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

This systematic review and meta-analysis aims to systematically assess the effects of concurrent chemo-radiotherapy (CRT) compared with radiotherapy (RT) alone for elderly Chinese patients with non-metastatic esophageal squamous cancer.. We searched PubMed, EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL), China Biomedical Literature Database (CBM), and China National Knowledge Infrastructure (CNKI) databases. We retrieved randomized controlled trials on concurrent CRT with Gimeraciland Oteracil Porassium (S-1) compared with RT alone for aged Chinese patients with non-metastatic esophageal squamous cancer performed until August 2016.. Eight eligible studies involving 536 patients were subjected to meta-analysis. As a response rate measure, a relative risk (RR) of 1.37 [95% confidence intervals (CIs): 1.24, 1.53; P = 0.00], which reached statistical significance, was estimated when concurrent CRT with S-1 was performed compared with RT alone. Sensitivity analysis on response rate confirmed the robustness of the pooled result. The RR values of 1.44 (95% CIs: 1.22, 1.70; P = 0.00) and 1.77 (95% CIs: 1.26, 2.48; P = 0.00) estimated for 1- and 2-year survival rate indices, respectively, were also statistically significant. The incidence of adverse events was similar in both groups.. This review concluded that concurrent CRT with S-1 can improve the efficacy and prolong the survival period of elderly Chinese patients with non-metastatic esophageal squamous cancer and does not significantly increase the acute adverse effects of RT alone.

Topics: Aged; Aged, 80 and over; Carcinoma, Squamous Cell; Chemoradiotherapy; Combined Modality Therapy; Drug Combinations; Esophageal Neoplasms; Female; Humans; Male; Oxonic Acid; Tegafur

A 7 4-year-old male was referred to our hospital for an abnormal chest shadow pointed out by a medical examination. A chest computed tomography revealed a tumor shadow 39 X 32mm in size in his left upper lobe in January, 2010. Pathological examination of biopsy specimens showed squamous cell carcinoma of the lung. Although there was no distant metastasis, multiple metastases to mediastinal lymph nodes was noted. He was diagnosed as Stage III A(cT2aN2M0). Considering his age and the histology of the disease, systemic chemotherapy with nedaplatin and S-1 was performed. The diameter of the primary lesion was decreased from 39mm to 18mm after 4 courses of chemotherapy, and was considered as partial response (PR)according to the RECIST criteria. The adverse events were grade 2 appetite loss, grade 3 neutropenia, and grade 2 thrombocytopenia. Recently, various new agents for treating non-squamous cell lung carcinoma have been developed, but there has been little progress in the treatment of squamous cell lung carcinoma. We experienced a patient with advanced squamous cell lung carcinoma who responded with CDGP/S-1 combination chemotherapy. We are now conducting a phase I / II clinical study to verify the usefulness of this regimen against advanced squamous cell lung carcinoma.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Squamous Cell; Drug Combinations; Humans; Lung Neoplasms; Male; Neoplasm Staging; Organoplatinum Compounds; Oxonic Acid; Tegafur; Tomography, X-Ray Computed

The patient was a 53-year-old woman who underwent colonoscopy for anal pain and melena. We diagnosed her with Stage I (T2N0M0) anal canal squamous cell carcinoma by biopsy specimen and CT scan. We recommended chemo-radiotherapy because she hoped to keep her anus. For this patient, we planned an S-1 administration at a dose of 120 mg/ body/day for consecutive 14 days followed by 7 days of rest period with whole pelvis and bilateral inguinal radiation (total 45 Gy/25 Fr). Then we added a booster radiation (14 Gy/7 Fr) to a local area for 5 days followed by 2 days of rest period. After 2 weeks of chemo-radiotherapy, we could not detect any tumors by colonoscopy. We diagnosed it as a pathological complete response for biopsy specimen.

Topics: Antimetabolites, Antineoplastic; Anus Neoplasms; Biopsy; Carcinoma, Squamous Cell; Chemoradiotherapy; Drug Combinations; Female; Humans; Middle Aged; Neoplasm Grading; Oxonic Acid; Tegafur

Most head and neck carcinomas are squamous cell carcinomas (HNSCCs). The combination of cisplatin with a continuous infusion of 5-fluorouracil (5-FU) has been a standard chemotherapy regimen for HNSCC. Based on basic and clinical studies, the critical plasma concentration of 5-FU is suspected to be about 0.1 microg/ml. The administration of the conventional dose of S-1 including dihydropyrimidine dehydrogenase (DPD), an metabolic inhibitor of 5-FU, results in exceeding the critical plasma concentration of 5-FU, and the long-term administration with high plasma concentration of 5-FU is considered to show clinical effectiveness in head and neck cancer. The results of early and late phase II studies on head and neck carcinoma were also described in the present paper.

Topics: Administration, Oral; Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Squamous Cell; Clinical Trials, Phase II as Topic; Drug Combinations; Fluorouracil; Head and Neck Neoplasms; Humans; Oxonic Acid; Tegafur; Uracil

The combination with cisplatin (CDDP) and 5-FU is considered the first choice chemotherapy for squamous cell carcinoma of the head and neck (HNSCC). S-1, a modulation of tegafur developed in Japan, is an active agent for HNSCC. Some clinical phase I/II studies about the combination with CDDP and S-1 have been reported. The combination showed a good response rate of 67.6% for advanced and recurrent HNSCC in our clinical phase I/II study. The regimens of S-1 combined with carboplatin or nedaplatin have also been reported. Regimens containing S-1 appear to have been effective for HNSCC. Multi-institutional phase II studies with a large sample size are needed in the future. The compliance for patients is better than a 5-FU injection because S-1 is orally administrated. The adverse effect, especially for bone mallow toxicity, is equal or upgraded compared with a 5-FU injection. The efficacy and adverse effects of CDDP plus S-1 should be studied in carefully designed phase II/III trials. S-1 will be one of the key drugs for HNSCC in the future.

Topics: Adult; Aged; Anemia; Anorexia; Antineoplastic Combined Chemotherapy Protocols; Bone Marrow; Carcinoma, Squamous Cell; Cisplatin; Clinical Trials, Phase I as Topic; Clinical Trials, Phase II as Topic; Drug Administration Schedule; Drug Combinations; Female; Head and Neck Neoplasms; Humans; Male; Middle Aged; Neoplasm Staging; Neutropenia; Oxonic Acid; Tegafur; Thrombocytopenia

Most cases of head and neck squamous cell carcinoma (HNSCC) are in the advanced stages, resulting in a poor prognosis. To improve the poor outcome, adjuvant chemotherapy is indispensable for advanced cases with a high relapse risk after standard definitive treatments including surgery and/or radiotherapy. To define an adequate administration schedule in adjuvant chemotherapy with S-1, a controlled randomized study in multi-institutes was done. The results showed the 2-week administration followed by 1-week rest was superior to the 4-week administration followed by the 2-week rest in terms of safety and efficacy. In the present paper, some problems of adjuvant chemotherapy were discussed, and the protocol was described in terms of a multi-institutional controlled randomized comparison study of S-1 versus UFT in an adjuvant chemotherapy setting for locally advanced HNSCC.

Topics: Anorexia; Antimetabolites, Antineoplastic; Carcinoma, Squamous Cell; Chemotherapy, Adjuvant; Drug Administration Schedule; Drug Combinations; Head and Neck Neoplasms; Humans; Leukopenia; Multicenter Studies as Topic; Oxonic Acid; Randomized Controlled Trials as Topic; Survival Rate; Tegafur

A randomized phase 3 study was performed to investigate the efficacy and safety of maintenance therapy with S-1 after induction therapy with carboplatin plus S-1 in patients with advanced squamous non-small cell lung cancer (NSCLC).. Chemotherapy-naive patients with advanced or relapsed squamous NSCLC were treated with carboplatin (area under the curve of 5 on day 1 every 3 weeks) plus S-1 (40 mg/m. Of the 365 patients enrolled in the study, 347 participated in the induction phase, and 131 of these individuals were randomized to receive S-1 plus BSC (n = 67) or BSC alone (n = 64). The risk of disease progression was significantly lower for patients in the S-1 plus BSC arm than those in the BSC-alone arm (hazard ratio, 0.548; 95% confidence interval, 0.374-0.802; P = .0019). The most common toxicities during maintenance therapy with S-1 included anorexia, anemia, and fatigue, but most cases were not severe.. Continued maintenance with S-1 plus BSC is an effective and well-tolerated treatment option for patients with advanced squamous NSCLC previously treated with carboplatin plus S-1.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carboplatin; Carcinoma, Squamous Cell; Cisplatin; Drug Combinations; Humans; Induction Chemotherapy; Lung; Lung Neoplasms; Male; Middle Aged; Oxonic Acid; Pemetrexed; Progression-Free Survival; Proportional Hazards Models; Tegafur; Treatment Outcome

Two courses of neoadjuvant therapy using S-1 plus cisplatin for clinical stage III esophageal squamous cell carcinoma did not achieve expected response rate according to endoscopic evaluation of primary tumors. Subsequent esophagectomy was safely performed.. In Japan, esophagectomy after two courses of 5-fluorouracil plus cisplatin is regarded a standard strategy for treating stage II or III esophageal squamous cell carcinoma (ESCC). However, 5-fluorouracil plus cisplatin does not benefit cohorts with clinical stage III ESCC, suggesting the need for a more effective regimen.. A single-arm, open-label phase II trial was conducted to evaluate the safety and efficacy of two courses of neoadjuvant chemotherapy using S-1 plus cisplatin (NAC-SP) for clinical stage III ESCC. The primary endpoint was overall response rate as defined by endoscopic evaluation of primary tumors.. We enrolled 26 patients. The completion rate for the two courses of NAC-SP was 61.5%. Grade 3 or higher adverse events were experienced by 38.4% of patients. The treatment response rate according to endoscopic findings, acquired before the second course, was 34.6% and below the expected level (55.0%). The morbidity rate of patients who underwent radical subtotal esophagectomy (96.2%) was 32.0%. Repeat surgery was unnecessary, and surgery-associated deaths did not occur. The 5-year progression-free survival (PFS) and overall survival (OS) rates were 84.6% and 92.2%, respectively.. We demonstrate safety of NAC-SP, but not its efficacy, for patients with clinical stage III ESCC. Subsequent esophagectomy was safely performed.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Squamous Cell; Cisplatin; Drug Combinations; Esophageal Neoplasms; Esophageal Squamous Cell Carcinoma; Esophagectomy; Female; Fluorouracil; Humans; Japan; Male; Middle Aged; Neoadjuvant Therapy; Neoplasm Staging; Oxonic Acid; Tegafur; Treatment Outcome

This study aimed to determine the maximum tolerance dose (MTD) and to estimate the recommended dose (RD) of concomitant S-1 with carbon-ion radiotherapy (RT) for sinonasal squamous cell carcinoma (SCC). Nine patients with sinonasal SCC received carbon-ion RT with escalating doses of S-1 according to phase I methods. Doses of 40, 60 and 80 mg/m2/day were administered twice daily in dose levels 1, 2 and 3, respectively, from days 1 to 14 and 22 to 35. Carbon-ion RT was administered at a dose of 70.4 Gy (relative biological effectiveness) in 32 fractions, 5 days a week. Two patients developed grade 3 acute dermatitis. However, none developed dose-limiting toxicities. Therefore, the MTD of S-1 could not be determined; the RD was estimated to be 80 mg/m2/day with concurrent carbon-ion RT. Partial response and stable disease were noted in 5 and 4 patients, respectively. The 2-year overall survival and local control rates were 56 and 74%, respectively. Overall, 2 patients developed ≥grade 3 late toxicities; among them, 1 patient developed grade 3 cataract and the other developed grade 4 cataract, optic nerve disorder and hearing impairment. To the best of our knowledge, this phase I study is the first clinical trial to evaluate concomitant S-1 with carbon-ion RT for sinonasal SCC. The MTD of S-1 could not be determined, and the RD was estimated to be 80 mg/m2/day. This study demonstrated a manageable safety profile for this combination. The observed outcomes may facilitate further evaluation of this novel therapy.

Topics: Adult; Aged; Carcinoma, Squamous Cell; Combined Modality Therapy; Drug Combinations; Female; Heavy Ion Radiotherapy; Humans; Kaplan-Meier Estimate; Male; Maxillary Sinus Neoplasms; Middle Aged; Oxonic Acid; Tegafur; Treatment Outcome

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

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 importance of definitive radiotherapy for elderly patients with esophageal and esophagogastric-junction cancer is pronounced. However, little is known in terms of the best way to combine radiotherapy with other treatment options. This study aims to compare the efficiency of SIB radiotherapy alone with SIB radiotherapy concurrent and consolidated with S-1 for elderly patients. Comprehensive geriatric assessment is also incorporated in the procedure of treatment.. The study is a two arm, open, randomized multicenter Phase III trial with patients over 70 years old with stage IIA-IVB (UICC 2002, IVB only with metastasis to supraclavicular or celiac lymph nodes) squamous cell carcinoma or adenocarcinoma of esophagus or gastroesophageal junction. A total of 300 patients will be randomized using a 1:1 allocation ratio stratified by disease stage and study site. Patients allocated to the SIB arm will receive definitive SIB radiotherapy (95%PTV/PGTV 50.4Gy/59.92Gy/28f) while those randomized to SIB + S-1 arm will receive definitive SIB radiotherapy concurrent and consolidated with S-1. The primary endpoint of the trial is 1-year overall survival. Secondary objectives include progression-free survival, recurrence-free survival (local-regional and distant), disease failure pattern, toxicity profile as well as quality of life. Besides, detailed radiotherapy protocol and quality assurance procedure have been incorporated into this trial.. The proportion of elderly patients in esophageal cancer is now growing, but there is a lack of evidence in term of treatment standard for this group of patients, which is what we aim to obtain through this prospective phase III study.. clinicaltrials.gov NCT02979691 . Registered November 22, 2016.

Topics: Adenocarcinoma; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Squamous Cell; Chemoradiotherapy; Drug Combinations; Esophageal Neoplasms; Esophagogastric Junction; Female; Fluorouracil; Humans; Male; Neoplasm Staging; Outcome Assessment, Health Care; Oxonic Acid; Prospective Studies; Radiotherapy, Intensity-Modulated; Stomach Neoplasms; Tegafur

Our previous trial with a docetaxel, cisplatin, and 5-fluorouracil (DCF) regimen showed high response rates in metastatic squamous cell carcinoma of the esophagus (SCCE). The observed increased toxicity of the DCF regimen, however, was clinically harmful. S-1, an oral anticancer drug, has been approved as a combination therapy for SCCE, and alternate-day regimen with S-1 has shown lower levels of toxicity. This prospective single-center phase I/II trial examines the efficacy and toxicity of a combination of docetaxel, cisplatin, and an alternate-day regimen of S-1 (modified DCS) for patients with metastatic SCCE. We use a two-stage design. Phase I is undertaken to determine the maximum tolerated dose and the recommended dose. The phase I trial adopts a three-patient cohort with escalating dose study design. In the phase II trial, the primary endpoint is the assessment of the overall response rate (Response Evaluation Criteria in Solid Tumors 1.1). The secondary endpoints are the evaluation of drug-related toxicity (National Cancer Institute Common Toxicity Criteria 4.0), overall survival, and progression-free survival. Fifty patients with metastatic SCCE participate in the phase II section. This study protocol is the first to test the effects of the modified DCS regimen for metastatic SCCE.

Topics: Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Squamous Cell; Cisplatin; Disease-Free Survival; Docetaxel; Drug Combinations; Esophageal Neoplasms; Esophageal Squamous Cell Carcinoma; Esophagus; Humans; Maximum Tolerated Dose; Oxonic Acid; Prospective Studies; Taxoids; 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

This study compared the efficiency and safety of definitive concurrent chemoradiotherapy (CCRT) using Paclitaxel plus Cisplatin (TP) versus S-1 plus Cisplatin (CS) in unresectable locally advanced esophageal squamous cell carcinoma (LAESCC). Between January 2009 and December 2013, 203 LAESCC patients were retrospectively reviewed. We performed a propensity score matching analysis; 41 patients treated with the CS regimen were matched 1:1 to patients who received the TP regimen. Patient- and disease-related characteristics were well-balanced between the two groups. The CS group showed significantly better treatment compliance (90.2% vs. 70.7%, P = 0.026) and less hospital stay (48 days vs 49 days, P = 0.025) over the TP group during the CCRT course. The complete response rate was comparable between the two groups (51.2% vs. 48.8%, P = 0.825). The 1- and 3-year overall survival (OS) rates in the TP group were 63.4% and 32.4% compared to 62.8% and 32.1% in the CS group, respectively (P = 0.796). The 1- and 3-year progression-free survival (PFS) rates in the TP group were 51.2% and 24.9%, compared to 53.6% and 18.9% in the CS group, respectively (P = 0.630). The incidence of severe and total neutropenia in the TP group was significantly higher compared to the CS group (P = 0.011 and 0.046, respectively). Multivariate analysis revealed that T stage and the complete response rate were strong prognostic factors associated with OS and PFS. In conclusion, both treatment regimens yielded satisfactory survival outcomes, but the CS regimen could significantly improve treatment compliance, reduce hematological toxicities and lengths of hospital stay. Future prospective studies in large cohorts are highly warranted to confirm the findings in our report.

Topics: Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Squamous Cell; Chemoradiotherapy; Cisplatin; Disease-Free Survival; Drug Combinations; Esophageal Neoplasms; Female; Fluorouracil; Humans; Male; Middle Aged; Nausea; Neutropenia; Oxonic Acid; Paclitaxel; Remission Induction; Retrospective Studies; Tegafur; Vomiting

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

Chemotherapy regimens are often a 2-drug regimen in concurrent chemotherapy and radiotherapy for esophageal cancer (EC). However, some retrospective studies have suggested that for patients with EC receiving radiotherapy combined with 2-drug chemotherapy have the severe toxicity. And S-1 alone with the combination of radiotherapy treatment effect is good, and achieved good clinical remission rate. The purpose of this trial is compare the efficacy and toxicity of combining S-1 or S-1 plus cisplatin with radiotherapy for esophageal squamous cell carcinoma.. The study is a randomized, controlled, multicenter trial, comparing S-1 versus S-1 plus cisplatin concurrent radiotherapy for patients with esophageal squamous cell carcinoma. Eighty-eight patients with unresectable or medically unfit for surgery esophageal squamous cell carcinoma (clinical stage I to III), will randomly assigned to receive four cycles (2 concomitant and 2 postradiotherapy) S-1 or S-1 plus cisplatin along with radiotherapy 60-66 Gy/30 to 33 fractions. The primary outcome is complete response rate of primary tumor which will be measured by endoscopy and computer screen at 3 months after the completion of treatment. Secondary outcomes include survival and toxicity.. To our knowledge, this study protocol is the first to test the effect between S-1 versus S-1 plus cisplatin concurrent intensity modulated radiation therapy in the treatment of esophageal squamous cell carcinoma. If the result will be the same effect and fewer side effects and less costly in S-1 plus radiotherapy. It will supply more treatment selection for esophageal squamous cell carcinoma.

Topics: Adolescent; Adult; Aged; Carcinoma, Squamous Cell; Chemoradiotherapy; Cisplatin; Drug Combinations; Esophageal Neoplasms; Female; Humans; Male; Middle Aged; Oxonic Acid; Tegafur; Young Adult

Although standard chemotherapy for esophageal cancer patients is fluorouracil and cisplatin, the prognosis is still unsatisfactory. A new therapeutic regimen combining docetaxel, cisplatin, and 5-fluorouracil was recently developed to improve both local and distant tumor control. We developed a new regimen of docetaxel, nedaplatin, and S1 (DGS) and previously reported the recommended dose in a phase I dose-escalation study. We then undertook a phase II study of DGS for advanced esophageal squamous cell carcinoma. Patients with clinical stage IB/II/III disease were eligible. Patients received two courses of chemotherapy: docetaxel 35 mg/m(2) with nedaplatin 40 mg/m(2) on day 8, 80 mg/m(2) S1 on days 1-14, and 2 weeks off. After completion of chemotherapy, patients underwent esophagectomy. The primary endpoint was the completion rate of protocol treatment (completion of two courses of preoperative chemotherapy and R0 surgery [no residual tumor]). We enrolled 32 patients. The completion rate of protocol treatment was 96.9%. During chemotherapy, the most common grade 3 or 4 toxicity was neutropenia (25.0%). No treatment-related deaths were observed, and the incidence of operative morbidity was tolerable. The overall response rate after chemotherapy was 83.3%. This DGS regimen was well tolerated and highly active. This trial is registered with the University Hospital Medical Information Network (UMIN ID: 000014626).

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Agents; Carcinoma, Squamous Cell; Docetaxel; Drug Combinations; Esophageal Neoplasms; Esophageal Squamous Cell Carcinoma; Esophagectomy; Female; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Neoadjuvant Therapy; Neoplasm Staging; Neutropenia; Organoplatinum Compounds; Oxonic Acid; Taxoids; Tegafur; Treatment Outcome

Objectives Maintenance therapy is a standard therapeutic strategy in non-squamous non-small-cell lung cancer. However, there is no consensus regarding the benefit of maintenance therapy for patients with squamous cell lung cancer. We assessed maintenance therapy with S-1, an oral fluoropyrimidine agent, following induction therapy with carboplatin and S-1 in patients with squamous cell lung cancer. Methods In this phase II trial, chemotherapy-naïve patients with squamous cell lung cancer were enrolled to induction therapy with four cycles of carboplatin (at an area under the curve of 5 on day 1) and S-1 (80 mg/m(2)/day on days 1-14) in a 28-day cycle. Patients who achieved disease control after induction therapy received maintenance therapy with S-1 in a 21-day cycle until disease progression or unacceptable toxicity. The primary endpoint was progression-free survival after administration of maintenance therapy. Results Fifty-one patients were enrolled in the study. The median progression-free survival from the start of maintenance therapy was 3.0 months (95 % confidence interval, 2.5-3.5). The most common toxicities associated with maintenance therapy were anemia, thrombocytopenia, and fatigue, but they were not severe. Conclusion S-1 maintenance therapy might be a feasible treatment option in patients with squamous cell lung cancer.

Topics: Aged; Aged, 80 and over; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Carboplatin; Carcinoma, Squamous Cell; Disease-Free Survival; Drug Combinations; Female; Humans; Lung Neoplasms; Male; Middle Aged; Oxonic Acid; 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

We conducted a phase III study to evaluate S-1 as compared with UFT as control in patients after curative therapy for stage III, IVA, or IVB squamous-cell carcinoma of the head and neck (SCCHN).. Patients were randomly assigned to the UFT group (300 or 400 mg day-1 for 1 year) or the S-1 group (80, 100, or 120 mg day-1 for 1 year). The primary end point was disease-free survival (DFS). Secondary end points were relapse-free survival, overall survival (OS), and safety.. A total of 526 patients were enrolled, and 505 were eligible for analysis. The 3-year DFS rate was 60.0% in the UFT group and 64.1% in the S-1 group (HR, 0.87; 95%CI, 0.66-1.16; p = 0.34). The 3-year OS rate was 75.8% and 82.9%, respectively (HR, 0.64; 95% CI, 0.44-0.94; p = 0.022). Among grade 3 or higher adverse events, the incidences of leukopenia (5.2%), neutropenia (3.6%), thrombocytopenia (2.0%), and mucositis/stomatitis (2.4%) were significantly higher in the S-1 group.. Although DFS did not differ significantly between the groups, OS was significantly better in the S-1 group than in the UFT group. S-1 is considered a treatment option after curative therapy for stage III, IVA, IVB SCCHN.. ClinicalTrials.gov NCT00336947 http://clinicaltrials.gov/show/NCT00336947.

Topics: Adult; Aged; Carcinoma, Squamous Cell; Chemotherapy, Adjuvant; Drug Combinations; Female; Head and Neck Neoplasms; Humans; Male; Middle Aged; Neoplasm Metastasis; Neoplasm Recurrence, Local; Oxonic Acid; Safety; Squamous Cell Carcinoma of Head and Neck; Tegafur; Treatment Outcome

To assess, in a randomized, phase 2 trial, the efficacy and safety of chemoradiotherapy with or without induction chemotherapy (ICT) of S1 and oxaliplatin for esophageal cancer.. Patients with stage II, III, or IVA esophageal cancer were randomly allocated to either 2 cycles of ICT (oxaliplatin 130 mg/m(2) on day 1 and S1 at 40 mg/m(2) twice daily on days 1-14, every 3 weeks) followed by concurrent chemoradiotherapy (CCRT) (46 Gy, 2 Gy/d with oxaliplatin 130 mg/m(2) on days 1 and 21 and S1 30 mg/m(2) twice daily, 5 days per week during radiation therapy) and esophagectomy (arm A), or the same CCRT followed by esophagectomy without ICT (arm B). The primary endpoint was the pathologic complete response (pCR) rate.. A total of 97 patients were randomized (arm A/B, 47/50), 70 of whom underwent esophagectomy (arm A/B, 34/36). The intention-to-treat pCR rate was 23.4% (95% confidence interval [CI] 11.2-35.6%) in arm A and 38% (95% CI 24.5% to 51.5%) in arm B. With a median follow-up duration of 30.3 months, the 2-year progression-free survival rate was 58.4% in arm A and 58.6% in arm B, whereas the 2-year overall survival rate was 60.7% and 63.7%, respectively. Grade 3 or 4 thrombocytopenia during CCRT was more common in arm A than in arm B (35.4% vs 4.1%). The relative dose intensity of S1 (89.5% ± 20.6% vs 98.3% ± 5.2%, P=.005) and oxaliplatin (91.4% ± 16.8% vs 99.0% ± 4.2%, P=.007) during CCRT was lower in arm A compared with arm B. Three patients in arm A, compared with none in arm B, died within 90 days after surgery.. Combination chemotherapy of S1 and oxaliplatin is an effective chemoradiotherapy regimen to treat esophageal cancer. However, we failed to show that the addition of ICT to the regimen can improve the pCR rate.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Squamous Cell; Chemoradiotherapy; Confidence Intervals; Drug Administration Schedule; Drug Combinations; Esophageal Neoplasms; Esophagectomy; Humans; Induction Chemotherapy; Intention to Treat Analysis; Middle Aged; Organoplatinum Compounds; Oxaliplatin; Oxonic Acid; Prospective Studies; Tegafur

We conducted a phase II study to evaluate the efficacy and safety of chemoradiotherapy concurrent with S-1 plus cisplatin in patients with unresectable locally advanced squamous cell carcinoma of the head and neck. Chemotherapy consisted of S-1 twice daily on days 1-14 at 60 mg/m(2) /day and cisplatin at 20 mg/m(2) /day on days 8-11, repeated twice at a 5-week interval. Single daily radiation of 70 Gy in 35 fractions was given concurrently starting on day 1. For patients achieving an objective response after chemoradiotherapy, two additional cycles of chemotherapy were administered. Of the 45 enrolled patients, the percentage of clinical complete remission, the primary endpoint, was 64.4% (8 complete response, 21 good partial response) on central review. After a median follow-up of 3.52 years, 3-year local progression-free survival was 62.2%, with 3-year progression-free survival of 60.0%, 3-year overall survival of 64.4%, and 3-year time to treatment failure of 48.9%. Grade 3 or 4 toxicity included pharyngeal mucositis (46.7%), oral mucositis (44.4%), dysphagia (46.7%), anorexia (42.2%), radiation dermatitis (26.7%), neutropenia (26.7%), and febrile neutropenia (4.4%). No treatment-related deaths were observed. This combination showed promising efficacy with acceptable toxicities.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Squamous Cell; Chemoradiotherapy; Cisplatin; Drug Combinations; Female; Head and Neck Neoplasms; Humans; Male; Middle Aged; Oxonic Acid; Prospective Studies; Squamous Cell Carcinoma of Head and Neck; Tegafur; Treatment Outcome

To improve the outcomes of radiotherapy alone for T2 glottic carcinoma (GC), we initiated a prospective study of concurrent chemoradiotherapy with S-1 for patients with early GC, primarily T2 cases. We report the efficacy and safety of this protocol.. Eligible patients had T1b or T2 glottic squamous cell carcinomas. Patients received S-1 (55.3 mg/m(2)/day, once daily) and radiotherapy (2 Gy/day, five days/week, to a total of 30 fractions).. Thirteen patients were eligible. Complete responses were observed in all 13 patients (100%). At a median follow-up duration of 53 months (range=23-68 months), the 3-year local control and overall survival rates were both 100%. Grade 3 dermatitis occurred in only one patient.. This chemoradiotherapy protocol is well -tolerated and effective in patients with early glottic carcinoma. Furthermore, due to its once-daily administration, this protocol is considered to be easier than usual chemoradiotherapy, and makes outpatient-treatment possible.

