-embedded (FFPE) tumor specimens were collected from advanced NSCLC patients enrolled in LETS phase III trial comparing first-line S-1/carboplatin with paclitaxel/carboplatin and subjected to multiplex genotyping for 214 somatic hotspot mutations in 26 genes (LungCarta Panel) and 20 major variants of ALK, RET, and ROS1 fusion genes (LungFusion Panel) with the Sequenom MassARRAY platform. MET amplification was evaluated by fluorescence in situ hybridization. A somatic mutation in at least one gene was identified in 48% of non-squamous cell carcinoma and 45% of squamous cell carcinoma specimens, with EGFR (17%), TP53 (11%), STK11 (9.8%), MET (7.6%), and KRAS (6.2%). Mutations in EGFR or KRAS were associated with a longer or shorter median overall survival, respectively. The LungFusion Panel identified ALK fusions in six cases (2.5%), ROS1 fusions in five cases (2.1%), and a RET fusion in one case (0.4%), with these three types of rearrangement being mutually exclusive. Nine (3.9%) of 229 patients were found to be positive for de novo MET amplification. This first multiplex genotyping of NSCLC associated with a phase III trial shows that MassARRAY-based genetic testing for somatic mutations and fusion genes performs well with nucleic acid derived from FFPE specimens of NSCLC tissue.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carboplatin; Carcinoma, Non-Small-Cell Lung; DNA Mutational Analysis; Drug Combinations; Female; Gene Expression Profiling; Humans; In Situ Hybridization, Fluorescence; Kaplan-Meier Estimate; Lung Neoplasms; Male; Mass Spectrometry; Middle Aged; Multiplex Polymerase Chain Reaction; Mutation; Oxonic Acid; Paclitaxel; Tegafur

For patients with advanced non-small cell lung adenocarcinoma that fail to respond to first-line chemotherapy and that do not involve epidermal growth factor receptor (EGFR) mutations, previous empirical analysis showed that a single second-line chemotherapy agent may be inadequate for the control of further tumor development. This study examines the combination of S-1 drugs and nedaplatin that has no cross-resistance to first-line treatments; 179 cases of IIIb-IV stage non-small-cell lung adenocarcinoma that failed to respond to first-line chemotherapy were included, and these subjects did not have mutated EGFRs. In the present study, S-1 plus nedaplatin chemotherapy was better than standard second-line chemotherapy options in the treatment of advanced lung adenocarcinoma that did not involve EGFR mutations and that failed to respond to first-line chemotherapy. Additionally, the combination of S-1 and nedaplatin seemed to be well tolerated, making this chemotherapy technique a potentially strong candidate for the treatment of advanced non-small-cell lung adenocarcinoma.

Topics: Adenocarcinoma; Adult; Aged; Anemia; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Non-Small-Cell Lung; Disease-Free Survival; Drug Combinations; Drug Therapy; ErbB Receptors; Female; Humans; Logistic Models; Lung Neoplasms; Male; Middle Aged; Multivariate Analysis; Mutation; Nausea; Neoplasm Staging; Organoplatinum Compounds; Oxonic Acid; Tegafur; Treatment Failure; Treatment Outcome; Vomiting

Although thoracic irradiation (TRT) is a standard treatment for elderly patients with locally advanced non-small-cell lung cancer (LA-NSCLC), treatment outcomes are poor. We previously reported a phase I trial combining S-1, an oral 5-fluorouracil derivative, and thoracic radiation, which yielded safe and effective outcomes.. In this phase II trial, 30 patients aged 76 years or older with LA-NSCLC received S-1 (80 mg/m(2) on days 1-14 and 29-42) and TRT (60Gy). The primary end-point was the response rate.. The median age and pre-treatment Charlson score were 79 years and 1, respectively. The mean proportions of the actual doses of S-1 and TRT delivered relative to the planned doses were 95% and 98%, respectively. Partial responses were observed in 19 patients (63%; 95% confidence interval: 45-82%), which did not attain the end-point. At a median follow-up time of 23.7 months, the median progression-free survival and median survival times were 13.0 months and 27.9 months, respectively. No difference in efficacy was observed upon stratification by tumour histology. Toxicities were generally mild, except for grade 3 or greater febrile neutropenia and pneumonitis in 7% and 10% of patients, respectively. No patient developed severe oesophagitis.. Although the primary end-point was not met, concurrent S-1 chemotherapy and radiotherapy yielded favourable survival data. Also, the combined treatment was well-tolerated in elderly patients with LA-NSCLC.

Topics: Aged; Aged, 80 and over; Carcinoma, Non-Small-Cell Lung; Disease Progression; Disease-Free Survival; Drug Combinations; Female; Fluorouracil; Humans; Lung Neoplasms; Male; Neoplasm Metastasis; Oxonic Acid; Recurrence; Tegafur; Tomography, X-Ray Computed; Treatment Outcome

S-1, a novel oral fluoropyrimidine, has potent antitumor activity against non-small-cell lung cancer (NSCLC). Meanwhile, leucovorin enhances the efficacy of 5-fluorouracil by inhibiting thymidylate synthase. Therefore, this phase II clinical trial evaluated the safety and efficacy of S-1 plus leucovorin combination therapy for previously treated patients with NSCLC.. Patients with stage IIIB or IV NSCLC were prospectively enrolled if they received 1 or 2 prior chemotherapy regimens. S-1 (40-60 mg) and leucovorin (25mg) were administered together orally twice per day for 7 consecutive days followed by 7 days of rest. This 2-week cycle was repeated for a maximum of 25 cycles until the onset of disease progression or unacceptable adverse events. Endpoints included objective tumor response, progression-free survival, overall survival, and safety.. Among 33 patients, 6 (18.2%), 14 (42.4%), and 11 (33.3%) had partial response, stable disease, and progressive disease, respectively. Median progression-free and overall survival times were 3.5 and 11.7 months, respectively. The common grade 3 toxicities included stomatitis (18.2%), anorexia (12.1%), and neutropenia (9.1%). One patient had pneumatosis cystoides intestinalis, and another experienced paralytic ileus. There were no treatment-related deaths.. S-1 plus leucovorin combination therapy demonstrated promising efficacy and an acceptable toxicity profile in previously treated patients with NSCLC.

Topics: Administration, Oral; Adult; Aged; Carcinoma, Non-Small-Cell Lung; Disease-Free Survival; Drug Combinations; Drug-Related Side Effects and Adverse Reactions; Female; Humans; Leucovorin; Male; Middle Aged; Oxonic Acid; Tegafur

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.. 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.. 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 %.. 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).

Topics: Aged; Aged, 80 and over; Carcinoma, Non-Small-Cell Lung; Chemotherapy, Adjuvant; Drug Administration Schedule; Drug Combinations; Feasibility Studies; Female; Humans; Male; Neoplasm Staging; Oxonic Acid; Pneumonectomy; Postoperative Period; Randomized Controlled Trials as Topic; Tegafur

To determine the recommended dose (RD) in concurrent conformal radiotherapy with S-1 and cisplatin chemotherapy for inoperable stage III non-small-cell lung cancer.. Eligible patients with inoperable stage III non-small-cell lung cancer, age ≥ 20 years, performance status 0-1 received 4 cycles of intravenous cisplatin (60 mg/m(2), day 1) and oral S-1 (80, 100, or 120 mg based on body surface area, days 1-14) repeated every 4 weeks. Radiation doses were 66, 70, and 74 Gy for arms 1, 2, and 3, respectively.. A total of 24 patients were enrolled in our study, including 6 in arm 1, 6 in arm 2, and 12 in arm 3. The patients consisted of 14 men and 10 women, with a median age of 63 years (range, 44-73 years). The median follow-up was 27.3 months (range, 8.5-42.6 months) for all patients and 33.9 months (range, 15.2-42.6 months) for those still alive. Grade 3 febrile neutropenia, lung toxicities, and heart toxicities occurred in 2, 2, and 2 patients, respectively. Dose-limiting toxicity occurred in 2, none, and 1 patient in arms 1, 2, and 3, respectively. The median survival was not reached, and the 2-year survival rate was 70% (95% CI, 51%-89%). Two-year local relapse-free survival and distant metastasis-free survival were 74% (95% CI, 56%-92%) and 45% (95% CI, 25%-65%), respectively.. High-dose radiotherapy with S-1 and cisplatin is feasible, and 74 Gy was determined as the recommended dose.

Topics: Adenocarcinoma; Adenocarcinoma, Bronchiolo-Alveolar; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Large Cell; Carcinoma, Non-Small-Cell Lung; Carcinoma, Squamous Cell; Chemoradiotherapy; Cisplatin; Dose Fractionation, Radiation; Drug Combinations; Female; Follow-Up Studies; Humans; Imaging, Three-Dimensional; Lung Neoplasms; Male; Middle Aged; Neoplasm Recurrence, Local; Neoplasm Staging; Oxonic Acid; Prognosis; Radiotherapy, Conformal; Survival Rate; Tegafur

A previous phase 3 trial demonstrated noninferiority in terms of overall survival for combined S-1 (an oral fluoropyrimidine) and carboplatin compared with combined paclitaxel and carboplatin as first-line treatment for advanced non-small cell lung cancer (NSCLC). In the current study, the authors evaluated the efficacy and safety of combined S-1, carboplatin, and bevacizumab followed by maintenance with S-1 and bevacizumab in chemotherapy-naive patients with advanced nonsquamous NSCLC.. Patients received carboplatin (area under the concentration-time curve, 5 mg mL(-1) per minute) and bevacizumab (15 mg/kg) on day 1 plus oral S-1 (80 mg/m2 per day) on days 1 through 14 every 21 days for up to 6 cycles. For patients without disease progression, S-1 and bevacizumab were continued until disease progression or unacceptable toxicity developed.. Forty-eight patients were enrolled in the phase 2 study; of these, 35 patients (72.9%) completed at least 4 cycles. Most toxicities of grade ≥3 were hematologic, and no increase in relative incidence associated with maintenance with S-1 and bevacizumab was observed. The objective response rate was 54.2% (95% confidence interval, 39.2%-68.6%), and the median progression-free survival was 6.8 months (95% confidence interval, 4.3-8.2 months).. The regimen of combined S-1, carboplatin, and bevacizumab followed by maintenance with S-1 and bevacizumab was active and feasible as first-line treatment for advanced nonsquamous NSCLC.

Topics: Adult; Aged; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Carboplatin; Carcinoma, Non-Small-Cell Lung; Disease-Free Survival; Drug Administration Schedule; Drug Combinations; Female; Humans; Lung Neoplasms; Male; Middle Aged; Oxonic Acid; Tegafur; Treatment Outcome

The purpose of this study was to evaluate the feasibility and compliance of adjuvant chemotherapy of S-1 plus carboplatin for patients with completely resected non-small cell lung cancer (NSCLC) of pathological stage IB-IIIB.. S-1 was given orally at a dose of 80 mg/m²/day for 2 weeks, followed by a 2-week period of no treatment. Carboplatin was given intravenously on day 8 at an area under the curve of 6. This regimen was repeated for four to six 28-day courses.. Seventeen patients were enrolled in this study. Fourteen of them completed at least 4 cycles of chemotherapy. Nine patients had grade 2 and three patients had grade 3 thrombocytopenia, respectively. Severe nonhematologic toxicities were uncommon. Treatment was delayed in a few patients because of prolonged thrombocytopenia.. We concluded that the regimen was feasible and tolerable for patients with completely resected NSCLC as adjuvant chemotherapy.

Topics: Aged; Antineoplastic Agents; Area Under Curve; Carboplatin; Carcinoma, Non-Small-Cell Lung; Chemotherapy, Adjuvant; Drug Combinations; Female; Humans; Lung Neoplasms; Male; Middle Aged; Neoplasm Staging; Oxonic Acid; ROC Curve; Tegafur; Thrombocytopenia; Treatment Outcome

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Non-Small-Cell Lung; Cisplatin; Docetaxel; Drug Combinations; Humans; Japan; Middle Aged; Oxonic Acid; Taxoids; Tegafur; Young Adult

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.. 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.. 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%).. 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.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Non-Small-Cell Lung; Chemotherapy, Adjuvant; Cisplatin; Docetaxel; Drug Administration Schedule; Drug Combinations; Feasibility Studies; Female; Humans; Lung Neoplasms; Male; Middle Aged; Oxonic Acid; Taxoids; Tegafur; Young Adult

To determine the efficacy and safety of oral S-1 in combination with cisplatin and thoracic radiotherapy in patients with unresectable stage III non-small-cell lung cancer (NSCLC).. S-1 (50mg/m(2)) was administered orally twice daily for 14 days, with cisplatin (40 mg/m(2)) on days 1 and 8 of each cycle every 3 weeks, for 2-4 cycles. Thoracic radiation therapy was administered in 2 Gy fractions five times weekly for a total dose of 60 Gy. The primary endpoint was the response rate, and secondary endpoints included progression-free survival, overall survival and safety.. Forty-one patients were enrolled in this study. The objective response rate was 87.8% (98% CI: 77.8-97.8%). The median progression-free survival was 467 days (15.4 months), and the median survival time was 904 days (29.7 months). The overall survival rates at 1- and 2-years were 85.7% and 52.9%, respectively. Hematological toxicities included grade 3/4 neutropenia (17%) and grade 3/4 leukopenia (27%). No grade 3 febrile neutropenia was detected, and grade 3/4 non-hematological toxicities were also mild. A grade 3 gastrointestinal hemorrhage was observed in one patient.. The combination of oral S-1 plus cisplatin with concurrent radiotherapy is a promising treatment with a high efficacy and lower toxicity in patients with locally advanced NSCLC.

Topics: Adult; Aged; Carcinoma, Non-Small-Cell Lung; Chemoradiotherapy; Cisplatin; Disease-Free Survival; Drug Combinations; Female; Humans; Leukopenia; Lung Neoplasms; Male; Middle Aged; Neoplasm Staging; Neutropenia; Oxonic Acid; Tegafur

A phase I study was performed to evaluate dose-limiting toxicity and the recommended dose for the oral fluoropyrimidine S-1 administered concurrently with thoracic radiotherapy (TRT) in elderly (≥ 70 years of age) patients with locally advanced non-small cell lung cancer.. S-1 was administered on days 1 to 14 and 22 to 35 at oral doses of 65 or 80 mg m(-2) day(-1). TRT was administered in 2-Gy fractions five times weekly for a total dose of 60 Gy. Twelve previously untreated patients were treated with S-1 at 65 (n=6) or 80 (n=6) mg m(-2) day(-1).. All patients completed the planned 60 Gy of TRT. Dose-limiting toxicity included pneumonitis (n=2), infection (n=1), and stomatitis (n=1), each of grade 3, but each event was reversible. The recommended dose for S-1 was determined to be 80 mg m(-2) day(-1). No patient experienced toxicity of grade 4. The dose intensity of S-1 was well maintained and the combination of S-1 plus TRT was well tolerated overall. The overall response rate was 83.3 %, with a median survival time of 34.0 months.. Administration of S-1 at 80 mg m(-2) day(-1) on days 1 to 14 and 22 to 35 can be safely combined with concurrent TRT in elderly patients with locally advanced non-small cell lung cancer.

Topics: Aged; Aged, 80 and over; Antimetabolites, Antineoplastic; Carcinoma, Non-Small-Cell Lung; Dose-Response Relationship, Drug; Drug Combinations; Female; Humans; Lung Neoplasms; Male; Maximum Tolerated Dose; Oxonic Acid; Tegafur

A phase III study (Lung Cancer Evaluation of TS-1) previously demonstrated noninferiority in terms of overall survival (OS) at interim analysis for carboplatin-S-1 compared with carboplatin-paclitaxel for first-line treatment of advanced non-small-cell lung cancer (NSCLC).. A total of 564 patients were randomly assigned to receive either carboplatin on day 1 plus oral S-1 on days 1-14 or carboplatin-paclitaxel on day 1 every 21 days. Updated results and post hoc subgroup analysis according to tumor histology are presented.. The updated analysis revealed a median OS of 15.2 months in the carboplatin-S-1 arm and 13.1 months in the carboplatin-paclitaxel arm, with a hazard ratio (HR) of 0.956 [95% confidence interval (CI) 0.793-1.151], consistent with the previous primary analysis. Median OS was 14.0 months in the carboplatin-S-1 arm and 10.6 months in the carboplatin-paclitaxel arm (HR 0.713; 95% CI 0.476-1.068) for patients with squamous cell carcinoma (SCC), with corresponding values of 15.5 and 13.9 months (HR 1.060; 95% CI 0.859-1.308) for those with non-SCC.. These results establish the efficacy and safety of carboplatin-S-1 in patients with advanced NSCLC regardless of tumor histology.

Topics: Adult; Aged; Antimetabolites, Antineoplastic; Antineoplastic Agents, Phytogenic; Antineoplastic Combined Chemotherapy Protocols; Carboplatin; Carcinoma, Non-Small-Cell Lung; Cross-Linking Reagents; Disease-Free Survival; Drug Combinations; Female; Humans; Japan; Lung Neoplasms; Male; Middle Aged; Oxonic Acid; Paclitaxel; Tegafur; Treatment Outcome; Young Adult

Both amrubicin (Am) and S-1 are effective against non-small-cell lung cancer (NSCLC), and preclinical studies have demonstrated that the effect of tegafur/uracil, the original compound of S-1, in combination with Am significantly inhibits tumor growth.. We conducted a phase I/II study of Am and S-1 against pretreated NSCLC without EGFR mutation. We fixed the dose of S-1 at 40 mg/m(2) on days 1-14 and escalated the Am dose in increments of 5 mg/m(2) from a starting dose of 30 mg/m(2)/day on days 1-3 and repeated the cycle every 4 weeks.. Twenty-six patients were registered. In phase I, at an Am dose of 35 mg/m(2)/day, three patients experienced grade 2 leukopenia during S-1 administration, and S-1 was withdrawn. Another patient developed grade 2 serum bilirubin in the first cycle. DLTs were observed in four of six patients at this dose level, and therefore, 30 mg/m(2)/day was set as the recommended dose for Am. Twenty patients received this recommended Am dose. Febrile neutropenia was observed in two patients, and one patient developed a grade 4 increase in serum creatinine. Grade 3 vomiting, infection, hypotension, and urinary retention were observed in one patient each, respectively. Other toxicities were mild, and there were no treatment-related deaths. Two patients showed a CR, three showed a PR, and the overall response rate was 25.0%. The median progression-free and the median survival times were 3.8 and 15.6 months, respectively, and the 1-year survival rate was 60%.. Am and S-1 every 4 weeks is an effective combination for pretreated NSCLC without EGFR mutation.

Topics: Adult; Aged; Anthracyclines; Antibiotics, Antineoplastic; Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Non-Small-Cell Lung; Disease-Free Survival; Dose-Response Relationship, Drug; Drug Combinations; ErbB Receptors; Female; Humans; Kaplan-Meier Estimate; Lung Neoplasms; Male; Middle Aged; Mutation; Oxonic Acid; Survival Analysis; Tegafur

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.

