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Background/aim: Although perioperative chemotherapy has improved patient survival, sarcopenia may occur during chemotherapy owing to decreased food intake and physical strength. However, reports on the occurrence of sarcopenia and changes in body composition in patients with pancreatic cancer during neoadjuvant chemotherapy are scarce. This study aimed to determine the effect of changes in skeletal muscle mass during neoadjuvant chemotherapy on the S-1 adjuvant chemotherapy clinical course in patients who underwent perioperative chemotherapy and surgical resection., Patients and Methods: We retrospectively enrolled 159 patients with pancreatic cancer who underwent neoadjuvant chemotherapy and surgical resection, followed by S-1 adjuvant chemotherapy. We evaluated changes in skeletal muscle mass during neoadjuvant chemotherapy using abdominal computed tomography and the SliceOmatic software. The association between the rate of change in skeletal muscle mass index (Δ%SMI) during neoadjuvant chemotherapy and the continuation of S-1 adjuvant chemotherapy was investigated., Results: Eighty-eight (55.3%) patients lost skeletal muscle mass (Δ%SMI <0) during neoadjuvant chemotherapy with a significantly low S-1 adjuvant completion rate (p=0.02). Δ%SMI <0 was an independent risk factor for the continuation of S-1 adjuvant chemotherapy (hazard ratio=1.924, 95% confidence interval=1.002-3.695, p=0.049). Moreover, the lower the Δ%SMI, the lower the S-1 continuation rate (p=0.022)., Conclusion: Loss of skeletal muscle mass during neoadjuvant chemotherapy for pancreatic cancer affected the continuation of S-1 adjuvant chemotherapy after pancreatic resection. Therefore, ameliorating loss of skeletal muscle mass during neoadjuvant chemotherapy should be carefully considered to improve the continuation rate of adjuvant chemotherapy and the survival of patients with pancreatic cancer., (Copyright © 2024 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: Glioma-associated oncogene 1 (GLI1) is an important transcription factor in the hedgehog signalling pathway and tumour formation. We evaluated the clinical significance of GLI1 expression as a prognostic factor in patients with locally advanced gastric cancer (GC)., Patients and Methods: GLI1 expression levels were measured by quantitative real-time polymerase chain reaction analysis of cancerous and adjacent normal mucosa specimens obtained from 142 patients with Stage II/III GC administered adjuvant chemotherapy with S-1 after curative resection. The associations of GLI1 expression with clinicopathological features and survival were evaluated., Results: Clinicopathological features and GLI1 expression showed no association. Overall survival was significantly poorer in the high compared to the low GLI1 expression group (p=0.04). Multivariate analysis revealed that GLI1 expression was a significant independent prognostic factor [p=0.019, hazard ratio (HR)=1.94, 95% confidence interval (CI)=1.70-3.38]., Conclusion: GLI1 expression may be a useful prognostic marker in patients with locally advanced GC., (Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: It remains unclear which chemotherapeutic regimens are better for the addition of bevacizumab. We conducted an exploratory randomized phase II trial comparing first-line S-1 plus cisplatin with bevacizumab and pemetrexed plus cisplatin with bevacizumab in patients with advanced non-squamous non-small cell lung cancer (NSCLC)., Patients and Methods: Chemotherapy-naïve patients received S-1 (80 mg/m 2 ) from day 1 to day 14 plus cisplatin (80 mg/m 2 ) on day 1 with bevacizumab (15 mg/kg) on day 1, followed by maintenance with bevacizumab plus S-1 (SCB) on day 1 every 3 weeks and pemetrexed (500 mg/m 2 ) on day 1 plus cisplatin (75 mg/m 2 ) on day 1 with bevacizumab (15 mg/kg) on day 1 followed by maintenance bevacizumab plus pemetrexed (PCB) on day 1 every 3 weeks. The expression of thymidylate synthase (TS) was analyzed using immunohistochemistry., Results: Forty-eight patients were enrolled in this study, and eligible patients were randomly assigned at 1:1 ratio to receive SCB (n=24) or PCB (n=24). The median number of chemotherapy and maintenance therapy for SCB and PCB was 4 (range, 1-6 cycles) and 4 (range, 2-6 cycles), and 5 (range, 0-39 cycles) and 5 (range, 0-28 cycles), respectively. The overall response rate (ORR) for PCB and SCB were 54.2% and 83.3%, respectively (p=0.06). The median progression-free survival (PFS) and overall survival (OS) for PCB and SCB were 406 and 351 days, (p=0.96), and 678 and 1190 days, respectively (p=0.23). The mild adverse events were observed in both regimens. TS expression was more predictive of the chemotherapeutic response in SCB compared to PCB, but not for PFS., Conclusion: The combination regimen of SCB was identified as having a similar activity and tolerability to that of PCB in patients with advanced non-squamous NSCLC., (Copyright© 2019, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: This study aimed to identify biomarkers for predicting the prognosis of advanced gastric cancer patients who received docetaxel, cisplatin, and S-1 (DCS)., Materials and Methods: Gene expression profiles were obtained from the Gene Expression Omnibus database (GSE31811). Gene-Ontology-enrichment and KEGG-pathway analysis were used for evaluating the biological functions of differentially-expressed genes. Protein-protein interaction (PPI) network and Kaplan-Meier survival analyses were employed to assess the prognostic values of hub genes., Results: A total of 1,486 differentially expressed genes (DEGs) were identified, including 13 up-regulated and 1,473 down-regulated genes. KEGG pathways such as metabolic pathways, cell adhesion molecules (CAMs), PI3K-Akt signaling pathway and pathways in cancer were significantly represented. In the PPI network, the top ten hub genes ranked by degree were GNG7, PLCB1, CALML5, FGFR4, GRB2, JAK3, ADCY7, ADCY9, GNAS and KDR. Five DEGs, including ANTXR1, EFNA5, GAMT, E2F2 and NRCAM, were associated with relapse-free survival and overall survival., Conclusion: ANTXR1, EFNA5, GAMT, E2F2 and NRCAM are potential biomarkers and therapeutic targets for DCS treatment in GC., (Copyright© 2019, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: Trastuzumab with S-1 plus cisplatin was proved to be effective for human epidermal growth factor receptor type 2 (HER2)-positive advanced gastric cancer with measurable lesions. However, the efficacy and safety of this regimen in the absence of measurable lesions are unknown., Patients and Methods: Patients with HER2-positive gastric cancer without measurable lesions received cisplatin plus trastuzumab intravenously on day 1 and oral S-1 on days 1-14 of a 21-day cycle. The primary end-point was overall survival, and 40 patients were planned to be enrolled., Results: Fifteen patients were enrolled. The median overall survival was 14.4 months. The 1- and 3-year overall survival rates were 66.7 % and 26.7 %, respectively. Major grade 3-4 adverse events included neutropenia (47%), anemia (40%), diarrhea (20%), nausea (20%), and anorexia (20%)., Conclusion: Trastuzumab with S-1 plus cisplatin might be effective and tolerable for HER2-positive advanced gastric cancer without measurable lesions., (Copyright© 2019, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: Although the efficacy is limited, standard therapy for Stage II/III esophageal cancer in Japan includes neoadjuvant chemotherapy with cisplatin plus 