Topics: Aged; Carcinoma, Squamous Cell; Chemoradiotherapy; Combined Modality Therapy; Drug Combinations; Female; Glottis; Head and Neck Neoplasms; Humans; Laryngeal Neoplasms; Male; Middle Aged; Oxonic Acid; Prospective Studies; Radiotherapy Dosage; Squamous Cell Carcinoma of Head and Neck; Survival Rate; Tegafur

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

It appears that patients with SCCHN should be recommended to take S-1 for more than 1 year and, if possible, more than 2 years, as adjuvant chemotherapy for SCCHN.. There is no established consensus on the duration of administration of S-1 as adjuvant chemotherapy for squamous cell carcinoma of the head and neck (SCCHN). Since it might be difficult to undergo prospective randomized study to identify the optimal duration of the administration period of S-1 without a standard, the authors have undergone a retrospective clinical study to decide the tentative standard of therapeutic duration of S-1 as adjuvant chemotherapy for SCCHN.. The clinical records of 89 patients with SCCHN who underwent adjuvant chemotherapy with S-1 were investigated.. The median duration of S-1 administration as adjuvant chemotherapy for SCCHN was 7 months (range = 0.1-58 months). Disease-free survivals (DFSs) were generally longer when S-1 administration periods were longer. After adjusting for prognostic factors, S-1 administration periods of 24 months or longer showed significantly lower hazard ratios (HRs) than 0-12 months.

Topics: Administration, Oral; Adult; Aged; Aged, 80 and over; Antimetabolites, Antineoplastic; Carcinoma, Squamous Cell; Chemotherapy, Adjuvant; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Combinations; Female; Follow-Up Studies; Head and Neck Neoplasms; Humans; Male; Middle Aged; Neoplasm Staging; Oxonic Acid; Prospective Studies; Squamous Cell Carcinoma of Head and Neck; Tegafur; Time Factors; Treatment Outcome

We carried out a phase I/II trial of chemoradiotherapy concurrent with S-1 and cisplatin to determine the maximum tolerated dose and recommended dose and to evaluate the efficacy and safety of this treatment in patients with esophageal carcinoma. Thoracic esophageal cancer patients with clinical stage II/III disease, excluding T4, were eligible. Chemotherapy consisted of S-1 at a dose of 60-80 mg/m(2) /day on days 1-14, and cisplatin at 75 mg/m(2) on day 1, repeated twice every 4 weeks. Single daily radiation of 50.4 Gy was given in 28 fractions concurrently starting on day 1. Patients achieving an objective response after chemoradiotherapy underwent two additional cycles of chemotherapy. Patient accrual was terminated early due to slow enrolment after 44 patients were accrued. In the phase I part, two of six patients experienced dose-limiting toxicities at each level of S-1 (S-1 60 or 80 mg/m(2) /day). Considering treatment compliance, the recommended dose was determined to be S-1 60 mg/m(2) /day. The complete response rate, the primary endpoint of phase II, was 59.5% (22/37; 90% confidence interval, 44.6-73.1%; weighted threshold, 57.2%; P = 0.46 by the exact binomial test) on central review. In the phase II part, 3-year progression-free survival was 48.4%, with a 3-year overall survival of 61.9%. Grade 3 or 4 toxicity in phase II included leukopenia (57.9%), neutropenia (50%), hyponatremia (28.9%), anorexia (21.1%), anemia (18.4%), thrombocytopenia (18.4%), and febrile neutropenia (2.6%). No treatment-related deaths were observed. Although this combination showed acceptable toxicity and favorable 3-year survival, the study did not meet its primary endpoint. This trial was registered at the UMIN Clinical Trials Registry as UMIN000000710.

Topics: Adult; Aged; Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Squamous Cell; Chemoradiotherapy; Cisplatin; Disease-Free Survival; Drug Combinations; Esophageal Neoplasms; Female; Humans; Male; Maximum Tolerated Dose; Middle Aged; Neoplasm Staging; Oxonic Acid; Prospective Studies; Pyridines; Radiotherapy Dosage; Tegafur; Treatment Outcome; Young Adult

S-1 is a novel oral anticancer agent containing a combination of two modulators and tegafur. We conducted a phase I study of concurrent chemoradiotherapy with S-1 for head and neck cancer.. S-1 was administered once daily, and radiotherapy was performed by 2 Gy/day, five days/week, for a total of 30 fractions. S-1 dosage was started at level 1 (55.3 mg/m(2)/day), and was increased to level 2 (66.7 mg/m(2)/day).. A total of 12 patients were registered. Concerning hematological toxicities, no grade ≥3 or more hematological toxicity was confirmed at any level. With regard to non-hematological toxicities, at level 2, three cases of grade 3 mucositis and two cases of grade 3 dermatitis were confirmed.. The results showed that the maximum tolerated dose was level 2 and that dose-limiting toxicity was mucositis. Having determined that the recommended dose is level 1, we have begun the phase II clinical study.

Topics: Adenocarcinoma; Administration, Oral; Adult; Aged; Carcinoma, Squamous Cell; Chemoradiotherapy; Dose Fractionation, Radiation; Dose-Response Relationship, Drug; Drug Combinations; Female; Follow-Up Studies; Head and Neck Neoplasms; Humans; Male; Maximum Tolerated Dose; Middle Aged; Neoplasm Staging; Oxonic Acid; Prognosis; Tegafur; Young Adult

The goals of treatment for head and neck cancer are cure and organ-function preservation. For organ preservation, primary treatment via radiotherapy alone is thought to be insufficient for Stage II squamous cell carcinoma of the larynx, oropharynx or hypopharynx. The objective of the present study was to investigate the efficacy and safety of concurrent chemoradiotherapy with S-1 for patients with Stage II squamous cell carcinoma of the pharynx or larynx for primary organ preservation.. Previously untreated patients with Stage II squamous cell carcinoma of the larynx, oropharynx or hypopharynx received three courses of S-1 (40 or 50 mg twice a day; 2 weeks of administration followed by 1 week of rest every 3 weeks) during conventional radiotherapy (a single daily fraction of 1.8 Gy) to a total dose of 70.2 Gy. The primary endpoint was the local control rate at 3 years.. From August 2009 to October 2012, 37 patients were evaluated for the study. The overall response rate was 100%. The 3-year local control rate was 89.0% (95% confidence interval, 78.9-99.2%), and the 3-year overall survival rate was 97.2% (95% confidence interval, 91.8-100%). Mucositis and dermatitis in the radiation field were the most common acute adverse events observed. The rates of Grade 3 mucositis and dermatitis were 27 and 35%, respectively. No patients experienced Grade 4 acute adverse events. The treatment completion rate was 89.2%.. Concurrent chemoradiotherapy with S-1 was safe and effective in improving local control for Stage II squamous cell carcinoma of the pharynx or larynx.

Topics: Aged; Antimetabolites, Antineoplastic; Carcinoma, Squamous Cell; Chemoradiotherapy; Drug Combinations; Female; Humans; Laryngeal Neoplasms; Male; Middle Aged; Neoplasm Staging; Oxonic Acid; Pharyngeal Neoplasms; Tegafur

The purpose of this study was to evaluate the efficacy and tolerability of weekly docetaxel, cisplatin, and S-1 (weekly TPS) as induction chemotherapy for patients with locally advanced head and neck squamous cell carcinoma (HNSCC).. A total of 35 patients with previously untreated, locally advanced HNSCC were enrolled. Seven patients (20%) were diagnosed with stage III HNSCC and 28 patients (80%) were diagnosed with stage IV. Induction treatment included 30 mg/m(2) docetaxel on day 1 and 8, 60 mg/m(2) cisplatin on day 1, and 70 mg/m(2) S-1 on days 1 to 14. The regimen was repeated every 21 days. After three courses of induction chemotherapy, patients received concurrent chemoradiotherapy.. Among the 35 patients, 30 (85.7%) completed induction chemotherapy. The response to induction chemotherapy was as follows: nine patients (25.7%) achieved a complete response (CR) and the overall response rate (ORR) was 85.7%. Grades 3-4 toxicity during induction therapy included neutropenia (28.5%), neutropenic fever (8.5%), and diarrhea (17.1%). After completion of concurrent chemoradiotherapy, the CR rate was 62.8% and the partial response (PR) was 22.8%. Estimates of progression-free and overall survival at 2 years were 73.2% and 79.3%, respectively.. Weekly TPS is a promising regimen that is well-tolerated, causes minimal myelosuppression and is effective as an outpatient regimen for locally advanced HNSCC.. ClinicalTrials.gov: NCT01645748.

Topics: Adult; Aged; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Squamous Cell; Chemoradiotherapy; Cisplatin; Docetaxel; Drug Combinations; Female; Head and Neck Neoplasms; Humans; Induction Chemotherapy; Male; Middle Aged; Oxonic Acid; Quality of Life; Survival Analysis; 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

We performed a pharmacokinetic phase I trial of the combination of S-1 granules and nedaplatin for head and neck squamous cell carcinoma (HNSCC).. Patients were treated with both nedaplatin on day 1 at a dose starting at 80 mg/m(2) (level 1) escalating up to 90 mg/m(2) (level 2), and S-1 granules at a daily dose of 80 mg/m(2) on days 1 to 14 every three weeks. The primary end-point was determination of the recommended dose.. Twenty patients were enrolled. Dose-limiting toxicities occurred in one out of six patients at dose level 1 (neutropenia) and in all three patients at level 2 (neutropenia and thrombocytopenia). The recommended dose was determined as level 1. Pharmacokinetic parameters of S-1 granule did not differ from the capsula formulation. The response rate was 42.1%.. This combination was well-tolerated and manifested a promising activity against HNSCC.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Squamous Cell; Drug Combinations; Female; Head and Neck Neoplasms; Humans; Male; Middle Aged; Organoplatinum Compounds; Oxonic Acid; Tegafur

We previously reported on the regimen of S-1 plus nedaplatin (NDP), with S-1 was administered orally for 14 days and NDP intravenously on day 8. The maximum tolerated dose (MTD) of NDP was determined to be 90 mg/m². The main toxicities were neutropenia and thrombocytopenia. This result was tolerated, but we believe there is a more effective and tolerable regimen. Thus, we investigated the S-1 regimen administered orally for 14 days, and NDP intravenously on day 1 in patients with locally advanced head and neck squamous cell carcinoma.. Oral administration of S-1 (days 1-14) and intravenous NDP (day 1) were tested for patients with advance head and neck cancer in a phase I setting. The dose of S-1 was fixed and the dose of NDP was escalated from 70 mg/m², with an increase of 10 mg/m² per step, to find the MTD.. A total of 15 patients were registered. The MTD of NDP was determined to be 100 mg/m². The main toxicities were neutropenia and thrombocytopenia. The response rate (RR) was 57.1%.. The recommended dose of NDP for a phase II study was determined to be 100 mg/m². We concluded that our regimen was well tolerated and that the RR was acceptable.

Topics: Administration, Oral; Aged; Antineoplastic Agents; Carcinoma, Squamous Cell; Drug Administration Schedule; Drug Combinations; Drug Therapy, Combination; Female; Head and Neck Neoplasms; Humans; Male; Maximum Tolerated Dose; Middle Aged; Neutropenia; Organoplatinum Compounds; Oxonic Acid; Tegafur; Thrombocytopenia; Treatment Outcome

This study investigated the maximum tolerated dose (MTD) of S-1 with concurrent radiotherapy in patients with head and neck cancer, based on the frequency of dose-limiting toxicities (DLT). S-1 was administered orally at escalating doses from 40 mg/m(2) b.i.d. on the days of delivering radiotherapy, which was given at a total dose of 64-70 Gy in 32-35 fractions over 6-7 weeks. A total of 12 patients (3 patients at 40 mg/m(2), 6 patients at 60 mg/m(2), and 3 patients at 80 mg/m(2)) were enrolled in this trial. At the dose of 80 mg/m(2), two of the three patients developed DLT (Grade 3 anorexia and rhabdomyolysis) due to S-1, so the MTD was determined to be 80 mg/m(2). Among the 12 enrolled patients, 9 (75%) showed a complete response and 3 (25%) showed a partial response. The overall response rate was 100%. The recommended dose of S-1 with concurrent radiotherapy is 60 mg/m(2).

Topics: Administration, Oral; Aged; Aged, 80 and over; Anorexia; Antimetabolites, Antineoplastic; Carcinoma, Squamous Cell; Combined Modality Therapy; Dose-Response Relationship, Drug; Drug Combinations; Female; Head and Neck Neoplasms; Humans; Male; Maximum Tolerated Dose; Middle Aged; Oxonic Acid; Rhabdomyolysis; Tegafur; Treatment Outcome

We evaluated whether preoperative chemotherapy with S-1 and concurrent radiotherapy is feasible and efficacious in the treatment of advanced oral squamous cell carcinoma.. Participants comprised 39 patients with oral carcinoma (stage III, n = 15; stage IVA, n = 24). All patients received a total radiation dose of 40 Gy, in once-daily 2-Gy fractions, and received S-1 at 65 mg/m(2)/day for 5 consecutive days, over 4 consecutive weeks with concurrent radiotherapy.. Hematological toxicity was mild and reversible. The most common non-hematological toxicity was grade 3 mucositis, but this was transient and tolerable. Radical surgery was performed for 37 patients, with the remaining 2 patients declining the surgery. Postoperatively, local failure developed in 1 patient, and neck failure in 2 patients. Distant metastases were identified in 4 patients. At a median follow-up of 38.0 months (range 23-88 months), locoregional control, disease-specific survival, and overall survival rates at 3 years were 91.5, 83.8, and 83.8 %, respectively.. Concurrent administration of S-1 and radiotherapy combined with surgery offers a well-tolerated method of successfully treating advanced oral squamous cell carcinoma. The locoregional control rate remains high even at 3 years of follow-up, and no serious adverse effects have been encountered.

Topics: Adult; Aged; Antimetabolites, Antineoplastic; Carcinoma, Squamous Cell; Chemoradiotherapy; Drug Combinations; Female; Humans; Male; Middle Aged; Mouth Neoplasms; Oxonic Acid; Survival Rate; Tegafur

This study evaluated long-term outcomes for patients who received adjuvant gemcitabine plus S-1 chemotherapy after resection for pancreatic carcinoma.. Seventy patients who underwent surgical resection of pancreatic carcinoma were enrolled prospectively into this study. All patients received adjuvant chemotherapy with 10 cycles of gemcitabine plus S-1 every 2 weeks. Each cycle consisted of intravenous gemcitabine 700 mg/m(2) on day 1 and oral S-1 50 mg/m(2) for seven consecutive days, followed by a 1-week pause of chemotherapy. Long-term survival results of adjuvant gemcitabine plus S-1 chemotherapy were analyzed for this cohort.. Median follow-up time was 51.2 months. Sixty percent of patients had node-positive disease and 79% of patients underwent R0 resection. Fifty-six patients (80%) completed adjuvant chemotherapy. Median overall and disease-free survival times were 35.4 and 23.8 months, respectively. Actuarial overall and disease-free survival rates were 89% and 64% at 1 year, 64% and 50% at 2 years, and 33% and 33% at 5 years, respectively. Only negative lymph node metastasis (P = 0.010) independently correlated with long-term survival by multivariate analysis.. Long-term results of adjuvant gemcitabine plus S-1 chemotherapy suggest this regimen may be safe and promising as treatment for this patient population.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Analysis of Variance; Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Carcinoma; Carcinoma, Squamous Cell; Chemotherapy, Adjuvant; Cohort Studies; Deoxycytidine; Disease-Free Survival; Drug Combinations; Female; Gemcitabine; Humans; Japan; Kaplan-Meier Estimate; Lymphatic Metastasis; Male; Middle Aged; Neoplasm Staging; Oxonic Acid; Pancreatic Neoplasms; Prospective Studies; Tegafur; Time Factors; Treatment Outcome

Concurrent chemoradiotherapy (CCRT) improves survival and organ preservation in patients with head and neck squamous cell carcinoma (HNSCC), compared with radiotherapy. However, such regimens are not always feasible because of substantial toxicities. Therefore, we evaluated the feasibility of S-1, administered on alternate days, and concurrent radiotherapy among elderly patients with HNSCC.. Nineteen eligible patients were treated with CCRT. S-1 was administered at a dose of 80 mg/day on alternate days with the intention to reduce the toxicity.. With a median follow-up period of 19.2 months, the two-year overall survival rates were 62.5% for patients with stage III disease and 50.0% for those with stage IV. The Complete Response (CR) rates were 100% for stage II and 66.7% for stage III/IV disease. Grade 3 mucositis occurred in three patients. Grade 3 or 4 hematological toxicities were not observed.. CCRT with S-1 administered on alternate days was effective and well-tolerated among elderly patients with HNSCC.

Topics: Aged; Aged, 80 and over; Antimetabolites, Antineoplastic; Carcinoma, Squamous Cell; Chemoradiotherapy; Drug Administration Schedule; Drug Combinations; Feasibility Studies; Female; Head and Neck Neoplasms; Humans; Male; Oxonic Acid; Radiotherapy, Conformal; Squamous Cell Carcinoma of Head and Neck; Tegafur

To evaluate the efficacy and safety of weekly paclitaxel combined with S-1 or fluorouracil in the first line treatment of advanced gastric carcinoma.. Two hundred and forty patients with untreated advanced gastric carcinoma were randomized into two arms, patients in the experimental arm were given paclitaxel and S-1, while those in the control arm received paclitaxel and fluorouracil. The regimen of experimental arm was paclitaxel 60 mg/m(2) by intravenous infusion, day 1, 8, 15; S-1 80 - 120 mg/day given by oral administration, day 1 - 14. The regimen of control arm was fluorouracil 500 mg/m(2) by intravenous infusion continuously, day 1 - 5; CF 20 mg/m(2) by intravenous infusion, day 1 - 5. The regimens in both arms were repeated every 28 days. The efficacy and safety of both arms were assessed.. Two hundred and twenty-eight patients were analyzed in the full analysis set, and 192 patients were analyzed in per-protocol set (experimental arm 100 patients, control arm 92 patients). The overall response rates of experimental and control arms were 50.0% and 28.3% (P = 0.002), and the disease control rates were 82.0% and 70.7% (P = 0.064), respectively. The primary endpoints of experimental arm were non-inferior to that of the control arm. The secondary endpoint of experimental arm in terms of median progression free survival was significantly better than that of control arm (5 months versus 4 months, P = 0.006). The experimental arm had a higher incidence of grade III-IV bone marrow suppression than the control arm, but the incidence of fever in both arms was not significantly different.. Oral administration of S-1 is an alternative option of venous infusional fluorouracil. Weekly paclitaxel combined with S-1 is a safe regimen and has a promising efficacy.

Topics: Adenocarcinoma; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Squamous Cell; Diarrhea; Disease-Free Survival; Drug Combinations; Female; Fluorouracil; Follow-Up Studies; Humans; Leukopenia; Male; Middle Aged; Neoplasm Staging; Oxonic Acid; Paclitaxel; Prospective Studies; Remission Induction; Stomach Neoplasms; 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

The aim of the present study was to determine the maximum tolerated dose (MTD) of S-1 in combination with chemoradiotherapy (CRT) in patients with unresectable locally advanced squamous cell carcinoma of the head and neck, and evaluate the difference in pharmacokinetics of S-1 when administered as a suspension via a feeding tube or orally as a capsule. Chemotherapy consisted of administration of S-1 twice daily on days 1-14 at escalating doses of 40, 60 and 80 mg/m(2) per day, and cisplatin at 20 mg/m(2) per day on days 8-11, repeated twice at a 5-week interval. Single daily radiation of 70 Gy in 35 fractions was given concurrently starting on day 1. Two additional cycles of chemotherapy were planned after the completion of CRT. Before starting CRT, each patient received S-1 via two different administration methods. Twenty-two patients were enrolled. The MTD was reached with S-1 at 80 mg/m(2) per day, with two of six patients experiencing febrile neutropenia lasting more than 4 days. All four patients whose creatinine clearance was decreased to <60 mL/min after the first cycle of chemotherapy developed febrile neutropenia lasting more than 4 days. Pharmacokinetic analysis revealed that the 5-fluorouracil area under the curve did not significantly differ by the administration route. S-1 at 60 mg/m(2) per day for 14 days was well tolerated with concurrent CRT. Administration of S-1 as a suspension or by whole capsule can be considered therapeutically interchangeable. Although these data are preliminary, activity was highly promising, and this approach warrants further investigation.

Topics: Administration, Oral; Aged; Antineoplastic Combined Chemotherapy Protocols; Area Under Curve; Capsules; Carcinoma, Squamous Cell; Cisplatin; Combined Modality Therapy; Drug Combinations; Female; Head and Neck Neoplasms; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Neoplasm Staging; Oxonic Acid; Radiotherapy; Suspensions; Tegafur

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

A Phase I/II trial of chemoradiotherapy concurrent with S-1 plus mitomycin C in patients with clinical Stage II/III squamous cell carcinoma of the anal canal was started in Japan. The aim of this trial is to determine the recommended dose of S-1 combined with a fixed dose of mitomycin C plus radiotherapy in Phase I and to evaluate the efficacy and safety in Phase II. The primary endpoint for the Phase II part of this study is the proportion of 3-year event-free survival, in which the following are defined as events: disease progression, residual tumor at the end of chemoradiotherapy, colostomy or death, whichever comes first. Secondary endpoints are progression-free survival, proportion of complete response and adverse events. In the Phase II part of this study, a total of 65 patients will be enrolled from 42 institutions over 6 years.

Topics: Adult; Aged; Antibiotics, Antineoplastic; Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Anus Neoplasms; Carcinoma, Squamous Cell; Chemotherapy, Adjuvant; Disease-Free Survival; Drug Combinations; Female; Humans; Male; Middle Aged; Mitomycin; Neoplasm Staging; Oxonic Acid; Patient Selection; Radiotherapy, Adjuvant; 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

More effective regimens are urgently needed for treatment of esophageal carcinoma; therefore, we conducted a phase I trial of a combination of docetaxel, nedaplatin, and S-1 (DGS) to determine the optimal dose in patients with advanced esophageal carcinoma.. We studied 14 patients with previously untreated advanced cervical esophageal carcinoma with T3-4 tumors and/or M1 staging and esophageal carcinoma with cervical lymph node metastasis. The patients received an infusion of docetaxel at different dose levels (levels 1, 2, 3, 4: 25, 30, 35, 40 mg/m(2), respectively) and an infusion of nedaplatin (40 mg/m(2)) on day 8 plus oral administration of S1 (80 mg/m(2)/day) for two consecutive weeks at two-week intervals.. Dose-limiting toxicities (DLTs) included febrile neutropenia and leukopenia. DLTs occurred in 2 out of 5 patients at level 4. The response rate was 78.6 (11/14)%, including a complete response rate of 35.7(5/14)%.. The DGS regimen reported here was well tolerated and toxicities were manageable. The maximum tolerated dose was level 4, and the recommended dose was determined to be docetaxel at 35 mg/m(2) with nedaplatin at 40 mg/m(2) plus S1 at 80 mg/m(2). We found that our regimen, administered on an outpatient basis, showed high activity and tolerance. A phase II study has been started.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Agents; Carcinoma, Squamous Cell; Docetaxel; Dose-Response Relationship, Drug; Drug Combinations; Esophageal Neoplasms; Female; Humans; Male; Middle Aged; Organoplatinum Compounds; Oxonic Acid; Taxoids; Tegafur; Tomography, X-Ray Computed

To determine the feasibility and efficacy of preoperative concurrent chemoradiation therapy (CCRT) with S-1, an oral fluoropyrimidine derivative, in patients with T4 oral squamous cell carcinoma (SCC).. Only patients with histologically proven T4 oral SCC were included. Radiotherapy (total dose, 30 Gy) was delivered in 2-Gy daily fractions over a period of 3 weeks. Concurrently, S-1 (80 mg/m(2)/day) was administered orally twice daily for 14 consecutive days.. We enrolled 46 patients. All underwent radiotherapy as planned; however, oral S-1 was discontinued in 3 patients who manifested acute toxicity. Grade 3 toxicities were mucositis (20%), anorexia (9%), and neutropenia (4%). We encountered no Grade 4 adverse events or serious postoperative morbidity requiring surgical intervention. After CCRT, 32 of the 46 patients underwent radical resection; in 17 (53%) of the operated patients, the pathologic response was complete. During follow-up ranging from 7 to 58 months (median, 22 months), tumor control failed in 5 (16%) of the 32 operated patients; there were 3 local and 2 regional failures. Of the 14 non-operated patients, 8 (57%) manifested local (n = 7) or regional failure (n = 1). The 3-year overall survival rate for all 46 patients was 69%; it was significantly higher for operated than for non-operated patients (82% vs. 48%; p = 0.0288).. Preoperative CCRT with S-1 is feasible and effective in patients with T4 oral SCC. Even in inoperable cases, CCRT with S-1 provides adequate tumor control.

Topics: Administration, Oral; Aged; Aged, 80 and over; Carcinoma, Squamous Cell; Combined Modality Therapy; Drug Administration Schedule; Drug Combinations; Feasibility Studies; Female; Humans; Male; Middle Aged; Mouth Neoplasms; Oxonic Acid; Preoperative Care; Prospective Studies; Radiation-Sensitizing Agents; Radiotherapy Dosage; Tegafur; Treatment Failure

The objectives of this study were to determine the maximum tolerated dose (MTD) and recommended dose (RD) of S-1 plus cisplatin (CDDP) and to evaluate safety and efficacy using the defined RD in advanced/recurrent head and neck cancer (HNC).. S-1 was administered orally at 40 mg/m(2) twice daily for 14 consecutive days, and CDDP was infused on day 8 at a dose of 60 and 70 mg/m(2). Each course was repeated every 4 weeks.. A total of 38 patients were registered, 10 patients for the Phase I study and an additional 28 patients for the Phase II study. Although no dose-limiting toxicity (DLT) was observed in the CDDP 60 mg/m(2) (Level 1) group, two of six patients in the CDDP 70 mg/m(2) (Level 2) group exhibited DLT (fatigue/diarrhea). The MTD was not achieved in the Phase I study. Level 2 was therefore determined as the RD. In the Phase II study, 34 patients, including 6 patients from the Phase I study, were evaluated. At the termination of treatment, the confirmed response rate was 44.1% (15/34, 95% CI: 27.4-60.8). The best response rate without an adequate duration time was 67.6% (95% CI: 51.9-83.4). The median survival period was 16.7 months, and the 1-year survival rate was 60.1%. The main toxicities of Grade 3 or above were anorexia (26.5%), nausea (14.7%), neutropenia/thrombocytopenia (11.8%) and anemia/fatigue (8.8%).. This is considered to be an effective regimen with acceptable toxicities for HNC.

Topics: Administration, Oral; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Bone Neoplasms; Carcinoma, Squamous Cell; Cisplatin; Drug Combinations; Female; Follow-Up Studies; Head and Neck Neoplasms; Humans; Infusions, Intravenous; Liver Neoplasms; Lung Neoplasms; Male; Maximum Tolerated Dose; Middle Aged; Neoplasm Recurrence, Local; Neoplasm Staging; Oxonic Acid; Prognosis; Survival Rate; Tegafur; Treatment Outcome; Young Adult

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

This study was conducted to identify a recommended dose for S-1, used in combination with 40-Gy radiation.. Thirty patients, 15 each with stage III and IVA oral carcinoma, were enrolled. All patients received a total dose of 40-Gy. For the S-1 treatment, patients were given either the standard Japanese dose, calculated according to body surface area, or a reduced dose. Groups consisting of at least three patients were given S-1 according to one of 8 regimens.. Hematologic toxicity was mild and reversible. The most common nonhematologic toxicity was mucositis. At level 8 that was the standard S-1 dose for 5 days per week for 4 weeks, dose-limiting toxicity was observed when 2 patients had grade 4 mucositis. This level was thus deemed the maximum tolerated dose for the regimen.. The recommended dose of S-1 with concurrent radiotherapy was the reduced dose of S-1 given for 5 days per week, for 4 consecutive weeks. Preoperative S-1 and concurrent radiotherapy was well tolerate and feasible and warrants a phase II study.

Topics: Administration, Oral; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Squamous Cell; Dose-Response Relationship, Radiation; Drug Combinations; Female; Humans; Male; Maximum Tolerated Dose; Middle Aged; Mouth Neoplasms; Neoplasm Metastasis; Oxonic Acid; Preoperative Period; Tegafur; Treatment Outcome

A Phase I/II study of S-1 combined radiation therapy was conducted in patients with Stage II (T2N0) glottic cancer. The purpose of the Phase I study was to identify the maximum tolerated dose, the recommended dose and the dose limiting toxicity. The objectives in the phase II study were to estimate the local control and the overall survival, and the incidence of adverse events.. In Phase I, S-1 was administered orally in a split-course fashion as two doses of 40 mg/m(2), for a total daily dose of 80 mg/m(2). The course involved a 2-week rest after a 2-week administration (Level 1) and a 1-week rest after a 3-week administration (Level 2). Radiation therapy was administered in 2-Gy daily (total 60-Gy) standard fractionation.. Seven patients were enrolled in the Phase I, and 19 in the Phase II study. Mucositis was the most common toxicity encountered. All 26 patients completed radiation therapy without delay. The overall response rate was 100% (26/26) with all patients showing a complete response. One patient developed a local recurrence 28 months after the treatment. The 3-year local control and overall survival rates were 94.7 and 85.4%, respectively (limited to 22 patients from Level 2).. The use of S-1 at 80 mg/m(2) per day in a split-course with 1-week rest during the course of radiation therapy was safe and effective for Stage II glottic cancer. The treatment strategy employing orally available S-1 proved to be beneficial over the conventional injection of antitumor agents for maintaining the patients' quality of life.