Topics: Aged; Antimetabolites, Antineoplastic; Carcinoma, Non-Small-Cell Lung; Disease Progression; Drug Combinations; Female; Humans; Lung Neoplasms; Male; Middle Aged; Oxonic Acid; Survival Rate; Tegafur; Treatment Outcome

To evaluate the efficacy and feasibility of the consolidation therapy of the oral fluoropyrimidine agent S-1 after concurrent chemoradiotherapy for unresectable stage III non-small cell lung cancer (NSCLC).. Eligible patients had unresectable stage III NSCLC with performance status of 0 or 1. Chemoradiotherapy at a total dose of 60 Gy consisted of cisplatin (80 mg/m(2)) on days 1 and 29, vinorelbine (20 mg/m(2)) on days 1, 8, 29 and 36. Sequential consolidation S-1 therapy was commenced at a dose of 80-120 mg twice daily on day 57 with two cycles of 4 weeks administration and 2 weeks withdrawal.. Of the 66 patients, 65 were evaluated. Chemoradiotherapy was completed in 57 (87.7%) patients, and S-1 consolidation therapy was administered in 45 (69.2%) and completed in 31 (47.6%). Grade 3 pneumonitis developed in three patients with one dying of it. The response rate was 61.5% (95% confidence interval [CI], 48.6-73.3%). The median progression-free survival was 10.2 (95%CI, 8.6-13.7) months and median survival time 21.8 (95%CI, 15.6-27.6) months. The 1- and 3-year survival rates were 73.9% and 34.0%, respectively.. Chemoradiotherapy with cisplatin and vinorelbine followed by S-1 consolidation demonstrated a reasonable overall survival in patients with stage III NSCLC. However, less than half of the patients completed this regimen, and the additional effect of S-1 was marginal compared with historical control. We concluded that chemoradiotherapy alone is still the recommended standard treatment for patients.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Non-Small-Cell Lung; Chemoradiotherapy; Cisplatin; Combined Modality Therapy; Drug Combinations; Female; Humans; Lung Neoplasms; Male; Middle Aged; Neoplasm Grading; Neoplasm Staging; Oxonic Acid; Tegafur; Treatment Outcome; Vinblastine; Vinorelbine

S-1, an oral fluoropyrimidine, is usually given for 4 weeks (80 mg/m2/day) followed by a 2-week rest. However, compliance with this regimen is unsatisfactory because of adverse events such as leukopenia, anorexia, and nausea. To reduce adverse effects and improve compliance, we studied a "5-day on/2-day off" low-dose regimen of S-1 and evaluated pharmacokinetics in patients with non-small-cell lung cancer (NSCLC).. Twelve patients with NSCLC were divided into 2 groups and received S-1 in a dose of 25 mg twice daily (level 1, n = 6) or 40 mg twice daily (level 2, n = 6) for 5 consecutive days followed by a 2-day rest (5 days on/2 days off) every week. Plasma 5-fluorouracil (5-FU) concentrations were measured.. The maximum concentration in plasma and the area under the plasma concentration-time curve from 0 to 9 h were respectively 55.3 ± 21.1 ng/ml and 290.2 ± 95.7 ng·hr/ml for level 1, as compared with 104.2 ± 33.5 ng/ml and 541.9 ± 232.3 ng·hr/ml for level 2. These values were similar to those previously reported for a continuous intravenous infusion of 5-FU. Adverse events were grade 1 fatigue (n = 1 in each group) and anorexia (n = 1 in each group).. A "5-day on/2-day off" low-dose (40 mg twice daily) regimen of S-1 is feasible for the treatment of NSCLC, with acceptable plasma 5-FU concentrations and minimal adverse effects. A phase II or III trial of this regimen in an adjuvant setting is warranted in patients with NSCLC.

Topics: Administration, Oral; Aged; Aged, 80 and over; Antimetabolites, Antineoplastic; Carcinoma, Non-Small-Cell Lung; Drug Combinations; Female; Follow-Up Studies; Gas Chromatography-Mass Spectrometry; Humans; Lung Neoplasms; Male; Middle Aged; Neoplasm Staging; Oxonic Acid; Patient Compliance; Pyridines; Tegafur; Treatment Outcome

Oral adjuvant chemotherapy without hospitalization might reduce the physiological and psychological burden on patients if effectiveness could be guaranteed. We conducted a multicenter feasibility study using S-1, an oral derivative of 5-fluorouracil, as postoperative adjuvant chemotherapy in patients with curatively resected pathologically stage IB-IIIA non-small-cell lung cancer.. Adjuvant chemotherapy comprised 8 courses (4-week administration, 2-week withdrawal) of S-1 at 80-120 mg per day. Fifty-one patients from 7 institutions were enrolled in this pilot study, from June 2005 to March 2007. The primary end point was the completion rate of scheduled adjuvant chemotherapy. Secondary end points were the incidence and grade of adverse reactions.. Fifty patients were eligible. The completion rate for the planned 8 courses of S-1 administration was 72.0% (36 patients). Total percentage administration amount was 71.1%. Grade 3 adverse reactions such as neutropenia (4.0%), anorexia (4.0%), thrombopenia (2.0%), anemia (2.0%), elevated total bilirubin (2.0%), hypokalemia (2.0%), nausea (2.0%), and diarrhea (2.0%) were observed, but no grade 4 adverse effects were encountered. Overall and relapse-free survival rates at 3 years were 87.7% and 69.4%, respectively.. Postoperative 1-year administration of S-1 seems feasible as oral adjuvant chemotherapy for lung cancer. The oral formulation and low incidence of adverse reactions permit treatment on an outpatient basis. The present study would be reasonable to follow up with a properly powered phase III trial.

Topics: Administration, Oral; Aged; Ambulatory Care; Antimetabolites, Antineoplastic; Carcinoma, Non-Small-Cell Lung; Chemotherapy, Adjuvant; Combined Modality Therapy; Dose-Response Relationship, Drug; Drug Combinations; Feasibility Studies; Female; Follow-Up Studies; Humans; Incidence; Lung Neoplasms; Male; Middle Aged; Neoplasm Recurrence, Local; Oxonic Acid; Tegafur; Treatment Outcome

This phase I/II study was designed to evaluate a combination of irinotecan and S-1 a new regimen for salvage chemotherapy in patients with advanced or metastatic non-small cell lung cancer (NSCLC).. The study group comprised patients with advanced or metastatic NSCLC who had previously received at least one platinum-containing chemotherapy. Patients received irinotecan on days 1, 15 and oral S-1 (40 mg/m(2) twice daily as a fixed dose) on day 1 to 14 of a 28-day cycle.. In the phase I part, irinotecan was given in escalating doses of 70 (Level 1), 80 (Level 2), and 90 mg/m(2) (Level 3). Three of the 5 patients given Level 3 had dose-limiting toxicity, and Level 2 (80 mg/m(2) of irinotecan) was designated as the recommended dose. In phase II, 38 patients received a median of 7.4 cycles of irinotecan at the recommended dose. The overall response rate was 15.8 % (90 % confidence interval (CI): 6.1-25.5 %), and the median progression-free and overall survival times were 4.5 months (95 % CI: 3.5-5.0) and 15.0 months (95 % CI: 9.5-20.6) months, respectively. Toxicity was generally mild. Grade 3 or higher toxicity included neutropenia in 17.9 % of the patients, thrombocytopenia in 5.1 % and nausea in 7.7 %.. Combination chemotherapy with S-1 and irinotecan was considered an effective salvage regimen in patients with advanced or metastatic NSCLC.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Carcinoma, Non-Small-Cell Lung; Disease-Free Survival; Dose-Response Relationship, Drug; Drug Combinations; Female; Humans; Irinotecan; Lung Neoplasms; Male; Maximum Tolerated Dose; Middle Aged; Oxonic Acid; Salvage Therapy; Survival Rate; Tegafur; Treatment Outcome

We investigated the efficacy and toxicity of a novel oral 5-fluorouracil (5-FU) formulation (S-1), administered according to a tailored dose regimen.. S-1 was administered orally for 28 days, followed by 14 days of no treatment, in 23 patients who received a tailored dose of S-1, adjusted on the basis of individual creatinine clearance and body surface area. In 8 of the patients, pharmacokinetic study was performed on the 6 points on 7th day after S-1 administration.. Of the 23 patients enrolled in this study, 2 (8.7 %) had a partial response and 14 (60.9 %) had stable disease. The disease control rate was 69.6 % (16/23) (95 % confidence interval, 50.8-88.4 %). Grade 3/4 hematologic and non-hematologic toxicities were minor. In the pharmacokinetic study group, the maximum plasma concentration (C (max)) and the area under the plasma concentration curve of 5-FU at all 6 points after administration of the tailored S-1 dose regimen were similar to the values reported in a previous study describing cancer patients with normal renal function who received a standard dose of S-1 (80 mg/m(2)/day).. Our results suggest that tailored S-1 monotherapy is safe and therapeutically useful as first-line treatment for elderly patients with advanced and recurrent non-small cell lung cancer.

Topics: Aged; Aged, 80 and over; Antimetabolites, Antineoplastic; Body Surface Area; Carcinoma, Non-Small-Cell Lung; Creatinine; Disease-Free Survival; Drug Administration Schedule; Drug Combinations; Female; Fluorouracil; Humans; Lung Neoplasms; Male; Oxonic Acid; Tegafur; Treatment Outcome

Combination of S-1, an oral fluorouracil derivative, plus docetaxel against non-small cell lung cancer (NSCLC) showed promising efficacy but clinically problematic emesis. A phase I/II study utilising a new schedule for this combination was conducted.. A biweekly regimen of docetaxel on day 1 with oral S-1 on days 1-7 was administered to previously treated NSCLC patients. Doses of docetaxel/S-1 were escalated to 30/80, 35/80, and 40/80 mg m(-2), respectively, and its efficacy was investigated at the recommended dose below maximum tolerated dose (MTD).. In phase I study employing 13 patients, dose-limiting toxicities were febrile neutropenia and treatment delay, with the respective MTDs for docetaxel 40 mg m(-2)/S-1 80 mg m(-2). In the phase II study, 34 patients were treated with docetaxel 35 mg m(-2)/S-1 80 mg m(-2) for a median cycle of 6. The response and disease control rates were 34.3% (95% confidence interval (CI), 18.6-50.0%) and 62.9% (95% CI, 46.8-72.9%), respectively. Median progression-free survival was 150.5 days. Haematologic grade 4 toxicities were observed in neutropenia (11.8%) and thrombocytopenia (2.9%). Regarding non-haematologic toxicities, including emesis, there were no grade 3/4 side effects.. Combination of 1-week administration of S-1 with biweekly docetaxel is safe and active for NSCLC.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Non-Small-Cell Lung; Disease-Free Survival; Docetaxel; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Combinations; Humans; Lung Neoplasms; Oxonic Acid; Taxoids; Tegafur

S-1, an oral 5-fluorouracil derivative, is effective against advanced non-small cell lung cancer (NSCLC) with mild toxicity and synergistic effects with radiation in preclinical trials. In this phase I study, we evaluated the dose-limiting toxicity and recommended dose of S-1 for a future phase II study when administered concurrently with thoracic radiation (total dose of 60 Gy at 2 Gy per daily fraction) in elderly patients (>75 years old) with localized advanced NSCLC. S-1 was administered on days 1-14 and 29-42 at the following dosages: 60, 70, and 80 mg/m(2)/day. Twenty-two previously untreated patients were enrolled in this study. Dose-limiting toxicity included febrile neutropenia, thrombocytopenia, stomatitis, and pneumonitis. One patient had grade 5 radiation pneumonitis. No other patient experienced radiation pneumonitis or esophagitis exceeding grade 2. The recommended dose for S-1 was determined to be 80 mg/m(2)/day, which produced an overall response rate of 75% (n=12). The median progression-free survival time was 11.5 months (95% confidence interval: 7.1-15.8 months) with a median follow-up time of 27.9 months. These results indicate that concurrent treatment with S-1 and thoracic radiation is a feasible option for NSCLC in the elderly. A phase II study is currently under way.

Topics: Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Non-Small-Cell Lung; Combined Modality Therapy; Dose-Response Relationship, Drug; Drug Combinations; Female; Humans; Lung Neoplasms; Male; Oxonic Acid; Survival Rate; Tegafur

We examined the safety and efficacy of the combination of S-1 and biweekly docetaxel in patients with previously treated advanced non-small-cell lung cancer (NSCLC).. Patients with previously treated advanced NSCLC were eligible if they had a performance status of 2 or less, were 80 years or younger, and had adequate organ function. Forty-nine patients (38 men and 11 women; median age, 66 years; range 43-79 years) were enrolled. Patients were treated with the combination of 80 mg/m(2) per day of S-1 for 14 consecutive days and 35 mg/m(2) of docetaxel on days 1 and 15 every 4 weeks.. The overall response rate was 16.3% (95% confidence interval, 7.6-30.5%). The disease-control rate was 49.0% (95% confidence interval, 34.4-63.7%). The median survival time after this treatment was 9 months (range 1-22 months). The median progression-free survival time was 3 months (range 1-11 months). Response rates and survival times did not differ significantly according to the histological type. Grade 3-5 toxicities included neutropenia in 51.0% of patients, thrombocytopenia in 2.0%, anemia in 20.4%, infection in 24.5%, anorexia in 12.2%, diarrhea in 14.3%, nausea in 6.1%, and dehydration in 4.2%. There was 1 treatment-related death due to severe anorexia, stomatitis, diarrhea, and, as consequence, dehydration.. The combination of S-1 and biweekly docetaxel is an acceptable therapeutic option in patients with previously treated advanced NSCLC regardless of the histological type.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Non-Small-Cell Lung; Disease-Free Survival; Docetaxel; Drug Combinations; Female; Humans; Lung Neoplasms; Male; Middle Aged; Oxonic Acid; Survival Rate; Taxoids; Tegafur; Treatment Outcome

Standard second-line chemotherapies for non-small cell lung cancer (NSCLC) have been established but have limited clinical relevance. S-1 is a recently developed agent with potential activity against NSCLC.. Patients with confirmed NSCLC recurrence after previous single- or two-regimen chemotherapy with platinum, performance status of 0 to 1, adequate organ functions, and measurable lesions were treated with S-1 (60 mg/m/d, twice a day) on days 1 to 14 and gemcitabine (1000 mg/m) on days 8 and 15, which were repeated every 3 weeks until tumor progression.. Treatment was administered for a median of 4 courses (range, 1-13) over a median of 125-day period in 34 patients. The overall response rate was 23.5% (no complete response and eight partial response; 95% confidence interval: 9.1-38.0%). The median progression-free and overall survival times were 6.6 and 19.9 months, respectively. The 1- and 2-year survival rates were 58.8 and 30.9%, respectively. Toxicity was mild during the entire treatment period, except for three grade 3 interstitial pneumonia.. The primary end point was met with the relatively high overall response rate. Randomized phase III studies for elucidating survival outcome of the regimen are warranted.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Large Cell; Carcinoma, Non-Small-Cell Lung; Carcinoma, Squamous Cell; Deoxycytidine; Drug Combinations; Drug Resistance, Neoplasm; Female; Gemcitabine; Humans; Lung Neoplasms; Male; Middle Aged; Neoplasm Recurrence, Local; Neoplasm Staging; Oxonic Acid; Platinum; Salvage Therapy; Survival Rate; Tegafur; Time Factors; Treatment Outcome

This phase I study was conducted to evaluate the feasibility and to determine the recommended doses of the combination therapy of S-1 and irinotecan (CPT-11) in patients with advanced non-small cell lung cancer (NSCLC) as second-line treatment.. Patients with NSCLC who were previously treated with one chemotherapy regimen and had a performance status of 0 or 1 were eligible. CPT-11 was administered at 60 mg/m² (level 1), 80 mg/m² (level 2) on days 1 and 8, and oral S-1 was administered at 80 mg/day for body surface area (BSA) less than 1.25 m², 100 mg/day for BSA 1.25-1.5 m², and 120 mg/day for BSA more than 1.5 m² on days 1-14 every 3 weeks. The dose-limiting toxicity (DLT) was defined as grade 4 leukocytopenia or neutropenia, grade ≥ 3 neutropenia with fever over 38°C, grade ≥ 3 thrombocytopenia, or grade ≥ 3 major nonhematological toxicities.. Nine patients were enrolled in the study. None of 3 patients enrolled in level 1 had any DLT. Of 6 patients in level 2, 2 patients had grade 3 diarrhea and one had grade 3 interstitial pneumonia. Level 1 was declared as the recommended dose.. The feasibility of the combination therapy of S-1 and CPT-11 was shown in the second-line setting for the treatment of advanced NSCLC. The recommended dose of CPT-11 was 60 mg/m² combined with standard dose of S-1 for phase II trials of pretreated advanced NSCLC patients.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Carcinoma, Non-Small-Cell Lung; Dose-Response Relationship, Drug; Drug Combinations; Female; Humans; Irinotecan; Lung Neoplasms; Male; Maximum Tolerated Dose; Middle Aged; Oxonic Acid; Tegafur

Although S-1 has been shown to have activity against advanced nonsmall-cell lung cancer (NSCLC), its efficacy for elderly patients remains unclear. This phase II study evaluated the efficacy and safety of S-1 as a first-line treatment for elderly patients. Chemotherapy-naïve patients aged 70 years or older with stages IIIB to IV or postoperative NSCLC and performance status 1 or lower were eligible. Patients received S-1 approximately equivalent to 80 mg/m/day for 2 weeks followed by a 1-week rest period every 3 weeks. The primary end point was the response rate. Secondary end points were toxicity, disease control rate, progression-free survival, and overall survival. Twenty-nine patients were eligible. The median age was 78 years (range, 70-85 years). The overall response rate and the disease control rate were 27.6 [95% confidence interval (CI), 11.3-43.9%] and 65.5% (95% CI: 48.2-82.8%), respectively. The median progression-free survival time was 4.0 months (95% CI: 4.0-9.8 months). The median overall survival was 12.1 months (95% CI: 13.8-25.5 months) and the 1-year survival rate was 53.6%. No grade 4 toxicities were observed. The only hematological toxicity of grade 3 was anemia in 6.9% of patients. The grade 3 nonhematological toxicities included hyponatremia, anorexia, nausea, oral mucositis, and diarrhea in 3.4% of patients and infection in 6.9% of patients. S-1 monotherapy was effective and well tolerated as a first-line treatment for elderly patients with advanced NSCLC. The results of this study warrant further investigations of this regimen, including a randomized controlled trial.

Topics: Aged; Aged, 80 and over; Antimetabolites, Antineoplastic; Carcinoma, Non-Small-Cell Lung; Disease-Free Survival; Drug Combinations; Female; Follow-Up Studies; Humans; Lung Neoplasms; Male; Neoplasm Staging; Oxonic Acid; Prospective Studies; Survival Rate; Tegafur; Treatment Outcome

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.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Antimetabolites, Antineoplastic; Carcinoma, Large Cell; Carcinoma, Non-Small-Cell Lung; Carcinoma, Squamous Cell; Drug Combinations; Female; Follow-Up Studies; Humans; Lung Neoplasms; Male; Middle Aged; Neoplasm Staging; Oxonic Acid; Prognosis; Salvage Therapy; Survival Rate; Tegafur

The aim of this study was to evaluate the efficacy and toxicity of a novel oral 5-fluorouracil formulation (S-1) as second-line therapy after platinum agent chemotherapy for advanced non-small cell lung cancer (NSCLC).. S-1 was administered orally at a dose of 80 mg/m(2) for 28 days, followed by 14 days of rest (1 cycle); treatment was repeated until disease progression, unacceptable toxicity, or patient refusal.. Of the 46 patients enrolled in this study, 44 were evaluable. Six patients (14%) exhibited a partial response and 28 (64%) showed stable disease. Disease-control rate was 77.3% (34/44) (95% CI, 64.9-89.7%). The overall response rate was 14% (6/44) (95% CI, 3.5-23.8%). Median progression-free survival was 4.2 months. The median survival time was 16.4 months, and the one-year survival rate 60.3%. Grade 3/4 hematological toxicities were minor. All of those adverse reactions were tolerable and reversible.. This study demonstrated the efficacy of S-1 monotherapy as second-line treatment for advanced NSCLC.