5-fluorouracil. A phase II trial was conducted on patients with resectable advanced esophageal cancer obtaining neoadjuvant chemotherapy with docetaxel, cisplatin plus S-1 (DCS)., Patients and Methods: A total of 40 patients were enrolled, each treated by the following DCS regimen: docetaxel 40 mg/m 2 , cisplatin 60 mg/m 2 on day 1, and S-1 80 mg/m 2 on days 1-14, repeated every four weeks, for a maximum of three cycles., Results: Clinical response rate was 76% and the pathological response rate (Grade 2/3) was 33%. Hematological toxicities of Grade 3/4 were leukopenia 50%, neutropenia 68%, and febrile neutropenia 18%., Conclusion: Neoadjuvant chemotherapy with DCS is a feasible therapeutic strategy for patients with advanced thoracic esophageal squamous cell carcinoma., (Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: Radiotherapy is not routinely used in metastatic pancreatic ductal adenocarcinoma (PDAC). We conducted a phase I study to investigate concurrent chemoradiotherapy (CCRT) followed by chemotherapy., Materials and Methods: S-1 was administered at 50-70 mg/m 2 /day with radiotherapy in 2.5-3.6 Gy/day for 10-12 fractions. After CCRT, gemcitabine (1,000 mg/m 2 on days 1 and 15) and S-1 (60-100 mg/day on days 1-7 and 15-21), were administered in a 4-week cycle., Results: After enrolling 10 patients, the study was terminated due to slow recruitment. Dose-limiting toxicities and maximum tolerated doses were not identified. Most patients experienced mild toxicities, including nausea, vomiting, and anorexia. One patient developed grade 3 infection. One patient achieved partial remission, while the remaining nine patients had stable disease, with a local disease control rate of 100% after CCRT., Conclusion: A short-course CCRT followed by chemotherapy was potentially feasible in patients with metastatic PDAC., (Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Aim: To determine the recommended dose of neoadjuvant chemotherapy of combined capecitabine and oxalipatin (G-XELOX) for locally advanced gastric cancer., Patients and Methods: Patients received two cycles of neoadjuvant chemotherapy with oxaliplatin on day 1 and capecitabine (2,000 mg/m 2 /day, b.i.d.) on days 1-14, repeated every 3 weeks. They then underwent gastrectomy with curative D2/3 lymph-node dissection followed by adjuvant therapy with S-1 for 1 year. De-escalation of oxaliplatin dose was planned (starting at level 1, oxalipatin 130 mg/m 2 )., Results: Six patients were enrolled. The maximum tolerated dose was not reached at level 1. Oxaliplatin at 130 mg/m 2 combined with capecitabine at 2,000 mg/m 2 /day, b.i.d. had acceptable toxicity. No treatment-related death occurred. Most frequent drug-related adverse events during neoadjuvant G-XELOX were nausea and peripheral sensory neuropathy. One patient declined surgical resection, leaving five undergoing resection with curative intent, of whom four achieved pathological down-staging after neoadjuvant G-XELOX., Conclusion: Neoadjuvant G-XELOX was feasible in patients with locally advanced gastric cancer., (Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: Significant efficacy of oxaliplatin-based chemotherapy has been demonstrated for advanced gastric cancer (AGC). However, the appropriate dose of oxaliplatin, and the efficacy and toxicity of administration of oxaliplatin subsequent to cisplatin therapy still remain unclear., Patients and Methods: In total, 55 patients with AGC that were scheduled to receive oxaliplatin-based chemotherapy were prospectively examined., Results: The median age was 67 years and oxaliplatin was administered to 39 (71%) patients as first-line and in 16 (29%) patients as second-line therapy. An initial dose of 130 or 100 mg/m 2 of oxaliplatin was administered to 11 and 36 patients, respectively. The overall response rates (ORR) and median progression free survival (mPFS) were 86 and 33%, and 7.2 and 7.8 months, respectively. Compared to 100 mg/m 2 , the relative dose intensity was significantly lower and severe toxicity tended to increase with oxaliplatin at 130 mg/m 2 A total of 10 patients (18%) had a prior cisplatin-based therapy. The ORR of the patients pretreated with cisplatin was 14% and the mPFS was 6.1 months., Conclusion: An initial oxaliplatin dose of 130 mg/m 2 resulted in a good response, but tended to increase the risk of toxicity. Subsequent oxaliplatin-based therapy after cisplatin exhibited modest efficacy, especially in cases with cisplatin intolerance., (Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: Gemcitabine (GEM) plus cisplatin (CDDP) chemotherapy has been used worldwide as the standard first-line treatment for advanced biliary tract cancer (BTC). A phase II trial has also suggested promising activity of GEM plus S-1 chemotherapy against advanced BTC. The aim of this study was to evaluate the efficacy and safety of GEM plus S-1 chemotherapy in patients with advanced BTC., Patients and Methods: The eligibility criteria were as follows: histologically-proven BTC, unresectable or recurrent disease, ECOG performance status (PS) 0-1 regardless of previous treatment. Gemcitabine was administered intravenously at the dose of 1,000 mg/m 2 over 30 min on days 1 and 8, and S-1 was administered orally at doses of 60/80/100 mg/day based on the BSA, from day 1 to day 14, every 3 weeks. The primary endpoint was the response rate according to RECIST, ver. 1.1, and the secondary endpoints were the frequency/severity of toxicities, progression-free survival (PFS) and overall survival (OS)., Results: A total of 38 patients were enrolled between August 2008 and November 2011. There were 19 men and 19 women, with a median age of 66 years (range=44-81 years). Seven patients had a previous history of first-line or adjuvant chemotherapy after surgery. The PS was 0 and 1 in 30 and 7 patients, respectively. The treatment response was classified as partial response in 6 patients (15.8%) and as stable disease in 18 patients (47.4%). The median PFS and OS were 5.8 and 15.9 months, respectively. The toxicity was generally mild, and the most common grade 3/4 toxicities were leukopenia (31.6%), neutropenia (36.8%), nausea/vomiting (2.6%), and diarrhea (2.6%). There was one treatment-related death due to interstitial pneumonia., Conclusion: Our study revealed that gemcitabine plus S-1 chemotherapy was well-tolerated and exhibited favorable antitumor activity in patients with advanced BTC., (Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: Gemcitabine and S-1 are drugs commonly used for treating locally advanced pancreatic cancer (LAPC). However, the safety and efficacy of combination of these agents for induction chemotherapy (IC) followed by chemoradiotherapy are not well-defined., Patients and Methods: Fifteen patients with LAPC (IC-CRT group) were treated with gemcitabine and S-1 IC, followed by S-1 chemoradiotherapy. The clinical outcomes were compared to a cohort of 38 patients who received chemoradiotherapy alone (CRT group)., Results: Disease control rates in the CRT and IC-CRT groups were 84% and 93%, respectively (p=0.024). The median time of disease progression was 10.8 and 15.4 months in the CRT and IC-CRT group, respectively (p=0.043). The median overall survival time was longer in the IC-CRT group compared to CRT (23.4 vs. 17.3 months), but this increase was not statistically significant., Conclusion: Gemcitabine and S-1 combination chemotherapy, followed by CRT, is a promising IC regimen for treating LAPC., (Copyright© 2017 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