Topics: Aged; Aged, 80 and over; Anemia; Carcinoma, Squamous Cell; Combined Modality Therapy; Drug Administration Schedule; Drug Combinations; Female; Follow-Up Studies; Glottis; Humans; Kaplan-Meier Estimate; Laryngeal Neoplasms; Male; Middle Aged; Nausea; Neutropenia; Oxonic Acid; Radiotherapy; 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

Cisplatin plus fluorouracil is widely used for the treatment of head and neck cancer. However, the cisplatin plus fluorouracil regimen necessitates hospitalization. Therefore, we planned to develop a new regimen that can be administered on an outpatient basis and performed a phase I study of S-1 + nedaplatin.. S-1 was given orally at a fixed dose for 14 days, and nedaplatin was administered intravenously on day 8 of S-1 administration. The dose of nedaplatin was increased in 10-mg/m(2) steps to find the maximum tolerated dose, depending on the appearance of dose-limiting toxicities.. A total of 14 patients were registered. The maximum tolerated dose of nedaplatin was determined to be 90 mg/m(2). The main toxicities were neutropenia and thrombocytopenia. The response rate was 57.1%.. The recommended dose of nedaplatin for a phase II study was determined to be 80 mg/m(2). We concluded that our regimen was well tolerated and that the response rate was acceptable.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma; Carcinoma, Squamous Cell; Cisplatin; Disease Progression; Drug Combinations; Female; Fluorouracil; Head and Neck Neoplasms; Humans; Male; Maximum Tolerated Dose; Middle Aged; Neoplasm Recurrence, Local; Neoplasms, Squamous Cell; Organoplatinum Compounds; Oxonic Acid; Squamous Cell Carcinoma of Head and Neck; Tegafur

This retrospective study evaluates the efficacy and safety of S-1 chemotherapy or S-1 followed by low-dose docetaxel chemotherapy for recurrent head and neck cancer.. S-1 was administered to 21 patients with recurrent head and neck cancer, in outpatient settings. Of these 21 patients, 8 were additionally administered a low dose of docetaxel fortnightly.. The survival rate of patients with squamous cell carcinoma of the head and neck was 59.1% for 12 months and 17.5% for 24 months, with a median survival time of 18 months. Time to progression of more than 12 months was shown by 4 patients (22.2%). Most adverse events were mild (up to grade 2).. S-1 therapy is considered a safe and effective treatment option. From the viewpoint of tumour dormancy, S-1 therapy is a useful vigorous anticancer treatment that can be provided while maintaining patients' quality of life in recurrent cases.

Topics: Adult; Aged; Aged, 80 and over; Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Squamous Cell; Docetaxel; Drug Combinations; Female; Head and Neck Neoplasms; Humans; Male; Middle Aged; Neoplasm Recurrence, Local; Oxonic Acid; Taxoids; Tegafur

A Phase II study was started in Japan to evaluate the efficacy and safety of concurrent chemoradiotherapy with S-1 plus cisplatin in patients with unresectable locally advanced squamous cell carcinoma of the head and neck. This study began in July 2008, and a total of 45 patients will be accrued from 13 institutions within 2 years. The primary endpoint is the clinical complete remission rate. The secondary endpoints are local progression-free survival, overall survival, progression-free survival, time to treatment failure, proportion of patients who achieve nutritional support-free survival and adverse events.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Squamous Cell; Cisplatin; Combined Modality Therapy; Drug Combinations; Female; Follow-Up Studies; Head and Neck Neoplasms; Humans; Male; Middle Aged; Neoplasm Staging; Oxonic Acid; Prognosis; Safety; Survival Rate; Tegafur; Treatment Outcome; Young Adult

How best to manage advanced esophageal cancer remains unresolved, especially in palliative care. Here, in a pilot study, we evaluated the efficacy and safety of concurrent chemoradiotherapy with S-1 and cisplatin in advanced esophageal cancer. Patients with locally advanced or metastatic squamous cell carcinoma of the esophagus received S-1 and cisplatin at doses of 70 mg/m(2)/day for 14 days and 70 mg/m(2) on day 1, respectively, every 3 weeks. Concurrently, radiotherapy was started at a dose of 200 cGy/day, up to a total of 5400 cGy. After concurrent chemoradiotherapy, additive chemotherapy was repeated up to six cycles. Thirty patients were enrolled in this study; of the 27 in whom efficacy could be evaluated, an objective response rate was seen in 20 (74.1%), including five (18.5%) complete pathologic responses in primary lesions. Improvement of dysphagia was seen in 21 (76%) patients. In patients with stage II or III esophageal cancer, the median progression-free survival and overall survival were 10.6 +/- 0.6 months (95% CI: 9.4-11.8) and 23.0 +/- 5.1 months (95% CI: 13.0-32.9), respectively. In patients with stage IV esophageal cancer, the median progression-free survival and overall survival were 5.4 +/- 1.6 months (95% CI: 2.2-8.6) and 11.6 +/- 1.6 months (95% CI: 8.4-14.8), respectively. The main hematological toxicity was neutropenia, but no neutropenic fever was observed. The major non-hematological toxicities were asthenia and vomiting, mostly of grades 1 and 2. Thus, concurrent chemoradiotherapy with S-1 and cisplatin may be a promising nonsurgical treatment in advanced esophageal cancer.

Topics: Aged; Antineoplastic Agents; Carcinoma, Squamous Cell; Cisplatin; Cohort Studies; Drug Combinations; Drug Therapy, Combination; Esophageal Neoplasms; Humans; Male; Middle Aged; Oxonic Acid; Pilot Projects; Radiotherapy, Adjuvant; Survival Rate; Tegafur; Treatment Outcome

The aim of this study was to investigate the efficacy and safety of an oral fluoropyrimidine anticancer agent, S-1, in patients with oral squamous cell carcinoma. Patients with pathologically confirmed squamous cell carcinoma and at least one measurable lesion were enrolled. Oral administration of S-1 (40 mg/m2 twice daily) for 28 days was followed by a 14-day rest period. A total of 41 consecutive eligible patients were enrolled in the study between October 2002 and August 2004. The sites of the primary tumor were the gingiva (n=18), the tongue (n=12), the palate (n=5), the oral floor (n=4), the buccal mucosa (n=1), and the labial mucosa (n=1). A median of two cycles of treatment (range, 1-5) was administered. A complete response was achieved in nine patients and a partial response in eight patients, for an overall response rate of 41.5% (95% confidence interval, 26.4-56.5%). The 3-year survival rate was 76.4% (95% confidence interval, 62.8-90.0%). Although grade 3 anemia and anorexia occurred in two patients each (4.9%), and grade 3 neutropenia, thrombocytopenia, nausea, vomiting, stomatitis, and diarrhea in one patient each (2.4%), no grade 4 toxicities were observed. S-1 exhibits definite antitumor activity in patients with oral squamous cell carcinoma and is well tolerated.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Agents; Carcinoma, Squamous Cell; Dose-Response Relationship, Drug; Drug Combinations; Female; Follow-Up Studies; Humans; Male; Middle Aged; Mouth Neoplasms; Oxonic Acid; Survival Analysis; Tegafur

Treatment of patients with unresectable recurrent oral cancer is quite difficult. In particular,there is no scientific evidence to select anti-cancer drugs for patients who were given previous radiation therapy. To select optional chemotherapy regimens, we have employed a new chemosensitivity testing method, a collagen gel droplet embedded culture sensitivity test (CD-DST) for patients with unresectable oral cancer. Six oral cancer patients with recurrence and/or metastatic disease were treated with the optional chemotherapy based on the results of CD-DST. No result was obtained due to a problem of poor growth of tumor cells in one case. In another case, we could not find a sensitive anti-cancer drug among the agents we examined. These 2 patients were treated with selected palliative pain control therapy. Optional chemotherapy based on the results of CD-DST was given to 4 patients showing sensitivity to the anti-cancer drugs examined. Tumor recession or tumor dormancy was observed clinically during a definite period. Toxicity was mild and the median survival was 10.9 months. We therefore conclude that the examination with CD-DST may provide important scientific evidence to determine a suitable chemotherapy for patients with advanced oral cancer.

Topics: Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Squamous Cell; Drug Administration Schedule; Drug Combinations; Drug Screening Assays, Antitumor; Humans; Lung Neoplasms; Mitomycin; Mouth Neoplasms; Neoplasm Recurrence, Local; Oxonic Acid; Pyridines; Tegafur

Chemotherapy plays an important role in the treatment of head and neck cancer (HNC) patients with recurrent and/or metastatic unresectable disease. The standard regimen for HNC has been a combination of cisplatin (CDDP) and 5-fluorouracil (5-FU). We planned to develop a new outpatient regimen that could be carried out safely and had an antitumor activity equivalent to the regimen of CDDP plus 5-FU. For this purpose, we selected a combination of S-1 and carboplatin. The overall response rate of 40.9% in this study was almost equivalent to the study previously reported on 5-FU plus CDDP. This regimen of S-1 plus carboplatin has the possibility of yielding tumor responses equivalent to a conventional regimen of 5-FU combined with CDDP in patients with recurrent and/or metastatic head and neck carcinoma as a second-line palliative chemotherapy.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carboplatin; Carcinoma, Squamous Cell; Drug Administration Schedule; Drug Combinations; Female; Head and Neck Neoplasms; Humans; Male; Middle Aged; Oxonic Acid; Survival Rate; Tegafur

We conducted a phase I study to determine a recommended dose (RD) of S-1 for chemo-radiotherapy consisting of S-1+ radiotherapy for T 2 N 0 larynx cancer. The method of administration used to assess the RD was irradiation with 2 Gy/day for 5 days a week until a total dose of 60 Gy, and concomitant administration of S-1 once a day for 2 weeks beginning on the day therapy was started followed by 2 weeks off the drug and 2 weeks on the drug with the dose escalating from S-1 60 mg/body/day (level 1) to 80 mg/body/day (level 2), and then to 100 mg/body/day (level 3). 18 patients were enrolled. 4 patients developed an adverse event of grade 3 radiation dermatitis which became a dose-limiting toxicity (DLT) at level 3. We then concluded that 100 mg/body/day was the maximum tolerated dose (MTD) of S-1 and decided that the RD of S-1 was 80 mg/body/day.

Topics: Aged; Antimetabolites, Antineoplastic; Carcinoma, Squamous Cell; Combined Modality Therapy; Deglutition Disorders; Drug Administration Schedule; Drug Combinations; Female; Glottis; Humans; Laryngeal Neoplasms; Leukopenia; Male; Maximum Tolerated Dose; Middle Aged; Oxonic Acid; Radiation Injuries; Radiodermatitis; Radiotherapy Dosage; Stomatitis; Tegafur

The standard care for unresectable locally advanced head and neck cancer (HNC) is concurrent chemoradiotherapy (CRT). Although there is no standard regimen of CRT, a platinum-based regimen has shown a better survival benefit than other regimens. The control arm in a randomized trial for unresectable locally advanced HNC is radiotherapy concurrent with CDDP (100 mg/m2, every 3 weeks), which has been considered to be too toxic for clinical practice in Western countries and has required frequent dose modifications. Because the Japanese also have been considered unable to tolerate this regimen, no prospective study of it has been conducted in Japan. Most Japanese patients with locally advanced head and neck cancer have received concurrent chemoradiotherapy with 5-FU and CDDP (70-80 mg/m2). S-1 has shown high activity in HNC with a response rate of 34%. Furthermore, a combination of cisplatin and S-1 therapy for HNC has been reported to have good efficacy. With this rationale in mind, we conducted a phase I study of CRT with S-1 and CDDP for unresectable locally advanced squamous cell carcinoma of the head and neck. The CR rate was very promising, though preliminary, and warrants further investigation. The Japan Clinical Oncology Group (JCOG) is planning a multicenter phase II study of concurrent chemoradiotherapy with S-1 and CDDP for locally advanced unresectable HNC.

Topics: Adult; Aged; Anemia; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Squamous Cell; Cisplatin; Deglutition Disorders; Drug Administration Schedule; Drug Combinations; Female; Head and Neck Neoplasms; Humans; Leukopenia; Male; Middle Aged; Neutropenia; Oxonic Acid; Radiation Injuries; Radiodermatitis; Radiotherapy Dosage; Tegafur

S-1 is a novel oral fluoropyrimidine inhibitory for dihydropyrimidine dehydrogenase (DPD). In the present study, we have examined the appropriate dose of S-1 in the combination with radiation and the safety and clinical efficacy. Radiation was given (2 Gy/day; 5 days/week) for a total of 60 Gy. S-1 was given orally every day for 2 weeks and then S-1 was stopped for 1 week. The levels were divided accordingly to the S-1 application as follows; level 0, 50 mg/m2/day; level 1, 65 mg/m2/day; level 2, 80 mg/m2/day. grade 3 toxicity of anorexia and the grade 3 toxicity increase in bilirubin level were observed in 2 cases of level 2. We decided that level 1 (65 mg/m2/day) was the recommended dose of the S-1 application as observed in compliance and efficacy. This therapy is a useful concurrent chemo-radiotherapy which may improve the response rate and quality of life (QOL) of patients with oral squamous cell carcinoma.

Topics: Adult; Aged; Antimetabolites, Antineoplastic; Carcinoma, Squamous Cell; Combined Modality Therapy; Drug Administration Schedule; Drug Combinations; Female; Humans; Male; Maximum Tolerated Dose; Middle Aged; Mouth Neoplasms; Nausea; Oxonic Acid; Quality of Life; Radiotherapy Dosage; Stomatitis; Tegafur

We investigated preoperative chemotherapy with S-1 and low-dose cisplatin for the untreated stage II-IV oral squamous cell carcinoma patients. The chemotherapy consisted of S-1 80 mg/m2/day (day 1-14) and CDDP 5 mg/m2/day (day 1-5 and day 8-12) intravenous drip (less than 1 hour). In the second phase clinical trial of 44 patients, the clinical response rate was 63.7% and the histological response rate by the Oboshi-Shimosato's evaluation was 61.4%. The main adverse events were myelosuppression and gastrointestinal disturbance such as nausea 36.4%, anorexia 27.3%, neutropenia 25% and leukopenia 25%. Grade 3 and 4 adverse events were neutropenia 11.4%, leukopenia 9.1%, thrombocytopenia 4.5% and oligochromemia 4.5%. The two-year overall survival rate was 92.6%. The advantages of this chemotherapy are high response rate, low adverse effects and not to prevent planned therapies such as surgery and radiation. These facts suggest that this chemotherapy is suitable for preoperative chemotherapy.

Topics: Administration, Oral; Adult; Aged; Aged, 80 and over; Anorexia; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Squamous Cell; Cisplatin; Combined Modality Therapy; Drug Administration Schedule; Drug Combinations; Humans; Infusions, Intravenous; Leukopenia; Male; Middle Aged; Mouth Neoplasms; Nausea; Neutropenia; Oxonic Acid; Preoperative Care; Survival Rate; Tegafur

The triple combination of 5-fluorouracil (5-FU), vitamin A and radiation (FAR therapy) has been effectively used to treat head and neck cancer. The biological anti-tumor effect of 5-FU depends on the activity of its metabolizing enzyme, dihydropyrimidine dehydrogenase (DPD). TS-1 is a novel oral DPD inhibitory fluoropyrimidine (DIF). To improve the anti-tumor effect of FAR therapy, we have applied TS-1 in place of 5-FU injection in the combination of Vitamin A and radiation (TAR therapy). In this study, we have examined the appropriate duration of TS-1 medication and the clinical efficacy and safety of TAR therapy. TS-1 was administered orally at a dose of 65 mg/m2 twice a day. Vitamin A (Retinol Palmitate: 50,000 U/day) was administered intra-musculary on each day of radiation. Radiation was given (1.5-2 Gy/day: 5 days/week) for 30-40 Gy. The levels were divided according to the length of TS-1 application as follows: level 1, 2 weeks; level 2, 3 weeks; level 4, 4 weeks. Grade 4 toxicity of anorexia was observed in one case of level 3. We decided that level 2 (3 weeks of TS-1 administration) was the appropriate length of TS-1 application. TAR therapy is a useful concurrent chemo-radiotherapy which might improve the response rate and QOL of patients with HNSCC.

Topics: Adult; Aged; Anorexia; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Squamous Cell; Drug Administration Schedule; Drug Combinations; Fluorouracil; Head and Neck Neoplasms; Humans; Maximum Tolerated Dose; Middle Aged; Oxonic Acid; Pyridines; Quality of Life; Radiotherapy Dosage; Tegafur; Vitamin A

The purpose of this study was to determine the feasible adjuvant therapy administration schedule of S-1 for locoregionally advanced squamous cell carcinoma of the head and neck (SCCHN). Patients receiving definitive treatments were randomly assigned to either arm A (51 cases) receiving oral S-1 of 2-week administration followed by 1-week rest for 6 months, or arm B receiving S-1 of 4-week administration followed by 2-week rest for 6 months. Planned treatment was given in 40% of patients in arm A and 29% in arm B. The cumulative rates of the relative total administration dose of S-1 at 100% were 54.9% (95% CI: 40.1-69.7%) in arm A and 34.3% (95% CI: 21.1-47.4%) in arm B, respectively (P=0.054). Adverse events were recorded in 41 patients (82.0%) in arm A and 48 patients (94.1%) in arm B (P=0.060). The incidences of diarrhoea (10 vs 28%; P<0.05) and skin toxicities (18 vs 37%; P<0.05) were significantly higher in arm B. One-year disease-free survival was similar in both arms: arm A 81.2% (95% CI: 70.0-92.4%); arm B 77.0% (95% CI: 65.0-89.0%). The schedule of 2-week administration followed by 1-week rest seems to be more feasible for oral 6-month administration of S-1 in adjuvant chemotherapy of locoregionally advanced SCCHN.

Topics: Administration, Oral; Adult; Aged; Antimetabolites, Antineoplastic; Carcinoma, Squamous Cell; Chemotherapy, Adjuvant; Disease-Free Survival; Drug Administration Schedule; Drug Combinations; Female; Head and Neck Neoplasms; Humans; Male; Middle Aged; Oxonic Acid; Pyridines; Tegafur; Treatment Outcome

We have treated head and neck carcinoma by concurrent chemoradiotherapy combined with 5-fluorouracil (5-FU) and cisplatin (CDDP). However,this chemoradiotherapy could not show an enormous effect in the advanced carcinoma of Stage III and IV. Therefore,we changed the contents of the chemotherapy, i.e., we replaced 5-FU, one of the agents with time dependency, to continuous administration of TS-1 for 2 weeks,also replacing CDDP, one of the agents with dose dependency, to nedaplatin (CDGP) in order to reduce kidney dysfunction. In this concurrent chemoradiotherapy, oral TS-1 was continued for 2 weeks and CDGP was administered on the 4 th day from the start of TS-1. In addition, radiotherapy was performed concurrently. In this way,we performed a phase I clinical trial of concurrent chemoradiotherapy combining TS-1 and nedaplatin (CDGP). As for the incidence of adverse events,grade 3 mucositis due to radiation was observed in two patients. As a result of the phase I clinical trial,we decided the maximum-tolerated dose (MTD) of TS-1 to be 80 mg/m2 (maximum 120 mg/body) and 100 mg/m2 for CDGP, and then determined the recommended dose(RD) of TS-1 as 80 mg/m2 (maximum 120 mg/ body) TS-1 and of CDGP as 9 0 mg/m2 CDGP.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Squamous Cell; Combined Modality Therapy; Drug Administration Schedule; Drug Combinations; Female; Head and Neck Neoplasms; Humans; Male; Maximum Tolerated Dose; Middle Aged; Organoplatinum Compounds; Oxonic Acid; Pyridines; Radiotherapy Dosage; Tegafur

TS-1 is a novel oral 5-fluorouracil containing tegaful (prodrug of 5-FU) and two biochemical modulators. These modulators feature effect-enhancing and adverse reaction-reducing activity. We investigated the histological response and toxicities of combination chemotherapy with TS- 1 and low-dose cisplatin and evaluated its usefulness as preoperative chemotherapy Forty-four newly diagnosed patients with stage Il-IV oral squamous cell carcinoma were enrolled in this study from February 2002 to April 2004. Patients were administered TS-1 80 mg/m2/day (days 1-14) and cisplatin 5 mg/m2/day (days 1-5 and 8-12) followed by radical surgery within 2 weeks. The histopathological effect of chemotherapy, which was a surrogate endpoint of this trial, was evaluated with surgical or biopsy specimens. The rate of histological antitumor effect was as follows: complete response (CR) 36.4%, partial response (PR) 25.0%, minor response (MR) 18.1% and no change (NC) 20.5%. The rate of histological response (CR + PR) was 61.4%. The CR rate of effective cases was 59.3%. The main toxicities occurred in bone marrow and the digestive tract. The incidence of severe toxicity such as grade 3 or 4 was 4.5% in anemia, 9% in leukocytopenia, 11.4% in neutropenia, 4.5% in thrombocytopenia and 2.3% in anorexia, diarrhea and urticaria. Most patients showed no toxicity or mild toxicities. TS- 1 with low-dose cisplatin has highly effective antitumor activity and mild toxicities. In particular, the CR rate was very high. It is suggested that this regimen is suitable for neoadjuvant chemotherapy. We expect that this chemotherapy will contribute to avoidance of surgery for small tumors (stages I and II) and will enable function-preserving surgery for advanced tumors.

Topics: Administration, Oral; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Squamous Cell; Cisplatin; Disease-Free Survival; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Combinations; Female; Humans; Male; Middle Aged; Mouth Neoplasms; Neoadjuvant Therapy; Neoplasm Staging; Oxonic Acid; Preoperative Care; Pyridines; 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

A late phase II clinical study of S-1, a novel oral antitumor agent of fluorinated pyrimidines, in patients with advanced/recurrent head and neck cancer was conducted in 25 institutions across Japan as a multi-institutional cooperative study from August 1995 to March 1998. Out of 59 eligible patients, the objective responses were 4 complete responses (CR) and 13 partial responses (PR). The response rate was 28.8% (17/59, 95% CI: 17.8-42.1%). The response rate in previously treated patients was 28.3% (15/53), whereas that in treatment naive patients was 33.3% (2/6). The response rate in patients with prior chemotherapy was 26.7% (12/45). Major adverse reactions of grade 2 or more were anemia (25.4%, 15/59), leucopenia (22.0%, 13/59), neutropenia (25.4%, 15/59), thrombocytopenia (3.4%, 2/59), anorexia (6.8%, 4/59), nausea/vomiting (1.7%, 1/59), stomatitis (1.7%, 1/59), skin symptoms including eruptions or desquamation (5.1%, 3/59), and malaise (1.7%, 1/59). Grade 4 anemia was observed in one case; however, this returned to the normal level after the termination of drug administration and the blood transfusion. Therefore, this event was confirmed to be reversible. Based on these results, we conclude that S-1 is an active agent for the treatment of advanced/recurrent head and neck cancer.

Topics: Administration, Oral; Adult; Aged; Antimetabolites, Antineoplastic; Carcinoma, Squamous Cell; Drug Administration Schedule; Drug Combinations; Female; Head and Neck Neoplasms; Humans; Lymphatic Metastasis; Male; Middle Aged; Oxonic Acid; Pyridines; Tegafur

In developing new anticancer agents, the most important thing is the balancing of antitumor activity and toxicity. To achieve high activity and low toxicity, S-1 was designed, in which tegafur, prodrug of 5-FU, was combined with two classes of modulators. CDHP, inhibitor of 5-FU degradation in liver and Oxo, inhibitor of 5-FU phosphoribosylation in digestive tract, respectively. This cooperative study with 15 nation-wide institutes was conducted to evaluate the antitumor activity and toxicity of S-1 in patients with advanced head and neck cancer from Jan. 1994 to March 1996 in Japan. Out of 26 patients, CR was achieved in 1 and PR in 11 with a response rate of 46.2%, while adverse events of grade 3 were as follows: hemoglobinemia (7.7%), leukocytopenia, neutropenia, stomatitis and anorexia (3.8%), each. Neither grade 4 adverse event nor treatment-related deaths were observed. Based on these findings, it was concluded that S-1 is a useful anticancer agent with the low grade toxicities for treatment of the patients with advanced head and neck cancer, and the effects of CDHP and Oxo found in preclinical studies might be also reflected in these results.

Topics: Administration, Oral; Adult; Aged; Anorexia; Antimetabolites, Antineoplastic; Carcinoma, Squamous Cell; Drug Administration Schedule; Drug Combinations; Female; Head and Neck Neoplasms; Humans; Leukopenia; Lymphatic Metastasis; Male; Middle Aged; Neutropenia; Oxonic Acid; Pyridines; Stomatitis; Tegafur

Squamous cell lung cancer is one of the major pathological types in patients with non-small cell lung cancer. Since treatment with angiogenic agents and target drugs in patients with advanced squamous cell lung cancer is not promising, there are limited strategies to improve the outcome in such patients. Herein, we report a pretreated patient with advanced squamous cell lung cancer, who received low-dose of apatinib combined with S-1 as salvage treatment, with good long-term response.. The patient complained of dry cough for one month without any relief by medication. Otherwise, she denied any other medical or family history.. According to the chest computed tomography, and pathologic findings from biopsy for lesion in lung, the patient was diagnosed with lung squamous cell lung cancer with enlargement of bilateral supraclavicular lymph nodes suggesting metastasis, staged as IIIb.. The patient received gemcitabine plus cisplatin as first line treatment, and gemcitabine as maintenance therapy. After progression, she received vinorelbine as second line treatment. After progression again, she received low-dose apatinib combined with S-1 as third line treatment.. With the follow-up period from October 21, 2014, to April 6, 2019, there were 15 months, 9 months, and 24 months of progression-free survival time for first line (including maintenance therapy), second line, and third line treatment, respectively. The only adverse event was neutropenia at grade 2 (CTC AE) occurring during the maintenance treatment.. This case indicated that low-dose apatinib combined with S-1 might be effective and safe in selected pretreated patients with advanced squamous cell lung cancer. It might be worthy to conduct further researches to investigate the efficacy and safety of the combination therapy in such patients.

Topics: Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Squamous Cell; Disease Progression; Drug Combinations; Female; Humans; Lung Neoplasms; Middle Aged; Oxonic Acid; Pyridines; Tegafur

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

Metaplastic squamous cell carcinoma(MSCC)of the breast is very unusual and is histologically characterized by rapid progression. Conventionalchemotherapy for ductalcarcinoma of the breast is ineffective against MSCC. Here, we report a case of MSCC of the breast successfully treated with S-1. A 57-year-old woman was admitted to our hospital because of a left breast tumor. A tumor approximately 10 cm in diameter was palpable in the lower-outer quadrant(D region)of the left breast. Core needle biopsy indicated estrogen receptor(ER)-negative, progesterone receptor(PR)-negative, and human epidermalgrowth factor receptor 2(HER2)-negative MSCC of the breast. Computed tomography(CT)showed left axillary lymph node metastases but did not indicate distant metastasis. A diagnosis of T4N3cM0, Stage ⅢC, MSCC of the left breast was made. Each treatment course consisted of the administration of S-1(120mg/body/day)for 4weeks, followed by 2 drugfree weeks. After the second course, significant tumor and lymph node reduction was observed. We concluded that S-1 chemotherapy seems to be effective for patients with MSCC of the breast.

Topics: Antimetabolites, Antineoplastic; Axilla; Biopsy, Large-Core Needle; Breast Neoplasms; Carcinoma, Squamous Cell; Drug Combinations; Female; Humans; Middle Aged; Oxonic Acid; Receptors, Estrogen; 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

In our department, patients with oral squamous cell carcinoma(OSCC)received preoperative chemotherapy containing S-1 to prevent the growth and dissemination of tumors during the waiting time before definitive surgery. We retrospectively evaluated the usefulness of this treatment.. One hundred and five patients comprising stages T1(26), T2(64), T3(7), and T4(8 cases)were enrolled in this study from July 2001 to June 2013. In principle, patients were administered S-1(80mg/m / 2/day, days 1-14)and followed by a drug holiday(days 15-21), continuing until 1 week before surgery.. The median administration period was 14 days(256 days). Ninety-eight patients underwent definitive surgery, but 7 patients who revealed clinical CR underwent only biopsy and showed histological CR. The histological responses of all patients were CR(24), PR(22), and NC(59), and the response rate was 43.8%. Almost all adverse effects were Grade 1 or 2, except 1 case of neutropenia(Grade 3)and 1 case of urticaria(Grade 3). The 5-year overall survival rates were 86.7% in all cases, 95.3% in CR/PR cases, and 79.7% in NC cases.. Preoperative S-1 administration during the waiting time was a safe and very effective method and was considered beneficial for patients with OSCC.