Topics: Administration, Oral; Aged; Carcinoma, Non-Small-Cell Lung; Disease Progression; Disease-Free Survival; Drug Combinations; Drug Resistance, Neoplasm; Female; Follow-Up Studies; Hematologic Diseases; Humans; Lung Neoplasms; Male; Middle Aged; Neoplasm Staging; Oxonic Acid; Platinum Compounds; Recurrence; Tegafur; Treatment Outcome

S-1 is a rationally designed oral agent that combines the 5-fluorouracil prodrug tegafur with gimeracil and oteracil, which inhibit 5-fluorouracil degradation by dihydropyrimidine dehydronase and phosphorylation within the gastrointestinal tract, respectively, to increase antineoplastic activity while reducing gastrointestinal toxicity. We investigated the activity and toxicity of S-1 in combination with cisplatin in patients with unresectable non-small cell lung cancer (NSCLC).. Cisplatin, 75 mg/m, was administered intravenously on day 1, with S-1, 25 mg/m PO two times a day, days 1 to 14, every 21 days for a maximum of six cycles. Primary end point was overall response.. A total of 58 patients received at least one cycle of protocol-specified therapy. The best overall response rate was 23.2% (95% confidence interval: 13.0-36.4), and the disease control rate was 67.9%. The median progression-free survival was 4.0 months (95% confidence interval: 3.3-5.5). There did not appear to be any relationship between response to therapy and tumor histology. The most frequently reported adverse events of G3 or more (≥10%) were neutropenia (28%), hyponatremia (19%), diarrhea (17%), hypokalemia (12%), fatigue (10%), dehydration (10%), and deep vein thrombosis (10%).. Although the S-1 + cisplatin regimen used in this study appeared to have a similar level of antitumor activity and toxicity to that of established cisplatin-based doublets in NSCLC, the protocol-specified criteria of sufficient efficacy to warrant further study with an objective response rate ≥30% was not achieved. Therefore, while S-1 appears to be a promising agent in NSCLC, further evaluation should be conducted to determine the optimal S-1-based regimen to take forward for additional study.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Large Cell; Carcinoma, Non-Small-Cell Lung; Carcinoma, Squamous Cell; Cisplatin; Drug Combinations; Female; Follow-Up Studies; Humans; Lung Neoplasms; Male; Middle Aged; Neoplasm Metastasis; Neoplasm Staging; Oxonic Acid; Survival Rate; Tegafur; Treatment Outcome

Platinum-free regimens can represent an alternative for advanced non-small cell lung cancer (NSCLC) if similar efficacy is provided with better tolerability. This study evaluated the efficacy and safety of combined irinotecan and S-1 for chemotherapy-naïve advanced NSCLC.. Chemotherapy consisted of 4-week cycles of intravenous irinotecan (100 mg/m(2), days 1 and 15) and oral S-1 (80 mg/m(2), days 1-14). The primary endpoint was response rate, while secondary endpoints were overall survival, progression-free survival (PFS), and safety.. A total of 112 cycles was administered to 40 patients (median 3 cycles; range 1-6 cycles). Twelve patients showed partial response and 17 patients had stable disease, representing a response rate of 30% and a disease control rate of 72.5%. Median survival time and median PFS were 16.1 and 4.8 months, respectively. Hematological toxicities of grade 3 or 4 were neutropenia (32.5%) and anemia (5.0%). The most common nonhematological toxicities of grade 3 or 4 included diarrhea (15.0%) and anorexia (17.5%). Patients homo- or heterozygous for UGTA1A*6 tended to show a higher incidence of grade 3 diarrhea (p = 0.055).. The combination of irinotecan and S-1 offers good efficacy and tolerability for previously untreated advanced NSCLC.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Carcinoma, Non-Small-Cell Lung; Drug Combinations; Female; Genotype; Glucuronosyltransferase; Humans; Irinotecan; Lung Neoplasms; Male; Middle Aged; Oxonic Acid; Tegafur

To evaluate the combination chemotherapy using oral antimetabolite S-1 plus cisplatin (SP) with concurrent thoracic radiotherapy (RT) followed by the consolidation SP for locally advanced non-small cell lung cancer.. Patients with stage III non-small cell lung cancer, 20 to 74 years of age, and Eastern Cooperative Oncology Group performance status 0 to 1 were eligible. The concurrent phase consisted of full dose S-1 (orally at 40 mg/m/dose twice daily, on days 1-14) and cisplatin (60 mg/m on day 1) repeated every 4 weeks for two cycles with RT delivered beginning on day 1 (60 Gy/30 fractions over 6 weeks). After SP-RT, patients received an additional two cycles of SP as the consolidation phase.. Fifty-five patients were registered between November 2006 and December 2007. Of the 50 patients for efficacy analysis, the median age was 64 years; male/female 40/10; Eastern Cooperative Oncology Group performance status 0/1, 21/29; clinical stage IIIA/IIIB 18/32; and adenocarcinoma/others 20/30. There were 42 clinical responses including one complete response with an objective response rate of 84% (95% confidence interval [CI], 71-93%). The 1- and 2-year overall survival rates were 88% (95% CI, 75-94%) and 70% (95% CI, 55-81%), respectively. The median progression-free survival was 20 months. Of the 54 patients for safety analysis, common toxicities in the concurrent phase included grade 3/4 neutropenia (26%), thrombocytopenia (9%), and grade 3 esophagitis (9%) and febrile neutropenia (9%). In one patient, grade 3 pneumonitis was observed in the consolidation phase. There were two treatment-related deaths caused by infection in the concurrent phase.. SP-RT showed a promising efficacy against locally advanced NCSLC with acceptable toxicity.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Non-Small-Cell Lung; Chemoradiotherapy; Cisplatin; Disease-Free Survival; Dose Fractionation, Radiation; Drug Combinations; Esophagitis; Female; Fever; Humans; Japan; Kaplan-Meier Estimate; Lung Neoplasms; Male; Middle Aged; Neoplasm Staging; Neutropenia; Oxonic Acid; Tegafur; Thrombocytopenia; Treatment Outcome

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.. 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.. 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.. 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.

Topics: Aged; Carcinoma, Non-Small-Cell Lung; Chemotherapy, Adjuvant; Combined Modality Therapy; Drug Combinations; Feasibility Studies; Female; Humans; Lung Neoplasms; Male; Middle Aged; Neoplasm Staging; Oxonic Acid; Tegafur

We conducted a phase II study of S-1 and carboplatin combination regimen in the treatment of patients with advanced non-small cell lung cancer (NSCLC). Chemotherapy-naïve patients with advanced NSCLC were treated with S-1 and carboplatin. S-1 was administered orally twice daily for 14 days and carboplatin AUC 5 on day 1 of each cycle, and this was repeated every 4 weeks. Twenty-nine patients were enrolled in this study. The main grade 3 or 4 toxicities observed during the first cycle were neutropenia (10.3%), thrombocytopenia (41%), and transaminase elevation. Objective responses were seen in 9 patients (response rate 31.0%). The median survival time and median progression-free survival were 16.0 months (95% CI, 12.1-19.0 months) and 4.5 months (95% CI, 3.2-6.1 months), respectively. Hematological adverse events reaching grade 3 or 4 were neutropenia (10.3%), anemia (3.4%), and thrombocytopenia (3.4%). No febrile neutropenia was detected. Nonhematological toxicities were also mild. Although grade 3 infection was observed in 1 patient, the patient improved without intervention. The combination of S-1 plus carboplatin is an active and well-tolerated regimen for the treatment of patients with advanced NSCLC. Further investigations are required to confirm our results in randomized trials.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carboplatin; Carcinoma, Non-Small-Cell Lung; Drug Combinations; Female; Humans; Lung Neoplasms; Male; Middle Aged; Neoplasm Staging; Neutropenia; Oxonic Acid; Tegafur; Thrombocytopenia

The purpose of this phase I/II study is to evaluate a new combination chemotherapy consisting of docetaxel and S-1 as front-line therapy for patients with untreated advanced non-small cell lung cancer (NSCLC). The treatment included docetaxel on day 1 and oral S-1 at a fixed dose of 40mg/m(2) administered twice daily on days 1-14 and repeated every 3 weeks. In phase I, docetaxel at escalating doses of 40 (level 0), 50 (level 1) and 60mg/m(2) (level 2) was administered starting from level 1. Because only one patient among the 6-patient cohort at level 1 and no patient among the 3-patient cohort at level 2 experienced defined dose-limiting toxicity (DLT), level 2 was determined as the recommended dose. In phase II, 60 patients were treated at the recommended dose for median 3 cycles, and the overall response rate was 30% (95% confidence interval [CI], 18.9-43.2%), and the median overall and progression-free survival times were 15.2 (95% CI: 10.5-17.7) and 4.9 (95% CI: 3.5-5.6) months, respectively. The most frequent toxicities experienced were neutropenia, febrile neutropenia and appetite loss; all toxicities were however well manageable. The present regimen showed a potent activity with mild toxicity in untreated NSCLC.

Topics: Administration, Oral; Adult; Aged; Carcinoma, Non-Small-Cell Lung; Disease Progression; Docetaxel; Drug Combinations; Drug Dosage Calculations; Drug Therapy, Combination; Female; Humans; Lung Neoplasms; Male; Middle Aged; Neoplasm Staging; Neutropenia; Oxonic Acid; Survival Analysis; Taxoids; Tegafur

The purpose of the present phase II study was to evaluate both the efficacy and toxicity of the combination of S-1 and docetaxel in previously treated patients with locally advanced or metastatic non-small cell lung cancer.. Thirty-eight previously treated patients with non-small cell lung cancer were treated with S-1 (80 mg/m(2), days 1-14, oral) and docetaxel (40 mg/m(2), day 1, intravenous) every 3 weeks.. No complete response was observed, and seven patients had a partial response, yielding an overall response rate of 18.4% (95% CI, 7.7-34.3%). The median overall survival time and 1-year overall survival rate were 16.1 months and 60%, respectively. The median progression-free survival time was 4.4 months. Myelosuppression was the main toxicity with grade 3 or 4 neutropenia and leukopenia in 50 and 21%, respectively. There was no irreversible toxicity in this study.. The combination of S-1 and docetaxel is well tolerable and has substantial activity for patients with locally advanced or metastatic non-small cell lung cancer. A phase III trial comparing docetaxel with or without S-1 would warrant further investigation.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Non-Small-Cell Lung; Disease-Free Survival; Docetaxel; Drug Combinations; Female; Follow-Up Studies; Humans; Leukopenia; Lung Neoplasms; Male; Middle Aged; Neoplasm Metastasis; Neutropenia; Oxonic Acid; Survival Rate; Taxoids; Tegafur; Treatment Outcome

This study was conducted to evaluate the efficacy and safety and to compare dosing schedules of gemcitabine combined with S-1 in chemo-naïve non-small cell lung cancer patients.. Patients with chemo-naïve stage IIIB/IV non-small cell lung cancer were randomized into two treatment arms. Patients were given oral S-1 (60 mg/m/d, twice a day) from days 1 to 14 with gemcitabine (1000 mg/m/d) on days 1 and 8 (arm A) or on days 8 and 15 (arm B). This cycle was repeated every 21 days.. A total of 80 patients were entered in this trial. The primary end point of this study was response rate. The response rates of arm A and arm B were 22.0 and 28.9%, respectively (p = 0.606). Median time to treatment failure in arm A was 3.6 months and 4.8 months in arm B. Median time to progression in arm A was 4.1 months and 5.5 months in arm B. Median survival time in arm A and arm B was 15.5 months and 18.8 months, respectively. The toxicity profile was relatively mild and did not differ very much between two arms.. The combination of gemcitabine and S-1 was determined to be feasible and effective for advanced non-small cell lung cancer. We selected arm B for further studies because of its higher response rate and survival data.

Topics: Adenocarcinoma; Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Non-Small-Cell Lung; Carcinoma, Squamous Cell; Deoxycytidine; Drug Combinations; Female; Gemcitabine; Humans; Lung Neoplasms; Male; Neoplasm Staging; Oxonic Acid; Safety; Survival Rate; Tegafur; Treatment Outcome

To determine the dose-limiting toxicity and recommended dose (RD) of cisplatin (CDDP) combined with S-1 (tegafur, 5-chloro-2, 4-dihydroxypyridine, and potassium oxonate) for patients with non-small cell lung cancer and to evaluate efficacy and toxicity of this regimen at RD.. Patients with stages III and IV non-small cell lung cancer received 3-week cycles of treatment, each consisting of oral administration of S-1 at 80 mg/m in 2 divided doses per day for 14 consecutive days, intravenous administration of CDDP (60 mg/m, 70 mg/m, or 80 mg/m) on the first day, and no medication during the subsequent 7 days. The primary objective of phase I study was to estimate the maximum tolerable dose and the RD, and the primary end point of phase II study was response.. RD of CDDP in the analysis of 18 eligible patients was 60 mg/m. Evaluation of efficacy and toxicity at RD in 55 eligible patients showed that partial response was observed in 18 patients (32.7%, 95% confidence interval: 20.7-46.7%). The median survival time was 18.1 months, and the time to disease progression was 3.8 months. Grade 3 or severer adverse events were observed in 27 patients (49.1%).. CDDP combined with S-1 showed a satisfactory overall survival time and acceptable toxicity profile. However, the response as the primary end point did not reach the predetermined threshold level.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Non-Small-Cell Lung; Carcinoma, Squamous Cell; Cisplatin; Drug Combinations; Female; Humans; Lung Neoplasms; Male; Maximum Tolerated Dose; Middle Aged; Neoplasm Staging; Oxonic Acid; Safety; Survival Rate; Tegafur; Treatment Outcome

The survival impact of single-agent treatment with docetaxel, the standard regimen for relapsed patients with non-small cell lung cancer (NSCLC), remains modest. We conducted a randomized phase II study to evaluate the efficacy and safety of the combination of docetaxel and S-1 in the second-line setting.. Patients with relapse of NSCLC after first-line platinum-based chemotherapy were randomly assigned to docetaxel alone (60 mg/m, day 1, q3 weeks; arm A) or a combination of docetaxel (40 mg/m, day 1, q3 weeks) and S-1 (80 mg/m, days 1-15; arm B). The primary end point was response rate, whereas secondary endpoints included overall survival, progression-free survival, and toxicity.. Between 2005 and 2008, a total of 60 patients were enrolled in the study. The objective response rates were 20.7% and 16.1% in arms A and B, respectively (p = 0.81). Progression-free survival was comparable in the two arms (median: 3.7 versus 3.4 months, p = 0.27), whereas overall survival time was longer in arm A (22.9 versus 8.7 months, p = 0.02). The major toxicity was myelosuppression with grade > or =3 neutropenia in 89.7% of patients versus 64.5% in arms A and B, respectively.. This study suggests that docetaxel monotherapy should continue to be considered the standard for second-line chemotherapy against NSCLC.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Carcinoma, Non-Small-Cell Lung; Carcinoma, Squamous Cell; Cisplatin; Docetaxel; Drug Combinations; Female; Humans; Irinotecan; Lung Neoplasms; Male; Middle Aged; Neoplasm Staging; Oxonic Acid; Salvage Therapy; Survival Rate; Taxoids; Tegafur; Treatment Outcome

The antimetabolic agent S-1 inhibits thymidylate synthase similar to pemetrexed, but through a different mechanism of action. Whether the antitumour activity of S-1 depends on histological type remains unclear. We analysed pooled data from 2 phase II clinical studies of cisplatin and S-1 in patients with previously untreated advanced non-small cell lung cancer.. We comprised 110 patients with stage IIIB or IV non-small cell lung cancer. Univariate and multivariate analyses were performed to determine the effects of histological type on progression-free survival and response rates.. On pooled analysis of the data, according to histological type, median progression-free survival was 3.8 months in patients with squamous cell carcinoma and 4.4 months in those with non-squamous cell carcinoma. Both analyses showed that progression-free survival and response rate did not differ significantly.. Unlike molecular targeted agents and pemetrexed, a combination of cisplatin and S-1 may be no difference in response according to histological type.

Topics: Adult; Aged; Antimetabolites, Antineoplastic; Carcinoma, Non-Small-Cell Lung; Disease-Free Survival; Drug Combinations; Female; Humans; Lung Neoplasms; Male; Middle Aged; Oxonic Acid; Survival Rate; Tegafur

The primary goal of this open-label, multicenter, randomized phase III trial was to determine whether treatment with carboplatin plus the oral fluoropyrimidine derivative S-1 was noninferior versus that with carboplatin plus paclitaxel with regard to overall survival (OS) in chemotherapy-naive patients with advanced non-small-cell lung cancer (NSCLC).. A total of 564 patients were randomly assigned to receive either carboplatin (area under the curve, 5) on day 1 plus oral S-1 (40 mg/m2 twice per day) on days 1 to 14 or carboplatin (area under the curve, 6) plus paclitaxel (200 mg/m2) on day 1 every 21 days.. At the planned interim analysis, with a total of 268 death events available, the study passed the O'Brien-Fleming boundary of 0.0080 for a positive result and noninferiority of carboplatin and S-1 compared with carboplatin and paclitaxel was confirmed for OS (hazard ratio, 0.928; 99.2% CI, 0.671 to 1.283). Median OS was 15.2 months in the carboplatin and S-1 arm and 13.3 months in the carboplatin and paclitaxel arm, with 1-year survival rates of 57.3% and 55.5%, respectively. Rates of leukopenia or neutropenia of grade 3/4, febrile neutropenia, alopecia, and neuropathy were more frequent in the carboplatin and paclitaxel arm, whereas thrombocytopenia, nausea, vomiting, and diarrhea were more common in the carboplatin and S-1 arm. The carboplatin and S-1 arm had significantly more dose delays than the carboplatin and paclitaxel arm.. Oral S-1 with carboplatin was noninferior in terms of OS compared with carboplatin and paclitaxel in patients with advanced NSCLC, and is thus a valid treatment option.

Topics: Administration, Oral; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carboplatin; Carcinoma, Non-Small-Cell Lung; Drug Combinations; Female; Humans; Lung Neoplasms; Male; Middle Aged; Oxonic Acid; Paclitaxel; Survival Analysis; Tegafur

We aimed to evaluate the efficacy and safety of combination chemotherapy with S-1 and low-dose weekly cisplatin in patients with advanced non-small cell lung cancer (NSCLC). In this phase II trial, previously untreated patients with stage IIIB/IV NSCLC were treated with oral administration of S-1 at 80 mg/m(2) for 21 days and three consecutive weekly low doses of cisplatin (25 mg/m(2)) followed by a 2-week rest period. Twenty-six patients were eligible for the assessment of efficacy and safety. Six partial responses were observed with an overall response rate of 23.1% (95% confidence interval: 12.3-31.6%). The median survival time and median progression-free survival were 13.4 months and 5.4 months, respectively. Grade 3/4 hematologic toxicities were observed in 9 patients (34.6%), including one grade 4 neutropenia and thrombocytopenia. As for non-hematologic adverse reactions, although grade 3 events were observed in 4 patients (15.3%), no severe renal toxicity or vomiting was found. S-1 and weekly low-dose cisplatin combination chemotherapy in patients with advanced NSCLC showed an acceptable response rate, overall survival time, and toxicity. Because this regimen can be performed in an outpatient setting, it might be an alternative useful and convenient option. Further investigations with a large population are required to confirm our results.

Topics: Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Non-Small-Cell Lung; Cisplatin; Disease-Free Survival; Drug Combinations; Female; Humans; Lung Neoplasms; Male; Middle Aged; Oxonic Acid; Tegafur; Time Factors; Treatment Outcome

To determine the maximum tolerated dose (MTD) and recommended dose (RD) of S-1 in combination with cisplatin and thoracic radiotherapy in patients with unresectable Stage III non-small-cell lung cancer (NSCLC).. S-1 was administered orally twice daily for 14 days and cisplatin on Days 1 and 8 of each cycle; this was repeated every 3 weeks. Doses of each drug were planned as follows: level 0, 50/40; level 1, 60/40; level 2, 70/40; level 3, 80/40 (S-1 [mg/m(-2)/day(-1)]/cisplatin [mg/m(-2)/day(-1)]). Thoracic radiation therapy was administered in 2 Gy fractions five times weekly to a total dose of 60 Gy.. Ten patients were enrolled in this study. All patients received 60 Gy of thoracic radiotherapy and 7 (70%) patients received four cycles of chemotherapy. At level 1, 2 of 3 patients experienced a delay exceeding 10 days in the cisplatin administration of Day 29. Grade 4 neutropenia and Grade 3 fever occurred in 1 and 1 patients, respectively. Nonhematologic toxicities were mild. None developed >or=Grade 3 esophagitis or lung toxicity. At level 0, 2 of 7 patients developed dose-limiting toxicity. Thus, level 1 was considered the MTD and Level 0 was selected as the RD. Objective responses were seen in all patients.. The RD is the level 0 dose, and this regimen is a feasible and well-tolerated regimen for the treatment of patients with Stage III NSCLC.