Background: It has not been elucidated whether the clinical efficacy of oral fluoropyrimidines for adjuvant chemotherapy of colorectal cancer varies with tumor biological characteristics., Patients and Methods: A multicenter randomized trial was performed comparing oral tegafur/gimeracil/oteracil (S-1) and uracil-tegafur/ leucovorin (UFT/LV) as adjuvant therapy for stage III colorectal cancer. Postoperative survival was compared based on the 5-FU-related mRNA levels in cancer tissues., Results: Among patients with tumor expressing dihydropyrimidine dehydrogenase (DPD) mRNA within the 66.7th percentile (lower 2/3) of all cases, overall survival (OS) was significantly better in the S-1 than in the UFT/LV group. In the S-1 group, patients with low DPD-expressing tumors had significantly better OS than those with highly expressing tumors. Patients with low thymidine synthase (TS)-expressing tumors had significantly better OS than those with highly expressing tumors., Conclusion: The efficacy of oral fluoropyrimidines as adjuvant chemotherapy for colorectal cancer may be influenced by the level of 5-FU-related mRNA in cancer tissues., (Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

Background/aim: S-1, cisplatin, and docetaxel (DCS) constitute an effective regimen for gastric cancer. We conducted a retrospective cohort study of systemic DCS and a prospective phase I trial of intraperitoneal DCS in the preoperative setting for marginally resectable gastric cancer., Patients and Methods: Under the systemic regimen, patients received cisplatin (60 mg/m(2)) plus docetaxel (40 mg/m(2)) intravenously on day 1 and S-1 (80 mg/m(2)) on days 1-14, of a 28-day cycle. With the intraperitoneal regimen, the schedule for S-1 and cisplatin was the same. Dose escalation for docetaxel started at 30 mg/m(2) (level 1)., Results: Between August 2010 and July 2013, 26 consecutive patients were treated with the systemic regimen. Grade 3-4 neutropenia occurred in 81% but the toxicity profile was very tolerable. The response rate based on the Response Evaluation Criteria in Solid Tumors (RECIST) was 89%. Between April 2012 and April 2014, 5 patients with linitis plastica, large ulcero-invasive type tumors, positive washing cytology or peritoneal metastasis were enrolled in the phase I trial of the intraperitoneal regimen. Grade 3-4 elevations in aspartate/ alanine aminotransferase (AST/ALT) occurred in the first 2 patients. The next 3 patients, who received docetaxel (20 mg/m(2)) on days 1 and 15 (level 0), had no dose-limiting toxicity. Four patients, including 3 with peritoneal metastasis and/or positive cytology before treatment, underwent R0 resection after intraperitoneal chemotherapy., Conclusion: Our studies revealed the efficacy of the systemic regimen and the safety of the intraperitoneal regimen. Further investigation of these two types of preoperative DCS chemotherapy is warranted., (Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