Topics: Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Squamous Cell; Drug Combinations; Humans; Mouth Neoplasms; Oxonic Acid; Retrospective Studies; Tegafur; Waiting Lists

S-1 is an oral anticancer agent containing tegafur, a prodrug of 5-fluorouracil (5-FU). Preoperative S-1 chemotherapy is performed to prevent tumor proliferation before surgery in oral squamous cell carcinoma (OSCC). The aim of this study was to evaluate the effects of preoperative S-1 chemotherapy on tumor budding.. We examined 248 cases of OSCC and evaluated the budding scores in biopsy and resected specimens by keratin immunohistochemistry.. In S-1-untreated patients, the budding scores in resected specimens tended to show a mild increase. S-1 treatment had the effect of lowering the budding score, although some cases with dramatically increased budding scores in resected specimens were found in the early phase of administration. Relapse-free survival showed a significant difference (P < .01) according to the presence or absence of S-1 treatment among patients with high budding scores.. The present findings indicate that S-1 administration may be more effective in patients with high budding scores than in those with lower budding scores.

Topics: Antimetabolites, Antineoplastic; Biopsy; Carcinoma, Squamous Cell; Drug Combinations; Humans; Mouth Neoplasms; Neoplasm Recurrence, Local; Oxonic Acid; Tegafur

Background: The recommended treatment strategies for early glottic carcinoma with intent of larynx preservation are\ primarily radiotherapy. However, the outcomes of radiotherapy for bulky T1 or T2 glottic carcinoma are unsatisfactory.\ We designed a protocol consisting of concurrent chemoradiotherapy using S-1 as the radiosensitizer. We have performed\ this protocol in patients with favorable T2 lesions and demonstrated its efficacy and safety. In contrast, we have\ treated non-bulky T1 glottic carcinomas with 2.25 Gy per fraction, for a total of 25-28 fractions, starting in 2011 to\ improve efficacy and shorten the treatment period. Since this treatment strategy was implemented for T1 disease, no\ local failure has occurred to date, and it appears to be almost as safe as radiotherapy using 2.0 Gy per fraction. With\ the aim of improving the local control rate and shortening the treatment period primarily for favorable T2 disease, we\ changed the dose of radiation in our protocol from 2.0 Gy to 2.25 Gy per fraction, for a total of 25 fractions (from 30\ fractions). The present study aims to evaluate the efficacy and safety of this new protocol. Methods: This study will\ be conducted as a clinical, prospective, single-armed, non-randomized trial. Patients are to receive S-1 (55.3 mg /m2\ /day, once daily) and radiotherapy (2.25 Gy per fraction, for a total of 25 fractions). S-1 and radiotherapy are started\ on the same day that radiotherapy is performed, 3-6 hours after oral administration of S-1. The primary study aim is\ the 3-year local control rate. The secondary study aims are overall survival, voice-preservation survival, disease-free\ survival, complete response rate, completion rate, and toxicity. Result and conclusion: This is the first single-center,\ non-randomized, prospective study of concurrent chemoradiotherapy with S-1 and hypofractionated radiotherapy to\ be conducted. The trial will evaluate the efficacy and safety of our protocol.

Topics: Adult; Aged; Aged, 80 and over; Carcinoma, Squamous Cell; Chemoradiotherapy; Drug Combinations; Female; Follow-Up Studies; Glottis; Humans; Laryngeal Neoplasms; Male; Middle Aged; Outpatients; Oxonic Acid; Prognosis; Prospective Studies; Research Design; Survival Rate; Tegafur; Young Adult

　Anticancer drugs induce cell-cycle arrest and apoptosis not only in tumor cells, but also in immune cells. However, many preclinical and clinical findings show that some chemotherapeutic agents can improve the antitumor efficacy of immunotherapy. We immunohistochemically analyzed the degree of immune cell infiltration and the relevance of programmed cell death 1 ligand-1 (PD-L1) expression in surgically resected oral squamous cell carcinoma (OSCC) specimens from patients who had undergone pretreatment with certain chemotherapies and other patients without pretreatment. We divided the patients into the group of neoadjuvant chemotherapy (NAC) patients (n=8) and the nNAC (without NAC) patient group (n=10). We observed that NAC induced infiltrations of CD4, CD8 T cells and CD56 NK cells into the tumor microenvironment. Decreased numbers of Tregs and PD-1-positive cells were observed in the NAC group. No significant difference was observed in the degree of immune-cell infiltration between the patient groups except for CD56 NK cells in the stroma and PD-1 cells in cancer nests. Eighty percent of the nNAC specimens showed intermediate-to-strong PD-L1 protein expression, whereas 75% of the NAC specimens showed down-regulation of the PD-L1 protein, indicating the effectiveness of the chemotherapeutic treatment before surgery.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Agents; B7-H1 Antigen; Carcinoma, Squamous Cell; Case-Control Studies; Drug Combinations; Female; Humans; Male; Middle Aged; Mouth Neoplasms; Neoadjuvant Therapy; Oxonic Acid; Retrospective Studies; Tegafur; Tumor Microenvironment

In patients with head and neck cancer, the management of second primary cancer (SPC) is particularly important for improving survival because of its high incidence and associated mortality. We evaluated the impact of combination chemotherapy on survival and SPC.. We retrospectively analyzed data from 49 patients treated with definitive radiation therapy (RT) for T2N0M0 laryngeal squamous cell carcinoma between 2003 and 2011. Among them, 22 patients received combined modality treatment with radiotherapy and S-1 (RT+CT group).. The median follow-up period was 71months (32-111months). A significant difference in overall survival (OS, P<0.01) was observed between the RT+CT group (n=22) and the RT alone group (n=27) though no significant differences were observed in local control and disease specific survival. Univariate analyses showed that an older age (P<0.05) and a higher grade (P<0.05) were associated with OS. Multivariate analysis identified chemotherapy as the most significant predictor of survival (OR, 0.056; 95% CI, 0.008-0.353, P<0.01). A significantly lower incidence of distant metastasis (DM)+SPC (5-year incidence: 5% vs. 19%, P<0.05) and fewer deaths from these causes (1 vs. 8: P<0.05) were observed in the RT+CT group. Multivariate analysis showed that chemotherapy was the most significant factor for the incidence of DM+SPC (OR, 0.074; 95% CI, 0.0065-0.84; P<0.05).. The findings of this study suggest the possibility that combined modality treatment with radiotherapy and S-1 improve survival by preventing distant metastasis and second primary cancer.

Topics: Aged; Antimetabolites, Antineoplastic; Carcinoma, Squamous Cell; Chemoradiotherapy; Drug Combinations; Female; Humans; Laryngeal Neoplasms; Male; Middle Aged; Neoplasm Metastasis; Neoplasms, Second Primary; Oxonic Acid; Survival Analysis; Tegafur

The aim of this study was to investigate the clinical features and prognosis of patients with squamous cell carcinoma (SCC) associated with sinonasal inverted papilloma (IP).. The medical records of 95 patients who were diagnosed with IP or SCC associated with IP were retrospectively reviewed. Out of 95 patients, 15 were diagnosed with SCC associated with IP. The clinical characteristics, treatment modalities, and survival outcomes of the patients were analyzed.. The incidence of SCC associated with IP was 15.8%. Although differential diagnosis between IP and SCC associated with IP is difficult, epistaxis may be the specific symptom in SCC associated with IP cases. The 3-year disease-specific survival rate was higher in cases with T1, 2 and 3 than in cases with T4. There was no significant difference in survival rate between maxillary sinus and other primary sites. On the other hand, there was a significant difference in survival rate between the microscopic SCC with IP cases and the other cases. In addition, the patients with <70 years old better than those with >70 years old with a 3-year disease free survival of 80% versus 0%.. Some T4 patients were found to have a highly aggressive disease. Therefore, complete surgical resection followed by chemo-radiation therapy is the recommended treatment for patients with T4 disease to control of the primary tumor site.

Topics: Adult; Age Factors; Aged; Aged, 80 and over; Antineoplastic Agents; Carcinoma, Squamous Cell; Chemoradiotherapy, Adjuvant; Disease-Free Survival; Drug Combinations; Epistaxis; Female; Fluorouracil; Head and Neck Neoplasms; Humans; Kaplan-Meier Estimate; Magnetic Resonance Imaging; Male; Maxillary Sinus Neoplasms; Middle Aged; Nasal Cavity; Nasal Obstruction; Neoplasm Staging; Neoplasms, Multiple Primary; Nose Neoplasms; Otorhinolaryngologic Surgical Procedures; Oxonic Acid; Papilloma, Inverted; Paranasal Sinus Neoplasms; Radiotherapy, Adjuvant; Retrospective Studies; Squamous Cell Carcinoma of Head and Neck; Tegafur; Tomography, X-Ray Computed

One in 1000-3000 carriers of human T-cell leukemia virus type 1 (HTLV-1) develops adult T-cell leukemia/lymphoma (ATLL) per year; however, the pathogenic mechanism is not completely clear. We have observed that some patients with squamous cell carcinoma (SCC) develop ATLL during treatment at our hospital. The aim of this study was to examine treatment factors associated with onset of ATLL through an evaluation of the therapeutic background of these patients.. The impact of radiotherapy, chemotherapy and surgery on occurrence of ATLL was evaluated in 146 patients with head and neck SCC who were treated at our hospital between April 2010 and December 2013.. Of 146 patients, 17 were HTLV-1 positive and 6 developed ATLL. There was a significant relationship between ATLL development and administration of S-1 chemotherapy (p=0.0003), but not with use of radiotherapy, surgery or other drugs.. The involvement of S-1 chemotherapy in ATLL development suggests that a test for HTLV-1 antibody should be performed before treatment and that S-1 should not be administered in HTLV-1 positive patients with head and neck carcinoma.

Topics: Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Squamous Cell; Cisplatin; Drug Combinations; Female; Fluorouracil; Head and Neck Neoplasms; Human T-lymphotropic virus 1; Humans; Leukemia-Lymphoma, Adult T-Cell; Male; Middle Aged; Neoplasms, Second Primary; Otorhinolaryngologic Surgical Procedures; Oxonic Acid; Radiotherapy; Squamous Cell Carcinoma of Head and Neck; Taxoids; Tegafur

In advanced esophageal squamous cell carcinoma (ESCC), paclitaxel plus cisplatin are considered as active and tolerable. The current clinical study was conducted to retrospectively compare the efficacy and safety of first-line paclitaxel/S-1(PS) and paclitaxel/cisplatin(TP) regimens in advanced ESCC.. The overall response rate of PS was slightly, but not significantly, higher (25 patients, 46%) than that of TP (23 patients, 39%, P = 0.432). Median overall survival (OS) was similar for PS and TP (11.5 months vs. 10.4 months, p = 0.37). However PS had longer median progression-free survival than TP (PFS: 5.5 months vs5.0months, p = 0.04). When compared with PS, more grade 3 or 4 adverse events were recorded for TP, including leukopenia, neutropenia, anemia, anorexia and vomiting (P < 0.05). No treatment-related deaths were recorded in either group.. Between 2008 and 2014, all patients diagnosed with advanced ESCC and treated with paclitaxel/S-1 or paclitaxel/cisplatin at Cancer Hospital Affiliated to Zhengzhou University were analyzed retrospectively. One hundred and thirteen patients were included in this study. Disease control rates and progression-free survival (PFS) and overall survival (OS) were recorded. Survival analysis was calculated by using Kaplan-Meier method.. The PS option improves PFS and its OS is similar to TP. Moreover, the PS regimen is an effective and safe first-line treatment for ESCC with less hematological and non-hematological toxicity.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Squamous Cell; China; Cisplatin; Disease Progression; Disease-Free Survival; Drug Combinations; Esophageal Neoplasms; Esophageal Squamous Cell Carcinoma; Female; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Oxonic Acid; Paclitaxel; Retrospective Studies; Tegafur; Time Factors; 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

Standard chemoradiotherapy (CRT) using cisplatin (CDDP) and 5-fluorouracil (5-FU) is an optional treatment for patients with stage II-III esophageal cancer. However, there are some demerits in this regimen because CDDP administration requires a large transfusion volume and 5-FU must be continuously infused over 24 h. Therefore, hospitalization is unavoidable. We collected retrospectively the data of definitive CRT with nedaplatin and S-1 as carried out in our institution.. Patients with early and advanced esophageal cancer and relapsed esophageal cancer after radical surgery were included. Nedaplatin 80 mg/m(2) was given on days 1 and 29, and S-1 80 mg/m(2) on days 1-14 and 29-42. No prophylactic treatment with granulocyte colony stimulating factor was administered. Patients received two courses of concurrent radiotherapy of more than 50 Gy with or without two additional courses as adjuvant therapy every 4 weeks.. Between August 2011 and June 2015, 89 patients (age range, 44-86 years; K-PS 90-100, 81 %; squamous cell carcinoma histology, 97 %; definitive/salvage CRT, 75/25 %) were collected. Twenty-one (24 %) patients completed four cycles, and 94 % received two or more cycles. Grade 4 leukopenia, thrombocytopenia, and anemia occurred in 12, 7, and 10 % of the patients, respectively. Five patients developed febrile neutropenia. Grade 3 non-hematological toxicity included infection in 12 %, mucositis/esophagitis in 3 %, kidney in 3 %, and fatigue in 3 %. Sixty-four patients (72 %) received the prescribed full dose and full cycles of chemotherapy. A complete response was achieved in 76 patients (85 %). The 3-year overall survival rate was 54.4 % in definitive CRT and 39.8 % in salvage CRT, respectively. Sixty-two subjects (70 %) received treatment as outpatients.. Nedaplatin and S-1 in combination with radiotherapy is feasible, and toxicity is tolerable. This treatment method has the potential to shorten hospitalization without impairing the efficacy of CRT.

Topics: Adult; Aged; Aged, 80 and over; Ambulatory Care; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Squamous Cell; Chemoradiotherapy; Cisplatin; Drug Administration Schedule; Drug Combinations; Esophageal Neoplasms; Female; Fluorouracil; Hospitalization; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Organoplatinum Compounds; Oxonic Acid; Retrospective Studies; Salvage Therapy; Tegafur

The purpose of this study was to assess the efficacy and safety of induction chemotherapy with docetaxel-S-1, and radiotherapy (RT) with concurrent daily cisplatin in locally advanced head and neck carcinoma.. Fifty patients received 2 cycles of induction chemotherapy with induction chemotherapy with docetaxel and S-1, followed by 7 cycles of RT with concurrent daily cisplatin.. The most frequent grade 3 to 4 hematologic toxicity was neutropenia (14%). Forty of 50 patients who completed induction chemotherapy with docetaxel and S-1 subsequently started RT with concurrent daily cisplatin, all within 3 to 4 weeks after the start of the second cycle of induction chemotherapy with docetaxel and S-1. The best response to induction chemotherapy with docetaxel and S-1 and after completion of RT with concurrent daily cisplatin was partial response (PR) in 52.5% and complete response in 47.5%, respectively. With a median follow-up of 61 months, 5-year progression-free survival (PFS) and overall survival (OS) were 63.3% and 65.7%, respectively.. Administration of induction chemotherapy with docetaxel and S-1 before RT with concurrent daily cisplatin chemoradiotherapy (CRT) resulted in a high response rate with good tolerability, and did not compromise subsequent CRT. © 2016 Wiley Periodicals, Inc. Head Neck 38: E1653-E1659, 2016.

Topics: Adult; Aged; Aged, 80 and over; Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Squamous Cell; Chemoradiotherapy; Cisplatin; Docetaxel; Drug Combinations; Female; Fluorouracil; Head and Neck Neoplasms; Humans; Induction Chemotherapy; Male; Middle Aged; Oxonic Acid; Taxoids; Tegafur; Young Adult

This retrospective study was designed to estimate the efficacy and toxicity of definitive radiotherapy with concurrent or sequential docetaxel/S-1 for patients with locally advanced esophageal squamous cell carcinoma (ESCC).. Of the 62 eligible patients enrolled in this study during January 1, 2010 to December 31, 2014 from Qilu Hospital, Shandong University, Shandong Province, 39 patients received 3 cycles of docetaxel/S-1 during and after radiotherapy (concurrent chemoradiotherapy, CCRT), and 23 patients had radiotherapy followed by 3 cycles of docetaxel and S-1 (sequential chemoradiotherapy, SCRT).. The CR of CCRT and SCRT groups were 48.72 and 21.74 %, respectively (p = 0.035). The median progress-free survival (PFS) of CCRT group (23.5 months) was significantly higher than SCRT group (11.7 months; p = 0.004). The median overall survival (OS) of CCRT group (33.5 months) also was significantly higher than SCRT group (24.0 months; p = 0.004). At 2 years, in this patient population, the rate of PFS of CCRT group was (44.2 ± 8.2 %), significantly higher than SCRT group (11.9 ± 9.6 %; p = 0.002). The 2-year OS rate of CCRT (68.6 ± 7.5 %) was significantly higher than SCRT group as well (42.0 ± 14.0 %; p = 0.002). The incidence of adverse events was higher in CCRT than SCRT group. No grade 4 or grade 5 adverse events occurred in our study.. Definitive radiotherapy with concurrent or sequential docetaxel and S-1 for inoperable locally advanced ESCC was very well tolerated and remarkably active. In both CCRT and SCRT groups, acute toxicities were manageable. This regimen holds promises for treatment of esophageal carcinoma and warrants further investigation.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Squamous Cell; Chemoradiotherapy; Docetaxel; Drug Combinations; Esophageal Neoplasms; Female; Follow-Up Studies; Humans; Male; Oxonic Acid; Prognosis; Retrospective Studies; Survival Rate; Taxoids; Tegafur

Reduced-RADPLAT for HPC achieved comparative survival and locoregional control rates with lower toxicities compared with concurrent chemoradiotherapies including original RADPLAT. S-1 adjuvant chemotherapy showed a survival benefit.. To evaluate the efficacy and toxicities of targeted intra-arterial (IA) infusion of cisplatin with concurrent radiotherapy with a reduced dose (reduced-RADPLAT) for resectable hypopharyngeal cancer (HPC).. Between 1999-2012, 50 patients with stage II-IVA HPC primarily treated by reduced-RADPLAT were analyzed. They were treated by 2-5 courses of IA cisplatin infusion (100 mg per body) with simultaneous systemic infusion of sodium thiosulfate concurrent with conventional radiotherapy (66-70 Gy). After 2003, S-1, an oral fluoropyrimidine, adjuvant chemotherapy was administered to all eligible patients.. During a median follow-up of 48.6 months, the estimated 3- and 5-year overall survival (OS), progression-free survival (PFS), locoregional control, and laryngoesophageal dysfunction-free survival (LEDFS) rates were 76.0% and 62.0%, 58.0% and 50.0%, 66.0% and 62.0%, and 56.0% and 54.0%, respectively. Grade 3 toxicities were observed in 30.0%. No patient had grade 4 or higher toxicities. No patient required tube feeding or tracheotomy at 3 months after treatment. T4-lesions and S-1 administration were significant factors predicting poor and good OS, PFS, and LEDFS, respectively.

Topics: Aged; Aged, 80 and over; Antineoplastic Agents; Carcinoma, Squamous Cell; Chemoradiotherapy; Chemotherapy, Adjuvant; Cisplatin; Drug Combinations; Female; Humans; Hypopharyngeal Neoplasms; Infusions, Intra-Arterial; Male; Middle Aged; Oxonic Acid; Retrospective Studies; Tegafur; Treatment Outcome

The prognosis of patients with locally advanced squamous cell carcinoma (SCC) of the tongue is poor. Postoperative chemoradiotherapy (CRT) improves locoregional control and survival in high-risk patients. We investigated the prognostic factors for clinical T4a tongue SCC, and elucidated whether postoperative CRT has a benefit for patients with poor prognosis in terms of survival.. We performed a retrospective analysis of 61 patients with stage T4a SCC of the tongue who underwent primary resection and neck dissection.. The median follow-up was 53.8 months. Multivariate analysis revealed a 4.26× relative risk of death for patients with the involvement of ≥5 regional lymph nodes (pN ≥5) compared with those with pN 0-4 (p = 0.002). In Kaplan-Meier analysis, patients with pN ≥5 who received CRT had longer overall survival rates than those who did not (hazard ratio = 0.31; p = 0.041).. pN ≥5 is the most powerful prognostic factor for clinical T4a SCC of the tongue. Postoperative CRT is recommended in patients with pN ≥5.

Topics: Aged; Antimetabolites, Antineoplastic; Antineoplastic Agents; Carcinoma, Squamous Cell; Chemoradiotherapy, Adjuvant; Chemotherapy, Adjuvant; Cisplatin; Drug Combinations; Female; Humans; Lymph Nodes; Lymphatic Metastasis; Male; Middle Aged; Neck Dissection; Neoplasm Staging; Oxonic Acid; Patient Care Team; Postoperative Care; Prognosis; Radiotherapy, Adjuvant; Retrospective Studies; Survival Rate; Tegafur; Tongue Neoplasms

We report a case of advanced esophageal and gastric cancer that was successfully treated via multimodal therapy. A 65- year-old man with hoarseness was referred to our hospital. He was diagnosed with clinical T4aN2M0, Stage IV esophageal squamous cell carcinoma and clinical T3N1M0, Stage II B gastric adenocarcinoma. He was treated with 3 courses of chemotherapy, administered over 4weeks, with S-1(80mg/m / / 2: day 1-14), cisplatin(60mg/m2: day 1), and docetaxel(40mg/m2: day 1). Computed tomography(CT)revealed shrinkage of the primary esophageal tumor, gastric tumor, and lymph node metastases. Next, we selected definitive radiation chemotherapy(CRT), because lymph node metastases remained around the bilateral recurrent laryngeal nerves. After CRT with a total 60 Gy plus administration of 5-fluorouracil and cisplatin, CT showed that the primary esophageal tumor and lymph node metastases had disappeared. Then, distal gastrectomy was performed for the remaining gastric cancer, as part of the multimodal therapy. After gastrectomy, no systemic chemotherapy was performed. At a follow-up examination 5 years and 6 months after the start of chemotherapy, the patient is alive without recurrence.

Topics: Adenocarcinoma; Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Squamous Cell; Chemoradiotherapy; Cisplatin; Docetaxel; Drug Combinations; Esophageal Neoplasms; Esophageal Squamous Cell Carcinoma; Gastrectomy; Humans; Male; Neoplasms, Multiple Primary; Oxonic Acid; Stomach Neoplasms; Taxoids; Tegafur

The most common histological classification of bile duct cancer is adenocarcinoma and squamous cell carcinoma (SCC) is relatively rare. We report a case of a 78-year-old man with SCC of the extrahepatic bile duct associated with metachronous para-aortic lymph node metastasis. He had undergone subtotal stomach-preserving pancreatoduodenectomy. The pathological findings demonstrated moderately differentiated SCC of the distal extrahepatic bile duct (T1N1M0, stage IIB). 6 months after surgery, recurrence of the para-aortic lymph node was shown in abdominal CT. 5 courses of tegafur/gimeracil/oteracil (S-1) plus cisplatin therapy was performed and the para-aortic lymph node disappeared, confirmed as complete response by imaging findings. The patient is alive without recurrence, 10 months after recurrence and chemotherapy.

Topics: Aged; Antimetabolites, Antineoplastic; Bile Duct Neoplasms; Bile Ducts, Extrahepatic; Carcinoma, Squamous Cell; Cholangiopancreatography, Endoscopic Retrograde; Cisplatin; Dose-Response Relationship, Drug; Drug Combinations; Humans; Lymph Nodes; Lymphatic Metastasis; Male; Neoplasms, Second Primary; Oxonic Acid; Tegafur; Tomography, X-Ray Computed

Nedaplatin and S-1 treatment with concurrent radiotherapy was effective, with acceptable toxicities. This regimen does not require extensive intravenous hydration and continuous infusion. Nedaplatin and S-1 may contribute to better clinical outcomes and improve quality of life for patients.. We retrospectively analyzed the clinical efficacy and toxicity of concurrent chemoradiotherapy with nedaplatin and S-1 for head and neck squamous cell cancer.. Forty-six patients with oropharyngeal, hypopharyngeal, and laryngeal cancer were treated with S-1 on days 1 through 14 and nedaplatin on day 1 every 4 weeks for two cycles of radiotherapy. Therapeutic responses and adverse events were assessed.. Primary site tumors and neck lymph nodes exhibited complete response rates of 91% and 64.3%, respectively. The 4-year relapse-free survival and overall survival rates were 76.2% and 85.3%, respectively. The main grade 3 and 4 toxicities were mucositis (30%), leukopenia (30%), anorexia (22%), dermatitis (15%), and thrombocytopenia (9%).

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Agents; Carcinoma, Squamous Cell; Chemoradiotherapy; Drug Combinations; Female; Head and Neck Neoplasms; Humans; Male; Middle Aged; Neoplasm Staging; Organoplatinum Compounds; Oxonic Acid; Retrospective Studies; Squamous Cell Carcinoma of Head and Neck; Tegafur; Treatment Outcome

S-1 granulated powder has recently been released to the market as an additional format to that of the capsule. Patients who previously found it difficult to swallow the capsules are now able to take S-1 in powder form. This study evaluated the feasibility of S-1 granulated powder as adjuvant chemotherapy for advanced head and neck cancer. S-1 was orally administered for 2  weeks, followed by 1  week of rest (one course) for 12  months (16 courses). Twenty-four stage III and IV head and neck cancer patients were enrolled in this study. In total, 10 (47.6%) of the patients follow the planned schedule and dose. Severe adverse events were observed in 22 patients (91.7%), whereas no grade 4 adverse events were observed. S-1 granulated powder should be presented as an additional option for the treatment of head and neck cancer, especially for patients experiencing difficulty in swallowing oral medications.

Topics: Administration, Oral; Adult; Aged; Antimetabolites, Antineoplastic; Carcinoma, Squamous Cell; Chemotherapy, Adjuvant; Drug Combinations; Fatigue; Feasibility Studies; Female; Follow-Up Studies; Head and Neck Neoplasms; Hematologic Diseases; Humans; Male; Middle Aged; Nausea; Neoplasm Staging; Oxonic Acid; Prognosis; Tegafur; Vomiting

The recommended S-1 chemotherapy schedule for head and neck cancer is daily treatment for 4 weeks, followed by 2 weeks of rest. However, this can lead to adverse events and sometimes treatment withdrawal. Alternate-day treatment with a pyrimidine anticancer agent is reported to reduce adverse events without compromising anticancer activity. We examined the indication of alternate-day treatment with S-1 for oral cancer. Fifteen patients(3 men and 12 women; average age: 81.3 years)with oral squamous cell carcinoma started consecutive-day treatment with S-1. Treatment had to be interrupted after 0.5-10 courses because of grade >2 myelosuppression, hepatorenal and electrolyte disorder, and grade 1 digestive toxicity. After a recovery period of 8-168 days from adverse events, alternate-day treatment with S-1 was started. Adverse events on this regimen were grade 2 leucopenia and hyperbilirubinemia in some patients. It was possible for 10 of the patients to continue this treatment for longer than 1 year or until death, but 5 patients could not continue because of a recurrence of a renal or electrolyte disorder, pneumonia, or disease progression. It is thought that alternate-day treatment with S-1 reduces the incidence of adverse events compared to consecutive-day treatment, and can allow continuous administration. Alternateday treatment with S-1 for female patients aged over 80 years with grade 1 leucopenia and/or thrombocytopenia before administration may help to maintain their quality of life.

Topics: Adult; Aged; Aged, 80 and over; Antimetabolites, Antineoplastic; Carcinoma, Squamous Cell; Drug Combinations; Female; Humans; Male; Middle Aged; Mouth Neoplasms; Oxonic Acid; Risk Factors; Tegafur

Topics: Aged; Antineoplastic Agents; Buttocks; Carcinoma, Squamous Cell; Chemoradiotherapy, Adjuvant; Cisplatin; Drug Combinations; Humans; Male; Oxonic Acid; Skin Neoplasms; Tegafur

Amino-acid transporters are necessary for the tumour cell growth and survival, and have a crucial role in the development and invasiveness of cancer cells. But, it remains unclear about the prognostic significance of L-type amino-acid transporter 1 (LAT1), system ASC amino-acid transporter-2 (ASCT2), and xCT expression in patients with tongue cancer. We conducted the clinicopathological study to investigate the protein expression of these amino-acid transporters in tongue cancer.. Eighty-five patients with surgically resected tongue cancer were evaluated. Tumour sections were stained by immunohistochemistry for LAT1, ASCT2, xCT, 4F2hc/CD98hc (4F2hc), Ki-67, and microvessel density (MVD) determined by CD34, and p53.. L-type amino-acid transporter 1 and 4F2hc were highly expressed in 61% (52 out of 85) and 45% (38 out of 47), respectively. ASC amino-acid transporter-2 and xCT were positively expressed in 59% (50 out of 85) and 21% (18 out of 85), respectively. The expression of both LAT1 and ASCT2 was significantly associated with disease staging, lymph-node metastasis, lymphatic permeation, 4F2hc expression and cell proliferation (Ki-67). xCT expression indicated a significant association with advanced stage and tumour factor. By univariate analysis, disease staging, lymphatic permeation, vascular invasion, LAT1, ASCT2, 4F2hc, and Ki-67 had a significant relationship with overall survival. Multivariate analysis confirmed that LAT1 was an independent prognostic factor for predicting poor prognosis.. L-type amino-acid transporter 1 and ASCT2 can serve as a significant prognostic factor for predicting worse outcome after surgical treatment and may have an important role in the development and aggressiveness of tongue cancer.