Topics: Administration, Oral; Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Non-Small-Cell Lung; Cisplatin; Combined Modality Therapy; Dose Fractionation, Radiation; Drug Administration Schedule; Drug Combinations; Female; Humans; Lung Neoplasms; Male; Maximum Tolerated Dose; Middle Aged; Oxonic Acid; Tegafur

A combination of S-1, a newly developed oral 5-fluorouracil derivative, and cisplatin is reported to show anti-tumour activity against advanced non-small cell lung cancer (NSCLC). Because S-1 shows synergistic effects with radiation, we conducted a phase I study to evaluate the maximum tolerated doses (MTDs), recommended doses (RDs), and dose-limiting toxicities (DLTs) of cisplatin and S-1 when combined with concurrent thoracic radiation (total dose of 60 Gy with 2 Gy per daily fraction) in patients with locally advanced NSCLC. Chemotherapy consisted of two 4-week cycles of cisplatin administered on days 1 and 8, and S-1 administered on days 1-14. S-1/cisplatin dosages (mg/m(2)/day) were escalated as follows: 60/30, 60/40, 70/40, 80/40 and 80/50. Twenty-two previously untreated patients were enrolled. The MTDs and RDs for S-1/cisplatin were 80/50 and 80/40, respectively. DLTs included febrile neutropaenia, thrombocytopaenia, bacterial pneumonia and delayed second cycle of chemotherapy. No patient experienced radiation pneumonitis>grade 2 and only one patient experienced grade 3 radiation oesophagitis. The overall response rate was 86.4% with a median survival time of 24.4 months. These results indicate that combination cisplatin-S-1 chemotherapy with concurrent thoracic radiation would be a feasible treatment option and a phase II study is currently under way.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Non-Small-Cell Lung; Cisplatin; Combined Modality Therapy; Dose-Response Relationship, Drug; Dose-Response Relationship, Radiation; Drug Administration Schedule; Drug Combinations; Female; Humans; Lung Neoplasms; Male; Middle Aged; Oxonic Acid; Tegafur

S-1 is a novel oral fluorouracil prodrug active against non-small cell lung cancer (NSCLC). To determine the feasibility of S-1 combined with weekly irinotecan for patients with advanced NSCLC, we performed a phase I study to determine the maximum tolerated dose (MTD) and the recommended dose (RD) of irinotecan.. Patients with advanced NSCLC received S-1 (80 mg/m(2)) on days 1-14 and irinotecan (50-80 mg/m(2)) on days 1, 8, and 15 of each 28-day cycle. Three to six patients were treated with each dose of irinotecan, with the MTD defined as the dose at which dose-limiting toxicity (DLT) appeared in 33% of patients.. At doses of 50-70 mg/m(2), no patients experienced any DLT, whereas, at a dose of 80 mg/m(2), two of four patients experienced DLTs. Two patients experienced grade 3 toxicities - neutropenia and diarrhea.. The MTD of weekly irinotecan was 80 mg/m(2), making its RD for phase II trials 70 mg/m(2).

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Carcinoma, Non-Small-Cell Lung; Drug Administration Schedule; Drug Combinations; Feasibility Studies; Female; Humans; Irinotecan; Lung Neoplasms; Male; Maximum Tolerated Dose; Middle Aged; Neoplasm Staging; Oxonic Acid; Tegafur; Treatment Outcome

TS-1 is a novel oral anticancer agent comprised of tegafur, a prodrug of 5- flurouracil, and two modulators. A phase i study of tS-1 plus carboplatin combination therapy was conducted to determine the maximum tolerated dose (MTD), recommended dose (RD), and dose limiting toxicities (DLT) in advanced non-small-cell lung cancer (NSClC). TS-1 was given orally at a dose of 80 mg/m(2)/day for 2 weeks, followed by a 2-week rest. Carboplatin was given intravenously on day 8 at a dose of 4.0, 5.0, 6.0 area under the curve (AUC) values. Fifteen patients with advanced NSClC were analyzed. the grade 3-4 toxicities observed during the first cycle were febrile neutropenia (6%), anemia (6%), anorexia (6%), and diarrhea (6%). these toxicities were reversible and manageable. The MTD for carboplatin was evaluated to be more than 6.0 AUC values, as one of six patients developed Dlt at this dose. the RD for carboplatin was estimated as 6.0 AUC values. Objective responses were seen in five patients (response rate 33%).

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Area Under Curve; Carboplatin; Carcinoma, Non-Small-Cell Lung; Drug Combinations; Female; Humans; Lung Neoplasms; Male; Maximum Tolerated Dose; Middle Aged; Oxonic Acid; Tegafur

To assess the efficacy and toxicity of an oral anticancer fluoropyrimidine derivative, S-1, for previously treated patients with advanced non-small cell lung cancer (NSCLC).. Patients with advanced (clinical stage IIIB-IV) NSCLC who had previously received one platinum-based chemotherapy were enrolled. S-1 was administered orally at the dosage decided by using the nomogram based on patient BSA b.i.d. for 28 consecutive days, repeated every 6 weeks.. Between August 2005 and July 2007, 50 patients were entered into this study. Six patients achieved partial response (PR), and the overall response rate of eligible patients was 12.5% (6/48) (95% confidence interval (95%CI), 3.1-21.9%). Disease control rate was 39.6% (19/48) (95%CI, 25.7-53.4%). Median progression-free survival was 2.5 months. Median survival time was 8.2 months, and 1-year survival rate was 29.6%. No grade 4 toxicities were encountered. Grade 3 hematological toxicities comprised neutropenia in one patient (2.1%) and anemia in one patient (2.1%). Grade 3 non-hematological toxicities were observed in only five patients (10.4%). Treatment-related death did not occur.. S-1 is an active and well-tolerated monotherapy for second-line treatment of advanced NSCLC.

Topics: Administration, Oral; Aged; Antimetabolites, Antineoplastic; Carcinoma, Non-Small-Cell Lung; Drug Combinations; Female; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Oxonic Acid; Survival Rate; Tegafur; Treatment Outcome

The objective of this phase I/II study was to determine the recommended dose (RD) of S-1 and carboplatin (CBDCA), and to evaluate the efficacy and safety of this combination in the treatment of patients with advanced non-small cell lung cancer (NSCLC). Chemotherapy-naïve patients were treated with S-1 given orally on days 1-14, and CBDCA infused intravenously on day 1, repeated every 3 weeks. RD was AUC5 of CBDCA and 80 mg/m(2) of S-1. Nineteen patients were treated at the RD. The overall response was 30.8% (95% confidence interval: 17.1-58.3%). The response rate in the RD was 36.8% (95% CI: 16.3-61.6%). The median overall survival time was 11.1 months (95% CI: 8.1-15.3 months) and the median progression-free survival time was 5.0 months (95% CI: 3.6-6.0 months). Major grades 3-4 toxicities were thrombocytopaenia (47%), anaemia (26%) and infection (16%). This is the first report to show promising activity of this combination in phase II, including survival data and manageable toxicity, especially in outpatients receiving treatment for advanced NSCLC.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carboplatin; Carcinoma, Non-Small-Cell Lung; Drug Combinations; Female; Humans; Lung Neoplasms; Male; Maximum Tolerated Dose; Middle Aged; Oxonic Acid; Tegafur

To assess the efficacy and safety of S-1 and cisplatin with concurrent thoracic radiation for unresectable stage III non-small-cell lung cancer (NSCLC).. Eligible patients were 20-74 years old and had histologically or cytologically confirmed NSCLC, a performance status of 0-1, and no prior chemotherapy. Patients were treated with cisplatin (60 mg m(-2) on day 1) and S-1 (orally at 40 mg m(-2) per dose, b.i.d., on days 1-14), with the treatment repeated every 4 weeks for four cycles. Beginning on day 2, a 60-Gy thoracic radiation dose was delivered in 30 fractions.. Of 50 patients, 48 were eligible. Partial response was observed in 42 patients (87.5%; 95% CI: 79.1-96.9%). This regimen was well tolerated. Common toxicities included grade 3/4 neutropenia (32%), grade 3/4 leukopenia (32%), grade 3/4 thrombocytopenia (4%), grade 3 febrile neutropenia (6%), grade 3 oesophagitis (10%), and grade 3 pneumonitis (5%). Median progression-free survival was 12.0 months and median overall survival was 33.1 months. The 1- and 2-year survival rates were 89.5 and 56%, respectively.. This chemotherapy regimen with concomitant radiotherapy is a promising treatment for locally advanced NSCLC because of its high response rates, good survival rates, and mild toxicities.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Non-Small-Cell Lung; Cisplatin; Combined Modality Therapy; Disease-Free Survival; Drug Combinations; Female; Humans; Lung Neoplasms; Male; Middle Aged; Neoplasm Staging; Oxonic Acid; Survival Rate; Tegafur

We conducted a phase I study to determine the maximum tolerated dose, the recommended dose and the safety profile of S-1 and gemcitabine combination regimen in the treatment of elderly patients (> or = 70 years) with advanced nonsmall cell lung cancer (NSCLC). Chemotherapy-naive patients with advanced NSCLC were treated with S-1 and gemcitabine. S-1 was administered orally twice daily for 14 days and gemcitabine on days 1 and 15 of each cycle, and this was repeated every 4 weeks. Doses of each drug were planned as follows: level 1, 800/60; level 2, 1000/60; level 3, 1000/70; and level 4, 1000/80 [gemcitabine (mg/m2/ day)/S-1 (mg/m2/day)]. The dose-limiting toxicity (DLT) of the regimen was assessed during the first chemotherapy cycle. Sixteen patients were enrolled in this study. The main grade 3 toxicities observed during the first cycle were neutropenia (43.7%), leukopenia (18.7%), and hyperglycemia. One of six patients in level 3 had DLT. Although no patients in level 4 experienced DLT, this level was considered the maximum tolerated dose. Level 4 was selected as the recommended dose. Objective responses were seen in four patients (response rate, 42.9%). The combination of S-1 plus gemcitabine is a feasible and well-tolerated regimen for the treatment of elderly patients with advanced NSCLC.

Topics: Administration, Oral; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Non-Small-Cell Lung; Deoxycytidine; Dose-Response Relationship, Drug; Drug Combinations; Female; Gemcitabine; Humans; Hyperglycemia; Leukopenia; Lung Neoplasms; Male; Maximum Tolerated Dose; Neutropenia; Oxonic Acid; Tegafur; Treatment Outcome

To evaluate the efficacy and toxicity of combination therapy with the oral fluoropyrimidine formulation S-1 and irinotecan for patients with advanced NSCLC.. Chemotherapy-naive patients with advanced NSCLC were treated with i.v. irinotecan (150 mg/m2) on day 1 and with oral S-1 (80 mg/m2) on days 1 to 14 every 3 weeks.. Fifty-six patients (median age, 63 years; range, 40-74 years) received a total of 286 treatment cycles (median, 5; range, 1-15). No complete responses and 16 partial responses were observed, giving an overall response rate of 28.6% [95% confidence interval (95% CI), 17.3-42.2%]. Twenty-four patients (42.9%) had stable disease and 12 patients (21.4%) had progressive disease as the best response. The overall disease control rate (complete response + partial response + stable disease) was thus 71.4% (95% CI, 57.8-82.7%). Median progression-free survival was 4.9 months (95% CI, 4.0-6.4 months), whereas median overall survival was 15 months. Hematologic toxicities of grade 3 or 4 included neutropenia (25%), thrombocytopenia (3.6%), and anemia (3.6%), with febrile neutropenia being observed in four patients (7.1%). The most common nonhematologic toxicities of grade 3 or 4 included anorexia (14.3%), fatigue (8.9%), and diarrhea (8.9%). There were no deaths attributed to treatment.. The combination of S-1 and irinotecan is a potential alternative option with a favorable toxicity profile for the treatment of advanced NSCLC. This nonplatinum regimen warrants further evaluation in randomized trials.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Carcinoma, Non-Small-Cell Lung; Disease-Free Survival; Drug Combinations; Female; Humans; Irinotecan; Japan; Kaplan-Meier Estimate; Lung Neoplasms; Male; Middle Aged; Oxonic Acid; Tegafur; Treatment Outcome

The aim of this study was to determine and evaluate the recommended dose of docetaxel in combination with a novel oral 5-fluorouracil analogue S-1 and evaluate the efficacy and safety in patients with previously treated non-small cell lung cancer.. In phase I, patients with previously treated non-small cell lung cancer were treated with docetaxel (starting dose 40 mg/m) intravenously on day 1 and oral administration of S-1 at a fixed dose of 80 mg/m on days 1 to14 every 3 weeks. The recommended dose was the dose level preceding the maximum tolerated dose; once determined, patients were enrolled in phase II.. The recommended dose of docetaxel was 40 mg/m in combination with S-1 80 mg/m/d. Of 30 patients enrolled in phase II part, 29 patients were eligible and analyzed. No complete response and 7 (24.1%) partial responses were observed, for an overall response rate of 24.1% (95% confidence interval, 10.3-43.5%). Median overall survival was 11.8 months. The 1-year survival rate was 42%. The grade 3 to 4 hematologic toxicities were neutropenia (34.5%), leukopenia (20.6%), and anemia (10.3%). The grade 3 to 4 nonhematological toxicities included fever 2 (6.9%), diarrhea 1 (3.4%), stomatitis 1 (3.4%), cerebral infarction 1 (3.4%), and pneumonitis 1 (3.4%). There was one treatment-related death due to relapse of drug induced pneumonitis.. This combination chemotherapy is highly active and well tolerated in previously treated patients with non-small cell lung cancer. These results are encouraging and warrant additional investigation.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Non-Small-Cell Lung; Docetaxel; Drug Combinations; Female; Humans; Lung Neoplasms; Male; Middle Aged; Neoplasm Staging; Oxonic Acid; Prognosis; Salvage Therapy; Survival Rate; Taxoids; Tegafur

The purpose of this study was to evaluate the efficacy and safety of a novel oral anticancer fluoropyrimidine derivative, S-1, in patients receiving initial chemotherapy for unresectable, advanced non-small-cell lung cancer (NSCLC). Between June 1996 and July 1998, 62 patients with NSCLC who received no previous chemotherapy for advanced disease were enrolled in this study. Fifty nine patients (22 in stage IIIB and 37 in stage IV) were eligible for the evaluation of efficacy and safety. S-1 was orally administered twice daily after meals. Three doses of S-1 were prescribed according to body surface area (BSA), so that they would be approximately equivalent to 80 mg/m2/day. One cycle of S-1 consisted of consecutive administration for 28 days followed by a 2-week rest, and the cycle was repeated up to 4 times. The partial response (PR) rate of the eligible patients was 22.0% (13/59) (95% confidence interval: 12.3-34.7%). Grade 4 neutropenia was observed in one of the 59 patients (1.7%). There were no irreversible, severe or unexpected toxicities. The median survival time (MST) of all of the patients was 10.2 months (95% confidence interval: 7.7-14.5 months), and the one-year survival rate was 41.1%. S-1 was considered to be an active single agent against NSCLC.

Topics: Administration, Oral; Adult; Aged; Anorexia; Antimetabolites, Antineoplastic; Carcinoma, Non-Small-Cell Lung; Drug Administration Schedule; Drug Combinations; Female; Humans; Lung Neoplasms; Male; Middle Aged; Neutropenia; Oxonic Acid; Quality of Life; Remission Induction; Tegafur

To evaluate the efficacy and toxicity of a novel combination chemotherapeutic regimen including cisplatin with an oral anticancer agent, S-1 that consisted of tegafur, 5-chloro-2, 4-dihydroxypyridine, and potassium oxonate, for non-small-cell lung cancer (NSCLC) patients.. In this phase II trial, patients with locally advanced and metastatic NSCLC were treated with the oral administration of S-1 at 40 mg/m(2) twice a day for 21 consecutive days while cisplatin (60 mg/m(2)) was administered intravenously on day 8. This schedule was repeated every 5 weeks.. Of 56 patients enrolled in the study, 55 patients were eligible and analyzed. The median number of cycles administered was 3 (range, 1-12 cycles). Among these 55 patients, one complete response and 25 partial responses were observed with an overall response rate of 47% (95% confidence interval, 34-61%). The median survival time was 11 months and the 1-year survival rate was 45%. Hematologic toxicities of grades 3 and 4 included neutropenia (29%) and anemia (22%). No grade 4 nonhematologic toxicity was observed. Grade 3 toxicity included anorexia (13%), vomiting (7%), or diarrhea (7%).. S-1 plus cisplatin combination chemotherapy showed a promising effectiveness with acceptable toxicity rates in patients with advanced NSCLC. These results warrant further investigations of this regimen including a randomized controlled trial for its use as a first line treatment for NSCLC.

Topics: Adenocarcinoma; Administration, Oral; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Non-Small-Cell Lung; Carcinoma, Squamous Cell; Cisplatin; Drug Administration Schedule; Drug Combinations; Female; Humans; Lung Neoplasms; Male; Middle Aged; Neoplasm Staging; Oxonic Acid; Pyridines; Survival Rate; Tegafur; Treatment Outcome

The purpose of this study was to evaluate the efficacy and safety of a novel oral anticancer fluoropyrimidine derivative, S-1, in patients receiving initial chemotherapy for unresectable, advanced non-small-cell lung cancer (NSCLC). Between June 1996 and July 1998, 62 patients with NSCLC who had not received previous chemotherapy for advanced disease were enrolled in this study. 59 patients (22 stage IIIB and 37 stage IV) were eligible for the evaluation of efficacy and safety. S-1 was administered orally, twice daily, after meals. 3 dosages of S-1 were prescribed according to body surface area (BSA) so that they would be approximately equivalent to 80 mg m(-2)day(-1): BSA < 1.25 m(2), 40 mg b.i.d.; BSA> or =1.25 but <1.5 m(2); 50 mg b.i.d., and BSA> or =1.5 m(2): 60 mg b.i.d. One cycle consisted of consecutive administration of S-1 for 28 days followed by a 2-week rest period, and cycles were repeated up to 4 times. The partial response (PR) rate of the eligible patients was 22.0% (13/59); (95% confidence interval: 12.3-34.7%). A PR was observed in 22.7% (5/22) of the stage IIIB patients and 21.6% (8/37) of the stage IV patients. The median response duration was 3.4 months (1.1-13.7 months or longer). Grade 4 neutropenia was observed in one of the 59 patients (1.7%). The grade 3 or 4 toxicities consisted of decreased haemoglobin level in 1.7% of patients (1/59), neutropenia in 6.8% (4/59), thrombocytopenia in 1.7% (1/59), anorexia in 10.2% (6/59), diarrhoea in 8.5% (5/59), stomatitis in 1.7% (1/59), and malaise in 6.8% (4/59), and their incidences were relatively low. There were no irreversible, severe or unexpected toxicities. The median survival time (MST) of all patients was 10.2 months (95% confidence interval: 7.7-14.5 months), and the one-year survival rate was 41.1%. The MST of the stage IIIB patients was 7.9 months, and that of the stage IV patients was 11.1 months. The one-year survival rates of the stage IIIB and IV patients were 30.7% and 47.4%, respectively. S-1 was considered to be an active single agent against NSCLC. Further study of S-1 with other active agents is warranted.

Topics: Administration, Oral; Adult; Aged; Antimetabolites, Antineoplastic; Carcinoma, Non-Small-Cell Lung; Drug Combinations; Female; Humans; Lung Neoplasms; Male; Middle Aged; Neutropenia; Oxonic Acid; Pyridines; Survival Analysis; Tegafur; Treatment Outcome

The efficacy and safety of S-1, a new oral fluoropyrimidine, were evaluated in patients with non-small-cell lung cancer (NSCLC). The objective of this study was to determine whether the drug should be investigated in a late phase II study.. Each treatment course consisted of an oral dose of S-1, 50 mg/body or 75 mg/body, twice a day for 28 days followed by a 2-week washout period.. Fifty-six eligible patients were enrolled. Five of the 40 previously untreated patients (12.5%; 90% confidence interval, 6.2%-23.5%) showed a partial response (PR), and no tumor response was observed in the 16 previously treated patients. The median survival duration in all eligible patients was 8.4 months, with a 1-year survival rate of 27.3%. The incidences of grade 3 or more severe adverse effects were: anemia, 5.4%; leukopenia, 5.4%; neutropenia, 5.4%; thrombocytopenia, 1.8%; anorexia, 3.6%; diarrhea, 3.6%; and general fatigue, 5.4%. These effects disappeared after cessation of the drug or appropriate treatment. One patient died as a result of aggravated interstitial pneumonitis, but the relationship of this event to S-1 was not clear.. S-1 showed modest activity with mild toxicity in the treatment of non-small-cell lung cancer. Based on this result, we will progress to the next stage of a late phase II study for advanced NSCLC, and a phase II study of S-1 and cisplatin for advanced gastric cancer. Final results will be reported as they are obtained.

Topics: Administration, Oral; Adult; Aged; Antimetabolites, Antineoplastic; Carcinoma, Non-Small-Cell Lung; Confidence Intervals; Drug Combinations; Female; Humans; Lung Neoplasms; Male; Middle Aged; Oxonic Acid; Pyridines; Tegafur

S-1 and pemetrexed (PEM) are key treatments for non-small cell lung cancer (NSCLC). However, the mechanism of anticancer activity of S-1 and PEM is similar. Cross-resistance between S-1 and PEM is of concern. This exploratory study was designed to evaluate the treatment effect of S-1 following PEM-containing treatment.. This retrospective study included patients with advanced (c-stage III or IV, UICC seventh edition) or recurrent NSCLC who received S-1 monotherapy following the failure of previous PEM-containing chemotherapy at six hospitals in Japan. The primary endpoint of the study was the overall response rate (ORR). The secondary endpoint was the disease control rate (DCR), time to treatment failure (TTF), progression-free survival (PFS), and overall survival (OS).. A total of 53 NSCLC patients met the criteria for inclusion in the study. Forty-six patients had adenocarcinoma (88.7%) and no patients had squamous cell carcinoma. Thirty-one patients (58.5%) received the standard S-1 regimen and 18 patients (34.0%) received the modified S-1 regimen. ORR was 1.9% (95% confidence interval [CI]: 0.00%-10.1%). Median TTF, PFS, and OS were 65, 84, and 385 days, respectively.. Although there were several limitations in this study, the ORR of S-1 after PEM in patients with nonsquamous (non-SQ) NSCLC was low compared to the historical control. One of the options in the future might be to avoid S-1 treatment in PEM-treated patients who need tumor shrinkage.