Unlabelled: The present study evaluated the efficacy of lafutidine, a histamine H2 receptor antagonist, for reducing gastrointestinal toxicities during adjuvant chemotherapy using oral fluorouracil anticancer drugs for gastric cancer., Patients and Methods: Patients with stage II (T1 cases excluded) or stage III gastric adenocarcinoma who underwent gastrectomy with D2 lymphadenectomy achieving R0 resection from 2011 to 2013 were prospectively enrolled in the study. Patients were randomly assigned to either S-1 treatment or S-1 plus lafutidine treatment. Quality of life and gastrointestinal toxicity were evaluated before chemotherapy and at 2, 4, and 6 weeks after the beginning of treatment., Results: The incidence of diarrhea during chemotherapy was significantly lower in the S-1 plus lafutidine group than in the group treated with S-1 alone (10% vs. 83%, respectively; p=0.002). The grades of diarrhea and nausea during chemotherapy were also significantly lower compared to those before chemotherapy in patients receiving S-1 plus lafutidine than in those administered S-1 alone. The rate of patients requiring a dose reduction or interruption of S-1 was significantly lower in the S-1 plus lafutidine group than in the group treated with S-1 alone (30% vs. 83%, respectively; p=0.027)., Conclusion: Lafutidine might be useful not only for preventing gastrointestinal toxicities during adjuvant chemotherapy for gastric cancer, but also for improving compliance with taking oral fluorouracil anticancer drugs. However, this indication needs to be confirmed in a larger, prospective, randomized, controlled trial., (Copyright© 2014 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