Topics: Adult; Aged; Aged, 80 and over; Amino Acid Transport System ASC; Amino Acid Transport System y+; Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Carcinoma, Squamous Cell; Chemotherapy, Adjuvant; Combined Modality Therapy; Disease-Free Survival; Docetaxel; Drug Combinations; Female; Fusion Regulatory Protein 1, Heavy Chain; Humans; Kaplan-Meier Estimate; Ki-67 Antigen; Large Neutral Amino Acid-Transporter 1; Lymphatic Metastasis; Male; Middle Aged; Minor Histocompatibility Antigens; Neoplasm Proteins; Neoplasm Staging; Oxonic Acid; Prognosis; Taxoids; Tegafur; Tongue Neoplasms; Treatment Outcome; Tumor Suppressor Protein p53

Squamous cell carcinoma (SCC) is the second most common type of skin cancer in Japan, and its incidence has been increasing in recent years. Early diagnosis and complete excision can provide a high cure rate. However, advanced cases of SCC showing local invasion, regional lymph node metastasis or distant metastasis are not curative and are difficult to treat with surgery alone. Some chemotherapy regimens have been used for treating advanced cutaneous SCC. However, almost all these regimens require intravenous administration and result in serious toxicities in elderly people. We gave S-1, a novel oral chemotherapeutic agent, for six patients with advanced cutaneous SCC. Three patients achieved complete response and one achieved partial response. Two patients showed stable disease. The overall response rate was 66.7% (four of six patients), and the disease control rate was 100%. Two of six patients developed grade 3 anaemia. Oral S-1 treatment is safe and effective for treating advanced cutaneous SCC. However, a prospective trial is necessary to confirm the effectiveness of oral S-1 for advanced cutaneous SCC.

Topics: Aged; Aged, 80 and over; Antimetabolites, Antineoplastic; Carcinoma, Squamous Cell; Drug Combinations; Humans; Male; Middle Aged; Oxonic Acid; Retrospective Studies; Skin Neoplasms; Tegafur

Squamous cell carcinoma of the breast is uncommon, but that of the nipple skin is rarer. The effect of chemotherapy in these cases is yet to reach consensus. We report a rare case in which primary squamous cell carcinoma of the nipple skin was successfully treated with S-1 alone. A 64-year-old woman was admitted to our hospital because of a granulomatous tumor mass over the right nipple, which she was aware of for 10 years; the tumor showed a rapid increase in growth before admission. The tumor was approximately 4 cm at the first visit, and was diagnosed as squamous cell carcinoma by incisional biopsy. We administered preoperative systemic chemotherapy owing to the presence of metastasis in an axillary lymph node. After 2 courses of chemotherapy with oralS -1 at 100mg/day for 28 days followed by a 14-day resting period, the primary tumor and metastatic lymph node showed a remarkable reduction in size. The patient subsequently underwent a radical operation and is currently healthy without any recurrence.

Topics: Antineoplastic Combined Chemotherapy Protocols; Biopsy; Breast Neoplasms; Carcinoma, Squamous Cell; Combined Modality Therapy; Drug Combinations; Female; Humans; Lymphatic Metastasis; Middle Aged; Nipples; Oxonic Acid; Tegafur

The patient was a 65-year-old man who underwent colonoscopy for melena. Following a biopsy, the patient was diagnosed with anal canal squamous cell carcinoma. A computed tomography (CT) scan revealed metastasis to the regional lymph nodes. The proposed treatment regimen comprised radiotherapy combined with S-1 and mitomycin C (MMC). Dur- ing radiotherapy (59.6 Gy in 32 fractions), 10mg/m² MMC was administered, as an intravenous bolus injection, on days 1 and 29. S-1 was administered orally, at a dose of 80 mg/m², on days 1-14 and 29-42. No serious adverse events were observed during chemoradiotherapy; the observed adverse events were leukemia (Grade 2), diarrhea (Grade 1), anorexia (Grade 1), and radiation dermatitis (Grade 1). After 8 weeks of treatment, no tumors, only scar tissue could be detected by using colonoscopy, and a CT scan revealed a remarkable reduction in regional lymph node metastases. The patient achieved a complete response.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Anus Neoplasms; Carcinoma, Squamous Cell; Chemoradiotherapy; Drug Combinations; Humans; Male; Mitomycin; Oxonic Acid; Tegafur

Squamous cell carcinoma (Sqc) of the pancreas is considered to be extremely rare. We report the case of a 79-year-old male with Sqc of the pancreas complicated by massive gastric ulcer fistula and multiple lymph node metastases. After completing two courses of S-1 chemotherapy, the gastric ulcer fistula and lymph node metastases improved. Sqc of the pancreas is usually associated with a poor prognosis. Various therapeutic regimens have been used for this type of cancer, but none has been proven effective. To the best of our knowledge, this report is the first on the effective response of pancreatic Sqc treated by S-1 chemotherapy.

Topics: Aged; Antimetabolites, Antineoplastic; Carcinoma, Squamous Cell; Drug Combinations; Humans; Male; Oxonic Acid; Pancreatic Neoplasms; Remission Induction; Tegafur

S-1 is widely used for various cancers. It may be useful for esophageal squamous cell carcinoma (ESCC); however, there are insufficient data. The purpose is to provide results of an analysis of S-1 monotherapy for unresectable and recurrent ESCC.. Twenty patients with histologically proven ESCC who were previously treated with other chemo(radio)therapies were treated with S-1 alone as second- or third-line chemotherapy.. A complete response (CR) was observed in 1 case (5%). A partial response (PR), stable disease (SD), and progressive disease (PD) were seen in 4 (20.0%), 7 (35.0%), and 8 (40.0%) cases, respectively. Two cases (10%) of anemia, 1 case (5%) of leukopenia, 3 cases (15%) of fatigue, and 3 cases (15%) of diarrhea were observed as grade 3 toxicity; however, there were no cases of grade 4 toxicity. The 1-year progression-free survival (PFS) rate was 10.0%, and the median PFS was 100 days. The 1-year overall survival (OS) was 30.5%, and the median OS was 330 days. The 1-year PFS rate in CR/PR/SD and PD was 16.7 and 0%, and the median survival time was 120 and 40 days.. S-1 is a promising new drug which can be used as a second- or third-line chemotherapy for ESCC.

Topics: Aged; Aged, 80 and over; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Squamous Cell; Disease Progression; Disease-Free Survival; Drug Combinations; Esophageal Neoplasms; Esophageal Squamous Cell Carcinoma; Female; Humans; Male; Middle Aged; Models, Statistical; Neoplasm Recurrence, Local; Oxonic Acid; Tegafur; Time Factors; Treatment Outcome

Metronomic chemotherapy is based on administration of anticancer agents at low-doses at close regular intervals with no prolonged breaks, and aims to inhibit vascular endothelial cells as well as tumor cells. Recently, it was suggested that metronomic chemotherapy exerts anti-angiogenic effects by inducing thrombospondin-1 (TSP-1) and early growth response-1 (EGR-1), and antitumor effects by suppressing cancer stem cells. S-1 is a novel orally administered anticancer drug that is a combination of tegafur, 5-chloro-2, 4-dihydroxypyridine and oteracil potassium for maintaining efficacious concentrations of 5-FU and reducing the serious gastrointestinal toxicity associated with 5-FU. In the present study, we tried to determine the suitable administration method of S-1 against oral squamous cell carcinoma as a metronomic chemotherapy. We performed in vivo experiments in which tumor-bearing nude mice were used to examine the antitumor activity of S-1 (6.9 mg/kg). HSC2 tumors were treated with three different regimens, given as 4-week treatment and 2-week rest (4W-2W, 1 cycle); 2-week treatment and 1-week rest (2W-1W, 2 cycles); or alternate days treatment (1D-1D, 6 weeks). A fourth group served as control. Antitumor effects and body weight changes were compared in each group. Expression of TSP-1, EGR-1, CD31 and CD44 in HSC2 tumors was examined by immunohistochemistry. The treated groups showed higher tumor growth inhibition compared to the control group, and the relative tumor growth inhibition was not different between the treated groups. Briefly, each relative tumor growth inhibition was 32.4% (4W-2W), 39.6% (2W-1W) and 37.0% (1D-1D). During treatment periods, body weights were lower in the mice with 4W-2W or 2W-1W than 1D-1D or control. Moreover, reduction of microvessel density and CD44 expression, and induction of TSP-1 and EGR-1 expression was markedly seen in 1D-1D-treated tumors compared to 4W-2W-, 2W-1W-treated tumors or untreated control tumors by immunohistochemistry. These findings suggest that the 1D-1D regimen is more useful than the 4W-2W or 2W-1W regimen as a metronomic chemotherapy.

Topics: Administration, Metronomic; Animals; Antineoplastic Combined Chemotherapy Protocols; Apoptosis; Carcinoma, Squamous Cell; Cell Line, Tumor; Cell Proliferation; Drug Combinations; Early Growth Response Protein 1; Humans; Mice; Mouth Neoplasms; Neovascularization, Pathologic; Oxonic Acid; Tegafur; Thrombospondin 1; Xenograft Model Antitumor Assays

This retrospective study evaluated the efficacy and safety of S-1 chemotherapy for unresectable or distant metastatic head and neck cancer. S-1 is an oral anticancer agent containing a combination of 2 modulators and tegafur, which is a pro-drug of 5-fluorouracil.. S-1 was orally administered to 27 patients with unresectable and/or distant metastatic head and neck cancer at a dose based on the patient's body surface area in an outpatient setting. S-1 was administered for either 14 or 28 consecutive days followed by a 7- or 14-day rest period, respectively. We investigated the response rate, the cumulative survival rate and the time-to-progression for these patients with adverse events.. The response rate was 11.1% (three out of the 27 cases: one case of a complete response and two cases of a partial response). The cumulative survival rate of patients with squamous cell carcinoma (n=18) was 7/18 (38.9%) and 4/18 (22.2%) at 12 and 24 months, respectively, with a median survival time of eight months. Most adverse events were mild (up to grade 2).. S-1 therapy is a useful, effective anticancer treatment for unresectable or distant metastatic head and neck cancer, with relatively mild side-effects, and can be administered while maintaining the quality of life of the patient.

Topics: Administration, Oral; Adult; Aged; Antimetabolites, Antineoplastic; Carcinoma, Squamous Cell; Drug Combinations; Drug Therapy; Female; Head and Neck Neoplasms; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Outpatients; Oxonic Acid; Tegafur

The purpose of this study was to investigate the effect of stereotactic radiosurgery on local control and organ preservation in cases of primary head and neck cancer.. In this retrospective study, 14 patients with a mean age of 73 years were treated between March 2006 and September 2007 with stereotactic radiosurgery for the management of primary head and neck cancer. The patients had biopsy confirmation of disease before treatment and all patients were confirmed with squamous cell carcinoma. The staging consisted of T2 (5 cases), T3 (3 cases), T4 (6 cases), N0 (13 cases), and N1 (1 case). Marginal doses were 3,500 to 4,200 cGy in 3 or 5 fractions. The outcome was assessed according to Response Evaluation Criteria in Solid Tumors criteria based on magnetic resonance imaging and positron emission tomography/computed tomography.. Significant tumor reduction was noted at the third month of follow-up with 5 complete responses and 9 partial responses. At a mean follow-up of 36 months (range, 14-40 mo) the local control and overall survival rates were 71.4% (10/14) and 78.6% (11/14), respectively.. These results show the feasibility of using stereotactic radiosurgery for primary head and neck cancer and its potential benefit in local control and organ preservation.

Topics: Aged; Aged, 80 and over; Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Squamous Cell; Chemotherapy, Adjuvant; Disease Progression; Drug Combinations; Feasibility Studies; Female; Fluorouracil; Follow-Up Studies; Head and Neck Neoplasms; Humans; Lymphatic Metastasis; Magnetic Resonance Imaging; Male; Middle Aged; Multimodal Imaging; Neoplasm Recurrence, Local; Neoplasm Staging; Oxonic Acid; Patient Care Planning; Positron-Emission Tomography; Radiosurgery; Remission Induction; Retrospective Studies; Survival Rate; Tegafur; Tomography, X-Ray Computed; Treatment Outcome

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

We retrospectively evaluated the relationship between computed tomography (CT)- and histopathological findings of parotid and submandibular glands in six patients treated for advanced oral cancer. Eligibility criteria were a pathologic diagnosis of oral squamous cell carcinoma, preoperative chemoradiation therapy (CRT) with a total dose of 30 Gy and oral S-1 (80 mg/m²/day), the availability of morphological assessments by CT and of functional assessments with the Saxon test before- and 2 weeks after CRT, and the availability of histopathological slides of irradiated parotid and submandibular glands. In the histopathological interpretation, gland structures were divided into acinar-, duct-, and adipose cells and other tissues. The Mann-Whitney test and the Spearman rank correlation test were used to determine histopathological changes. After 30-Gy irradiation, saliva production and parotid and submandibular volumes were significantly decreased (P < 0.05 each). Histopathological analysis demonstrated that 30-Gy irradiation resulted in a loss of acinar cells although acinar cells in the submandibular gland were relatively retained; the median acinar rate in the parotid and submandibular glands was 1.1% and 19.0%, respectively. The CT values after CRT were inversely correlated with adipose ratios (r = -0.98, P < 0.01) and there was a strong correlation between CT values before and after CRT (r = 0.97, P < 0.01). Our results suggested that acinar cell loss is a main contributor to changes in the volume and function of irradiated human parotid and submandibular glands. The CT value may reflect the adipose ratio rather than salivary function.

Topics: Aged; Antineoplastic Agents; Carcinoma, Squamous Cell; Chemoradiotherapy; Drug Combinations; Female; Humans; Male; Middle Aged; Mouth Neoplasms; Oxonic Acid; Parotid Gland; Preoperative Period; Retrospective Studies; Salivation; Submandibular Gland; Tegafur; Tomography, X-Ray Computed

To assess the clinical activity and toxicity of a combination chemotherapy regimen of S-1 and cisplatin in patients with recurrent and/or metastatic head and neck squamous cell carcinoma (HNSCC) in a retrospective study.. A total of 49 patients were treated in an outpatient setting with S-1 80 mg/m(2) on days 1-14 and with cisplatin 70 mg/m(2) on day 1 every 3 weeks for a maximum of six cycles as a first-line palliative chemotherapy. Patients who achieved complete response (CR), partial response (PR) or stable disease (SD) after six cycles received S-1 monotherapy as a maintenance therapy.. The median patient age was 55 years (range 33-79), 89.8 % were male, and the Eastern Cooperative Oncology Group performance status distribution was 0/1/2 (20.4 %/73.5 %/6.1 %). Of the 43 evaluable patients, 2 (4.1 %) achieved CR and 20 (40.8 %) had a PR, for an overall response rate of 44.9 %. Thirteen patients (26.6 %) had SD. The median number of chemotherapy treatments was 4 (range 1-18). Nine patients received maintenance S-1 monotherapy after six cycles of combination chemotherapy. With a mean 10.5 months (range 1.3-25.1) of follow-up, the median progression-free and overall survival were 4.5 (95 % CI, 3.7-5.3 months) and 10.8 months (95 % CI, 5.9-15.6 months), respectively. The main grade 3-4 toxicities were neutropenia (37 %), anemia (16 %) and general weakness (8 %). Other toxicities, including nausea/vomiting, mucositis and neuropathy, were mostly grade 1-2 and easily manageable.. The combination of S-1/cisplatin therapy had a favorable efficacy with manageable toxicity as a first-line chemotherapy regimen for advanced head and neck squamous cell carcinoma patients.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Squamous Cell; Cisplatin; Drug Combinations; Female; Head and Neck Neoplasms; Humans; Male; Middle Aged; Neoplasm Metastasis; Neoplasm Recurrence, Local; Oxonic Acid; Squamous Cell Carcinoma of Head and Neck; Tegafur

Radiation Therapy Oncology Group study 91-11 found that in resectable advanced laryngeal cancer, the locoregional control rate achieved with reduced intra-arterial cisplatin and concurrent radiotherapy (RADPLAT) was comparable to that of a concurrent chemoradiotherapy arm, with reduced toxicities. However, distant metastases were more frequent. Our study retrospectively evaluated the efficacy and feasibility of adjuvant chemotherapy with S-1, an oral fluoropyrimidine, for distant metastases following reduced RADPLAT.. We analyzed 61 patients who were treated with reduced RADPLAT and achieved a complete response at the primary site. After the use of reduced RADPLAT, 24 patients were administered S-1 for 2 weeks followed by 1 week of rest, and the cycle was repeated for 6 months (S-1+ group). Thirty-seven patients were not administered S-1 (S-1-group).. The hazard ratio for distant metastases in the S-1+ group was 0.114 (95% confidence interval, 0.015 to 0.881; p = 0.0374). There was a significant difference in disease-free survival in favor of the S-1+ group (p = 0.0455). Nineteen patients (79.2%) in the S-1+ group received S-1 according to the planned schedule and dose. Grade 3 toxicities were observed in 2 patients (8.3%), but there was no grade 4 event.. In resectable advanced laryngeal cancer, S-1 adjuvant chemotherapy is an effective and feasible treatment option to control distant metastases following reduced RADPLAT.

Topics: Administration, Oral; Aged; Antimetabolites, Antineoplastic; Carcinoma, Squamous Cell; Chemotherapy, Adjuvant; Cisplatin; Disease-Free Survival; Dose-Response Relationship, Drug; Drug Combinations; Feasibility Studies; Female; Humans; Laryngeal Neoplasms; Larynx; Male; Neoplasm Metastasis; Neoplasm Recurrence, Local; Organ Sparing Treatments; Oxonic Acid; Radiation-Sensitizing Agents; Radiotherapy Dosage; Radiotherapy, Adjuvant; Retrospective Studies; Tegafur

A resected case of complete response after treatment with S-1 for recurrent squamous cell carcinoma component of the breast is presented.A 65-year-old woman was admitted to another hospital because of a left breast tumor. A tumor approximately 6 cm in diameter was palpable in the subareolar-lower (DBE) region of the left breast; the diagnosis was breast cancer. We performed mastectomy and axillary lymph node dissection. The pathological diagnosis revealed squamous cell carcinoma of the left breast(pT3N1M0, Stage III A). FEC chemotherapy, a standard chemotherapy regimen for general breast cancer, was performed as first-line adjuvant therapy, but was withdrawn after 1 course due to sepsis shock. Weekly PTX chemotherapy as second-line treatment was also withdrawn after six courses due to interstitial pneumonia. Few skin rashes were observed along the incision scar of the left breast, but biopsy revealed skin invasion by local recurrence of squamous cell carcinoma of the breast. Treatment with S-1 was performed for 8 months, and she underwent resection of left skin, fat tissue, and underlying muscle, including the recurrent region. No residual primary carcinoma foci was found in the resected specimen; therefore, the pathological diagnosis revealed complete response for the squamous cell carcinoma component.

Topics: Aged; Antimetabolites, Antineoplastic; Breast Neoplasms; Carcinoma, Squamous Cell; Combined Modality Therapy; Drug Combinations; Female; Humans; Neoplasm Staging; Oxonic Acid; Recurrence; Tegafur

Topics: Administration, Oral; Aged, 80 and over; Antimetabolites, Antineoplastic; Carcinoma, Squamous Cell; Drug Combinations; Eyelid Neoplasms; Female; Head and Neck Neoplasms; Humans; Magnetic Resonance Imaging; Neoplasm Invasiveness; Oxonic Acid; Skin Neoplasms; Squamous Cell Carcinoma of Head and Neck; Tegafur

We present a case in which chemoradiation therapy was effective in a geriatric patient with Stage IV anal canal cancer. The patient is an 81-year-old woman who complained of proctorrhagia and anal pain. She was referred to us by her family doctor who suspected rectal cancer. Tumors as large as 6.5 cm in diameter mainly on the right side of the rectum as well as 2 palpable enlarged lymph nodes on the right inguinal area, were found during the initial physical examination. Squamous cell carcinoma was elevated to 16 ng/mL. A CT scan revealed that irregularly shaped masses as large as 7 cm in diameter were externally exposed on the right side of the rectum along with enlarged lymph nodes on the right inguinal area and metastasis at S7 lesion in the liver. Squamous cell carcinoma was diagnosed from biopsy results. Due to her age, the chemotherapy regimen was S-1+CDDP with radiation therapy and 4-port irradiation (50.4 Gy) of the primary tumor, interior of the pelvis, and inguinal lymph nodes. Partial response was observed upon completion of treatment, and complete response was obtained after 6 months. She is currently an outpatient taking S-1: 60 mg/day orally. There is no indication of cancer recurrence after 1 year and 3 months, and she continues to visit an outpatient clinic for regular follow-ups. These results demonstrate the effectiveness of chemoradiation therapy for geriatric patients with Stage IV anal canal cancer.

Topics: Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Anus Neoplasms; Carcinoma, Squamous Cell; Chemoradiotherapy; Cisplatin; Drug Combinations; Female; Humans; Neoplasm Staging; Oxonic Acid; Tegafur

Induction chemotherapy (ICT) has been used to select patients for organ preservation and determine subsequent treatments in patients with locally advanced squamous cell carcinoma of the head and neck (LASCCHN). Still, the clinical outcomes of LASCCHN patients who showed response to ICT are heterogeneous. We evaluated the efficacy of interim 18-fluoro-2-deoxy-glucose positron emission tomography (FDG-PET) after ICT in this specific subgroup of LASCCHN patients who achieved partial response (PR) after ICT to predict clinical outcomes after concurrent chemoradiotherapy (CCRT).. Twenty-one patients with LASCCHN who showed PR to ICT by Response Evaluation Criteria In Solid Tumors before definitive CCRT were chosen in this retrospective analysis. FDG-PET was performed before and 2-4 weeks after ICT to assess the extent of disease at baseline and the metabolic response to ICT, respectively. We examined the correlation of the metabolic response by the percentage decrease of maximum standardized uptake value (SUVmax) on the primary tumor or lymph node after ICT or a specific threshold of SUVmax on interim FDG-PET with clinical outcomes including complete response (CR) rate to CCRT, progression-free survival (PFS), and overall survival (OS).. A SUVmax of 4.8 on interim FDG-PET could predict clinical CR after CCRT (100% vs. 20%, p=0.001), PFS (median, not reached vs. 8.5 mo, p<0.001), and OS (median, not reached vs. 12.0 months, p=0.001) with a median follow-up of 20.3 months in surviving patients. A 65% decrease in SUVmax after ICT from baseline also could predict clinical CR after CCRT (100% vs. 33.3%, p=0.003), PFS (median, not reached vs. 8.9 months, p<0.001) and OS (median, not reached vs. 24.4 months, p=0.001) of the patients.. These data suggest that interim FDG-PET after ICT might be a useful determinant to predict clinical outcomes in patients with LASCCHN receiving sequential ICT followed by CCRT.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma; Carcinoma, Squamous Cell; Cisplatin; Combined Modality Therapy; Drug Combinations; Female; Fluorodeoxyglucose F18; Head and Neck Neoplasms; Humans; Male; Middle Aged; Neoplasms, Squamous Cell; Oxonic Acid; Positron-Emission Tomography; Radiopharmaceuticals; Radiotherapy Dosage; Radiotherapy, Conformal; Remission Induction; Retrospective Studies; Squamous Cell Carcinoma of Head and Neck; Tegafur; Treatment Outcome

We investigated the efficacy and toxicity of concurrent chemoradiotherapy with nedaplatin and S-1 for head and neck cancer, as an alternative to cisplatin and 5-fluorouracil.. A total of 31 patients were enrolled in this study. S-1 was administered orally twice a day for 14 days followed by a 2-week rest. Nedaplatin was intravenously administered on day 4. If possible, two courses of chemotherapy were performed. The radiotherapy was started concurrently with the administration of S-1.. The overall complete response rate was 81%. The 2-year overall survival rate was 96%. The 2-year relapse-free survival rate was 94%. The main adverse events were hematological toxicity, mucositis and dermatitis.. Our findings suggest that this therapeutic regimen has either an equal or lower toxicity than the conventional cisplatin and 5-fluorouracil, and that it has equal efficacy with regard to the clinical response and short-term outcome. Moreover, it is possible to successfully perform this treatment in an outpatient setting.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Squamous Cell; Combined Modality Therapy; Drug Combinations; Female; Follow-Up Studies; Head and Neck Neoplasms; Humans; Lymphatic Metastasis; Male; Middle Aged; Neoplasm Staging; Organoplatinum Compounds; Oxonic Acid; Radiotherapy; Survival Rate; Tegafur; Treatment Outcome

The optimal chemotherapeutic regimen for inoperable thymic carcinoma remains uncertain and little information is available regarding the usefulness of salvage chemotherapy. S-1, a newly developed oral fluorouracil antitumor drug, has been reported to be effective in the treatment of gastrointestinal tumors and non-small cell lung cancer. This case study reports a case of chemorefractory thymic cancer with a good response to S-1 monotherapy. S-1 was used as sixth-line chemotherapy and the response was the first remarkable tumor regression in the patient's clinical course. S-1 appears to have significant activity against thymic carcinoma.

Topics: Antimetabolites, Antineoplastic; Carcinoma, Squamous Cell; Drug Combinations; Drug Resistance, Neoplasm; Female; Humans; Middle Aged; Oxonic Acid; Salvage Therapy; Tegafur; Thymus Neoplasms; Treatment Outcome

We describe the case of a 74-year-old male patient with synchronous double primary lung cancers: adenocarcinoma in the right lower lobe and squamous cell carcinoma in the left upper lobe (LUL). These tumors were difficult to differentiate radiographically from a single metastatic primary cancer, but their eventual diagnoses were triggered by their responses to chemotherapy, which included pemetrexed. After two courses of chemotherapy with pemetrexed and carboplatin, the right lower lobe mass had partially resolved; however, the LUL mass had increased. When S-1 was used as fourth-line chemotherapy, the size of the LUL mass decreased. Pemetrexed is a potentially useful drug for treating nonsquamous cell carcinoma, but may not be appropriate in cases with a coexisting squamous cell carcinoma. Our experience with this interesting case leads us to propose that S-1 monotherapy may provide a treatment option in pemetrexed-refractory cases.

Topics: Adenocarcinoma; Aged; Antineoplastic Combined Chemotherapy Protocols; Carboplatin; Carcinoma, Squamous Cell; Drug Combinations; Glutamates; Guanine; Humans; Lung Neoplasms; Male; Neoplasms, Multiple Primary; Oxonic Acid; Pemetrexed; Tegafur

We report a case of disease -free survival with combination chemotherapy against squamous cell carcinoma(SCC)of an unknown primary. A 54-year-old male had an intraabdominal malignant lymph node tumor beside the common hepatic artery which was revealed by image studies including CT, MRI and PET-CT. After extirpation of the tumor, the resected specimens were diagnosed as metastatic SCC in the lymph nodes by pathology and immunohistochemistry. Cancers of an unknown primary are divided into two sub-groups, favorable and unfavorable, based on their clinical output. During hesitation to cure because of the unfavorable sub-group, the authors recognized multiple Virchow's and para-aortic lymph node metastases in this case. However, chemotherapy with CDDP/5-FU, followed by S-1, and then DOC were effective, resulting in a CR. The patient has been well without any sign of recurrence over 3 years after the first chemotherapy and about 2 years after the last chemotherapy. If a primary site is not found immediately after careful detection cancer of an unknown primary should be cured.

Topics: Antineoplastic Combined Chemotherapy Protocols; Aorta; Carcinoma, Squamous Cell; Cisplatin; Drug Combinations; Fluorouracil; Humans; Lymphatic Metastasis; Male; Middle Aged; Neoplasms, Unknown Primary; Oxonic Acid; Positron-Emission Tomography; Remission Induction; Tegafur; Tomography, X-Ray Computed

The purpose of this study was to evaluate the effectiveness and adverse events of combination chemotherapy with oral S-1 administration following docetaxel (DOC) treatment by superselective intra-arterial infusion as neo-adjuvant chemotherapy (NAC) for patients with oral squamous cell carcinoma. Thirteen patients were enrolled in this study (9 men and 4 women, with a mean age of 61. 0 years). All patients were given S-1 65mg/m(2) per day for 14 days, and DOC 40-50mg/m(2) by intraarterial infusion was administered. The locoregional response evaluated 3 weeks after administration was 100%, including a 69. 2% complete response. According to Oboshi and Shimosato's classification, histological evaluation of surgical specimens revealed that 3 cases were Grade II a, 4 cases Grade II b, 1 case Grade IV a, and 4 cases Grade IV c. The severe side effects were neutropenia and cerebral infarction. The present study suggests that combination chemotherapy with S-1 and DOC by superselective intra-arterial infusion would be an effective and safe regimen in NAC for oral squamous cell carcinomas.