Topics: Adult; Aged; Aged, 80 and over; Antimetabolites, Antineoplastic; Antineoplastic Agents; Carcinoma, Non-Small-Cell Lung; Disease-Free Survival; Drug Combinations; Female; Humans; Lung Neoplasms; Male; Middle Aged; Oxonic Acid; Pemetrexed; Retrospective Studies; Tegafur

S-1 combined with cisplatin is known to be noninferior to taxanes plus platinum as the first-line treatment for patients with advanced nonsmall cell lung cancer (NSCLC) in the Japanese population. This study aimed to evaluate the efficacy and safety profiles of oral S-1 plus cisplatin (SP) in Taiwanese patients.. Patients with previously untreated stage IIIB or IV NSCLC were prospectively recruited to receive 40-60 mg of S-1 twice daily on days 1-21 plus 60 mg/m. A total of 55 patients from five cancer centers in Taiwan were enrolled. Among the 46 evaluable patients, those administered with SP achieved disease control rate of 69.6% (partial response, 19.6%; stable disease, 50.0%), with median overall survival and progression-free survival (PFS) of 15.1 and 5.7 months, respectively. Moreover, a better survival trend was observed in epidermal growth factor receptor mutation-positive patients versus mutation-negative patients treated with SP (PFS, 8.6 vs 5.6 months). The most commonly observed treatment-related adverse events (AEs) were nausea (41.8%), followed by decreased appetite, anemia, and diarrhea. Grade of ≥3 AEs related to the study treatment occurred in 11 patients (20.0%). No febrile neutropenia or treatment-related death was found in this study.. This study demonstrated that SP is an effective and safe first-line regimen for Taiwanese patients with advanced NSCLC.

Topics: Adult; Aged; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Non-Small-Cell Lung; Cisplatin; Drug Combinations; Female; Humans; Lung Neoplasms; Male; Middle Aged; Oxonic Acid; Survival Analysis; Taiwan; Tegafur

Studies have suggested that chemotherapy after immune checkpoint inhibitors may confer an improved response for non-small cell lung cancer (NSCLC). However, potential selection bias in such studies has not been addressed. We therefore applied propensity score analysis to investigate the efficacy of chemotherapy after PD-1 inhibitor treatment (CAP) compared with chemotherapy alone.. We conducted a retrospective observational cohort study for patients treated at 47 institutions across Japan between April 1, 2014 and July 31, 2017. Eligible patients had advanced or recurrent NSCLC who have undergone chemotherapy. Patients subsequently treated with chemotherapy (docetaxel with or without ramucirumab, S-1 or pemetrexed) either after PD-1 inhibitor therapy (CAP cohort) or alone (control cohort) were included. The primary end point was objective response rate (ORR). Inverse probability weighting (IPW) was applied to adjust for potential confounding factors.. A total of 1439 patients (243 and 1196 in the CAP and control cohorts, respectively) was available for unadjusted analysis. Several baseline characteristics-including age, histology,. After accounting for selection bias by propensity score analysis, CAP showed a significantly higher ORR compared with chemotherapy alone, with the primary end point of ORR being achieved. However, these results did not translate into a PFS or OS advantage, suggesting that prior administration of PD-1 inhibitors may result in a synergistic antitumor effect with subsequent chemotherapy, but that such an effect is transient. CAP therefore does not appear to achieve durable tumor control or confer a lasting survival benefit.

Topics: Adult; Aged; Aged, 80 and over; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Non-Small-Cell Lung; Docetaxel; Drug Combinations; Drug Synergism; Female; Humans; Immune Checkpoint Inhibitors; Kaplan-Meier Estimate; Lung Neoplasms; Male; Middle Aged; Oxonic Acid; Pemetrexed; Programmed Cell Death 1 Receptor; Progression-Free Survival; Propensity Score; Ramucirumab; Retrospective Studies; Tegafur

The purpose of this study was to analyze the safety and feasibility of low-dose apatinib combined with S-1 as a second-line therapy or beyond in Chinese patients with pulmonary and/or hepatic metastases of nasopharyngeal carcinoma (NPC).. Forty-one Chinese NPC patients with pulmonary and hepatic metastases were treated with low-dose apatinib plus S-1. The S-1 dose was determined according to each patient's body surface area (BSA): 40 mg twice a day for BSA <1.25 m. Treatment efficacy was evaluated in all 41 patients after four courses of chemotherapy. The objective response rate was 34.1%, and the disease control rate was 80.4%. The median progression-free survival was 9.7 months (95% confidence interval, 6.2-13.8 months), and the median overall survival was 22.1 months (95% confidence interval, 15.1-28.9 months). The 2-year survival rate was 41.5%. The most common toxicities included loss of appetite in 39.0% of patients, dyslipidemia in 34.1%, hypertension in 31.7%, myelosuppression in 24.4%, fatigue in 21.9%, and hand-foot syndrome in 17.1%. Seven patients received dose adjustment of apatinib due to side effects.. In patients with pulmonary and/or hepatic metastases of NPC, low-dose apatinib plus S-1 yielded an excellent survival benefit, and the toxicities were mild and tolerable.

Topics: Administration, Oral; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Asian People; Carcinoma, Non-Small-Cell Lung; Combined Modality Therapy; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Combinations; Feasibility Studies; Female; Humans; Liver Neoplasms; Lung Neoplasms; Male; Middle Aged; Nasopharyngeal Carcinoma; Nasopharyngeal Neoplasms; Oxonic Acid; Pyridines; Survival Rate; Tegafur; Young Adult

Adjuvant chemotherapy with platinum-based regimens for completely resected early-stage non-small cell lung cancer (NSCLC) provides overall survival benefit in several clinical trials.. We conducted this prospective study to evaluate the efficacy and safety of adjuvant chemotherapy with carboplatin and S-1 for patients with completely resected stage II to IIIA NSCLC.. Patients with completely resected stage IIA to IIIA NSCLC were treated with four cycles of carboplatin with area under the concentration time curve of 5 mg/mL/min on day 1 plus S-1 at 80-120 mg/bodyweight per day for two weeks, followed by one-week rest as adjuvant chemotherapy. The primary endpoint was the completion rate of three cycles of the treatment. The secondary endpoints were safety and two-year survival rate.. A total of 19 patients were enrolled, until the study was terminated prematurely because of fatal pulmonary embolism in two patients. The median number of treatment cycles was three (range: 1-4). The completion rate of three cycles was 78.9% (95% confidence interval [CI]: 56.6-91.4%). Two-year disease-free survival rate was 57.8%. Grade 3 or 4 hematological toxicities included neutropenia (26.2%), anemia (5.2%), and thrombocytopenia (15.7%). Grade 3 or 4 nonhematological toxicities were anorexia (10.5%) and nausea (10.5%). Febrile neutropenia developed in 5.2%. In two patients (10.5%), grade five pulmonary embolism was observed, and the causal relationship with treatment could not be denied.. Carboplatin and oral S-1 had modest survival benefit, but this regimen was not tolerable in an adjuvant setting because fatal pulmonary embolism occurred in two patients.. Carboplatin and oral S-1 had modest survival benefit but this regimen was not tolerable. Fatal pulmonary embolism occurred in this regimen.

Topics: Adenocarcinoma of Lung; Administration, Oral; Aged; Antineoplastic Combined Chemotherapy Protocols; Carboplatin; Carcinoma, Non-Small-Cell Lung; Carcinoma, Squamous Cell; Chemotherapy, Adjuvant; Drug Combinations; Female; Follow-Up Studies; Humans; Lung Neoplasms; Male; Middle Aged; Neoplasm Staging; Oxonic Acid; Pilot Projects; Prospective Studies; Survival Rate; Tegafur

S-1 monotherapy is effective and feasible for previously treated patients with advanced non-small cell lung cancer (NSCLC). However, it is not clear whether its effectiveness and tolerability in elderly patients are equivalent to those in younger patients. Hence, this study aimed to evaluate the efficacy and feasibility of S-1 monotherapy in elderly patients with NSCLC who had previously received other treatments.. We included 96 elderly patients (aged ≥75 years) with advanced NSCLC treated with S-1 alone as a subsequent-line treatment at 12 medical facilities between January 2005 and March 2018 in this study. The baseline characteristics of the patients, response to S-1 monotherapy, and adverse events (AEs) were investigated, retrospectively.. A total of 68 male and 28 female patients (median age, 78 [range: 75-86] years) were analyzed. In elderly patients who were treated with S-1 monotherapy as a subsequent-line treatment, the objective response rate, disease control rate, median progression-free survival (PFS), and overall survival (OS) were 8.3%, 43.8%, 3.4 months, and 9.6 months, respectively. Observed AEs included anorexia, anemia, nausea, fatigue, reduced platelet count, and skin hyperpigmentation. Treatment-related death was observed in one patient because of pneumonitis. In patients who experienced no progressive disease, subsequent-line S-1 alone was associated with longer PFS and OS.. S-1 monotherapy is effective and feasible as a subsequent-line treatment in elderly patients who were previously treated for NSCLC, and it produces results. S-1 monotherapy could be one of the treatment choices for elderly patients with previously treated NSCLC.

Topics: Aged; Aged, 80 and over; Carcinoma, Non-Small-Cell Lung; Drug Combinations; Female; Humans; Lung Neoplasms; Male; Oxonic Acid; Retrospective Studies; Tegafur

Topics: Antineoplastic Combined Chemotherapy Protocols; Carboplatin; Carcinoma, Non-Small-Cell Lung; Chemotherapy, Adjuvant; Drug Combinations; Humans; Lung Neoplasms; Oxonic Acid; Tegafur

Objective A subset analysis of the LETS study suggested that S-1 plus carboplatin was more beneficial than paclitaxel plus carboplatin in terms of the overall survival (OS) in squamous cell lung cancer. However, the benefit of maintenance therapy for squamous cell non-small cell lung cancer (NSCLC) patients is still unknown. We herein report a phase II study to evaluate the efficacy and safety of a tailored dose of S-1 plus carboplatin followed by maintenance S-1 in chemotherapy-naive advanced squamous cell NSCLC. Methods Patients received carboplatin on day 1 plus S-1 on days 1 to 14 every 21 days. The dose of S-1 was determined by the body surface area and creatinine clearance. After four cycles of induction, non-progressive patients continued to receive S-1 until disease progression or unacceptable toxicity occurred. The primary endpoint was an objective response rate (RR) with a threshold value of 15%. The secondary endpoints were the progression-free survival (PFS) and OS from enrollment, the PFS in the maintenance phase, and safety. Results In the 33 patients analyzed, the rate of patients who met the primary endpoint was 30.3% (95% confidence interval: 15.6-48.7%), and the disease control rate was 75.8%. The median PFS and OS were 3.5 and 11.3 months, respectively. Ten patients received maintenance S-1, and the median PFS from the beginning of induction treatment was 5.3 months. Grade 3/4 toxicities with a frequency of more than 5% were all controllable. Conclusion Tailored-dose S-1 plus carboplatin followed by maintenance S-1 is an effective and feasible treatment for advanced squamous cell NSCLC.

Topics: Adult; Aged; Aged, 80 and over; Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Carboplatin; Carcinoma, Non-Small-Cell Lung; Carcinoma, Squamous Cell; Drug Combinations; Epithelial Cells; Female; Humans; Lung Neoplasms; Male; Middle Aged; Oxonic Acid; Paclitaxel; Tegafur

Cytotoxic chemotherapy for advanced non-small cell lung cancer (NSCLC) as second-line or subsequent treatment generally results in a poor treatment outcome. Several reports have indicated that subsequent cytotoxic chemotherapy in patients who have received immune checkpoint inhibitors (ICIs) might have relatively better efficacy.. The clinical data of advanced NSCLC patients treated with nivolumab during clinical practice at the National Cancer Center Hospital between 17 December 2015 and 31 August 2017 were consecutively reviewed, and the treatment outcomes of docetaxel-based chemotherapy (docetaxel +/- ramucirumab) or S-1 after nivolumab were analyzed. The results were then compared with those of advanced NSCLC patients treated with docetaxel or S-1 but not ICIs during clinical practice between 17 December 2014 and 16 December 2015.. Thirty patients were administered docetaxel-based chemotherapy and 21 patients were administered S-1 in any line after nivolumab. Twenty-four patients were administered docetaxel-based chemotherapy and 15 patients were administered S-1 immediately after nivolumab. Sixty-six patients were administered docetaxel and 23 patients were administered S-1 without ICIs. The objective response rate, disease control rate, and median progression-free survival duration were 28.6%, 53.6%, and 5.26 months for patients receiving docetaxel-based chemotherapy or S-1 immediately after nivolumab treatment; 24.3%, 51.4%, and 3.88 months for patients receiving docetaxel-based chemotherapy or S-1 in any line after nivolumab; and 16.4%, 56.7%, and 2.74 months, for patients receiving docetaxel or S-1 without ICIs, respectively.. Subsequent cytotoxic chemotherapy, especially immediately after nivolumab, has better treatment efficacy than that of regimens without ICI pretreatment.

Topics: Adult; Aged; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Non-Small-Cell Lung; Docetaxel; Drug Combinations; Female; Humans; Kaplan-Meier Estimate; Lung Neoplasms; Male; Middle Aged; Nivolumab; Oxonic Acid; Ramucirumab; Retreatment; Tegafur; Treatment Outcome

Non-small cell lung cancer (NSCLC) is the most common lung cancer. Numerous clinical studies have reported that the combination of carboplatin and S-1 (CS) can be used to treat NSCLC effectively. However, no systematic review has been conducted to assess its efficacy and safety for NSCLC. This systematic review aims to evaluate the efficacy and safety of CS for treatment of patients with NSCLC.. This study will retrieve the following electronic databases from inception to the February 1, 2019: Cochrane Library, EMBASE, MEDILINE, CINAHL, AMED, and 4 Chinese databases without any language limitations. This systematic review will include randomized controlled trials (RCTs) and case-control studies for assessing the efficacy and safety of CS for the treatment of NSCLC. Cochrane risk of bias will be used as methodological quality assessment for each qualified study. The RevMan V.5.3 software will be utilized to synthesize the data and conduct the meta-analysis if it is allowed. The data will be pooled by using the random-effects model or fixed-effects model.. The primary outcome is overall response rate. The secondary outcomes are overall survival, progression-free survival, the disease control rate, and any adverse events.. It will provide latest evidence to determine the efficacy and safety of CS for treatment of patients with NSCLC.. No research ethic approval is needed in this study because this study will not analyze individual patient data. The results are expected to disseminate through peer-reviewed journals.. PROSPERO CRD42019124860.

Topics: Antineoplastic Combined Chemotherapy Protocols; Carboplatin; Carcinoma, Non-Small-Cell Lung; Drug Combinations; Humans; Lung Neoplasms; Meta-Analysis as Topic; Oxonic Acid; Randomized Controlled Trials as Topic; Systematic Reviews as Topic; Tegafur

Background: Copper transporter 1 (CTR1) is a critical determinant of the uptake and cytotoxic effect of the platinum\ drugs carboplatin and cisplatin. Thymidylate synthase (TS) is an enzyme involved in DNA synthesis and is associated\ with resistance of tumor cells to 5-fluorouracil. We investigated the correlation between CTR1 and TS expression levels\ and treatment outcomes in patients with advanced non-small-cell lung cancer (NSCLC) treated with S-1/carboplatin\ doublet chemotherapy. Methods: Twenty-nine patients were enrolled in this study. Tumor expression of CTR1 and\ TS was measured immunohistochemically and analyzed for correlation with tumor response, progression-free survival\ (PFS), and overall survival (OS). Results: Tumor response was significantly better in patients with CTR1High tumors\ than in patients with CTR1Low tumors (64% vs. 18%, P = 0.02). Patients with TSLow tumors had a significantly longer OS\ (median 21.2 vs. 8.5 months, P = 0.02), but not PFS, than patients with TSHigh tumors. When CTR1 and TS co-expression\ was analyzed, patients with either CTR1High or TSLow tumors showed a significantly better tumor response (50% vs. 0%,\ P = 0.01), longer PFS (median 4.2 vs. 2.1 months, P = 0.03), and longer OS (median 21.2 vs. 8.5 months, P = 0.01) than\ patients with both CTR1Low and TSHigh tumors. Conclusions: Our study suggests that combined CTR1/TS expression\ status has the potential to be an important predictor of good treatment outcomes in patients with advanced NSCLC\ treated with S-1/carboplatin doublet chemotherapy.

Topics: Adenocarcinoma; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Carboplatin; Carcinoma, Non-Small-Cell Lung; Cation Transport Proteins; Copper Transporter 1; Drug Combinations; Female; Follow-Up Studies; Humans; Lung Neoplasms; Male; Middle Aged; Neoplasm Staging; Oxonic Acid; Survival Rate; Tegafur; Thymidylate Synthase; Treatment Outcome

To investigate the potential radiosensitization of S-1 and gefitinib in human non-small cell lung cancer (NSCLC) in vitro and in vivo.. The impact of radiation, 5-fluorouracil (5-Fu), and gefitinib on the proliferation and apoptosis of human NSCLC A549, H1299, H1975, and HCC827 cells was examined by MTT and flow cytometry. The effect of radiation, 5-Fu, and gefitinib on the clonogenicity of H1975 and HCC827 cells was determined by colony formation assay. The effect of radiation, 5-fluorouracil (5-Fu), and gefitinib on the EGFR, AKT, and ERK1/2 activation in H1975 cells was determined by Western blot. The therapeutic efficacy of radiation, S-1, and gefitinib in the growth of implanted H1975 tumors and the AKT activation in the tumors were examined in vivo and immunohistochemistry, respectively.. Combination of radiation, 5-Fu, and gefitinib significantly inhibited the proliferation of H1975 cells and triggered their apoptosis, but not other NSCLC cells tested. The combination therapy significantly mitigated the clonogenicity and attenuated the activation of EGFR and AKT signaling in H1975 cells. Furthermore, combination of S-1, gefitinib, and radiation significantly inhibited the growth of implanted H1975 tumors in mice and remarkably reduced the AKT phosphorylation in the tumors.. Our data indicated that combination of S-1 and gefitinib significantly increased radiosensitivity of H1975 cells. The triple combination therapies may benefit patients with the EGFR T790M mutant NSCLC.

Topics: Animals; Antineoplastic Combined Chemotherapy Protocols; Apoptosis; Carcinoma, Non-Small-Cell Lung; Cell Proliferation; Chemoradiotherapy; Drug Combinations; Drug Resistance, Neoplasm; Gamma Rays; Gefitinib; Humans; Lung Neoplasms; Male; Mice; Mice, Inbred BALB C; Mice, Nude; Oxonic Acid; Phosphorylation; Radiation-Sensitizing Agents; Tegafur; Tumor Cells, Cultured; Xenograft Model Antitumor Assays

Adjuvant chemotherapy with uracil tegafur (UFT) improved survival among patients with completely resected stage I lung adenocarcinoma. S-1, an oral dihydropyrimidine dehydrogenase (DPD)-inhibitory 5-fluorouracil, is a more potent DPD inhibitor than UFT;therefore, we hypothesized that postoperative adjuvant chemotherapy with S-1 would be effective for advanced non-small cell lung cancer (NSCLC). We conducted a feasibility study of S-1 as postoperative adjuvant chemotherapy in patients with curatively resected pathological stage bold I back 10 bold I and bold I back 10 bold I back 20 bold I A NSCLC.. Adjuvant chemotherapy consisted of 9 courses (4-week administration, 2-week withdrawal) of S-1 at 80-120 mg/body per day. Twenty-four patients with completely resected NSCLC were enrolled in this study from November 2007 through December 2010. The primary endpoint was the rate of completion of the scheduled adjuvant chemotherapy. The secondary endpoints were safety, overall survival, and relapse-free survival.. Five patients were censored because of disease recurrence. The planned 9 courses of S-1 were administered to completion in 8 patients. Twelve patients completed more than 70% of the planned courses. Grade 3 adverse reactions, such as elevated total bilirubin (4.2%) and pneumonitis (4.2%), were observed, but there were no Grade 4 adverse reactions. Patients who completed more than 70% of the 9 courses demonstrated better overall survival than those who completed less than 70%.. Postoperative administration of S-1 may be possible with few severe adverse events as adjuvant chemotherapy for patients with curatively resected pathological stage bold I back 10 bold I -bold I back 10 bold I back 20 bold I A NSCLC. J. Med. Invest. 65:90-95, February, 2018.