Background: 5-Fluorouracil (5-FU), leucovorin, and oxaliplatin (FOLFOX) therapy and 5-FU, leucovorin, and irinotecan (FOLFIRI) therapy are standard chemotherapies to treat advanced/recurrent colorectal cancer. However, these chemotherapies require continuous infusion of 5-FU for a prolonged time of 40 h or more, every two weeks. Accordingly, these chemotherapies require hospitalization and placement of a central venous catheter. Because of frequent catheterization, long-term use of these therapies potentially risks complications such as infection and thrombosis. In contrast, S-1 (tegaful, gimeracil, oteracil) combined with irinotecan (IRIS) therapy involves giving one drug orally and infusing the other for about two hours every two weeks, so placement of a central venous catheter is not necessary. The current study examined the efficacy and safety of IRIS therapy in 90 patients at this Hospital who underwent such therapy to treat advanced/recurrent colorectal cancer., Patients and Methods: The study comprised 90 patients who underwent IRIS therapy to treat advanced/recurrent colorectal cancer from December 2004 to December 2011., Results: The ratio of male-to-female patients was 64:26. The mean age at the start of IRIS therapy was 64.5 years, and patients underwent an average of 11 courses of therapy. The response rate to IRIS therapy was 14.8%, the disease control rate was 60.5%, and the overall survival time was 26.7 months. The incidence of adverse events was 70.0%, and the incidence of grade 3 or more severe adverse reactions was 17.8%., Conclusion: In comparison to the standard therapies of FOLFOX and FOLFIRI, IRIS therapy had a lower response rate but led to an equivalent overall survival time. IRIS therapy had a low incidence of serious adverse events and allowed patients to continue therapy on an out-patient basis. These findings indicate that IRIS therapy may be a useful form of chemotherapy to treat advanced/recurrent colorectal cancer., (Copyright© 2014 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

Aim: We undertook a prospective phase II study to evaluate the efficacy of S-1 plus trastuzumab combination regimen for human epidermal-growth factor receptor-2 (HER2)-positive metastatic breast cancer (MBC)., Patients and Methods: HER2-positive MBC patients received oral administration of S-1 (80 mg/m2/day, days 1 to 28, every 6 weeks) and intravenous weekly trastuzumab (2 mg/kg), according to the results of a prior Phase I trial of our group., Results: A total of 28 patients were enrolled and received a median of 3.5 (range 1-10) cycles of treatment. Overall response rate and clinical benefit rate were 53.6% and 75.0%, respectively. Progression-free survival was 30 weeks. With regard to grade 3 and 4 adverse effects, leucopenia, neutropenia, increase in serum alanine aminotransferase, and diarrhea were observed., Conclusion: Combination of S-1 and trastuzumab was tolerable and had excellent efficacy with good response and disease control in this trial., (Copyright© 2014 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

Background: S-1-based regimens are commonly used for advanced gastric cancer (AGC) in Japan. We performed this trial to evaluate the efficacy and safety of S-1 plus irinotecan (SIri) and S-1 plus paclitaxel (SPac) as first-line treatments for AGC in order to select the optimal regimen for a subsequent phase III trial., Patients and Methods: Patients with previously untreated, locally advanced or metastatic measurable gastric adenocarcinoma were randomly assigned to receive SIri (irinotecan 80 mg/m(2) was administered intravenously (i.v.) on day 1 and 15, while 40 mg/m(2) S-1 was orally administered twice daily for three weeks from days 1-21 followed by a two-week pause) or SPac (paclitaxel 50 mg/m(2) was administered i.v. on day 1 and 8, while 40 mg/m(2) S-1 was orally administered twice daily for two weeks from day 1-14 followed by a one-week pause) regimen. The primary end-point was the overall response rate (ORR), and the secondary end-points were progression-free survival (PFS), overall survival (OS), and toxicity., Results: A total of 102 patients were enrolled. The ORR was 33.3% for SIri and 31.4% for SPac, which did not achieved the predicted ORR in either group. PFS and OS were 5.7 and 12.4 months for SIri, 4.6 and 11.9 months for SPac respectively. No treatment-related deaths occurred during the study. Although grade 3/4 neutropenia and anemia were more frequent in the Siri group, both regimens were well-tolerated., Conclusion: Both regimens were well-tolerated in patients with AGC, but we conclude that neither regimen was optimal for a phase III trial.

