s-1-(combination) and Carcinoma--Large-Cell

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

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

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

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

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

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

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

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

A 73-year-old man was referred to our hospital because of appetite loss and weight loss in January 2009. Endoscopy showed an advanced type II gastric tumor at the middle of the gastric wall, and computed tomography showed multiple liver metastases. Immunohistological examination confirmed a diagnosis of large cell neuroendocrine carcinoma which was chromogranin A(+), CD56(+), and synaptophysin(+). Oral administration of S-1(100mg/body)was given 5 days on and 2 days off, while cisplatin(CDDP 40 mg/body)was administered intravenously once every 2 weeks. The patient achieved a partial response(PR), and no serious adverse effects were observed. This case suggests that S-1/CDDP chemotherapy may be an effective treatment in patients with large cell neuroendocrine carcinoma of the stomach.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Large Cell; Carcinoma, Neuroendocrine; Cisplatin; Drug Combinations; Fatal Outcome; Humans; Liver Neoplasms; Male; Oxonic Acid; Stomach Neoplasms; 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

A 56-year-old Japanese man who was suffering from dry cough and right neck mass visited our hospital. Chest X-ray revealed a lung mass shadow in the lower left lung field. We diagnosed it as an advanced large cell carcinoma after conducting transbronchial lung biopsy and neck lymphnode biopsy. A right neck mass enlarged after three chemotherapy regimens of carboplatin and vinorelbine for first-line, docetaxel for second-line, and TS-1 and cisplatin for third-line. Finally, cisplatin (80 mg/m(2), day 1) and gemcitabine (800 mg/m(2), day 1, 8) were administered as fourth-line therapy. Partial response was observed after completing four chemotherapy cycles.. In this case, the fourth-line chemotherapy, consisting of cisplatin and gemcitabine, proved effective for refractory NSCLC. Further research should be conducted regarding third-line chemotherapy for NSCLC patients with good performance status.

Topics: Antineoplastic Combined Chemotherapy Protocols; Carboplatin; Carcinoma, Large Cell; Cisplatin; Deoxycytidine; Docetaxel; Drug Administration Schedule; Drug Combinations; Gemcitabine; Humans; Lung Neoplasms; Lymph Nodes; Lymphatic Metastasis; Male; Middle Aged; Oxonic Acid; Remission Induction; Taxoids; Tegafur; Vinblastine; Vinorelbine