Topics: Administration, Oral; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Squamous Cell; Cerebral Infarction; Docetaxel; Drug Combinations; Female; Humans; Infusions, Intra-Arterial; Male; Middle Aged; Mouth Neoplasms; Neoplasm Staging; Neutropenia; Oxonic Acid; Taxoids; Tegafur

Consecutive daily low-dose S-1 therapy was less toxic and its efficacy was not inferior to the conventional administration schedule. Consecutive daily low-dose S-1 chemotherapy appears to be a treatment option for patients in whom it is difficult to continue the conventional administration schedule of S-1 due to adverse events.. To evaluate the safety and efficacy of consecutive daily low-dose S-1 therapy in an adjuvant setting.. This study investigated 52 patients with absence of local residual tumor, lymph node metastasis or distant metastasis after radical treatment for advanced head and neck squamous cell carcinoma. After receiving informed consent from patients, half of the usual dose of S-1 was administered daily for 2 years. The safety, feasibility, and efficacy of this approach were evaluated.. Hematologic toxicity was seen in 51 of 52 patients (98.1%), but grade 3 hematologic toxicity was found in only 2 patients (3.8%). Nonhematologic toxicity was observed in 15 patients (28.8%) and all were grade 1. Forty-three patients (82.7%) were able to complete the chemotherapy for 2 years without dose reduction. The 3-year disease-free survival rate and 3-year survival rate were 82.6% and 94.0%, respectively.

Topics: Adult; Aged; Aged, 80 and over; Antimetabolites, Antineoplastic; Carcinoma, Squamous Cell; Chemotherapy, Adjuvant; Disease-Free Survival; Drug Combinations; Female; Head and Neck Neoplasms; Humans; Male; Middle Aged; Oxonic Acid; Retrospective Studies; Squamous Cell Carcinoma of Head and Neck; Tegafur

Platinum compounds play pivotal roles in treatment for squamous cell carcinoma of the head and neck. The objective was to evaluate the efficacy of S-1 monotherapy in patients with recurrent or metastatic squamous cell carcinoma of the head and neck after failure of platinum-based chemotherapy.. We retrospectively analyzed 39 consecutive patients with recurrent or metastatic squamous cell carcinoma of the head and neck who received S-1 monotherapy after failure of platinum-based chemotherapy or chemoradiotherapy at the Shizuoka Cancer Center between August 2003 and October 2010. S-1 was given orally twice daily (80 mg/m(2)/day) for 28 days followed by a 14-day rest.. The median follow-up period in survivors was 31.5 months. Among 38 patients with measurable lesions, 9 (24%) showed partial response and 15 (39%) showed stable disease. The median progression-free survival was 4.9 months and the median overall survival was 13.2 months. The median progression-free survival for oropharyngeal cancer (n= 7) was significantly longer than for other cancers (n = 32) (14.9 vs. 4.7 months, P= 0.035). The response rate in patients with a recurrence-free interval since the last platinum administration >6.0 months was significantly better than with a recurrence-free interval <6.0 months (40 vs. 13%, P= 0.0102). Recurrence-free interval >6.0 months also showed a significantly better progression-free survival (6.0 vs. 2.6 months, P= 0.045). The frequency of Grade 3/4 toxicities was less than 10%.. S-1 monotherapy shows promising signs of efficacy and tolerability in patients with recurrent or metastatic squamous cell carcinoma of the head and neck after failure of platinum-based chemotherapy in this retrospective cohort and warrants further investigation in this population.

Topics: Adult; Aged; Antimetabolites, Antineoplastic; Carcinoma, Squamous Cell; Disease-Free Survival; Drug Combinations; Drug-Related Side Effects and Adverse Reactions; Female; Head and Neck Neoplasms; Humans; Japan; Male; Middle Aged; Neoplasm Recurrence, Local; Oxonic Acid; Platinum Compounds; Retrospective Studies; Survival Analysis; Tegafur; Treatment Failure

The purpose of this study was to investigate the effectiveness and safety of palliative chemotherapy using S-1 alone. We clinically analyzed 8 oral squamous cell carcinoma patients showing a complete response(CR)to chemotherapy with S-1 alone. These patients received chemotherapy consisting of 2 weeks' administration, including 5-days' administration and 2- days' termination, following a 1-week rest. Adverse effects were observed in 4 patients. However, all of them were grade 1 toxicities. The average length of S-1 administration before achieving CR was 9. 8 ± 3. 1 weeks(3. 3 ± 1. 0 courses). Seven patients had a recurrence. The prognosis of this group was 5 deaths by local recurrence, and 1 death by lymph node metastasis. The average length of disease progression was 447. 4 ± 479. 5 days. Two patients, one who received surgery and the other who received irradiation after chemotherapy by S-1, are alive without tumors. The 1-year and 3-year disease-free survival rates were 100% and 37. 5%, respectively.

Topics: Aged; Aged, 80 and over; Antimetabolites, Antineoplastic; Carcinoma, Squamous Cell; Drug Combinations; Female; Humans; Male; Middle Aged; Mouth Neoplasms; Oxonic Acid; Recurrence; Survival Rate; Tegafur

A 79-year-old woman was reffered to our hospital with the chief complaint of hematochezia. Type-2 tumor was found on anal canal by colonoscopy, and pathologic examination revealed a poorly differentiated squamous cell carcinoma. Computed tomography of the abdomen demonstrated obturatory node metastasis. The patient was diagnosed as having squamous cell carcinoma of the anal cana (l cStage III). After four months from chemoradiation (66 Gy/33 Fr plus S-1), the ulcer side was improved completely to epithelization, and abdominal CT scan showed a remarkable reduction of obturatory node metastasis. She was obtained a complete response. Now the patient is disease-free for ten months after chemoradiation.

Topics: Aged; Antimetabolites, Antineoplastic; Anus Neoplasms; Carcinoma, Squamous Cell; Chemoradiotherapy; Drug Combinations; Female; Humans; Lymphatic Metastasis; Neoplasm Staging; Oxonic Acid; Tegafur; Tomography, X-Ray Computed

S-1 is a newly developed oral fluoropyrimidine derivative that is now widely used as a chemotherapeutic agent in the treatment of oral squamous cell carcinoma (SCC). Thymidylate synthase (TS) is the rate-limiting enzyme in the de novo DNA biosynthetic pathway, and improves clinical response to chemotherapy with fluoropyrimidines. We have retrospectively evaluated the predictive value of thymidylate synthase activity in 75 patients with oral SCC with an enzyme-linked immunosorbent assay (ELISA). Mean (SD) activity (pmol/mg) in the specimens was 0.078 (0.080) (median 0.059). The median value was taken as the cut-off value based on which the patients were divided into high and low activity groups. Both the clinical and histopathological responses to chemotherapy and radiochemotherapy were higher in the group with low TS activity. The group with low TS activity also differed significantly in their clinical response to S-1-based chemotherapy (p<0.05). However, there was no significant difference in cause-specific survival. Measurement of TS activity may aid in predicting the clinical response to chemotherapy including S-1 for oral SCC.

Topics: Adult; Aged; Aged, 80 and over; Antimetabolites, Antineoplastic; Carcinoma, Squamous Cell; Drug Administration Schedule; Drug Combinations; Enzyme-Linked Immunosorbent Assay; Female; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Mouth Neoplasms; Oxonic Acid; Prognosis; Retrospective Studies; Statistics, Nonparametric; Tegafur; Thymidylate Synthase

In this study, we evaluated the feasibility, efficacy and toxicity of concurrent chemoradiotherapy with S-1 (tegafur-gimeracil-oteracil potassium) for T2N0 glottic carcinoma. A total of 23 patients with T2N0 glottic carcinoma received chemoradiotherapy with S-1. Radiotherapy consisted of five daily fractions of 2 Gy per week, to a total median dose of 70 Gy. S-1 was administered 65 mg/m(2) per day for 4 weeks, beginning on the day therapy was started, followed by 2 weeks off the drug and twice a day until the end of radiotherapy. Initial local control rate of the primary tumor was achieved in all patients. The median follow-up period for all patients was 38 months. The 3-year local control rate was 95.4%. Regarding adverse reactions, grade 3 mucositis upon clinical examination, mucositis upon functional/symptomatic examination, dysphagia, hepatic toxicity and anemia were observed in 13, 2, 2, 1 and 1 patients, respectively. This chemoradiotherapy did not result in grade 4 acute toxicity or severe late toxicity. Chemoradiotherapy with S-1 was feasible, well tolerated and effective. This therapy is suggested as a possible regimen for improving local control of T2N0 glottic carcinoma.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Squamous Cell; Combined Modality Therapy; Drug Combinations; Glottis; Humans; Kaplan-Meier Estimate; Laryngeal Neoplasms; Male; Middle Aged; Oxonic Acid; Pyridines; Radiation-Sensitizing Agents; Tegafur

Primary cutaneous squamous cell carcinoma (SCC) is a malignant tumor that arises from keratinizing cells of the epidermis or its appendages. We present a patient with cutaneous SCC on the left instep with metastases to multiple lymph nodes in the para-aortic, iliac and groin region. We chose a combination of surgery and concurrent chemoradiotherapy. The chemotherapeutic agent S-1/cisplatin was selected based on results of the histoculture drug response assay. The patient responded dramatically to this multidisciplinary treatment and complete remission was achieved.

Topics: Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Squamous Cell; Cisplatin; Combined Modality Therapy; Drug Combinations; Humans; Lymphatic Metastasis; Male; Middle Aged; Oxonic Acid; Skin Neoplasms; Tegafur; Treatment Outcome

Chemotherapy has shown little antitumor activity against advanced oral squamous cell carcinoma (OSCC) patients. Therefore, there is an urgent need to develop more effective therapeutic methods for patients with advanced OSCC. Lentinan, beta-(1-->3)-D-glucan, an extract from the edible mushroom, Lentinus edodes, has been reported to show direct antitumor effects and various immunomodulatory effects. S-1 is an oral antineoplastic agent that can induce apoptosis in various types of cancer cells, including OSCC. Hence, combined treatment of cancer cells with Lentinan and S-1 might exert dramatic antitumor effects on OSCC cells. In this study, the response of human OSCC cells to Lentinan alone and in combination with S-1 was examined using nude mouse xenograft models. S-1 (6.9 mg/kg/day, 7 times/week) was administered orally and Lentinan (0.1 mg/kg/day, 2 times/week) was injected into peritumoral tissue for three weeks. Apoptotic cells were detected by a TUNEL method. The gene expression level of thymidylate synthase (TS), dihydropyrimidine dehydrogenase (DPD) and orotate phosphoribosyl transferase (OPRT) was determined using microdissection and RT-PCR, and their protein levels were determined using ELISA. Combined therapy of Lentinan and S-1 markedly exerted antitumor effects on human OSCC xenografts and significantly induced apoptotic cells in tumors treated with Lentinan plus S-1. Microdissection and RT-PCR revealed that the expression of TS and DPD mRNA was down-regulated and that expression of OPRT mRNA was up-regulated in tumors administered the combined treatment. Moreover, ELISA indicated that the protein levels of TS and DPD were down-regulated, and that OPRT was up-regulated in tumors treated with the combined therapy. During the experimental period, no loss of body weight was observed in mice treated with the combined therapy. These findings demonstrate that the combination of Lentinan and S-1 is effective against OSCC and has the potential of being a new therapeutic tool for future treatment of these tumors.

Topics: Animals; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Squamous Cell; Cell Line, Tumor; Drug Combinations; Female; Fluorouracil; Humans; Lentinan; Mice; Mice, Nude; Mouth Neoplasms; Oxonic Acid; Tegafur; Xenograft Model Antitumor Assays

Several clinical trials examining treatment strategies for advanced laryngeal cancer have demonstrated that concurrent chemoradiotherapy is the most effective treatment for improving the patient response to radiotherapy and laryngeal preservation. We evaluated a new regimen of S-1/CDGP(Nedaplatin) with radiotherapy (RT), and established that it represented an effective new treatment option that allowed for the preservation of the larynx.. A total of 16 patients with stage II to IV laryngeal cancer(excluding T4 stage)who had been treated at our institution from 2001 to 2007 were recruited for the present study. All patients had histologically-confirmed squamous cell carcinomas.. The administration of S-1/CDGP/RT led to a complete response (CCR) in all patients with stage II or IV disease, with preservation of the larynx in all of these cases. For patients with stage III disease, 6 (85%) experienced CR, and 1 patient (15%) had a partial response. The laryngeal preservation rate for these patients was 85%. Severe toxicities, i. e., neutropenia, thrombocytopenia, and dermatitis of grade 3, were observed. The overall five-year survival rate was 72%, and the disease specific survival rate was 92%.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Squamous Cell; Combined Modality Therapy; Drug Combinations; Female; Humans; Laryngeal Neoplasms; Male; Middle Aged; Neoplasm Staging; Organoplatinum Compounds; Oxonic Acid; Survival Rate; Tegafur

The aim of this study was to evaluate the feasibility and toxicity of concurrent chemoradiotherapy (CCRT) with S-1 in patients with locally advanced squamous cell carcinoma of the head and neck (SCCHN) in elderly cases and/or cases with comorbidity.. Fifty eligible patients with stage III (15 cases) or stage IV (35 cases) SCCHN were treated with CCRT. Thirteen cases had an advanced age of over 75 years and 37 cases had comorbidity. Definitive radiotherapy was delivered up to a total dose of 66-70.2 Gy. The patients received two courses of oral S-1 (40 or 50 mg twice a day [80 or 100 mg/day]) for 2 weeks followed by 1 week of rest while receiving CCRT.. All the patients received the planned radiotherapy and at least one course of S-1. Grade 3 mucositis occurred in 20% of the patients (10/50). Grade 3 neutropenia occurred in 12% (6/50) and leukocytopenia occurred in 6% (3/50) of the cases. Pathologically, the complete response rates were 93% in stage III and 54% in stage IV.. Concurrent chemoradiotherapy with S-1 is a safe, well-tolerated and effective regimen for locally advanced SCCHN in elderly cases and/or cases with comorbidity.

Topics: Adult; Aged; Aged, 80 and over; Antimetabolites, Antineoplastic; Carcinoma, Squamous Cell; Combined Modality Therapy; Drug Combinations; Female; Head and Neck Neoplasms; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Oxonic Acid; Survival Analysis; Tegafur; Treatment Outcome

Chemotherapy has shown little antitumor activity against advanced oral squamous cell carcinoma (OSCC) patients. Therefore, there is an urgent need to develop more effective therapeutic methods for patients with advanced OSCC. Cepharanthine is a biscoclaurine alkaloid extracted from Stephania cepharantha Hayata, which is widely used for the treatment of many acute and chronic diseases, and can exert antitumor effects on several human cancer cells. S-1 is a new oral antineoplastic agent that can induce apoptosis in various types of cancer cells, including OSCC. Hence combined treatment of cancer cells with cepharanthine and S-1 might exert dramatic antitumor effects on OSCC cells.. In this study, the response of human OSCC cells to cepharanthine alone and in combination with S-1 was examined using nude mouse xenograft models. S-1 (10 mg/kg/day, 5 times/week) was administered orally and cepharanthine (20 mg/kg, 5 times/week) was injected into peritumoral tissue for three weeks. Apoptotic cells were detected by a TUNEL method. The protein expression of thymidylate synthase (TS), dihydropyrimidine dehydrogenase (DPD), and orotate phosphoribosyl transferase (OPRT) were assessed using immunohistochemistry; their gene expression was determined using microdissection and RT-PCR, and their protein levels using ELISA.. Combined therapy of cepharanthine and S-1 exerted antitumor effects on human OSCC xenografts markedly and significantly induced apoptotic cells in tumors treated with cepharanthine plus S-1. Immunohistochemistry showed that the expressions of TS and DPD were down-regulated, and that OPRT expression was up-regulated in tumors treated with cepharanthine plus S-1. In the same way, microdissection and RT-PCR revealed that the expression of TS and DPD mRNA was down-regulated and that expression of OPRT mRNA was up-regulated in tumors administered the combined treatment. Moreover, ELISA indicated that the protein levels of TS and DPD were down-regulated, and that OPRT was up-regulated in tumors treated with the combined therapy. During the experimental period, no loss of body weight was observed in mice treated with the combined therapy.. These findings demonstrate that the combination of cepharanthine and S-1 is effective against OSCC and has the potential of being a new therapeutic tool for future treatment of these tumors.

Topics: Animals; Antineoplastic Combined Chemotherapy Protocols; Apoptosis; Benzylisoquinolines; Blotting, Western; Carcinoma, Squamous Cell; Cell Proliferation; Dihydrouracil Dehydrogenase (NADP); Drug Combinations; Enzyme-Linked Immunosorbent Assay; Female; Humans; Immunoenzyme Techniques; In Situ Nick-End Labeling; Male; Mice; Mice, Nude; Mouth Neoplasms; Orotate Phosphoribosyltransferase; Oxonic Acid; Tegafur; Thymidylate Synthase; Tumor Cells, Cultured; Xenograft Model Antitumor Assays

Palliative treatments are applied for older adult cases that are not indicated for either surgery or potential chemotherapy, as well as in cases with unresectable primary lesions, distant metastases, and serious complications among head and neck cancer cases. There is no established treatment for such cases, and therefore treatment has to be selected on a case-by-case basis. Two cases showing sustained QOL after long administration of S-1 are presented in this paper. The first is an 84-year-old male patient with cancer of the hypopharynx (T3N2aM1, stage IVc). The second is a 70- year-old male patient who had recurrent cancer of the larynx (T1N0M0, stage I) after primary treatment. However, we were unable to perform surgery due to possible complications of severe emphysema. Regulating the dosage and intervals of S-1 enabled the patients in both cases to survive with cancer as outpatients for 2 years and 2 months after the initial visit (1 year and 10 months from the start of the administration of S-1) in the former case and 3 years from the initial visit (2 years and 1 month from the start of the administration of S-1) in the latter case.

Topics: Aged; Aged, 80 and over; Antimetabolites, Antineoplastic; Carcinoma, Squamous Cell; Drug Combinations; Humans; Hypopharyngeal Neoplasms; Laryngeal Neoplasms; Male; Oxonic Acid; Quality of Life; Tegafur

S-1, an oral fluorouracil antitumor drug, is composed of three agents: tegafur (FT), 5-chloro-2,4-dihydroxypyridine (CDHP), and potassium oxonate (Oxo). Approximately 50% of oral squamous cell carcinomas (OSCC) exhibit cervical lymph node metastasis. The extent of lymph node involvement is a major determinant in both staging and prognosis of the majority of OSCC. The purpose of this study was to examine the effect of S-1 on the metastatic potential of OSCC cells. We used orthotopic green fluorescence protein (GFP) SAS-L1, in BALB/c nu/nu mice. Mice received oral doses of either 5% hydroxypropylmethylcellulose (HPMC) for control or S-1 (20 mg/kg) and were autopsied at 2 weeks. We also performed in vitro experiments using concomitant 5-fluorouracil (5-FU) and CDHP as a drug model of S-1 to determine the effect of S-1 on OSCC invasion and metastasis. Although 100% (11 of 11) of mice not treated with S-1 showed cervical lymph node metastasis, only 54.4% (6 of 11) of S-1 treated mice demonstrated metastasis. In in vitro experiments, OSCC cells treated with 5-FU and CDHP showed a marked reduction in invasiveness and in adhesion to laminin coated plates. Western blot analysis revealed that treatment with 5-FU and CDHP suppressed expression of integrins alphav, alpha3, alpha6, beta1, beta3, beta4, beta5, and beta6. These results suggest that S-1 inhibits tumor proliferation and lymph node metastasis in OSCC cells. Moreover, expression of integrin subunits and the integrin signal transduction pathway may be closely related to metastasis suppression.

Topics: Animals; Antimetabolites, Antineoplastic; Blotting, Western; Carcinoma, Squamous Cell; Cell Line, Tumor; Drug Combinations; Gene Expression; Green Fluorescent Proteins; Humans; Integrins; Lymphatic Metastasis; Mice; Mice, Nude; Mouth Neoplasms; Oxonic Acid; Signal Transduction; Tegafur; Xenograft Model Antitumor Assays

We report two successful remnant and recurrent cases of head and neck cancer treated with S-1. Case 1, a 52-year-old man, was diagnosed as supraglottic laryngeal carcinoma (T3N2cM0, squamous cell carcinoma: SCC) on January 25, 2000, and concurrent chemoradiotherapy (CCRT) was applied. After the treatment, a remnant tumor in the larynx was found by biopsy. He was followed using UFT at 400mg/day because he had refused surgery. Pulmonary metastasis was detected by chest CT on June 14, 2001, and the administration of S-1 was started. After 2 courses, the mass in the lung disappeared, and the primary lesion was also judged to be a complete response(CR). The administration of S-1 is still continuing and remnant tumors have not been found. Case 2, a 76-year-old man, was diagnosed with hypopharyngeal carcinoma (T3N2bM0, SCC) on December 14, 2001, and CCRT was applied resulting in CR in the hypopharynx and the neck. He was followed using UFT at 300 mg/day after discharge. A supraclavicular lymph node became palpable on March 27, 2003. Pathological examination by fine needle aspiration cytology showed SCC, class V. After 2 courses administering S-1 at 100mg/day, the supraclavicular lymph node disappeared. S-1 was changed to UFT at 300 mg/day on July 31, 2003, because adverse events of grade 3 appeared. Administration of UFT was continued for one year. No recurrence has been found for 5 years.

Topics: Aged; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Squamous Cell; Drug Combinations; Head and Neck Neoplasms; Humans; Hypopharyngeal Neoplasms; Laryngeal Neoplasms; Lung Neoplasms; Male; Middle Aged; Oxonic Acid; Tegafur; Tomography, X-Ray Computed; Treatment Outcome

S-1 is an oral 5-fluorouracil (5-FU) anticancer agent and has shown promising effects in the treatment of a wide range of carcinomas, including head and neck cancer. In addition to being used as adjuvant chemotherapy, S-1 is a promising agent for palliative treatment. Its ease of administration makes it an ideal drug to treat patients in the outpatient setting while maintaining adequate quality of life. However, the clinical role of S-1 in patients with recurrent/metastatic head and neck cancer is still uncertain. We retrospectively reviewed 16 patients with recurrent/metastatic head and neck cancer who received S-1 monotherapy. Thirteen patients with squamous cell carcinoma (SCC) and 3 patients with non-SCC who had recurrent/metastatic disease received S-1 monotherapy as outpatients. One patient with nasopharyngeal undifferentiated carcinoma and 1 patient with maxillary adenosquamous carcinoma showed complete response (CR), while all SCC patients showed stable disease (SD) or progressive disease (PD). Median time to progression (TTP) was 12 weeks. Five patients showed grade 3 and 4 adverse reactions, all hematological. Except for one episode of grade 4 leucopenia which required hospitalization and granulocyte colony-stimulating factor (GCSF) treatment, all adverse events resolved with dose reduction or dose omission. S-1 was safely administered in outpatients and showed some efficacy in the treatment of recurrent/metastatic head and neck cancer in patients who had received previous chemotherapy. S-1 could be used as palliative treatment in patients with recurrent/metastatic head and neck cancer.

Topics: Administration, Oral; Aged; Antimetabolites, Antineoplastic; Carcinoma, Adenosquamous; Carcinoma, Squamous Cell; Drug Combinations; Female; Head and Neck Neoplasms; Hematologic Diseases; Humans; Male; Middle Aged; Neoplasm Recurrence, Local; Oxonic Acid; Palliative Care; Retrospective Studies; Tegafur; Treatment Outcome

We report a case of left inguinal lymph node metastasis of anal canal carcinoma, treated effectively with chemotherapy consisting of S-1 and CDDP combined with radiotherapy. In February 2006, a 76-year-old woman underwent resection of a tumor diagnosed as squamous cell carcinoma of the anal canal. The patient refused additional surgical therapy. In August 2007, a painful lymphnode swelling was noticed in the left inguinal region. Biopsy was performed, and specimens were shown to include squamous cell carcinoma cells. The patient was treated using chemotherapy concurrent with radiotherapy. The chemotherapy consisted of oral S-1 (80 mg/body/day; 5 days/week) and intravenous CDDP (5 mg/body/day; 5 days/week), both administered for 4 weeks. Radiotherapy at 2 Gy/day was administered 25 times (total dose 50 Gy). The metastatic tumor in the lymph node responded well to the treatment and decreased remarkably in size by December 2007. After chemoradiotherapy, the oral administration of S-1 alone (80 mg/body) for 2 weeks followed by a 2-week rest period as one course was continued for 1 year. The lymph node metastasis had disappeared 1 year after chemoradiotherapy, as determined by computed tomography (CT) and positron emission tomography-CT, representing a complete response. Chemotherapy consisting of S-1 and CDDP concurrent with radiotherapy maybe effective for treating metastatic lymph node metastasis of anal canal carcinoma.

Topics: Administration, Oral; Aged; Anal Canal; Antimetabolites, Antineoplastic; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Anus Neoplasms; Carcinoma, Squamous Cell; Cisplatin; Combined Modality Therapy; Drug Combinations; Female; Humans; Inguinal Canal; Injections, Intravenous; Lymphatic Metastasis; Oxonic Acid; Radiotherapy Dosage; Tegafur

A male patient in his seventies presented at our hospital with a chief complaint of an abnormal shadow on a chest scout film. We suspected non-small cell carcinoma of the right upper lobe on computed tomography (CT). The patient underwent partial resection of the right upper lobe by video-assisted thoracoscopic surgery in May 2004, frozen sections of which showed poorly differentiated squamous cell carcinoma, consistent with the tumor size 2.5 x 1.7 cm. We performed right upper lobectomy and lymphadenectomy. Final pTNM was T1N0M0, stage IA. The patient had been followed every three months until a coin lesion appeared in the right lower lobe in April 2007. He chose radiation therapy of 48 Gy in total at another hospital with the result that the lesion disappeared. However, the disease recurred in May 2008. Bilateral multiple lung metastases and mediastinal lymph nodes involvement were confirmed by CT. Two courses of docetaxel 60 mg/m(2) (90 mg/body) and cisplatin 80 mg/m / 2 (120 mg/body) were not effective with adverse reaction grade 3. Less docetaxel and cisplatin resulted in a grade 4 reaction. The regimen was changed to S-1 60 mg per day with three weeks on and two weeks off. After two courses complete remission was confirmed at a chest X-ray examination. He has been free of disease with tegafur/uracil 600 mg per day for 4 months.

Topics: Aged; Antimetabolites, Antineoplastic; Carcinoma, Squamous Cell; Drug Combinations; Humans; Lung Neoplasms; Lymph Node Excision; Male; Neoplasm Recurrence, Local; Oxonic Acid; Pneumonectomy; Remission Induction; Tegafur

A 72-year-old male had suffered from a recurrent pulmonary squamous cell carcinoma. He had a history of systemic chemotherapy including carboplatin+paclitaxel(CBDCA+PTX)and docetaxel(DOC). As third-line chemotherapy, this patient was treated with 100 mg of S-1 daily for 4 weeks followed by 2 weeks of rest. Maximal effect was acquired 3.5 months after start of S-1 and resulted in partial response. Since tumors re-grew, S-1 was stopped and other chemotherapies including gemcitabine+vinorelbine(GEM+VNR)and gefitinib were tried but proved ineffective. The tumors gradually grew and, subsequently, right total atelectasis occurred. Re-administration of S-1 showed tumor regression and atelectasis improved. Now this patient is continuing treatment with S-1 monotherapy.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Carcinoma, Squamous Cell; Drug Combinations; Humans; Lung Neoplasms; Male; Neoplasm Recurrence, Local; Oxonic Acid; Tegafur; Tomography, X-Ray Computed

This study was performed to assess the efficacy and safety profile of combination treatment with S-1 and cisplatin in patients with locally advanced squamous cell carcinoma of the head and neck.. Eligibility criteria comprised: histologically confirmed squamous cell carcinoma of the head and neck; stage three or four disease with no evidence of distant metastasis; evaluable lesions; adequate organ function; age 20-80 years; and a performance status of two or less. Cisplatin was infused over one hour on day one (75 mg/m2) and S-1 was administered orally for 14 consecutive days (days two to 15). The dosages of S-1 were calculated according to the patients' body surface area: 50 mg twice a day (body surface area 1.5 m2). Each course was repeated every three weeks. After two courses, tumour response was evaluated by computed tomography and laryngoscopy. If a response was evident (either complete or partial), the patient received one more course of chemotherapy, before undergoing radical treatment such as radiotherapy or surgery.. All 30 patients were assessable for toxicity, and 29 patients for treatment response. The overall response was 89.7 per cent (complete response: nine; partial response: 17). The two-year estimated overall survival rate was 79.2 per cent. Adverse reactions occurred 128 times during 81 courses in the 30 cases. The most common grade three to four adverse event was neutropenia, which occurred in eight patients. Cases of non-haematological grade three or four toxicity included nausea and vomiting in four patients, stomatitis in two and diarrhoea in one.. S-1 plus cisplatin combination chemotherapy is effective against locally advanced squamous cell carcinoma of the head and neck, with only mild toxicity.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Squamous Cell; Cisplatin; Combined Modality Therapy; Drug Combinations; Female; Head and Neck Neoplasms; Humans; Lymphatic Metastasis; Male; Middle Aged; Neoplasm Staging; Oxonic Acid; Remission Induction; Tegafur; Treatment Outcome

The patient was a 63-year-old man who consulted our hospital with complaints of a cough and breathing difficulties. His chest CT revealed a 25-mm mass in his right S1 hilar area with spiculation, disseminated nodule in right lung, and pericardial effusions. Also, bronchoscope and TBLB revealed squamous cell carcinoma. This patient was diagnosed as lung cancer (cT4N3M1, stage IV), and chemotherapy was initiated. The chemotherapy was given in the order of CBDCA (AUC3) +GEM (1,000 mg/m(2)), DOC (60 mg/m(2)), and VNR (25 mg/m(2)), and the tumor response was PD. S- 1 (120 mg/body/day, continuous administration for 2 weeks followed by 1 week of rest) was chosen as fourth-line treatment, and a breast CT detected tumor size reduction following completion of the first course. However, after completion of three courses, the breast CT found tumor-enlargement again. Then the chemotherapy was changed to amrubicin (35 mg/m(2)), but the treatment was discontinued due to skin rash. We once experienced a size reduction with S-1, so S-1 (100 mg/body/day, day 1-14) plus CPT-11 (60 mg/m(2), day 1, 7, 14) combination chemotherapy was conducted at 4-week intervals. After two courses were completed, tumor size reduction was observed by breast XP and CT. The response rate was 40.0%. Currently, seven courses were completed, and we will continue this treatment due to the tumor response of SD. The S-1 single treatment and S-1+CPT-11 combination chemotherapy showed efficacy for this difficult case of NSCLC with refractoriness to multiple cancer drug chemotherapy. This combination treatment should be investigated further for its therapeutic benefit.