Background: 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., Patients and Methods: 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., Results: 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)., Conclusion: 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.

Background/aim: This study assessed the toxicity and activity of biweekly docetaxel and S-1 combination therapy in elderly patients with advanced gastric cancer., Patients and Methods: One-hundred and thirteen patients were enrolled: 35 were 75 years old or more. The objective response rate, toxicity, progression-free survival (PFS), and overall survival (OS) were compared., Results: Dose reduction was significantly frequent in the elderly group (24/35 versus 25/78, p<0.001). The overall response rate was 54.9%. Out of these, 18 (15.9%) underwent gastrectomy (13 R0 gastrectomy). The median OS was 17.3 months and the median PFS was 8.0 months. Neutropenia was the most frequently observed hematological toxicity at grade 3 and 4 (34.5%), followed by leukopenia (24.8%). Most non-hematological toxicities were of grade 1 or 2. There were no significant differences in overall response rate, median OS, median PFS, or toxicities between the two groups., Conclusion: This combination offers favourable survival benefits with controllable tolerance for therapy of AGC in the elderly.

Background: Triplet combination chemotherapy has the potential to improve the prognosis of patients with unresectable gastric cancer. We conducted a phase I trial of triplet combination chemotherapy consisting of paclitaxel, cisplatin, and S-1 (PCS) for unresectable gastric cancer., Patients and Methods: Patients with metastatic or incurable disease were enrolled. S-1 was administered on days 1-14. Paclitaxel and cisplatin were infused on days 1 and 15. The starting doses of paclitaxel and cisplatin were 100 and 20 mg/m(2), respectively. Dose levels of paclitaxel and cisplatin were escalated as follows: 120 and 20 mg/m(2), respectively (level 2); 120 and 30 mg/m(2), respectively (level 3). End-points: Dose-limiting toxicities included grade 3 nausea, vomiting, and general fatigue, and grade 4 febrile neutropenia. The maximum tolerated dose and recommended dose were established at level 3 and level 2, respectively., Conclusion: Although further clinical trials are recommended to more thoroughly evaluate safety and efficacy, PCS appears to be an excellent candidate for a standard treatment strategy for unresectable gastric cancer.

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

Background: 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., Patients and Methods: 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., Results: 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., Conclusion: CCRT with S-1 administered on alternate days was effective and well-tolerated among elderly patients with HNSCC.

Aim: The current study aimed to assess the long-term efficacy of combination therapy with oral S-1, a fluoropyrimidine prodrug, plus irinotecan in previously untreated patients with metastatic colorectal cancer., Patients and Methods: Between April 2004 and February 2005, 41 patients with previously untreated advanced or recurrent colorectal cancer were enrolled in the study. Chemotherapy consisted of oral administration in S-1 at 40 mg/m(2) twice daily on days 1 to 14 and intravenous infusion of irinotecan at 150 mg/m(2) on day 1 in a 21-day cycle., Results: The median patient follow-up was 78.0 months. The median survival time was 23.7 months, and the 2-year survival rate was 50%. The median time to tumor progression was 8.3 months., Conclusion: The results of this long-term update confirmed that first-line combination therapy with oral S-1 plus irinotecan was effective in patients with metastatic colorectal cancer.

Aim: A preliminary study with the aim of evaluating the safety and efficacy of a single intraperitoneal administration of paclitaxel, combined with intravenous administration of paclitaxel plus S-1, was carried out in gastric cancer patients with peritoneal metastasis., Patients and Methods: Paclitaxel was administered intraperitoneally at 80 mg/m(2). After one to two weeks, S-1 was administered at 80 mg/m(2)/day for 14 consecutive days, followed by seven days' rest. Paclitaxel was administered intravenously at 50 mg/m(2) on days 1 and 8. The safety, pharmacokinetic analysis and efficacy of this therapy were investigated., Results: Fifteen patients were enrolled in this study. The toxic effects of the intraperitoneal chemotherapy were mild. The toxic effects with the systemic chemotherapy were acceptable. The ratio of (AUC peri)/(AUC pla) was 1065:1 in the pharmacokinetic analysis. The one-year overall survival rate was 10/15 (66.7%)., Conclusion: A single intraperitoneal administration of paclitaxel combined with intravenous administration of paclitaxel plus S-1 is a well-tolerated and feasible treatment for patients with gastric cancer with peritoneal metastasis.