Topics: Aged; Carcinoma, Non-Small-Cell Lung; Chemotherapy, Adjuvant; Drug Combinations; Feasibility Studies; Female; Humans; Lung Neoplasms; Male; Middle Aged; Neoplasm Staging; Oxonic Acid; Tegafur

We investigated the efficacy of concurrent radiotherapy plus S-1 (CRS) for treating unresectable stage III advanced non-small-cell lung cancer (ANSCLC).Seventy five ANSCLC patients were included in this retrospective study. Of those, 40 patients were assigned to an intervention group, and received S-1 (orally at 40 mg/m) twice daily for 14 consecutive days. Then, concurrent radiotherapy was administered in 2 Gy fractions, 5 times weekly for a total dose of 60 Gy. The other 35 patients were assigned to a control group, and underwent concurrent radiotherapy (the same as the intervention group) and cisplatin (60 mg/m on day 1 (CRC). The outcome measurements included overall response rate (ORR), overall survival (OS), progression-free survival (PFS), and toxicity.The 3-year ORR was 60.7% and 43.9% for intervention group and control group, respectively (P = .031). The median OS was 34.1 months and 25.3 months in the intervention and control groups, respectively (P = .041). The median PFS was 31.5 months for intervention group, while it was 22.4 months for control group (P = .048). No significant difference in toxicity was found between the 2 groups.The results demonstrated that the efficacy of CRS was superior to the CRC in ANSCLC patients with similar toxicity.

Topics: Adult; Aged; Aged, 80 and over; Antimetabolites, Antineoplastic; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Non-Small-Cell Lung; Chemoradiotherapy; China; Cisplatin; Combined Modality Therapy; Disease-Free Survival; Drug Combinations; Female; Humans; Lung Neoplasms; Male; Middle Aged; Neoplasm Staging; Oxonic Acid; Retrospective Studies; Tegafur; Treatment Outcome

There is no standard treatment for advanced non-small cell lung cancer (NSCLC) after the failure of two lines of chemotherapy, S-1 as the third generation of fluorouracil derivate with well safety and low toxicity, presented some efficacy in lung cancer treatment. The aim of this study is to explore the efficacy of S-1 for advanced NSCLC patients treated with two or more prior chemotherapy regimens.. We performed a retrospective analysis of 105 NSCLC patients treated with S-1 monotherapy or S-1 contained chemotherapy as the third or more line of treatment in our hospital from January 2014 to April 2017. S-1 was administrated orally twice daily for 2 weeks, followed by one week of rest, the dose of drug was determined by body surface area (<1.25 m2, 80 mg/d; 1.25 m2-1.5 m2, 100 mg/d; ≥1.5 m2, 120 mg/d), platinum or the third-generation chemotherapy drugs could be combinedly used. Clinical response was assigned every cycle according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, Kaplan-Meier analysis was used to estimate progression-free survival (PFS).. 42 patients received S-1 monotherapy, the other 63 patients received combined regimens, the median treatment line was 4 (3-11) and the median treatment cycle was 2 (1-14). No complete response (CR) were observed, there were 4 patients with partial response (PR), 34 patients with stable disease (SD) and 67 patients with progressive disease (PD), the objective response rate (ORR) was 3.81%, disease control rate (DCR) was 36.19%. The median PFS was 1.90 months (0.67 months-10.83 months), no difference between monotherapy and combined group (DCR: 28.56% vs 41.27%, P=0.185), the liver metastasis showed poorer PFS (1.40 months vs 1.93 months , P=0.042).. S-1 presented some activity in advanced NSCLC treated with more than two lines of treatment. The addition of other drugs cannot improve efficacy. S-1 monotherapy can be used as a choice for heavily-treated patients.. 【中文题目：替吉奥治疗晚期非小细胞肺癌三线及以上
患者的疗效分析】 【中文摘要：背景与目的 晚期非小细胞肺癌一二线治疗后进展，目前尚无标准的治疗方案，替吉奥作为安全低毒的第三代氟脲嘧啶衍生物，对肺癌具有一定疗效，本研究旨在探讨替吉奥在晚期三线及以上非小细胞肺癌患者中的疗效。方法 回顾性分析105例2014年1月-2017年4月我院收治的使用替吉奥单药或联合方案治疗三线及以上晚期非小细胞肺癌患者的临床资料，替吉奥使用方法：体表面积<1.25 m2，每日80 mg；1.25 m2-1.5 m2，每日100 mg；≥1.5 m2，每日120 mg，分2次口服，连续使用1 d-14 d，21 d为1个周期。可联合铂类或其他第三代化疗药物。每周期根据实体瘤疗效评价标准（Response Evaluation Criteria in Solid Tumors, RECIST）1.1标准评价近期疗效，采用Kaplan-Meier方法统计生存数据。结果 替吉奥单药治疗42例，联合用药63例，中位治疗线数4（3-11），中位周期数2（1-14）。无完全缓解患者，部分缓解患者4例，疾病稳定患者34例，疾病进展患者67例。客观有效率3.81%，疾病控制率36.19%。中位无进展生存期1.90个月（95%CI: 0.67-10.83），单药或联合治疗疗效相似（疾病控制率：28.56% vs 41.27%，P=0.185），肝转移患者预后更差（中位无进展生存期：1.40个月 vs 1.93个月，P=0.042）。结论 在晚期非小细胞肺癌患者三线及以上抗肿瘤治疗中，替吉奥具有一定疗效，联合用药不能进一步提高疗效，替吉奥单药可作为多程治疗后患者的选择之一。】 【中文关键词：替吉奥；肺肿瘤；化疗；药物耐药】.

Topics: Adult; Aged; Antineoplastic Agents; Carcinoma, Non-Small-Cell Lung; Drug Combinations; Female; Fluorouracil; Humans; Lung Neoplasms; Male; Middle Aged; Oxonic Acid; Retrospective Studies; Safety; Survival Analysis; Tegafur; Treatment Outcome

To elucidate the evolution of a lung-sparing strategy with sleeve lobectomy (SL) and induction therapy for non-small cell lung cancer (NSCLC).. We retrospectively reviewed 205 patients with NSCLC who underwent pneumonectomy (PN, n = 54) or SL (n = 151) from 1994 to 2013. The study period was divided into four 5-year periods, and surgical trends were analyzed, focusing on the PN:SL ratio.. PN was associated with a significantly advanced pathological stage, a larger tumor size and less pulmonary function compared with SL. The PN group had higher 30-day (3.7 vs. 0 %, p = 0.018) and 90-day (13.0 vs. 1.3 %, p = 0.0003) mortality than the SL group. The overall 5-year survival rate was significantly higher with SL (71.5 %) versus PN (42.8 %, p = 0.011) for patients with pN0-1. The ratio of PN among total surgeries decreased significantly over the four periods (1994-1998, 1999-2003, 2004-2008, and 2009-2013) from 5.63 % to 3.17, 1.40, and 1.38 %, respectively (p < 0.0001); in contrast, the PN:SL ratio increased significantly from 1.64 to 2.50, 3.71, and 5.44, respectively (p = 0.041). During the last period, when we introduced induction therapy, 38 of 651 who received surgery underwent induction therapy. The PN:SL ratios of those who did and did not undergo induction therapy were 15 (PN: 1, SL: 15) and 4.25 (PN: 8, SL: 34), respectively.. A lung-sparing strategy with SL for NSCLC can decrease the PN rate to less than 2 % with less mortality. Induction therapy may facilitate SL and increase the PN:SL ratio.

Topics: Adenocarcinoma; Aged; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Carcinoma, Large Cell; Carcinoma, Non-Small-Cell Lung; Carcinoma, Squamous Cell; Chemoradiotherapy; Deoxycytidine; Drug Combinations; Female; Gemcitabine; Humans; Induction Chemotherapy; Lung; Lung Neoplasms; Lymph Nodes; Male; Middle Aged; Neoadjuvant Therapy; Neoplasm Staging; Organ Sparing Treatments; Oxonic Acid; Paclitaxel; Platinum Compounds; Pneumonectomy; Remission Induction; Retrospective Studies; Survival Rate; Tegafur; Tumor Burden

We present the case of a 77-year-old Japanese man diagnosed with lung squamous cell carcinoma with mediastinal lymph node metastasis. He was treated with induction chemoradiotherapy for T1bN2M0 stage IIIA disease. Considering his age, we selected S-1 as the chemotherapeutic drug. Observing an objective response with no severe adverse events, we performed a left upper lobectomy with sleeve resection of the pulmonary artery. No residual tumor cells were found in the resected specimens, and no critical complication was observed in the clinical course. This case suggests that induction chemoradiotherapy using S-1 combined with concurrent radiation followed by surgery can be a therapeutic option for elderly patients with locally advanced non-small-cell lung cancer.

Topics: Aged; Antimetabolites, Antineoplastic; Carcinoma, Non-Small-Cell Lung; Chemoradiotherapy; Drug Combinations; Humans; Lymphatic Metastasis; Male; Mediastinal Neoplasms; Oxonic Acid; Pneumonectomy; Tegafur

There is no established standard regimen for non-small cell lung cancer (NSCLC) patients with interstitial lung disease (ILD). For them, we performed a pilot study to evaluate the feasibility of chemotherapy with carboplatin and S-1, which are known as cytotoxic drug with rare development of ILD as adverse event.. A total of 21 chemotherapy-naive NSCLC patients with ILD were prospectively enrolled between March 2009 and September 2011. Every 3 weeks, carboplatin at a dose of AUC 5 on day 1 and S-1 at a dose of 80 mg/m2 daily for 14 days were administered.. The median age at initiating chemotherapy was 67. Histological examination revealed 10 patients (48 %) with adenocarcinoma. Before chemotherapy, partial pressure of arterial O2 (PaO2) was low with a median of 71 Torr on room air. The median number of cycles administered was four, and the overall response rate and disease control rate were 33 and 67 %, respectively. At the time of data cut-off, all patients were deceased. The median progression-free survival (PFS) and median overall survival (OS) periods were 4.2 and 9.7 months. There was no significant difference of PFS and OS according to tumor histology. Acute exacerbation (AE) of ILD following S-1 plus carboplatin occurred in two patients (10 %, 2/21) within first course treatment. However, they were successfully managed with steroid therapy and survived for 7.0 and 8.8 months, respectively, after AE-ILD development.. This is the first prospective study to evaluate the safety and efficacy of S-1 plus carboplatin treatment for NSCLC patients with ILD. This regimen could be a feasible option for NSCLC patients with ILD, regardless of tumor histology. Our results would support to carry out a large-scale clinical trial to confirm the feasibility of this regimen.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Carboplatin; Carcinoma, Non-Small-Cell Lung; Disease-Free Survival; Drug Combinations; Female; Humans; Kaplan-Meier Estimate; Lung Diseases, Interstitial; Lung Neoplasms; Male; Middle Aged; Oxonic Acid; Pilot Projects; Prospective Studies; Tegafur

Concurrent chemoradiotherapy (CCRT) is the preferred treatment for stage III unresectable non-small cell lung cancer (NSCLC). However, there have been few reports on combination chemotherapy with radiation for second- and third-generation antitumor drugs, although clinical guidelines have recommended the use of these drugs along with platinum agents.. We retrospectively analyzed the efficacy and toxicity of cisplatin and either S-1 or vinorelbine for treating stage III unresectable NSCLC patients who were treated with CCRT.. Between September 2006 and May 2014, 56 patients with unresectable stage III NSCLC were treated with CCRT with S-1 and cisplatin (median age: 63 years) and 58 patients were treated with CCRT with vinorelbine and cisplatin (median age: 61 years). The median follow-up time was 14.6 months in the S-1 arm and 28.0 months in the vinorelbine arm. We found no significant difference in progression-free survival (15.8 months vs. 10.1 months; p=0.15) and overall survival (33.7 months vs. 31.1 months; p=0.63) between the S-1 and vinorelbine arms, respectively. Severe (more than grade 3) leukopenia (35.7% vs. 98.2%; p<0.01), neutropenia (44.6% vs. 98.2%; p<0.01), and febrile neutropenia (1.8% vs. 46.6%, p<0.01) were significantly less frequent in the S-1 arm than in the vinorelbine arm. Treatment-related deaths were not observed in either arm.. CCRT with both S-1 or vinorelbine with cisplatin appears feasible based on their efficacy and toxicity profiles. Both treatments may be recommended as treatment options for patients with stage III unresectable NSCLC.

Topics: Adult; Aged; Antineoplastic Agents; Carcinoma, Non-Small-Cell Lung; Chemoradiotherapy; Cisplatin; Drug Combinations; Female; Humans; Lung Neoplasms; Male; Middle Aged; Oxonic Acid; Retrospective Studies; Tegafur; Vinblastine; Vinorelbine

Post-operative adjuvant chemotherapy has been considered an effective strategy to reduce cancer recurrence and improve survival for resected non-small-cell lung cancer. The Japan Clinical Oncology Group has completed patient accrual for a randomized Phase III study (JCOG0707), which compares the survival benefit of UFT and S-1 for completely resected pathological Stage I (T1 >2 cm and T2 in TNM classification version 6) non-small-cell lung cancer. However, there is a growing concern that those who participated in clinical trials are highly selected patients and do not represent the 'real-world' population. This multicenter observational cohort study aims to analyze the backgrounds, pattern of care and outcomes of the patients who were excluded from the JCOG0707 study during the accrual period. The results of this cohort study will be useful for external validity of the results of clinical trial such as JCOG0707.

Topics: Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Non-Small-Cell Lung; Chemotherapy, Adjuvant; Cohort Studies; Disease-Free Survival; Drug Combinations; Female; Fluorouracil; Humans; Kaplan-Meier Estimate; Lung Neoplasms; Male; Middle Aged; Neoplasm Recurrence, Local; Neoplasm Staging; Oxonic Acid; Patient Selection; Postoperative Period; Prodrugs; Proportional Hazards Models; Tegafur; Uracil

We report 3 cases of long-term control achieved via S-1 monotherapy in elderly patients with advanced non-small-cell lung cancer. In case 1, a 75-year-old man clinically diagnosed with stage IIIA lung adenocarcinoma received S-1 as fourthline chemotherapy. PR was achieved, and PFS was 8 months. In case 2, a 78-year-old woman clinically diagnosed with stage IV lung squamous cell carcinoma received S-1 as third-line chemotherapy. A PR was achieved, and PFS was 14 months. In case 3, an 83-year-old man clinically diagnosed with stage IV lung squamous cell carcinoma received CBDCA plus PTX, followed by S-1 on alternate days. Although tumor size was not reduced, SD was maintained for 11 months.

Topics: Aged; Aged, 80 and over; Antimetabolites, Antineoplastic; Carcinoma, Non-Small-Cell Lung; Drug Combinations; Female; Humans; Lung Neoplasms; Male; Neoplasm Staging; Oxonic Acid; Tegafur; Tomography, X-Ray Computed

S-1 is one of the effective chemotherapy regimens for treating non-small cell lung cancer. We report of an elderly patient with non-small cell lung cancer who responded to S-1 monotherapy following gefitinib therapy. An 83-year-old woman was diagnosed with advanced adenocarcinoma of the lungs (cT3N3M1a, Stage IV). Considering her age, monotherapy with vinorelbine was administered as first-line chemotherapy. Despite the completion of four courses, she was diagnosed with progressive disease. Thereafter, after considering her status as a non-smoking woman, gefitinib was introduced as second-line chemotherapy, which resulted in significant tumor size reduction.Tumor regrowth was identified 16 months later, and gefitinib was switched to erlotinib, but the tumor kept increasing in size.S -1 monotherapy was introduced as fourth-line chemotherapy, and the tumor began to decrease in size again. A partial response was obtained after 10 months, without serious adverse effects. Gefitinib following S-1 monotherapy resulted in long-term tumor size control for a total of 27 months in an elderly patient with advanced non-small cell lung cancer.S -1 monotherapy might be one of the options for salvage therapy after gefitinib treatment becomes ineffective.

Topics: Aged, 80 and over; Antimetabolites, Antineoplastic; Antineoplastic Agents; Carcinoma, Non-Small-Cell Lung; Disease Progression; Drug Combinations; Fatal Outcome; Female; Gefitinib; Humans; Lung Neoplasms; Oxonic Acid; Quinazolines; Salvage Therapy; Tegafur

The aim of the present study was to analyze factors that affect progression-free survival (PFS) of patients with previously treated advanced non-small cell lung cancer (NSCLC) after S-1 therapy, in particular epidermal growth factor receptor (EGFR) mutation status.. Between October 2009 and June 2013, 56 patients with advanced NSCLC were analyzed for EGFR somatic mutations and treated with S-1 with or without bevacizumab. Risk factors associated with PFS were evaluated using a Cox proportional hazards regression model with a step-down procedure. Proportional hazards assumptions were checked and satisfied and only variables with statistical significance in univariate analysis were included in multivariate analysis.. The median PFS of patients with EGFR mutations who received S-1 therapy was significantly longer than that of patients with wild-type EGFR. The median PFS of patients with good performance status (PS) was significantly longer than that of patients with poor PS. In multivariate analysis, wild-type EGFR and poor PS were significant and independent negative factors that affect PFS after S-1 therapy.. EGFR mutation and good PS were positive predictive factors for PFS after S-1 therapy, suggesting that S-1 therapy is efficacious for patients with EGFR-activating mutations even in a multi-line setting.

Topics: Aged; Aged, 80 and over; Angiogenesis Inhibitors; Antibodies, Monoclonal, Humanized; Antimetabolites, Antineoplastic; Bevacizumab; Carcinoma, Non-Small-Cell Lung; Disease-Free Survival; Drug Combinations; ErbB Receptors; Female; Humans; Lung Neoplasms; Male; Middle Aged; Multivariate Analysis; Mutation; Oxonic Acid; Retrospective Studies; Tegafur; Vascular Endothelial Growth Factor A

Concurrent chemoradiotherapy using S-1 containing tegafur, an oral 5-FU prodrug, plus cisplatin has been reported to show promising efficacy against locally advanced non-small cell lung cancer with acceptable toxicity. The purpose of this study is to assess the impact of this induction treatment followed by surgery on survival for those patients.. Potentially resectable locally advanced non-small cell lung cancer patients were eligible. The concurrent phase consisted of S-1 (orally at 40 mg/m² twice a day on days 1 to 14 and 22 to 36) and cisplatin (60 mg/m² on days 1 and 22) with radiation of 40 Gy/20 fractions beginning on day 1 followed by surgical resection.. Forty-two consecutive patients, between June 2005 and February 2011, were retrospectively analyzed. The median age was 59 (42 to 77) years, there were 34 males and 8 females, 26 cStage IIIA and 16 IIIB, each 21 adenocarcinomas and others. There were 26 partial responses and 16 stable disease cases after current induction treatment without uncontrollable toxicity. Of the 42 patients, 39 underwent surgical resection; 27 underwent a lobectomy and 12 pneumonectomies. One patient died due to thoracic empyema 65 days after surgery. The median follow-up time was 32.0 months. Three- and 5-year disease-free survival rates in all 39 resected patients were 52.0% and 44.0%, respectively, and 3- and 5-year overall survival rates were 77.4% and 61.7%, respectively.. Concurrent chemoradiotherapy using S-1 plus cisplatin followed by surgery may provide a better prognosis for locally advanced non-small cell lung cancer patients. Further prospective clinical investigation should be required.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Non-Small-Cell Lung; Chemoradiotherapy; Cisplatin; Drug Combinations; Female; Humans; Lung Neoplasms; Male; Middle Aged; Neoplasm Staging; Oxonic Acid; Preoperative Care; Retrospective Studies; Tegafur

An 80-year-old man with no complaint was referred to our department because of high serum CEA level. He was diagnosed as non-small cell lung cancer(adenocarcinoma)of the left lower lobe(c-T2aN0M0, stage I B), and therefore the left lower lobectomy with lymph node dissection was performed. Pathological staging was p-T2aN1(#10)M0, stage II A, and EGFR mutation was negative. Adjuvant chemotherapy with UFT was started, but multiple hilar and mediastinal lymph nodes metastases soon appeared. Carboplatin(CBDCA)+paclitaxel(PTX), erlotinib, and docetaxel(DOC)were attempted after that, but the lymph nodes increased in size and the CEA level was up to 159.8 ng/mL. At about the same time, brain and pulmonary metastases were recognized. After radiation for the chest lymph nodes and stereotactic radiosurgery(SRS)for the brain metastasis, oral S-1 monotherapy was introduced. Soon after, the lymph nodes shrinked and the CEA level decreased. Also, the pulmonary metastasis disappeared. Although a right supraclavicular lymph node metastasis was resected during the clinical course, the S-1 monotherapy has been continued with no serious adverse event. He is well(PS 0)without recurrent lesion, and his serum CEA level is within the normal limit.