Topics: Antigens, Neoplasm; Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Camptothecin; Carcinoma, Squamous Cell; Drug Combinations; Drug Resistance, Neoplasm; Humans; Irinotecan; Keratin-19; Keratins; Lung Neoplasms; Male; Middle Aged; Oxonic Acid; Tegafur; Tomography, X-Ray Computed

Concurrent chemoradiotherapy (CCRT) can be used in order to increase both the local and systemic control of head and neck carcinoma. This report shows for the first time the assessment of CCRT with S-1 as a treatment modality for squamous cell carcinoma (SCC) of the lower lip. Surgical excision is usually the first choice for the treatment of SCC of the lower lip, followed by reconstruction. Such a treatment choice more or less compromises the cosmetic and/or functional status of the lip. We present our experience of utilizing CCRT with S-1 as a mode of treatment for SCC of the lower lip that yielded significant results while preserving the integrity of the lip.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Squamous Cell; Combined Modality Therapy; Drug Combinations; Female; Humans; Lip Neoplasms; Male; Middle Aged; Oxonic Acid; Tegafur

Early glottic carcinoma has a good prognosis compared to other head and neck carcinomas, but we must aim for larynx preservation in the treatment. Regarding T1N0, larynx preservation rates are favorable even with radiotherapy alone. However for T2N0, the treatment strategies differ in each institution, and larynx preservation rates range from 72% to 85%, and are not high enough. We conducted a study to determine the efficacy of the concurrent chemoradiotherapy with S-1 for T2N0 glottic carcinoma. In this study, 12 patients with T2N0 glottic type laryngeal squamous cell carcinoma enrolled from the year 2004 to 2006, received one reduction dose of S-1 (80 or 100 mg/day) with concomitant irradiation with a total dose of 60-70 Gy (2.0 Gy/fr). The 2-week administration of S-1 followed by one-week rest was repeated during irradiation. In terms of adverse events of Grade 3 and above, Grade 3 mucositis and dermatitis were found in 2 patients each, but there was no cancellation nor interruption of S-1 or irradiation. All patients achieved pathological CR at the time of evaluation after the primary treatment, and no recurrences have been seen yet in any of the primary sites. Concurrent chemoradiotherapy with S-1 showed efficacy in T2N0 glottis carcinoma. Further investigation of this treatment with long-term follow up results is warranted.

Topics: Adult; Aged; Antimetabolites, Antineoplastic; Carcinoma, Squamous Cell; Combined Modality Therapy; Drug Combinations; Glottis; Humans; Laryngeal Neoplasms; Male; Middle Aged; Oxonic Acid; Radiotherapy; Radiotherapy Dosage; Tegafur

It has been reported that S-1 can exert antitumor effects on various human cancers including oral squamous cell carcinoma (OSCC). However, little is known about the detailed mechanisms of the antitumor activity of S-1. In the present study, we determined whether S-1 could suppress the angiogenesis and growth of human OSCC cells in vitro and in vivo. The S-1 component (5-FU plus CDHP) significantly suppressed the growth and migration of OSCC cells and BAEC, which inhibited tubule formation in HUVECs in vitro. Also, S-1 inhibited the nuclear factor-kappaB (NF-kappaB) activity in human OSCC cells in vitro. Moreover, S-1 inhibited the expression of survival signal, phosphorylated Akt (p-Akt), and of two major proangiogenic molecules, vascular endothelial growth factor (VEGF) and fibroblast growth factor-2 (FGF-2), in cells implanted into the subcutaneous tissue of nude mice. The decreased expression of p-Akt, VEGF and FGF-2 correlated with decreased tumorigenicity and decreased vascularization of lesions in vivo. These findings suggest that S-1 can suppress the angiogenesis and growth of OSCC cells by inhibiting the expression of p-Akt, VEGF and FGF-2 involved in the blockade of Akt/NF-kappaB pathway.

Topics: Animals; Antimetabolites, Antineoplastic; Carcinoma, Squamous Cell; Cell Line, Tumor; Drug Combinations; Endothelium, Vascular; Fibroblast Growth Factor 2; Gene Expression Regulation, Neoplastic; Humans; Mice; Mice, Nude; Mouth Neoplasms; Neovascularization, Pathologic; NF-kappa B; Oxonic Acid; Phosphorylation; Proto-Oncogene Proteins c-akt; Tegafur; Vascular Endothelial Growth Factor A

An 80-year-old man was admitted to our hospital for treatment of recurrent esophageal cancer in December, 2004. He was diagnosed as having esophageal cancer of stage IVa (T2N4M0) in October, 2002, and he received chemoradiotherapy (nedaplatin (CDGP)/5-fluorouracil (5-FU) total 6 course+60 Gy). Afterwards, lymph nodes recurred, and two courses of CDGP/vindesine were given. Then, the primary lesion showed a complete response (CR), and lymph nodes a partial response (PR). In December, 2004, paraesophageal lymph nodes were enlarged to the size of 7 cm. On admission, because of renal disturbance and dementia with advanced age, we chose chemotherapy with TS-1 (100 mg/body/day, three weeks of administration, then two weeks of withdrawal). He had adverse effects of hematotoxicity of grade 3, and non-hematotoxicity of grade 1. He received 6 courses of this regimen and eventually showed CR. Serum SCC was decreased from 4.7 ng/mL to 0.9 ng/mL. At present,the lesions have not recurred during the follow-up for 18 months.

Topics: Aged, 80 and over; Antimetabolites, Antineoplastic; Carcinoma, Squamous Cell; Combined Modality Therapy; Drug Administration Schedule; Drug Combinations; Esophageal Neoplasms; Humans; Lymph Nodes; Lymphatic Metastasis; Male; Oxonic Acid; Quality of Life; Remission Induction; Tegafur

A resected case of squamous cell carcinoma associated with ductal carcinoma in the hemilateral breast successfully treated by FU plus cisplatin (CDDP) adjuvant therapy against recurrent metastases is reported with some discussion. A 42-year-old woman was admitted to our hospital because of right breast tumor. By physical examination, mammography, ultrasound examination and aspirated cytology, we diagnosed squamous cell carcinoma of the right breast. Before operation SCC antigen was elevated. Standard mastectomy was performed, and SCC antigen was decreased within normal range. Then, a standard regimen of chemotherapy using docetaxel with anti-hormonal therapy by LH-RH analog and tamoxifen was done as first-line adjuvant therapy. Four months after operation the SCC antigen level was elevated again, and recurrence of cancer (skin and liver metastases) was recognized. Next, we tried 5-FU/UFT plus CDDP for squamous cell carcinoma of other organs such as the esophagus. These anti-tumor drugs proved effective, and no metastasis of the skin was detected thereafter, and liver metastatic lesion was decreased in ten months. The SCC antigen level was within the normal range again. Additionally, when metastases redeveloped, TS-1 plus CDDP controlled growth of tumors in seven months. Based on the present findings,we recommend adjuvant chemotherapy by FU plus CDDP for squamous cell carcinoma of the breast.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Carcinoma, Squamous Cell; Chemotherapy, Adjuvant; Cisplatin; Combined Modality Therapy; Drug Administration Schedule; Drug Combinations; Female; Fluorouracil; Humans; Mastectomy; Neoplasm Invasiveness; Oxonic Acid; Skin Neoplasms; Tegafur; Uracil

The purpose of this study was to investigate the effectiveness and safety of palliative chemotherapy using S-1. We treated 19 advanced oral SCC patients including 8 men and 11 women with S-1. Of the 19 patients studied, two patients were classified as UICC Stage II, two patients as Stage III, 14 patients as Stage IV A, and one patient was classified as StageIV C. The ages varied from 54 to 9 1 years (mean ages; 78.3 years-old). The patients received this chemotherapy (80-120 mg/day) consisting of 2 weeks' administration including 5-days' administration and 2-days' termination (named 'Weekday-on/Weekend-off administration schedule' ) following 1 week rest. After this treatment, 7 CR and 4 PR were achieved, but the toxicities were only anorexia, leukopenia, thrombocytopenia, and uritication of NCI-CTC grade 1. The prognosis of 19 cases was 7 terminal by primary disease, 3 terminal by other disease, 7 lives with tumor bearing, and 2 lives without tumor bearing. We concluded that our novel S-1 administration method was extremely effective for oral SCC, including lymph node metastasis, providing high potential without any severe adverse effects for palliative therapy.

Topics: Aged; Aged, 80 and over; Antimetabolites, Antineoplastic; Carcinoma, Squamous Cell; Combined Modality Therapy; Drug Administration Schedule; Drug Combinations; Female; Humans; Male; Middle Aged; Mouth Neoplasms; Oxonic Acid; Palliative Care; Tegafur

A 68-year-old patient with advanced oral squamous cell carcinoma (T3N2bM0, Stage IVA) was treated by concurrent radiotherapy with S-1.S-1 (120 mg/body/day) was orally administered for 4 weeks followed by a 2-week rest period as one course, and radiation was given (1.8 Gy/day; 5 days/week) for a total of 61.2 Gy. After 61.2 Gy radiation and two courses of S-1, the primary region showed a complete response (CR), and that the tumor cell was not identified as a result of biopsy. In addition, the metastatic lymph nodes in the neck were no longer seen on head and neck computed tomography (CT). Although the patient is still taking UFT, he is well with no signs of recurrence 27 months from the initial treatment.

Topics: Aged; Antimetabolites, Antineoplastic; Carcinoma, Squamous Cell; Combined Modality Therapy; Drug Administration Schedule; Drug Combinations; Humans; Lymph Nodes; Lymphatic Metastasis; Male; Mouth Neoplasms; Oxonic Acid; Radiotherapy Dosage; Remission Induction; Tegafur

The patient is a 65-year-old man, who underwent curative resection for maxillary sinus carcinoma after chemoradiation. Lung metastases were observed two months following resection, and were treated with S-1 at a dose of 120 mg/day. One course of the S-1 administration regimen consisted of 2 weeks and a 1-week interval. The patient achieved long survival for 527 days with no adverse reaction. Therefore, this treatment on an outpatient basis greatly contributed to his quality of life. We consider S-1 as a first-line anti-cancer drug for tumor dormancy therapy.

Topics: Aged; Antimetabolites, Antineoplastic; Carcinoma, Squamous Cell; Combined Modality Therapy; Drug Administration Schedule; Drug Combinations; Humans; Lung Neoplasms; Male; Maxillary Sinus Neoplasms; Oxonic Acid; Survivors; Tegafur

We report a case of postoperative multiple pulmonary metastases of NSCLC successfully treated with S-1. A 72-year-old man underwent rt. lower lobectomy + ND 2 a by VATS. The histopathological examination showed squamous cell carcinoma, pT4 (satellite nodules in same lobe) N0M0. Multiple pulmonary metastases appeared 3 months after operation. We started combination chemotherapy with S-1 and CBDCA. S-1 (100 mg/body) was administered on days 1-21. CBDCA (AUC=5.0) was administered on day 8. Multiple pulmonary metastases almost disappeared after 2 courses of combination chemotherapy. After 6 courses of combination chemotherapy with S-1 and CBDCA, we then converted to S-1 only. Every cycle was repeated every 5 weeks. One year later, there was no sign of disease progression. S-1 is considered to be effective and safely administered in patients with NSCLC.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Carboplatin; Carcinoma, Squamous Cell; Combined Modality Therapy; Drug Administration Schedule; Drug Combinations; Humans; Lung Neoplasms; Lymph Node Excision; Male; Neoplasm Staging; Oxonic Acid; Pneumonectomy; Postoperative Period; Quality of Life; Tegafur; Thoracic Surgery, Video-Assisted

The long-term results of a multi-institutional study were analyzed in 101 cases (27 with stage III and 74 with stage IV) with advanced head and neck squamous cell carcinoma (HNSCC) given S-1 administration for 6 months after definitive treatments. The 3-year disease-free survival rate was 66.3% in cases overall. In terms of the survival rates in two groups with different administration methods, i.e., 2-week administration followed by 1-week rest or 4-week administration followed by 2-week rest, there was no significant difference. The risk factors of relapse were examined by multivariate analysis. The relapse rate increased according to the advancement of N staging and the higher risk of distant metastasis in cases with laryngeal (especially, supraglottic type) or hypopharyngeal carcinomas. Now, the efficacy of S-1 administration as adjuvant chemotherapy after definitive treatments for advanced HNSCC is under investigation,and the adequate administration period of S-1 should be evaluated in a controlled randomized study in future.

Topics: Antimetabolites, Antineoplastic; Carcinoma, Squamous Cell; Disease-Free Survival; Drug Administration Schedule; Drug Combinations; Head and Neck Neoplasms; Humans; Neoplasm Recurrence, Local; Oxonic Acid; Prognosis; Proportional Hazards Models; Risk Factors; Survival Rate; Tegafur

A 76-year-old patient with oral squamous cell carcinoma was treated by chemotherapy with S-1. S-1 (100 mg/body/day) was orally administered for 4 weeks followed by a 2-week rest period as one course. The primary lesion markedly decreased at 7 days after the beginning of S-1 treatment, and disappeared after one course of S-1. After two courses, the primary lesion was assessed to show a complete response (CR),and no tumor cells were identified as a result of biopsy. In addition, the value of tumor marker SCC decreased from 2.13 ng/mL before treatment to 0.68 ng/mL after two courses of S-1. Although the patient is still taking UFT, she is well with no signs of recurrence 50 months from the initial treatment.

Topics: Administration, Oral; Aged; Antigens, Neoplasm; Antimetabolites, Antineoplastic; Biomarkers, Tumor; Carcinoma, Squamous Cell; Drug Combinations; Female; Humans; Mouth Neoplasms; Oxonic Acid; Serpins; Tegafur; Treatment Outcome

In the present study, we examined the appropriate schedule of S-1 medication in the combination with radiation by investigating the safety, the clinical efficacy, and antitumor effects on tumors in nude mice. In the patients with oral squamous cell carcinoma (OSCC), S-1 was given orally according to a 4-week application followed by 2-week rest regimen (4-week regimen), or a 2-week application followed by a 1-week rest regimen (2-week regimen). Radiation was given (2 Gy/day; 5 days/week) for a total of 60 Gy. In nude mouse models, human oral cancer cell lines were used as subcutaneous xenografts in nude mice. The mice were treated by S-1 (10 mg/kg) and radiation (1 Gy) with a 4-week regimen or a 2-week regimen. Apoptotic cells were detected by TUNEL method. In the patients with OSCC, the response rate with the 4-week regimen was 100% and the response rate with the 2-week regimen was 92.3%. However, a high frequency of adverse effect was found in the 4-week regimen when compared to the 2-week regimen. Grade 3 toxicity of leukopenia, neutropenia and stomatitis were seen in 3 cases, grade 3 toxicity of anorexia and nausea were seen in 2 cases, and grade 3 toxicity of decrease of hemoglobin level, heartburn/dyspepsia and increase of bilirubin level were seen in a case of the 4-week regimen. On the other hand, grade 3 toxicity of stomatitis, anorexia, nausea, heartburn/dyspepsia and increase of bilirubin level were seen in a case of the 2-week regimen. In nude mouse models, the 2-week regimen was more effective than the 4-week regimen. In addition, significant increase in the percentage of apoptotic cells was observed in the tumors treated with the 4-week regimen when compared with the tumors treated with the 2-week regimen. No loss of body weight was observed in mice treated with the 2-week regimen during the experimental period. These results suggested that the 2-week regimen might reduce adverse effects, and enhance therapeutic effects compared to the 4-week regimen. Briefly, this 2-week regimen may be a useful concurrent chemo-radiotherapy improving the quality of life (QOL) of patients with OSCC.

Topics: Aged; Animals; Antimetabolites, Antineoplastic; Apoptosis; Carcinoma, Squamous Cell; Combined Modality Therapy; Drug Combinations; Female; Humans; In Situ Nick-End Labeling; Male; Maximum Tolerated Dose; Mice; Mice, Nude; Middle Aged; Mouth Neoplasms; Oxonic Acid; Radiotherapy Dosage; Tegafur; Tumor Cells, Cultured

Severe advanced head and neck carcinoma which can not be removed via surgical procedure combined with a large lymph node metastasis has a poor prognosis. We administered concurrent chemoradiotherapy with S-1 for a lower gingival carcinoma. As a direct result, we discovered that the treatment greatly reduced the size of tumor, and we consider that this treatment prolonged the patient.s life. The treatment results suggest that the so-called dormancy state of the tumor was continued. In this case study, radiotherapy with S-1 showed a highly effective response from the viewpoint of QOL improvement.

Topics: Antimetabolites, Antineoplastic; Carcinoma, Squamous Cell; Combined Modality Therapy; Drug Administration Schedule; Drug Combinations; Gingival Neoplasms; Humans; Male; Middle Aged; Oxonic Acid; Quality of Life; Radiotherapy Dosage; Tegafur

The purpose of this study was to evaluate the effectiveness and adverse events of combination chemotherapy with S-1 and docetaxel (DOC) as neo-adjuvant chemotherapy (NAC) for patients with oral squamous cell carcinomas. Fifteen patients were enrolled in this study (11 men and 4 women, with a mean age of 65.9 years). All patients given S-1 80 mg/body per day for 14 days and following were administered a dose of DOC 60 mg/m(2) by drip infusion for 120 minutes. The locoregional response was evaluated 3 weeks after the administration. As a result, the locoregional response rate was 60.0%, including 46.7% complete response. According to Oboshi and Shimosato's classification, histological evaluation of surgical specimens revealed that 3 cases were Grade I , 3 cases Grade IIa, 4 cases Grade IIb, 1 case Grade III, 3 cases Grade IVb, and 1 case Grade IVc. The severe side effect was neutropenia. The present study suggests that combination chemotherapy with S-1 and DOC is an effective and safe regimen in NAC for oral squamous cell carcinomas.

Topics: Aged; Antimetabolites, Antineoplastic; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Squamous Cell; Docetaxel; Drug Combinations; Female; Humans; Infusions, Intravenous; Male; Middle Aged; Mouth Neoplasms; Neoadjuvant Therapy; Oxonic Acid; Taxoids; Tegafur

We experienced a 49-year-old man with cancer of the lower lip (squamous cell carcinoma, T1N2cM0). We planned surgical treatment including bilateral neck dissection and started a new TS-1 administration method as a neo-adjuvant chemotherapy. One course of this chemotherapy consisted of 3 weeks'administration including 5-day administration and 2-day termination following 1 week rest. TS-1 was given at 120 mg/day. After the first course of chemotherapy, the primary tumor disappeared, and the neck lymph node metastases were markedly reduced. There was no obvious side effect except mild stomatitis. Since we assumed that the lymph node palpated in left neck was a residual tumor, we performed left neck dissection. Histopathological examination revealed that there was no cancer cell but hyalinization in the removed specimen of lymph node, suggesting that the effect of the chemotherapy was a pathologically complete response. We concluded that our novel TS-1 administration method was extremely effective for head and neck squamous cell carcinomas with high potential and without any severe side effects.

Topics: Antimetabolites, Antineoplastic; Carcinoma, Squamous Cell; Chemotherapy, Adjuvant; Drug Administration Schedule; Drug Combinations; Head and Neck Neoplasms; Humans; Lip; Lymph Nodes; Lymphatic Metastasis; Male; Middle Aged; Neck Dissection; Oxonic Acid; Pyridines; Remission Induction; Tegafur

The patient was a 66-year-old man who had undergone right upper lobectomy and ND 2a systematic lymph node dissection for lung cancer (M/D adenocarcinoma, p-stage IB) in March of 1999 . On November 2003, postoperative routine chest computed tomography(CT) demonstrated a mass in left S6, and pathological diagnosis revealed P/D squamous cell carcinoma (cT1N2M0, stage IIIA) by CT-guided needle biopsy and mediastinoscopy. At first, we tried two courses of a combination chemotherapy consisting of carboplatin (CBDCA) and paclitaxel every 3 weeks. After 2 courses, the regimen was stopped because of grade 3 arthritis. Then, two courses of CBDCA and gemcitabine were performed. The evaluation of the response was SD by the guidelines of Response Evaluation Criteria in Solid Tumor Groups. Next, gefitinib was orally administered for 6 months but the tumor and mediastinal lymph nodes were growing. In January 2005, oral administration of TS-1 (60 mg/1, 2 courses, 75 mg/3-6 courses) was begun twice a day for 21 consecutive days while cisplatin (60 mg/m(2)) was administered intravenously on day 8. The response was PR (the tumor decreased by 46%), no serious adverse effect was observed, and the patient maintained good quality of life throughout the chemotherapy. This case suggests that TS-1+CDDP chemotherapy may be an effective treatment in patients with advanced lung cancer even after many protocols of chemotherapy.

Topics: Adenocarcinoma; Administration, Oral; Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Squamous Cell; Cisplatin; Combined Modality Therapy; Drug Administration Schedule; Drug Combinations; Humans; Lung Neoplasms; Lymph Node Excision; Lymph Nodes; Lymphatic Metastasis; Male; Neoplasm Staging; Neoplasms, Second Primary; Oxonic Acid; Pneumonectomy; Pyridines; Tegafur

The purpose of this research was to evaluate the predictive value of expression of thymidylate synthase (TS), dihydropyrimidine dehydrogenase (DPD), thymidine phosphorylase (TP), or orotate phosphoribosyltransferase (OPRT) genes for response to S-1. Twenty-five patients with oral squamous cell carcinoma (OSCC) received S-1 80 mg/m2/day. Pretreatment tumor biopsies were analyzed for TS, DPD, TP or OPRT mRNA expression by real-time reverse transcription-PCR. TS protein expression was evaluated by immunohistochemistry using a polyclonal TS antibody. Twenty-five patients were evaluable for response and gene expression. Six of the 25 (24%) achieved complete remission and 4 of the 25 (16%) had a partial response. Median TS/beta-actin was 2.51 (range 0.98-7.07). Median TS/beta-actin was 1.26 in responding patients and 3.43 in non-responders (P=0.0001). Ten of 11 patients with TS/beta-actin <1.80 and 0 of 15 with higher values responded (P<0.0001). Overall survival was 29.7 months in patients with TS/beta-actin <1.80 and 41.7 months in patients with higher values (P=0.0013). No correlations were seen between expression of DPD, TP or OPRT mRNA and response or survival. Weak TS staining was seen in 6 of 25 tumors evaluable for immunohistochemistry, including 5 responders. All 4 of the patients with both weak staining and TS/beta-actin <1.80 responded. High TS mRNA expression predicts non-response to S-1. On the other hand, high levels of DPD or TP mRNA and low levels of OPRT mRNA are not associated with S-1 resistance. TS mRNA expression is considered to be a useful prognostic factor in OSCC patients with S-1 single-agent therapy.

Topics: Adult; Aged; Aged, 80 and over; Carcinoma, Squamous Cell; Dihydrouracil Dehydrogenase (NADP); Drug Combinations; Female; Humans; Male; Middle Aged; Mouth Neoplasms; Multienzyme Complexes; Orotate Phosphoribosyltransferase; Orotidine-5'-Phosphate Decarboxylase; Oxonic Acid; RNA, Messenger; Tegafur; Thymidine Phosphorylase; Thymidylate Synthase

A 70-year-old man suffering from advanced esophageal cancer (Stage II) underwent subtotal esophagectomy in December 2000. He then had postoperative chemotherapy, called low-dose FP, and was followed in an ambulatory setting. In December 2003, he was diagnosed as a recurrence of esophageal cancer with multiple liver metastases and upper mediastinum lymph node, so he was treated by combined chemotherapy consisting of TS-1 and docetaxel as a second-line chemotherapy. After 3 courses of this therapy, CT scan showed that the size of liver and lymph node metastases was reduced and the effect of this therapy was PR. PR continued for about 6 months. This chemotherapy made it possible to treat liver and lymph node metastasis in an ambulatory setting. It is conceivable that this combination chemotherapy might be a promising regimen for a short period.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Squamous Cell; Chemotherapy, Adjuvant; Docetaxel; Drug Administration Schedule; Drug Combinations; Esophageal Neoplasms; Esophagectomy; Humans; Lymph Nodes; Lymphatic Metastasis; Male; Mediastinum; Oxonic Acid; Pyridines; Taxoids; Tegafur

We report a patient with advanced esophageal cancer who achieved a complete response to combination chemotherapy of TS-1, docetaxel and CDDP. A 74-year-old man was admitted to our hospital for advanced esophageal cancer with a complaint of dysphagia. He received chemotherapy, consisting of TS-1 100 mg/body, docetaxel 35 mg/m(2), and CDDP 10 mg/m(2), every 3 weeks. TS-1 was administered for 14 days followed by 7 days rest; docetaxel and CDDP were administered by intravenous infusion at day one and day 8 after beginning TS-1. After three cycles of chemotherapy, his dysphagia disappeared, and endoscopic examination of the primary esophageal tumor showed a complete response. Endoscopic examination with biopsy confirmed the disappearance of the esophageal cancer. No severe side effects were observed during this chemotherapy. Combination chemotherapy of TS-1, docetaxel, and CDDP can thus be effective for advanced esophageal cancer.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Squamous Cell; Cisplatin; Docetaxel; Drug Administration Schedule; Drug Combinations; Esophageal Neoplasms; Humans; Male; Oxonic Acid; Quality of Life; Remission Induction; Taxoids; Tegafur

A 76-year-old male patient was diagnosed with advanced double cancer of the lung and stomach. He had also been suffering from interstitial pneumonitis for several years. He was treated with combination of cisplatin and TS-1. TS-1 (120 mg/body/day) was administered for 21 days from day 1, and cisplatin (60 mg/m(2)) was given on day 8 followed by a 14-days interval. After two courses of chemotherapy,the dose of cisplatin was reduced to 48 mg/m(2) because of grade 1 serum creatinine elevation. The lesions of the lung and stomach were improved significantly without exacerbation of the interstitial pneumonitis.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Squamous Cell; Cisplatin; Drug Administration Schedule; Drug Combinations; Humans; Lung Diseases, Interstitial; Lung Neoplasms; Male; Neoplasms, Multiple Primary; Oxonic Acid; Remission Induction; Stomach Neoplasms; Tegafur

We need more effective treatments for refractory non-small cell lung cancer.. A 61-year-old man had a recurrence in the left ninth rib invading the chestwall 4 years after resection of squamous cell lung cancer. The metastatic lesion grew larger even after 3 different regimens of systemic chemotherapy and local irradiation. Then he started to receive 120 mg of TS-1 daily for 28 days followed by 14 days of rest (1 course). A partial response was achieved after 2 courses of the treatment and continued for 6 weeks. Doses of oxycodone hydrochloride could be reduced to one-sixth of the initial dose according to tumor regression.. This is the first report to show the effectiveness of TS-1 for a refractory recurrence of lung cancer to the bone.