Background: Developed as a biological response modifier (BRM), lentinan mitigates patients' symptoms by boosting the immune system. In combination with S-1 (tegafur, gimeracil, oteracil), lentinan is reported to mitigate adverse reactions to therapy for unresectable recurrent gastric cancer and prolong survival. However, there are few reports from actual clinical practice, and precise methods of using lentinan have not yet been established. This study retrospectively examined the usefulness of lentinan in patients., Patients and Methods: The subjects of this study were 39 patients who were diagnosed with unresectable gastric cancer, based on preoperative examinations or findings at laparotomy in our Department. These patients underwent S-1/paclitaxel therapy. Nineteen of the patients received lentinan while 20 did not, and these two groups of patients were compared., Results: There were no significant differences in patients' characteristics such as the male:female ratio, age at the start of chemotherapy, and staging classification of the 19 patients receiving lentinan and the 20 patients not receiving lentinan. Comparison of the two groups revealed no significant differences in overall survival time, but comparison of the duration of therapy revealed that therapy tended to be longer for the group taking lentinan than the group not taking lentinan. Adverse events were noted in 61.5% (24 patients) of the total patients group; such events tended to occur less frequently in the group receiving lentinan., Conclusion: Lentinan inclusion in therapy did not seem to prolong survival. Nevertheless, the duration of therapy tended to be longer for patients taking lentinan. This may be due to the fact that adverse events tended to occur less frequently in these patients during therapy. A decline in the incidence of adverse events increases the duration of therapy and improves the patients' quality of life (QOL); it may also prolong survival. Optimal methods of using lentinan need to be established.

Background/aim: S-1 plus cisplatin is the standard first-line chemotherapy for metastatic gastric cancer (MGC) in Japan, but the relationship between dose intensity and antitumor effects remains unclear., Patients and Methods: We retrospectively studied 64 patients who received S-1 plus cisplatin for MGC from January 2006 to December 2010 in two Japanese hospitals., Results: The median relative dose intensity (RDI) of S-1 plus cisplatin was 87% (range, 59.5%-100%). The cut-off value of RDI of S-1 plus cisplatin was identified to be 80% by a receiver operating characteristic analysis of the tumor response. In the RDI<80% (n=19) and the RDI≥80% (n=45) groups, the response rates were 20.0% and 37.5% (p=0.182), the median survival times were 394 and 376 days (p=0.915), and the median progression-free survival (PFS) was 188 and 170 days (p=0.851), respectively., Conclusion: An appropriate RDI reduction may be permitted for patients with MGC in palliative settings.

Background/aim: C-reactive protein (CRP) has been associated with the development of many carcinomas, but the significance of CRP remains unclear for metastatic gastric cancer (MGC)., Patients and Methods: Sixty one patients who received S-1 plus cisplatin for MGC were retrospectively identified and categorized into two groups depending on the serum CRP level before chemotherapy., Results: Overall survival was significantly shorter in the CRP≥1.0 group than in the CRP<1.0 group (median, 292 days versus 451 days; p=0.0004). Moreover, progression-free survival was significantly shorter in the CRP≥1.0 group than in the CRP<1.0 group (median, 115 days versus 188 days; p=0.0010). In a multivariate analysis, serum CRP level before chemotherapy was an independent prognostic factor for MGC (hazard ratio 4.20 [95% CI, 1.66 to 10.64] p=0.002)., Conclusion: Serum CRP level before chemotherapy might be a potential prognostic factor for MGC.

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

Background: Based on its potent inhibition of dihydropyrimidine dehydrogenase (DPD), S-1 is expected to be more active than other flouropyrimidines against tumors with higher DPD activity, such as hepatocellular carcinoma (HCC)., Patients and Methods: We retrospectively investigated the efficacy of S-1 and platinum in HCC. Patients received S-1 (80 mg/m(2)/day on days 1-14) with either cisplatin (60 mg/m(2) on day 1) or oxaliplatin (130 mg/m(2) on day 1) every 3 weeks. The primary end point was overall response rate., Results: Among the 21 HCC patients, 12 and 9 patients received S-1-based chemotherapy as a first-line and salvage treatment, respectively. Partial response was seen in 5 patients and stable disease in 6. The median time-to-progression was 4.0 months (95% confidence interval [CI], 2.4-5.6) and median overall survival was 14.0 months (95% CI, 6.7-21.3). Most patients were tolerable to chemotherapy and no grade 4 toxicity was observed. Tumors with lower DPD expression were more responsive to the therapy (response rate 60.0% in lower vs. 0.0% in higher DPD, p=0.045)., Conclusion: S-1 and platinum combination chemotherapy shows favorable efficacy and tolerability in advanced HCC.