Topics: Aged, 80 and over; Carcinoma, Non-Small-Cell Lung; Combined Modality Therapy; Drug Combinations; Humans; Lung Neoplasms; Male; Oxonic Acid; Recurrence; Tegafur

The efficacy of third-line and further-line chemotherapy for advanced non-small-cell lung cancer (NSCLC) remains unknown.. We evaluated the clinical outcome of third- and fourth-line chemotherapy for the treatment of advanced NSCLC in consecutive patients who received first-line chemotherapy at our institute between July 2002 and June 2006. From a hospital-based registry, the following data were extracted: (a) patient characteristics, (b) type of chemotherapeutic agents, and (c) objective response and survival data.. A total of 599 patients were included in this analysis. Overall, 69.3%, 38.4%, 17.7%, and 6.0% of the patients received second-, third-, fourth-, and fifth-line chemotherapy, respectively. Significant differences in age (P < .0001), performance status at the start of first-line chemotherapy (P < .0001), and histology (P = .0175) were observed between patients who received third-line chemotherapy and those who did not. Docetaxel, gefitinib, and S-1 were the most frequently used regimens for third- or fourth-line chemotherapy. Five percent of the patients had participated in phase I trials of investigational new drugs. The objective response rates and disease control rates of third- and fourth-line chemotherapy were 17.0% and 34.4% and 11.3% and 24.5%, respectively. The median survival times (95% confidence interval [CI]) from the start of first-, second-, third-, and fourth-line chemotherapy until death were 15.3 months (95% CI, 13.8-16.5 months), 12.8 months (95% CI, 10.7-14.5 months), 12.0 months (95% CI, 9.3-14.2 months), and 9.9 months (95% CI, 8.6-12.0 months), respectively.. As many as 38% of patients with advanced NSCLC who received first-line chemotherapy could receive third-line chemotherapy. This result emphasizes the need for randomized controlled trials of third-line treatment in patients with advanced NSCLC.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Large Cell; Carcinoma, Non-Small-Cell Lung; Carcinoma, Squamous Cell; Docetaxel; Drug Combinations; Female; Follow-Up Studies; Gefitinib; Humans; Lung Neoplasms; Male; Middle Aged; Neoplasm Recurrence, Local; Neoplasm Staging; Oxonic Acid; Quinazolines; Retrospective Studies; Taxoids; Tegafur; Treatment Outcome

Based on the results of phase I/II studies, S-1 plus cisplatin (CDDP) and vinorelbine (VNR) plus CDDP are commonly used chemoradiotherapeutic regimens for the treatment of non-small cell lung cancer(NSCCLC) in Japan. However, there have been no studies that have compared S-1 and CDDP combined with thoracic radiotherapy (TRT) with VNR and CDDP combined with TRT.. A total of 39 and 50 patients with stage III non-small cell lung cancer (NSCLC) were treated with S-1 and CDDP plus concurrent TRT, or with VNR and CDDP plus concurrent TRT, respectively, between 2002 and 2010.. In the S-1 plus CDDP plus TRT group, the median progression-free survival (PFS) and the median overall survival (OS) were 327 days and 1012 days, respectively. In the VNR plus CDDP plus TRT group, the median PFS and the median OS were 328 days and 905 days, respectively. The differences in the PFS and OS were not statistically significant. Grade 3 or more leukopenia and neutropenia were significantly more common in the VNR plus CDDP plus TRT group. Grade 3 or more thrombocytopenia, esophagitis and eruption tended to be more common in the S-1 plus CDDP plus TRT group.. Due to the difference in the toxicity profiles of the two combinations, S-1 plus CDDP plus TRT or VNR plus CDDP plus TRT should be selected depending on each patient's baseline characteristics.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Non-Small-Cell Lung; Chemoradiotherapy; Cisplatin; Drug Combinations; Female; Humans; Lung Neoplasms; Male; Middle Aged; Neoplasm Staging; Oxonic Acid; Retrospective Studies; Survival Rate; Tegafur; Treatment Outcome; Vinblastine; Vinorelbine

In a previous study, we reported a patient who responded to non-small cell lung cancer treatment with S-1 and concurrent radiotherapy over an extended period. This time, we report a long-term follow-up of the same case, and a new case which had a complete response to S-1 and concurrent radiotherapy. Case 1 is a 35-year-old woman with a pathological diagnosis of stage T2N2M0 lung adenocarcinoma. This case was already reported till 36 months postoperatively. 71 months postoperatively, PET-CT inspection revealed no obvious metastasis, unusual accumulations of FDG, or unusual shadows which may suggest recurrence. Case 2 is a 37-year-old woman with a pathological diagnosis of stage T2N2M0 right lung adenocarcinoma. After CBDCA/GEM and gefitinib were used as anterior chemotherapies, the right lung was partially resected. However, since the metastasis was developed, a total amount of 60 Gy/30 Fr was used to irradiate the mediastinum of the right cervix. Around the same time, S-1 treatment was started[a dose of 50mg/day(35m2/day)in two divided doses for 2 weeks, followed by 1 week of rest). As a result of S-1 treatment with concurrent radiotherapy, the patient had a long-term response. Sixteen months postoperatively, there has been no observable recurrence by CT inspection.

Topics: Adult; Antimetabolites, Antineoplastic; Carcinoma, Non-Small-Cell Lung; Chemoradiotherapy; Drug Combinations; Female; Humans; Lung Neoplasms; Lymphatic Metastasis; Neoplasm Staging; Oxonic Acid; Tegafur; Time Factors; Tomography, X-Ray Computed

About 30% of patients with non-small cell lung cancer (NSCLC) have locally advanced cancer (stage IIIA or IIIB) at the time of presentation. Many institutions have reported treatment with preoperative chemoradiotherapy (PCRT) followed by curative resection in patients with stage III NSCLC, but the optimal therapeutic protocol for this group has not been established.. Nineteen patients with stage III NSCLC were treated with PCRT, followed by surgery at the Hamanomachi Hospital, Fukuoka, Japan from May 2000 to November 2011. We evaluated the effectiveness of PCRT for inducing downstaging using mainly three chemoradiotherapy regimens; cisplatin plus Tegafur-Gimeracil-Oteracil Potassium (S-1), cisplatin plus Tegafur-Uracil (UFT), or 1,1'cyclobutanedicarboxylate (Carboplatin, CBDCA) plus paclitaxel, with concurrent radiation therapy in 19 patients with stage III NSCLC.. The overall 5-year survival rate was 57.1%, which is higher than the average survival rate for patients with stage III NSCLC in Japan. Among the regimens used, only cisplatin plus S-1 with concurrent radiation therapy significantly induced downstaging. There was a significant difference in survival time between the downstaged and non-downstaged groups. However, there was no significant difference in survival time between the S-1 plus cisplatin group and the other groups combined, because of the short observation period for the S-1 plus cisplatin group.. PCRT using cisplatin plus S-1 with concurrent radiation therapy is useful for inducing downstaging in patients with locally advanced stage III NSCLC.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Non-Small-Cell Lung; Chemoradiotherapy; Cisplatin; Drug Combinations; Female; Humans; Kaplan-Meier Estimate; Lung Neoplasms; Male; Middle Aged; Neoadjuvant Therapy; Neoplasm Staging; Oxonic Acid; Retrospective Studies; Tegafur

Recently, multiple-line chemotherapy has become popular for non-small cell lung cancer (NSCLC). The survival time of patients is influenced by patient characteristics and subsequent treatments.. The usefulness of paclitaxel plus S1 (PTX+S1) was evaluated in 46 pretreated NSCLC patients. Time from the start of individual regimens till the start of the next one (TNR) was calculated for regimens administered to the study population including PTX+S1 and analyzed by the shared frailty Cox model.. The response rate and the median progression-free survival time of PTX+S1 were 32.6% and 253 days, respectively. Substantial difference in TNR was observed in epidermal growth factor receptor mutation status and in line and type of regimens, but not in stage, age, sex, performance status and histology, by univariate analysis. Multivariate analysis revealed that PTX+S1 was only one factor to prolong TNR.. Because of long progression-free survival and long TNR, further evaluation of PTX+S1 is necessary.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Non-Small-Cell Lung; Disease-Free Survival; Drug Administration Schedule; Drug Combinations; ErbB Receptors; Female; Humans; Lung Neoplasms; Male; Middle Aged; Multivariate Analysis; Mutation; Oxonic Acid; Paclitaxel; Proportional Hazards Models; Retrospective Studies; Survival Rate; Tegafur; Time Factors; Treatment Outcome

S-1 is an oral fluoropyrimidine derivative that is active against non-small cell lung cancer (NSCLC). Development of S-1 combination chemotherapy for advanced NSCLC is under way. Given the importance of designing therapeutic strategies based on specific tumor biology, we have evaluated the relation between immunohistochemical expression levels of thymidylate synthase (TS), orotate phosphoribosyltransferase (OPRT), or dihydropyrimidine dehydrogenase (DPD) and the response to treatment with S-1 plus carboplatin in patients with advanced NSCLC. Chemotherapy-naïve patients with advanced (stage IIIB or IV) NSCLC, an Eastern Cooperative Oncology Group performance status of 0 or 1, adequate organ function, and archival tumor tissue were assigned to receive S-1-carboplatin (n=22). The predictive or prognostic relevance of the molecular markers was also examined by their evaluation in patients treated with paclitaxel plus carboplatin (n=25). Expression levels of TS, OPRT, or DPD in tumor specimens did not differ significantly between patients treated with S-1-carboplatin and those treated with paclitaxel-carboplatin. A low expression level of TS or of DPD was associated with a better response and longer survival in patients treated with S-1-carboplatin but not in those treated with paclitaxel-carboplatin. Tumor expression levels of TS and DPD are predictive of response to S-1-carboplatin chemotherapy in patients with advanced NSCLC.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Carboplatin; Carcinoma, Non-Small-Cell Lung; Dihydrouracil Dehydrogenase (NADP); Disease-Free Survival; Drug Combinations; Female; Humans; Kaplan-Meier Estimate; Lung Neoplasms; Male; Middle Aged; Neoplasm Recurrence, Local; Neoplasm Staging; Orotate Phosphoribosyltransferase; Oxonic Acid; Paclitaxel; ROC Curve; Tegafur; Thymidylate Synthase; Treatment Outcome

Our patient was a 57-year-old male with a history of esophageal cancer. He was referred to our hospital for squamous cell lung carcinoma(SCC). Chest computed tomography identified a mass in the left lung field, which was suspected to be invading the reconstructed gastric tube, left subclavian artery, common carotid artery, and distal aortic arch. He was diagnosed as primary pulmonary squamous cell carcinoma(SCC)because six years had already passed since a previous surgery for early esophageal cancer. He received three courses of induction chemotherapy including S-1/CDDP. We evaluated the therapy as a partial response. He underwent an extended resection of distal aortic arch and left subclavian artery with left upper lobectomy, and those vessels were reconstructed using prosthetic grafts. Pathological findings showed the tumor as a well differentiated SCC of pT4N0M0 at stage III A, with a residual tumor on the reconstructed gastric tube, even though the effect of induction chemotherapy was Ef2. He received three courses of S-1/CDDP after surgery. The patient has been well without recurrence for 31 months after surgery.

Topics: Antineoplastic Combined Chemotherapy Protocols; Aorta, Thoracic; Carcinoma, Non-Small-Cell Lung; Cisplatin; Drug Combinations; Humans; Lung Neoplasms; Male; Middle Aged; Neoplasm Invasiveness; Neoplasm Staging; Neovascularization, Pathologic; Oxonic Acid; Tegafur; Time Factors

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).. 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.. 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.. 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.

Topics: Administration, Oral; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Non-Small-Cell Lung; Chemoradiotherapy; Cisplatin; Cohort Studies; Combined Modality Therapy; Disease-Free Survival; Drug Combinations; Feasibility Studies; Female; Humans; Infusions, Intravenous; Kaplan-Meier Estimate; Lung Neoplasms; Male; Middle Aged; Neoadjuvant Therapy; Neoplasm Invasiveness; Neoplasm Staging; Oxonic Acid; Patient Selection; Pneumonectomy; Prognosis; Risk Assessment; Survival Analysis; Tegafur; Treatment Outcome

A 35-year-old woman with a clinical diagnosis of stage T2N2M0 lung adenocarcinoma received 3 courses of preoperative chemotherapy with cisplatin and docetaxel. The treatment response was no change. A left inferior lobectomy with mediastinal and hilar lymph-node dissection (ND2a) was performed. The pathological diagnosis was stage T2N2M0 lung cancer. Gefitinib was administered postoperatively. After 2 months of oral treatment, gefitinib was discontinued because of enlarged subcarinal lymph nodes and an elevated level of serum Sialyl LewisX-i antigen (SLX). Starting 4 months after surgery, the mediastinum was irradiated with a total dose of 50 Gy. Chemotherapy with S-1 was started 5 months after surgery. S-1 was administered in a dose of 100 mg/day in two divided doses for 4 weeks, followed by 2 weeks of rest. The patient received 6 courses of chemotherapy with S-1, without increasing the dose. The enlarged mediastinal lymph nodes disappeared, and the serum SLX level returned to normal. The patient had a complete response, and was subsequently followed on an outpatient basis while receiving oral UFT. More than 36 months have elapsed since surgery, with no evidence of recurrence.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Non-Small-Cell Lung; Combined Modality Therapy; Drug Combinations; Drug Resistance, Neoplasm; Female; Gefitinib; Humans; Lung Neoplasms; Oxonic Acid; Positron-Emission Tomography; Quinazolines; Remission Induction; Tegafur; Tomography, X-Ray Computed

No investigation of S-1 monotherapy in previously treated advanced non-small-cell lung cancer (NSCLC) patients has yet been reported. We conducted a retrospective study to evaluate the efficacy and tolerability of S-1 in patients with failure of second- or further-line chemotherapy.. The records of NSCLC patients who had received S-1 monotherapy between January 2005 and November 2006 with the following eligibility criteria were reviewed: previously treated with at least two regimens including platinum and docetaxel in the case of nonadenocarcinoma patients, and including platinum, docetaxel and epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKI) in the case of adenocarcinoma patients. S-1 was administered for 28 consecutive days, followed by a 14-day drug-free period (42 days in one course). The drug was administered in two divided doses daily at 80 mg/day for patients with a body surface area <1.25 m(2), 100 mg/day for those with a body surface area of 1.25-1.5 m(2), and 120 mg/day for those with a body surface area > or = 1.5 m(2).. Thirty-five patients were registered. The median number of courses administered per patient was 2 (range 1-9). The toxicity profile was mild, and grade 3 or more severe toxicity was rare. The overall response and disease control rates were 5.7% and 40%, respectively. The median survival time was 208 days.. S-1 exhibits modest activity and acceptable toxicity when used as a third or subsequent line of chemotherapy in patients with advanced NSCLC.

Topics: Adult; Aged; Antimetabolites, Antineoplastic; Carcinoma, Non-Small-Cell Lung; Disease-Free Survival; Drug Combinations; Female; Humans; Lung Neoplasms; Male; Middle Aged; Oxonic Acid; Retrospective Studies; Salvage Therapy; Survival Analysis; Tegafur; Time Factors; Treatment Outcome

The combination therapy of CPT-11, a prodrug of SN-38, with S-1, a dihydropyrimidine dehydrogenase inhibitory fluoropyrimidine, shows a high clinical response rate in non-small cell lung cancer (NSCLC). However, this combination causes severe toxicities such as diarrhea. Here, we investigated the advantages of treatment with the SN-38-incorporating polymeric micelles NK012 over CPT-11 in combination with S-1 in mice bearing a NSCLC xenograft in terms of antitumor activity and toxic effects, particularly intestinal toxicity. In vitro cytotoxic effects were examined in human NSCLC cell lines (A549, PC-9, PC-14, EBC-1 and H520). In vivo antitumor effects were evaluated in PC-14- and EBC-1-bearing mice after NK012 or CPT-11 administration on Days 0 and 7 and S-1 administration on Days 0-13. Pathological changes in the small intestine were also investigated. The in vitro growth inhibitory effects of NK012 were 56.8- to 622-fold more potent than those of CPT-11. NK012/S-1 treatment showed significantly higher antitumor activity both in PC-14-bearing (p = 0.0007) and EBC-1-bearing mice (p < 0.0001) than CPT-11/S-1 treatment. The deformity and decrease in the density of intestinal villi were more severe in CPT-11/S-1-treated mice than in NK012/S-1-treated mice. NK012/S-1 combination is a promising candidate regimen against NSCLC without inducing toxicities such as severe diarrhea and therefore warrants clinical evaluation.

Topics: Animals; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Carcinoma, Non-Small-Cell Lung; Cell Line, Tumor; Dihydrouracil Dehydrogenase (NADP); Drug Combinations; Drug Delivery Systems; Drug Synergism; Female; Humans; Intestinal Mucosa; Irinotecan; Lung Neoplasms; Mice; Mice, Inbred BALB C; Mice, Nude; Micelles; Oxonic Acid; RNA, Messenger; Tegafur; Thymidylate Synthase; Xenograft Model Antitumor Assays

It is desirable to find more appropriate therapeutic opportunities in non-small-cell lung cancer (NSCLC) due to the current poor prognosis of affected patients. Recently, several histone deacetylase (HDAC) inhibitors, including suberoylanilide hydroxamic acid (SAHA), have been reported to exhibit antitumor activities against NSCLC. S-1, a novel oral fluorouracil anticancer drug, has been developed for clinical use in the treatment of NSCLC in Japan. Using an MTT assay, we analyzed the growth-inhibitory effect of 5-fluorouracil (5-FU), S-1, and SAHA against three NSCLC cell lines, as well as the breast cancer cell line MCF7 which is known to be highly sensitive to 5-FU. Combined treatment with low-dose SAHA enhanced 5-FU- and S-1-mediated cytotoxicity and resulted in synergistic effects, especially in 5-FU-resistant cells. Both the mRNA and protein expression levels of thymidylate synthase (TS), dihydropyrimidine dehydrogenase (DPD), and orotate phosphoribosyltransferase (OPRT), which are associated with 5-FU sensitivity/response, were analyzed in the cells undergoing treatment. 5-Fluorouracil-resistant lung cancer cells displayed high expression of TS mRNA and protein. Suberoylanilide hydroxamic acid down-regulated TS mRNA and protein expression, as well as repressed the rapid induction of this factor during 5-FU treatment, in all examined cell types. We also examined the status of the Rb-E2F1 pathway, with SAHA up-regulating p21(waf1/cip1) expression via promoter histone acetylation; this, in turn, blocked the Rb-E2F1 pathway. We conclude that combination therapy with SAHA and S-1 in lung cancer may be promising due to its potential to overcome S-1 resistance via modulation of 5-FU/S-1 sensitivity-associated biomarker (TS) by HDAC inhibitor.

Topics: Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Non-Small-Cell Lung; Cell Line, Tumor; Cyclin-Dependent Kinase Inhibitor p21; Drug Combinations; E2F1 Transcription Factor; Fluorouracil; Gene Expression Regulation; Histone Deacetylase Inhibitors; Humans; Hydroxamic Acids; Lung Neoplasms; Oxonic Acid; Retinoblastoma Protein; RNA, Messenger; Tegafur; Thymidylate Synthase; Vorinostat

Most non-small cell lung cancer (NSCLC) tumors with activating mutations of the epidermal growth factor receptor (EGFR) are initially responsive to first-generation, reversible EGFR tyrosine kinase inhibitors (TKI) such as gefitinib, but they subsequently develop resistance to these drugs through either acquisition of an additional T790M mutation of EGFR or amplification of the proto-oncogene MET. We have now investigated the effects of combination treatment with thymidylate synthase (TS)-targeting drugs and the second-generation, irreversible EGFR-TKI BIBW2992 on the growth of NSCLC cells with the T790M mutation. The effects of BIBW2992 on EGFR signaling and TS expression in gefitinib-resistant NSCLC cells were examined by immunoblot analysis. The effects of BIBW2992 and the TS-targeting agents S-1 (or 5-fluorouracil) or pemetrexed on the growth of gefitinib-resistant NSCLC cells were examined both in vitro and in vivo. The combination of BIBW2992 with 5-fluorouracil or pemetrexed synergistically inhibited the proliferation of NSCLC cells with the T790M mutation in vitro, whereas an antagonistic interaction was apparent in this regard between gefitinib and either of these TS-targeting agents. BIBW2992 induced downregulation of TS in the gefitinib-resistant NSCLC cells, implicating depletion of TS in the enhanced antitumor effect of the combination therapy. The combination of BIBW2992 and either the oral fluoropyrimidine S-1 or pemetrexed also inhibited the growth of NSCLC xenografts with the T790M mutation to an extent greater than that apparent with either agent alone. The addition of TS-targeting drugs to BIBW2992 is a promising strategy to overcome EGFR-TKI resistance in NSCLC with the T790M mutation of EGFR.