Topics: Administration, Oral; Antimetabolites, Antineoplastic; Bone Neoplasms; Carcinoma, Squamous Cell; Combined Modality Therapy; Drug Administration Schedule; Drug Combinations; Humans; Lung Neoplasms; Male; Middle Aged; Oxonic Acid; Pneumonectomy; Postoperative Period; Quality of Life; Ribs; Tegafur

A 76-year-old man had complained of hoarseness, productive cough and left chest pain in June 2005. Chest radiograph and computed tomography showed a tumor 7.5x5 cm in size which contacted the aortic arch, some nodules in left upper lobe and right lower lobe of lung and left pleural effusion. The broncho-fiberscopic biopsy histologically proved the tumor to be moderately differentiated squamous cell carcinoma in the left upper lobe of lung. The patient was diagnosed as a non-resectable lung cancer with clinical stage IV (c-T4N2M1). In July 2005, he was treated with oral administration of TS-1 (120 mg/day) and Jyu-zen daiho toh (7.5 g/day). After one week, he complained of grade 2 leukopenia and grade 1 skin rash. Then TS-1 was reduced to 100 mg/day. After this modulation of the treatment, he could take TS-1 and Jyu-zen daiho toh days 1-14, every 3 weeks. The patient then received 17 courses until June 2006. The left pleural effusion and left chest pain disappeared only 2 weeks after taking TS-1. In June of 2006, central necrosis of the left lung tumor was confirmed by positron emission computed tomography. No serious adverse effect was observed, and the patient maintained good quality of life. This case suggests that TS-1 with Jyu-zen daiho toh may be an effective treatment for elderly advanced lung cancer.

Topics: Aged; Antimetabolites, Antineoplastic; Carcinoma, Squamous Cell; Drug Administration Schedule; Drug Combinations; Drugs, Chinese Herbal; Humans; Lung Neoplasms; Male; Neoplasm Staging; Oxonic Acid; Quality of Life; Tegafur

A 78-year-old man was admitted to our hospital complaining of dysphagea on April 8, 2005. Upper gastrointestinal endoscopic examination showed type 2 esophageal cancer in the lower thoracic area and type 3 gastric cancer in the upper body. Computed tomography showed No. 3 lymph node swelling, but no distant metastasis. Surgery was contraindicated because of many complications, so the patient was given combined chemotherapy with TS-1 and low-dose cisplatin. Chemotherapy was started on April 18. After 2 courses of chemotherapy the esophageal lesion showed a complete response, and after 5 courses the gastric lesion evidenced a complete response.

Topics: Adenocarcinoma; Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Squamous Cell; Cisplatin; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Combinations; Esophageal Neoplasms; Humans; Male; Neoplasms, Multiple Primary; Oxonic Acid; Remission Induction; Stomach Neoplasms; Tegafur

We investigated the histological response and toxicities of combination chemotherapy with TS-1 and low-dose CDDP, and evaluated the usefulness of this regimen as a preoperative chemotherapy. Fourteen patients were enrolled in this study (two men and 12 women, with a mean age of 54.5 years). Patients were administered TS-1 80 mg/m2/day (days 1-14) and CDDP 5 mg/m2/day (days 1-5, 8-12) and followed by radical surgery or biopsy within 2 weeks. Ten patients completed 1 cycle of chemotherapy, two received 0.5 cycle and two others 1.5 cycle. The histological antitumor effects were evaluated with Ohboshi & Shimosato's classification using surgical or biopsy specimens of primary tumors. The response rate was 64.3% in clinical evaluation and 50.0% in histological evaluation. The number of patients who showed CR were 7/14 (50.0%) and 5/14 (35.7%) by histological and clinical evaluation, respectively. Two patients showed grade 3 neutropenia. Almost all patients revealed no or mild toxicities. TS-1 with low-dose CDDP represents a highly effective antitumor activity and mild toxicities. Especially, the CR rate was very high. These data suggested that this regimen was useful to avoid surgery or to realize minimal surgery for oral squamous cell carcinoma patients.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Squamous Cell; Cisplatin; Drug Administration Schedule; Drug Combinations; Female; Humans; Male; Middle Aged; Mouth Neoplasms; Neutropenia; Oxonic Acid; Pyridines; Tegafur

The combination with cisplatin (CDDP) and 5-FU is considered the chemotherapy of choice for squamous cell carcinoma of the head and neck (HNSCC). TS-1, a modulation of tegafur developed in Japan, is an orally administered active agent for HNSCC. Some clinical phase I/II studies on the combination of CDDP and TS-1 have been reported. The combination showed a good response rate, 67.6% for both advanced and recurrent HNSCC, in our clinical phase II study. Regimens of TS-1 combined with carboplatin or nedaplatin are also reported.TS-1 containing regimens appear to be effective for HNSCC, and multi-institutional phase II studies with large sample size are needed in future. The combination TS-1 and radiotherapy, its dose and schedule,are being studied in phase I trials for advanced HNSCC. Patient compliance is better than with 5-FU injection because TS-1 is orally administered. The adverse effect, especially in terms of bone marrow toxicity, is equal or better than with 5-FU injection. The TS-1 combination with radiotherapy is a useful regimen for outpatients. The efficacy and adverse effects should be studied in carefully designed phase I/II trials. TS-1 will be one of the key drugs for HNSCC in future.

Topics: Antineoplastic Combined Chemotherapy Protocols; Carboplatin; Carcinoma, Squamous Cell; Cisplatin; Clinical Trials, Phase I as Topic; Clinical Trials, Phase II as Topic; Combined Modality Therapy; Docetaxel; Drug Administration Schedule; Drug Combinations; Fluorouracil; Head and Neck Neoplasms; Humans; Organoplatinum Compounds; Oxonic Acid; Pyridines; Taxoids; Tegafur

We report a case of right maxillary carcinoma with metastases to the cervical lymph nodes (T4N2cM0, Stage IV). A 76-year-old woman was administered preoperative chemoradiotherapy, followed by curative surgery. TS-1 (80 mg/day), CDDP (5 mg/m2/day) and concurrent radiation (total 40 Gy) induced a complete response. Grade 2 neutropenia, thrombocytopenia and stomatitis were observed. In the primary tumor and cervical metastatic lymph nodes, no viable carcinoma cells were detected and cancer nests were replaced with marked fibrous tissue.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Squamous Cell; Chemotherapy, Adjuvant; Cisplatin; Drug Administration Schedule; Drug Combinations; Female; Humans; Lymph Nodes; Lymphatic Metastasis; Maxillary Neoplasms; Neck; Neutropenia; Oxonic Acid; Pyridines; Radiotherapy, Adjuvant; Stomatitis; Tegafur; Thrombocytopenia

A 70-year-old patient with advanced esophageal cancer with invasion to the aorta was treated by combined chemotherapy of TS-1 and CDDP with radiotherapy. TS-1 (80 mg/m2) was administered for 14 days followed by 14 days rest, CDDP (70 mg/m2) was administered by 24 h continuous intravenous infusion at day 8 after the start of TS-1. Radiotherapy (5 days/week) at 2 Gy/day was concurrently started from the beginning of chemotherapy for 3 weeks. After the end of the first course, leukocytopenia of grade 2 and thrombocytopenia of grade 2 were observed. The second course of chemoradiotherapy was suspended for 1 week. After recovery from the toxicity, the second course was started. After the 2 courses of chemoradiotherapy, endoscopic examination with biopsy revealed the disappearance of the esophageal cancer. Combined chemotherapy of TS-1 and CDDP was administered 2 times after chemoradiotherapy. After this therapy, endoscopy and a CT showed a complete clinical response. No severe adverse effects were observed during this therapy. Combined chemotherapy of TS-1 and CDDP with radiotherapy can be effective for advanced esophageal cancer.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Squamous Cell; Cisplatin; Combined Modality Therapy; Drug Administration Schedule; Drug Combinations; Esophageal Neoplasms; Humans; Male; Oxonic Acid; Pyridines; Quality of Life; Remission Induction; Tegafur

We report a case of synchronous esophageal and gastric cancer in a patient with severe liver dysfunction who was treated successfully using TS-1/CDDP therapy combined with irradiation therapy. A 56-year-old man with a chief complaint of dysphagia was diagnosed with thoracic esophageal cancer by endoscopy, and was referred to our hospital. Synchronous esophageal and gastric cancer were diagnosed by endoscopy and barium swallow. The preoperative diagnosis was T3N0M0, Stage II esophageal cancer and T1N0M0, Stage I A gastric cancer, both of which were diagnosed to be resectable. However, surgery was contraindicated because of severe liver dysfunction, due to an ICG15 of 35%. TS-1 (80 mg/day) and CDDP (3 mg/day) therapy was combined with irradiation, 60 Gy given in a T-pattern to the mediastinum. The patient did not suffer any side-effects, and endoscopy performed 44 days after the start of treatment showed that the esophageal lesion was now only a scar. Only a slight elevation of the esophagus was seen by endoscopy 219 days after the start of the therapy. The patient is currently undergoing only TS-1 treatment as an outpatient and is under observation. No metastasis to the liver or any other organ has been detected. TS-1 and CDDP therapy combined with radiotherapy appears to be effective in treating thoracic esophageal cancer.

Topics: Adenocarcinoma; Administration, Oral; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Squamous Cell; Cisplatin; Combined Modality Therapy; Drug Administration Schedule; Drug Combinations; Esophageal Neoplasms; Humans; Male; Middle Aged; Neoplasms, Multiple Primary; Oxonic Acid; Pyridines; Radiotherapy Dosage; Stomach Neoplasms; Tegafur

We report a case of hypopharyngeal carcinoma with recurrent neck metastasis. Preoperative chemoradiation and pharyngo-laryngo-esophagectomy with bilateral neck dissection was done as first-line therapy. Six months later, the carcinoma metastasized to the right paratracheal lymph node. Because of resistance to chemoradiation (CBDCA) as second-line therapy, we administered TS-1 for the treatment after 60 Gy radiation. The chemotherapy with TS-1 resulted in complete response by diagnostic imaging (CT). There was no sign of recurrence for 1 year after 5 courses of treatment. TS-1, which allows oral chemotherapy on an outpatient basis, would be a useful drug for treatment with radiotherapy in patients with advanced and/or recurrent head and neck cancer.

Topics: Antimetabolites, Antineoplastic; Carcinoma, Squamous Cell; Drug Administration Schedule; Drug Combinations; Humans; Hypopharyngeal Neoplasms; Lymph Nodes; Lymphatic Metastasis; Male; Middle Aged; Neck; Oxonic Acid; Pyridines; Tegafur

We report a case of advanced squamous cell carcinoma in the left buccal mucosa, upper gingiva, and maxillary sinus (T4N0M0) showing a complete response to oral chemotherapy with TS-1. The patient was an 89-year-old female with severe dementia. We carried out chemotherapy with TS-1 50 mg/day, without surgical treatment. The tumor disappeared clinically at 4 months after 3 courses of the TS-1 administration. Adverse drug reactions, including vomiting, leukopenia and thrombopenia, forced a stop of the administration of TS-1. Although she finally died of in senescence 2 months from the cease of administration, there was no recurrence of the cancer at the time.

Topics: Aged; Aged, 80 and over; Antimetabolites, Antineoplastic; Carcinoma, Squamous Cell; Drug Administration Schedule; Drug Combinations; Female; Gingival Neoplasms; Humans; Leukopenia; Maxillary Sinus Neoplasms; Mouth Mucosa; Mouth Neoplasms; Neoplasm Invasiveness; Oxonic Acid; Pyridines; Remission Induction; Tegafur; Thrombocytopenia; Vomiting, Anticipatory

A 51-year-old male patient with esophageal cancer and cervical, thoracic and celiac artery lymph node metastases was treated by combination chemotherapy of TS-1 and cisplatin. TS-1 (80 mg/m2/day) was administered for 14 days followed by 14 days rest as 1 course. Cisplatin (70 mg/m2/day) was administered in 24-hour continuous intravenous infusion at day 8 after the start of TS-1. Before treatment, the tumor marker, CEA showed 27,060 ng/ml. After 5 courses of chemotherapy, endoscopy revealed that the primary tumor had disappeared and no cancer cells were detected by endoscopic biopsy. Chest and abdominal CT scan also showed almost total disappearance of the lymph nodes metastases. CEA decreased to 710 ng/ml. No high-grade toxicities (WHO grade 3 or 4) were seen during the chemotherapy. He is now very well. This TS-1/cisplatin chemotherapy regimen might be a useful treatment for metastatic esophageal cancer.

Topics: Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Squamous Cell; Cisplatin; Drug Administration Schedule; Drug Combinations; Esophageal Neoplasms; Humans; Lymph Nodes; Lymphatic Metastasis; Male; Mediastinum; Middle Aged; Neck; Oxonic Acid; Pyridines; Stomach Neoplasms; Tegafur

We evaluated the orally administered S-1, in combination with ionizing radiation both in vivo and in vitro against human oral cancer cell lines. Human oral cancer cell lines were used as subcutaneous xenografts in nude mice. S-1 (10 mg/kg) was administered orally 1 h before radiation treatments (1.5 Gy), or 1 h after radiation for five consecutive days. Apoptotic cells were detected by TUNEL method. For in vitro analysis, attached cells were treated with S-1 (50 microg/ml) for 1 h and then irradiated (3, 6, 9, 12, 15 Gy), or they were treated with S-1 for 1 h after radiation. Cell survival was determined by clonogenic assay. The combination of S-1 and radiation was more effective than either agent alone. In addition, S-1 administration before radiation was more effective than S-1 administration after radiation. Moreover, the combination of S-1 and radiation could induce apoptosis significantly than either agent alone (P < 0.01). In vitro clonogenic survival experiments demonstrated the dose enhancement ratio of 1.22 (radiation + S-1), 1.45 (S-1 + radiation) in B88 cells, and 1.16 (radiation + S-1), 1.28 (S-1 + radiation) in HSG cells. These data demonstrate that the combination of S-1 and fractionated radiotherapy is more effective against human oral cancer xenografts than either agent alone, and that S-1 administration before radiation is more effective than after radiation, suggesting a potential clinical applicability of combination treatment of S-1 and radiation in oral cancer therapies.

Topics: Animals; Antimetabolites, Antineoplastic; Apoptosis; Carcinoma, Squamous Cell; Cell Survival; Combined Modality Therapy; Drug Combinations; Humans; In Situ Nick-End Labeling; Male; Mice; Mice, Inbred BALB C; Mice, Nude; Mouth Neoplasms; Neoplasm Transplantation; Oxonic Acid; Pyridines; Tegafur; Transplantation, Heterologous; Tumor Cells, Cultured; Tumor Stem Cell Assay

A 52-year-old man was hospitalized for evaluation of dysphagia. Esophagography depicted an irregular narrowing extending 7 cm from the cervical esophagus to the upper thoracic esophagus. Esophagoscopy with biopsy showed cervical esophageal cancer narrowing the lumen. Surgery was contraindicated because of a previous cardiac infarction. The patient selected concurrent chemoradiotherapy with TS-1 and cisplatin. The first course included 30 Gy of radiotherapy given over 3 weeks, together with daily oral administration of TS-1 (120 mg/day) for 2 weeks, and a 24-h infusion of cisplatin (70 mg/m2) on day 8. After a second course of chemoradiotherapy, 4 courses of chemotherapy with TS-1 and cisplatin were administered at 4-week intervals. After additional chemotherapy, esophagoscopy and cervical CT showed that the primary lesion had disappeared. Two years after initial hospitalization, no recurrence has been detected.

Topics: Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Squamous Cell; Cisplatin; Combined Modality Therapy; Drug Administration Schedule; Drug Combinations; Esophageal Neoplasms; Humans; Male; Middle Aged; Oxonic Acid; Pyridines; Radiotherapy Dosage; Remission Induction; Tegafur

The syndrome of inappropriate antidiuretic hormone secretion (SIADH) is characterized by hyponatremia and the plasma hypoosmolality induced by water retention attributable to persistent antidiuretic hormone (ADH) release. It has been reported that SIADH may occur due to various factors in patients with malignant tumor. We report a case of hypopharyngeal cancer complicated by SIADH following chemotherapy. A 72-year-old woman with hypopharyngeal cancer was treated by oral administration of S-1 and intravenous administration of low-dose cisplatin following radiation therapy. General fatigue and coma occurred during the third course of this chemotherapy, using S-1 and low-dose cisplatin. We believed that she had SIADH because of the results of examinations including hyponatremia, serum hypoosmolality and increasing serum ADH level. We treated her by fluid restriction and intravenous administration of hypertonic saline and furosemide, and she recovered. Unfortunately, her hypopharyngeal cancer gradually progressed and she died of acute pneumonia three months later.

Topics: Aged; Antimetabolites, Antineoplastic; Antineoplastic Agents; Carcinoma, Squamous Cell; Cisplatin; Drug Combinations; Fatal Outcome; Female; Humans; Hyponatremia; Hypopharyngeal Neoplasms; Inappropriate ADH Syndrome; Osmolar Concentration; Oxonic Acid; Pyridines; Radiotherapy, Adjuvant; Tegafur; Vasopressins

A 66-year-old patient, who had advanced esophageal cancer with lymph node metastasis, was treated by neoadjuvant chemo-radiotherapy, followed by curative surgery. Chemotherapy of TS-1 (80 mg/m2) was administered orally for 21 days, and weekly intravenous administration of CDDP (20 mg/m2) was done 3 times. Radiotherapy at 2 Gy/day was combined 15 times (total 30 Gy). The tumor responded well to the treatment, and the size was remarkably reduced. Chemoradiotherapy using TS-1 and weekly CDDP revealed their efficacy for esophageal cancer.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Squamous Cell; Cisplatin; Drug Administration Schedule; Drug Combinations; Esophageal Neoplasms; Humans; Male; Neoadjuvant Therapy; Oxonic Acid; Preoperative Care; Pyridines; Tegafur

We report a recent case of squamous cell carcinoma originating in the right tonsil, with metastasis to the right superior cervical lymph nodes (T3N2bM0: stage IVA). Chemo-radiotherapy was administered as first-line therapy; and adjuvant chemotherapy with TS-1 was applied during the subsequent 4-week period for the treatment of the residual tumor in the neck. In this patient (female, 61 years old), the primary tonsillar tumor showed a complete response to the first-line therapy, however, the metastatic lesions in the cervical lymph nodes persisted, although the nodes also decreased markedly in size. Subsequent chemotherapy with TS-1 (80 mg/day) given for a 4-week period resulted in complete disappearance of the residual malignancy (CR), as determined by palpation and diagnostic imaging. No serious adverse events occurred during the therapy. Surgical treatment in patients with advanced head and neck cancer often results in a diminished quality of life. Although further accumulation of cases is necessary, TS-1, which allows oral chemotherapy on an outpatient basis, would seem to be a useful drug for adjuvant chemotherapy following radical irradiation in patients with advanced head and neck cancer.

Topics: Antimetabolites, Antineoplastic; Carcinoma, Squamous Cell; Chemotherapy, Adjuvant; Combined Modality Therapy; Drug Combinations; Female; Humans; Lymphatic Metastasis; Middle Aged; Oropharyngeal Neoplasms; Oxonic Acid; Pyridines; Tegafur

A 64-year-old male with primary squamous cell carcinoma of the tongue (T3N0M0) was treated with the novel fluoropyrimidine oral anticancer drug TS-1 and selective intra-arterial infusion of CDDP. His past history revealed pulmonary emphysema as a complication. Since his pulmonary function was reduced and it would have been difficult to perform surgery under general anesthesia, we started administration of TS-1 (100 mg/day) first and added selective arterial infusion of CDDP (5 mg/day) after one week of TS-1. On day 8 of TS-1 administration (day 2 of arterial infusion), the tumor had shrunk considerably, and on day 15 of TS-1 administration (day 9 of arterial infusion) the tumor had almost completely disappeared. Nausea and vomiting developed as adverse effects on day 20 of TS-1 administration (day 14 of arterial infusion), and administration of the anticancer drugs was stopped. Nutrition management and an antiemetic agent were started by intravenous drip infusion, and the adverse effects improved one week after administration was stopped. By the 5th week after the start of treatment, the tumor had disappeared macroscopically, and a CR had been achieved. Interstitial radiotherapy was performed as supplemental therapy, and as of this writing, September 3, 2002, 16 months after the start of treatment, the patient is being followed on an outpatient basis. His course has been favorable and recurrence-free. Although there were some slight adverse reactions, they were relatively mild, and since sufficient efficacy was observed, oral TS-1 plus selective intra-arterial CDDP therapy was concluded to be an effective method of treatment for patients with a past medical history making their general condition unfavorable.

Topics: Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Squamous Cell; Cisplatin; Drug Administration Schedule; Drug Combinations; Humans; Infusions, Intra-Arterial; Male; Middle Aged; Nausea; Oxonic Acid; Pyridines; Remission Induction; Tegafur; Tongue Neoplasms; Vomiting, Anticipatory

A 75-year-old female with squamous cell carcinoma in the left margin of the tongue (T2N0M0) was referred to our hospital. She was treated with oral administration TS-1 80 mg/day as preoperative chemotherapy. After commencement of TS-1 administration, the tumor size was reduced at 1 week and had disappeared clinically at 4 weeks. Oral administration of TS-1 was done in 2 courses at the same dose. After two courses, histological examination reveled a complete disappearance of the cancer cells. No adverse effects were seen during the treatment period. She remains under oral administration of UFT for maintenance chemotherapy and there is no evidence of recurrence of the tumor.

Topics: Administration, Oral; Aged; Antimetabolites, Antineoplastic; Antineoplastic Agents; Carcinoma, Squamous Cell; Drug Administration Schedule; Drug Combinations; Female; Humans; Oxonic Acid; Pyridines; Remission Induction; Tegafur; Tongue Neoplasms; Uracil

We report here a patient with advanced oral cancer in which concurrent chemoradiotherapy with TS-1 was performed. The patient was an 82-year-old male who had a 41 x 22 mm tumor mass around the left lower gingiva, whose X-ray showed a bone resorption image reaching the mandibular canal. We carried out concurrent chemoradiotherapy with TS-1. After 4 weeks, severe side effects, i.e., stomatitis and diarrhea, force us to discontinue the treatment. However, the tumor had begun to shrink from the 2nd week of treatment, and had clinically disappeared by the 8th week. The histopathological examination also indicated a complete response (CR). Thus, this treatment was very effective and may be useful for advanced cases.

Topics: Aged; Aged, 80 and over; Antimetabolites, Antineoplastic; Carcinoma, Squamous Cell; Drug Administration Schedule; Drug Combinations; Gingival Neoplasms; Humans; Male; Mandible; Oxonic Acid; Pyridines; Radiotherapy Dosage; Tegafur

A 66-year-old man was found to have both advanced cancer of the middle thoracic esophagus and advanced cancer of the middle third of the stomach with paraaortic lymph node metastases. The prognosis was poor because of local advanced disease and distant metastasis. The patient was therefore given combined chemotherapy with TS-1 and cisplatin. TS-1 (80 mg/day) was administered on days 1 to 5, 8 to 12, 15 to 19, and 22 to 26 (weekday-on/weekend-off schedule), and cisplatin (70 mg/m2 intravenously over the course of 2 hours) was administered on days 1 and 15 of a 28-day cycle. After 2 courses of chemotherapy the esophageal lesion had a complete response, and the gastric lesion had a partial response (reduction ratio, 71.4%). However, stomatitis and anorexia of grade 2 (NCI-CTC) occurred. Two courses of TS-1 alone (80 mg/m2) were therefore given. The esophageal lesion continued to show a complete response and the gastric lesion a partial response (reduction ratio, 85.7%). There was no change in the para-aortic lymph node metastasis (No. 16a2 latero). No adverse reaction to chemotherapy was severer than grade 3, and a good response was obtained. These findings indicate that chemotherapy with a combination of TS-1 and cisplatin is effective against advanced esophageal cancer and advanced gastric cancer.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Signet Ring Cell; Carcinoma, Squamous Cell; Cisplatin; Combined Modality Therapy; Drug Administration Schedule; Drug Combinations; Esophageal Neoplasms; Gastrectomy; Humans; Lymph Nodes; Lymphatic Metastasis; Male; Neoplasms, Multiple Primary; Oxonic Acid; Pyridines; Stomach Neoplasms; Tegafur

A 60-year-old man had a recurrence of squamous cell carcinoma at the right side of the tongue base. Chemotherapy with TS-1 (100 mg/day) was begun. Each course of chemotherapy consisted of 4 weeks of TS-1, followed by 2 weeks of no treatment. After the completion of two courses, macroscopic examination revealed a complete response. From the third course of TS-1 treatment, the dose was increased to 120 mg/day. The complete response persisted on macroscopic examination. A biopsy done during the ninth course of TS-1 treatment confirmed the complete response histologically, with no evidence of malignancy. After 12 courses of TS-1 treatment, the drug was switched to 600 mg/day of UFT. Although there were no signs or symptoms of recurrence, the patient died of cancer of the pancreas. There was no recurrence of the oropharyngeal cancer, even at the time of death.

Topics: Antimetabolites, Antineoplastic; Carcinoma, Squamous Cell; Drug Administration Schedule; Drug Combinations; Humans; Male; Middle Aged; Oropharyngeal Neoplasms; Oxonic Acid; Pyridines; Remission Induction; Tegafur

A 75-year-old male patient was hospitalized for examination of abdominal trouble. Endoscopic examination simultaneously revealed 0-I pl + II c esophageal cancer and type 3 gastric cancer. Endoscopic treatment is impossible to resect the lesion completely. It is difficult for the patient to undergo an operation because he has suffered from a cardiac infarction and pulmonary trouble. Thus, gastric cancer was treated by chemotherapy and esophageal cancer by concurrent chemoradiotherapy with chemotherapy used for gastric cancer. Chemotherapy consisted of CDDP and TS-1 every 4 weeks. TS-1 (100 mg/day) was administered on days 1 to 21, and CDDP (70 mg/m2) was infused for 24 hours on day 8. Radiotherapy (5 days/week) at 2 Gy/day was concurrently started from the beginning of chemotherapy. At day 8 in the 2nd course of chemotherapy, leucocytopenia of grade 2 and appetite loss of grade 3 (NCI-CTC) were seen. Chemoradiotherapy was then suspended for one week. After recovery from toxicity, treatment was continued for a week. A total of 64 Gy was administered. After treatment, endoscopic examination with biopsy revealed the disappearance of gastric and esophageal cancer.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Squamous Cell; Cisplatin; Drug Administration Schedule; Drug Combinations; Esophageal Neoplasms; Humans; Male; Neoplasms, Multiple Primary; Oxonic Acid; Pyridines; Remission Induction; Stomach Neoplasms; Tegafur

The patient was a 78-year-old man. Gastric cancer, type 3, was diagnosed by endoscopy in the subtotal stomach used for posterior mediastinal reconstruction after resection of thoracic esophageal cancer. Surgery was not considered to be feasible in this case because of cerebral infarction and decreased pulmonary functions; instead, the patient received TS-1 chemotherapy. Drug administration was started at the dose of 100 mg/day, one level lower than the standard dose of TS-1. Reduction in tumor size was noted endoscopically during the first course of treatment. At the end of the 4th course of treatment, the ulcerous lesion was found to have disappeared almost completely, and only mild mural irregularity was noted. The incidence of gastric cancer in the stomach tissue used for mediastinal reconstruction after esophagectomy has been reported to be 0.8%. In many of these cases, the cancer is already advanced at the time of diagnosis, precluding surgical resection. In this situation, chemotherapy with TS-1 is expected to be an effective method of treatment that can be administered at home in elderly patients with a variety of complications.

Topics: Aged; Antimetabolites, Antineoplastic; Carcinoma, Squamous Cell; Drug Administration Schedule; Drug Combinations; Esophageal Neoplasms; Esophagectomy; Esophagoplasty; Humans; Male; Mediastinum; Oxonic Acid; Pyridines; Stomach Neoplasms; Tegafur

1 M Tegafur (FT)-0.4 M 5-chloro-2,4-dihydroxypridine (CHDP)-1 M potassium oxonate (Oxo) (S-1), was developed as a new oral antineoplastic agent based on biochemical modulation of fluorouracil (5-FU) by CHDP and Oxo. The antitumor effect of S-1 on human head and neck squamous carcinoma cells was evaluated in xenografts and a metastasis model, in comparison with combined drug of 1 M FT and 4 M uracil (UFT). Mice treatment with S-1 showed a significant higher concentration of 5-FU in the tumor and the serum than UFT treated mice. S-1 showed higher tumor growth inhibition and metastasis inhibition than UFT. The mice in which metastasis was inhibited lived more than twice as long as the control mice. These results suggest that S-1 will have a higher clinical therapeutic effect against advanced squamous cell carcinoma of the head and neck in humans.

Topics: Administration, Oral; Animals; Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Squamous Cell; Dose-Response Relationship, Drug; Drug Combinations; Female; Fluorouracil; Head and Neck Neoplasms; Humans; Lung Neoplasms; Mice; Mice, Inbred BALB C; Mice, Nude; Mice, SCID; Neoplasm Transplantation; Oxonic Acid; Pyridines; Survival Rate; Tegafur; Transplantation, Heterologous; Tumor Cells, Cultured; Uracil