Topics: Afatinib; Amino Acid Substitution; Animals; Antineoplastic Agents; Apoptosis; Carcinoma, Non-Small-Cell Lung; Cell Line, Tumor; Cell Proliferation; Drug Combinations; Drug Resistance, Neoplasm; Drug Synergism; E2F1 Transcription Factor; ErbB Receptors; Fluorouracil; Gefitinib; Glutamates; Guanine; Humans; Lung Neoplasms; Mice; Mutation; Oxonic Acid; Pemetrexed; Phosphatidylinositol 3-Kinases; Protein Kinase Inhibitors; Proto-Oncogene Mas; Quinazolines; Tegafur; Thymidylate Synthase; Xenograft Model Antitumor Assays

A 71-year-old woman was admitted to our hospital, because of an abnormality on her chest radiograph findings. After extensive examination, she was diagnosed with primary lung adenocarcinoma (cT4N2M1, stage IV). She was treated by carboplatin+gemcitabine, gefitinib and docetaxel and the responses were stable disease in any treatment. As the fourth-line treatment, she received oral chemotherapy using S-1 at 100 mg/day (80 mg/m2 day) for 28 days, followed by withdrawal for 14 days. Tumor size was reduced 29.2% after 1 course, 62.5% after 5 courses and 83.3% after 10 courses (14 months). Hematologic and non-hematologic toxicities were mild with the S-1 administration. We experienced a case of continuation of tumor shrinkage over a year without serious adverse events by S-1 treatment. Therefore, oral administration of S-1 could be useful for the treatment of recurrent non-small cell lung cancer over a long time.

Topics: Administration, Oral; Aged; Antimetabolites, Antineoplastic; Carcinoma, Non-Small-Cell Lung; Drug Combinations; Female; Humans; Lung Neoplasms; Oxonic Acid; Radiography; Tegafur

Most non-small cell lung cancer (NSCLC) tumors with activating mutations in the epidermal growth factor receptor (EGFR) are initially responsive to EGFR tyrosine kinase inhibitors (EGFR-TKI) such as gefitinib and erlotinib, but they almost invariably develop resistance to these drugs. A secondary mutation in EGFR (T790M) and amplification of the MET proto-oncogene have been identified as mechanisms of such acquired resistance to EGFR-TKIs. We have now investigated whether addition of the oral fluoropyrimidine derivative S-1 to gefitinib might overcome gefitinib resistance in NSCLC cell lines.. The effects of gefitinib on EGFR signaling and on the expression both of thymidylate synthase and of the transcription factor E2F-1 in gefitinib-resistant NSCLC cells were examined by immunoblot analysis. The effects of S-1 (or 5-fluorouracil) and gefitinib on the growth of NSCLC cells were examined in vitro as well as in nude mice.. Gefitinib induced down-regulation of thymidylate synthase and E2F-1 in gefitinib-resistant NSCLC cells with MET amplification but not in those harboring the T790M mutation of EGFR. The combination of 5-fluorouracil and gefitinib synergistically inhibited the proliferation of cells with MET amplification, but not that of those with the T790M mutation of EGFR, in vitro. Similarly, the combination of S-1 and gefitinib synergistically inhibited the growth only of NSCLC xenografts with MET amplification.. Our results suggest that the addition of S-1 to EGFR-TKIs is a promising strategy to overcome EGFR-TKI resistance in NSCLC with MET amplification.

Topics: Animals; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Non-Small-Cell Lung; Drug Combinations; Drug Resistance, Neoplasm; Drug Screening Assays, Antitumor; E2F1 Transcription Factor; ErbB Receptors; Fluorouracil; Gefitinib; Gene Amplification; Genes, erbB-1; Humans; Lung Neoplasms; Male; Mice; Mice, Nude; Mutation; Oxonic Acid; Proto-Oncogene Mas; Proto-Oncogene Proteins c-met; Quinazolines; Tegafur; Thymidylate Synthase

An 81-year-old man presented with right shoulder pain 10 months after surgery for non-small cell lung cancer (p- T3N0M0, Stage II b). FDG-PET revealed an increased uptake in the multiple bone and mediastinal lymph nodes, suggestive of recurrence of lung cancer. He was given combined chemotherapy of gemcitabine plus S-1 as first-line treatment. This regimen was performed as a phase I trial for an elderly patient with advanced non-small cell lung cancer, and the treatment proved effective. No toxic events were observed due to this therapy, so he was treated as an outpatient for one year. He was considered to have good quality of life.

Topics: Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Bone Neoplasms; Carcinoma, Non-Small-Cell Lung; Deoxycytidine; Drug Combinations; Gemcitabine; Humans; Lung Neoplasms; Male; Oxonic Acid; Positron-Emission Tomography; Tegafur

A 78-year-old man had underwent right upper lobectomy for lung adenocarcinoma in July 1998(pT1N0M0, pStage Ia). In January2003, computed tomography showed a tumor in right lower lobe of lung, which grew slowly. He was treated with UFT. In April 2004, computed tomographyshowed multiple nodules in both lung, which was considered of metastasis of lung cancer. The increase of the nodules were observed, and treatment with gefitinib was started. Insertion mutation at EGFR in exon 20 was seen from the primarylung cancer. Since tumor growth occurred despite gefitinib administration, we converted gefitinib into S-1 using 80 mg/day for 28 days, followed by 14 days rest. Chest computed tomographyshowed a partial response. No side effect was observed, and continued internal use of S-1 until January 2007 when it was impossible to continue, and meanwhile, the increase of the tumor was not seen.

Topics: Aged; Carcinoma, Non-Small-Cell Lung; Drug Combinations; Drug Resistance, Neoplasm; ErbB Receptors; Gefitinib; Humans; Lung Neoplasms; Male; Mutation; Oxonic Acid; Quinazolines; Tegafur; Tomography, X-Ray Computed

We evaluated retrospectively single-agent S-1 chemotherapy in non-small cell lung cancer patients in clinical practice.. Sixteen consecutive patients treated with single-agent S-1 for NSCLC between July 2005 and June 2007 at the Department of Thoracic Surgery, Tsuchiura Kyodo General Hospital. The treatment schedule comprised oral administration of S-1 at 80-120 mg/day. One cycle of S-1 consisted of consecutive administration to 14 (10 cases)or 28(6 cases)days followed by a 14-day rest.. Patients profiles were: M/F: 11/5, median age 68 years old(range 51-83), PS 0/1/2/3: 2/6/5/3, adeno/squamous/large: 13/2/1, clinical stage 3A/3B/4: 3/4/9, prior chemotherapy regimens 0/1/2/3/4: 2/3/4/5/2, prior surgery/radiation: 12/5 were performed. Median number of delivered cycles was 5 cycles(range 1-13). Grade 3 hematological toxicities were anemia(6%)and thrombocytopenia(6%). Grade 3 non-hematological toxicities were nausea(6%)and vomiting(6%). Response of 13 patients could be evaluated after 2-4 cycles of S-1. Four partial responses were observed, for a response rate of 31%. The survival time was 67-852 days(average 14.0 months), 1-year survival rate was 74.0%, median time to progression was 4.6 m, and 1- year progression free survival was 25.0%.. Single-agent S-1 chemotherapy has modest activity and is the one of the important regimens and tolerable for elderly, poor-PS, recurrent patients with NSCLC in clinical practice.

Topics: Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Non-Small-Cell Lung; Disease Progression; Drug Combinations; Female; Humans; Lung Neoplasms; Male; Middle Aged; Oxonic Acid; Survival Rate; Tegafur

The objective of this study was to evaluate the efficacy and toxicity of S-1 monotherapy in patients with pretreated advanced non-small cell lung cancer(NSCLC).. We prospectively analyzed patients previously treated with a platinum-containing regimen or monotherapy with a third-generation chemotherapeutic drug. S-1 was orally administered at approximately 80 mg/m / 2day for 28 days followed by a 2-week rest period. We evaluated the efficacy and toxicities.. A total of 15 patients received S-1 monotherapy. Three partial responses were observed among them with an overall response rate of 20%. Toxicities of grade 3 or higher included anemia(13%), thrombocytopenia( 6%), fatigue(6%), anorexia(13%), diarrhea(13%), interstitialpneumonitis(6%)and infection(6%). The ratio of outpatient treatment period was 73.5%. The median time to progression, median survivaltime and 1-year survival rate were 4.2 months, 7.8 months and 27.8% respectively.. S-1 monotherapy was suggested to be effective and tolerable in patients with pretreated advanced NSCLC.

Topics: Aged; Aged, 80 and over; Antimetabolites, Antineoplastic; Carcinoma, Non-Small-Cell Lung; Drug Combinations; Female; Humans; Lung Neoplasms; Male; Middle Aged; Oxonic Acid; Prospective Studies; Survival Rate; Tegafur

Bronchioloalveolar carcinoma (BAC) is a distinct subtype of non-small cell lung cancer for which there is no optimal therapy for non-resectable or recurrent disease. This report describes a patient with BAC refractory to conventional chemotherapy but with a partial response to S-1, oral fluoropyrimidine, resulting in symptom improvement and weaning from oxygen supplementation. Our observation suggests that S-1 is a novel option for the treatment of advanced BAC.

Topics: Adenocarcinoma, Bronchiolo-Alveolar; Antimetabolites, Antineoplastic; Carcinoma, Non-Small-Cell Lung; Drug Combinations; Female; Humans; Lung Neoplasms; Middle Aged; Oxonic Acid; Tegafur; Treatment Outcome

There is at present no defined role for S-1 chemotherapy in patients with advanced non-small cell lung cancer (NSCLC) who previously failed chemotherapy. Two cases of multidrug-resistant, NSCLC that were successfully treated with S-1 as fifth-line chemotherapy are reported. A 75-year-old man was diagnosed as having pulmonary adenocarcinoma, cT1N3M0, stage III B. He was treated with S-1 as fifth-line chemotherapy after treatment with cisplatin(CDDP)and vinorelbine(VNR), docetaxel (DOC), gemcitabine (GEM) and VNR, and amrubicin (AMR). After completing two courses, chest computed tomography(CT)showed a partial response( PR)of the recurrent tumors, and the serum carcinoembryonic antigen level decreased. Currently, seven courses have been completed, and this treatment will be continued due to the tumor response of stable disease. A 65-year-old woman was referred for treatment of recurrent pulmonary adenocarcinoma after right upper lobe resection. She was treated with S-1 as fifth-line chemotherapy after treatment with GEM and VNR, carboplatin(CBDCA) and paclitaxel ( PTX), DOC, and gefitinib. After completing five courses, chest CT showed PR of the intrapulmonary metastases. Though grade 3 toxicity-anemia in the first case and an elevated serum amylase level in the second case were observed in both cases, the patients' quality of life was preserved. S-1 could therefore be a treatment option for patients with advanced NSCLC who previously underwent chemotherapy unsuccessfully.

Topics: Adenocarcinoma; Aged; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Non-Small-Cell Lung; Disease Progression; Drug Combinations; Fatal Outcome; Female; Humans; Lung Neoplasms; Male; Oxonic Acid; Quality of Life; Recurrence; Salvage Therapy; Tegafur; Tomography, X-Ray Computed; Treatment Outcome

The patient was a 36-year-old male. He visited our department in February 2004 as a prior chest X-ray revealed multiple nodular shadows. After further examinations, he was diagnosed with stage IV adenocarcinoma of the lung. As treatment, 5 courses of carboplatin (CBDCA)+docetaxel (DOC), 3 courses of CBDCA+gemcitabine (GEM), 6 weeks of gefitinib, and 3 courses of GEM were administered. However, the tumor progressed, and S-1 (120 mg/day, 2 weeks on, 1 week off) was administered as the sixth regimen from May 2006. No severe side effects were observed, and an antitumor action was achieved over a relatively long period. Therefore, it was suggested that a single administration of S-1 for non-small cell lung cancer, which had been treated with other multiple regimens, is safe, and long-term control of the disease can be expected.

Topics: Adenocarcinoma; Adult; Antimetabolites, Antineoplastic; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Carboplatin; Carcinoma, Non-Small-Cell Lung; Deoxycytidine; Docetaxel; Drug Combinations; Gefitinib; Gemcitabine; Humans; Lung Neoplasms; Male; Oxonic Acid; Quinazolines; Taxoids; Tegafur

The patient was an 86-year-old female who suffered from advanced non-small cell-lung cancer (cT4N3M1, Stage IV). She was treated with combined chemotherapy of gemcitabine and S-1 as first-line therapy. This regimen was performed as a phase I trial for elderly patients with advanced non-small cell lung cancer. The treatment assessment was evaluated as partial response. No toxic events were observed due to this therapy, so she was treated as an outpatient. She was considered to have good quality of life.

Topics: Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Non-Small-Cell Lung; Deoxycytidine; Drug Combinations; Female; Gemcitabine; Humans; Lung Neoplasms; Oxonic Acid; Positron-Emission Tomography; Tegafur; Tomography, X-Ray Computed

The therapeutic effect of concurrent chemoradiotherapy with TS-1 has been confirmed in various solid tumors; however, the detailed mechanism of action has not yet been fully elucidated. In the present study, we identified hypoxia-inducible factor-1 (HIF-1) as one of the targets of TS-1 in chemoradiotherapy. In growth delay assays using a tumor xenograft of non-small-cell lung carcinoma, H441, TS-1 treatment enhanced the therapeutic effect of single gamma-ray radiotherapy (14 Gy) and significantly delayed tumor growth by 1.58-fold compared to radiotherapy alone (P < 0.01). An optical in vivo imaging experiment using a HIF-1-dependent 5HRE-luc reporter gene revealed that TS-1 treatment suppressed radiation-induced activation of HIF-1 in the tumor xenografts. The suppression led to apoptosis of endothelial cells resulting in both a significant decrease in microvessel density (P < 0.05; vs radiation therapy alone) and a significant increase in apoptosis of tumor cells (P < 0.01; vs radiation therapy alone) in tumor xenografts. All of these results indicate that TS-1 enhances radiation-induced apoptosis of endothelial cells by suppressing HIF-1 activity, resulting in an increase in radiosensitivity of the tumor cells. Our findings strengthen the importance of both HIF-1 and its downstream gene, such as vascular endothelial cell growth factor, as therapeutic targets to enhance the effect of radiotherapy.

Topics: Animals; Antimetabolites, Antineoplastic; Apoptosis; Carcinoma, Non-Small-Cell Lung; Cell Line, Tumor; Combined Modality Therapy; Drug Combinations; Endothelial Cells; Humans; Hypoxia-Inducible Factor 1; Immunohistochemistry; Lung Neoplasms; Mice; Mice, Inbred BALB C; Oxonic Acid; Tegafur; Vascular Endothelial Growth Factor A

S-1 is an oral fluorouracil anticancer drug that contains the 5-FU prodrug tegafur. Tegafur has been shown to be converted enzymatically to 5-FU to exert its antitumor effect, and this conversion is principally catalyzed by CYP2A6. Forty-six non-small-cell lung cancer patients were enrolled. The frequencies of the CYP2A6*4C, CYP2A6*7, and CYP2A6*9 alleles were 17.4, 19.6, and 15.2%, respectively. In the S-1 pharmacokinetic analysis, the area under the concentration-time curve from 0 to 10 h (AUC(0-10)) ratios of 5-FU/tegafur showed large interindividual variabilities, ranging from 5.14 to 112.6. The AUC(0-10) for tegafur was 1.5-fold higher in patients with the CYP2A6*4C allele than in patients without the CYP2A6*4C allele P < 0.05). Furthermore, patients with the CYP2A6*4C allele had a significantly lower maximum plasma concentration (102.6 +/- 32.9 ng/ml) for 5-FU than patients without the CYP2A6*4C allele (157.0 +/- 65.5 ng/ml, P < 0.05). Genotyping of CYP2A6 polymorphisms may provide vital information for effective cancer therapy using S-1.

Topics: Adult; Aged; Alleles; Antimetabolites, Antineoplastic; Area Under Curve; Aryl Hydrocarbon Hydroxylases; Asian People; Carcinoma, Non-Small-Cell Lung; Cytochrome P-450 CYP2A6; Drug Combinations; Female; Fluorouracil; Genotype; Humans; Lung Neoplasms; Male; Middle Aged; Mixed Function Oxygenases; Oxonic Acid; Smoking; Tegafur

We report two cases with recurrent non-small cell lung cancer (NSCLC) successfully treated with cisplatin and S-1 after multiple chemotherapy. A 64-year-old woman was diagnosed with adenocarcinoma, yield-T4N2M1, stage IV. She was treated with cisplatin 60 mg/m(2) (day 8) and S-1 80 mg/m(2) (days 1-21) as sixth-line chemotherapy after treatment with paclitaxel and irinotecan, cisplatin and gemcitabine, docetaxel, gefitinib, and vinorelbine. Chest computed tomography (CT) showed partial response of recurrent tumors. Another woman (56 years old) was diagnosed with adenocarcinoma, yield-T0N1M1, stage IV. She was also treated with cisplatin and S-1 as fourth-line chemotherapy after treatment with nedaplatin and gemcitabine, docetaxel and irinotecan, and gefitinib. Chest CT showed a partial response of recurrent tumors. Additionally, we retrospectively reviewed 10 cases with recurrent NSCLC treated with cisplatin and S-1 during the same period. Grade 3 to 4 hematologic toxicity included neutropenia in 30% of these 10 patients, thrombocytopenia in 20%, and anemia in 60%. Grade 3 non-hematologic toxicity included hyperglycemia and hyponatremia in 20% of the 10 patients. All side effects were manageable and there was no case of treatment-related death. Cisplatin combined with S-1 could be an option for recurrent NSCLC.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Non-Small-Cell Lung; Cisplatin; Drug Combinations; Female; Humans; Lung Neoplasms; Male; Middle Aged; Oxonic Acid; Recurrence; Tegafur; Tomography, X-Ray Computed

Topics: Alleles; Antimetabolites, Antineoplastic; Aryl Hydrocarbon Hydroxylases; Asian People; Body Size; Carcinoma, Non-Small-Cell Lung; Cytochrome P-450 CYP2A6; Drug Combinations; Fluorouracil; Humans; Lung Neoplasms; Oxonic Acid; Tegafur

The patient was an 84-year-old male. About 7 months after surgery for a non-small cell lung cancer StageIII B, granular shadows were noted on his bilateral lungs on CT; and the level of CA 19-9 , a tumor marker, had increased. These findings led to a diagnosis of intrapulmonary tumor metastasis. Treatment with a platinum-based antineoplastic agent was recommended,but the patient refused it because of his age. The patient was thus placed under observation. Because the tumor appeared to increase in size, treatment was initiated using S-1 capsules (hereafter abbreviated to S-1) alone. Each course consisted of S-1 at a dosage of 100 mg/body/day, twice daily for 21 days, followed by 14 days of drug withdrawal. After the completion of one course, the level of the tumor marker was reduced to normal. After 6 courses were completed, CT indicated a marked reduction or elimination of the intrapulmonary metastatic foci. Malignant phenomenon exceeding grade 3 was no longer recognized,and it was possible to deliver the scheduled dosage of S-1 throughout the entire series of courses. At the end of the 14th course, no signs of exacerbation or recurrence were recognized. It has been about 18 months after the S-1 single therapy was started. This therapy is still being continued.

Topics: Aged, 80 and over; Antimetabolites, Antineoplastic; Carcinoma, Non-Small-Cell Lung; Drug Administration Schedule; Drug Combinations; Humans; Lung Neoplasms; Male; Oxonic Acid; Quality of Life; Tegafur; Tomography, X-Ray Computed