Background: There is a great need for effective outpatient chemotherapy for advanced gastric cancer in patients with good performance status. The present pilot study evaluated the use of combination chemotherapy with S-1 and fractional CDDP for unresectable-recurrent gastric cancer in an outpatient setting., Patients and Methods: A total of 41 patients with unresectable or recurrent gastric cancer were treated with this combination chemotherapy. S-1 was administered orally every day on days 1-28 and CDDP was infused on days 1, 15, and 29., Results: Thirty-six patients had measurable lesions and 19 patients had partial responses, resulting in an overall response rate of 52.8%. The median survival time was 494 days. There was no grade 4 haematological toxicity, no grade 3 or more non-haematological toxicity, and no treatment-related death., Conclusion: This combination chemotherapy has no serious toxicities in patients with unresectable and recurrent gastric cancer and can be used effectively in an outpatient setting.

Background: S-1 is an orally administered fluorinated pyrimidine with high activity in metastatic breast carcinoma (MBC) and in chemotherapy-pretreated metastatic breast carcinoma., Patients and Methods: Forty patients with MBC who did not respond to capecitabine-based chemo-therapy and then received S-1 were identified from our data base of records between 2006 and 2008. The clinico-pathological data and outcomes of these patients were then reviewed., Results: The overall response rate was 27.8%. The median survival was 19.2 months, and the median time to disease progression was 6.2 months. The most common treatment-related adverse events (all grades) were hand-foot syndrome (15%), nausea (15%), vomiting (7.5%), disorder of taste (7.5%), and diarrhea (5%). However, the majority were mild to moderate in intensity, and only one patient experienced grade 3 (according to the National Cancer Institute of Canada Common Toxicity criteria) adverse events. Myelosuppression and alopecia were rare, and there were no reported treatment-related deaths., Conclusion: The results of the current study demonstrate that S-1 is an effective and well-tolerated treatment in patients with capecitabine-resistant MBC. In addition, it is a convenient, orally administered drug, which makes it an attractive agent for use in outpatient treatment.

Background: Gastric cancer with cancer cells on peritoneal cytology has very poor prognosis because of the existence of simultaneous peritoneal metastasis. Here we performed a dose-escalation study of intraperitoneal docetaxel (DTX) combined with S-1 to determine the maximum-tolerated dose (MTD) and recommended dose (RD) in gastric cancer with peritoneal dissemination., Patients and Methods: Twelve gastric cancer patients with positive cytology were enrolled in this study. Peritoneal lavage specimens were obtained under local anesthesia or staging laparoscopy before treatment and the combination chemotherapy was applied in patients with positive cytology. DTX was administered on day 1 intraperitoneally with initial dose of 40 mg/m(2), stepped up to 50 or 60 mg/m(2). S-1 was administered at a fixed dose of 80 mg/m(2)/day on days 1-14, followed by 7 days of rest. After two cycles of the combination chemotherapy, staging laparoscopy was performed to evaluate the effect of the chemotherapy. Simultaneous gastrectomy was performed in cases without peritoneal deposits at staging laparoscopy., Results: The MTD of intraperitoneal DTX was not determined and the RD was defined as 60 mg/m(2) because dose-limiting toxicity occurred in only one patient at level II (DTX: 50 mg/m(2)). Out of twelve patients given the combination chemotherapy, nine had cytologically negative peritoneal lavage and had no peritoneal metastases at surgery after chemotherapy., Conclusion: The combined chemotherapy of S-1 plus intraperitoneal DTX was revealed to be safe and may be effective for gastric cancer with peritoneal dissemination.

Unlabelled: Feasibility and efficacy of S-1 and cisplatin followed by surgery was evaluated, and factors contributing to survival benefit were analyzed., Patients and Methods: In total, 120 consecutive patients with highly advanced gastric cancer were treated with S-1 (80 mg/m(2) for 21 consecutive days) and cisplatin (50 mg/m(2) on day 8)., Results: The response rate was 62.5% overall, and 75.7% for these with metastatic lymph nodes. Grade 3/4 adverse events were less than 10%. The median survival time was 41.9 months among 93 patients whose primary lesion was resected. Liver metastasis, R2 resection, poor performance status and lack of response were identified as independent risk factors by a multivariate analysis., Conclusion: Preoperative chemotherapy with S-1 and cisplatin was effective. The results show the need for different approaches in the treatment of patients with metastases and these without.

Background: 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., Patients and Methods: 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., Results: 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)., Conclusion: 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.

Background: Docetaxel and S-1 are novel antitumour chemotherapeutic agents with distinct toxicities. Here a phase I study of combined docetaxel and S-1 therapy for advanced gastric cancer is reported., Patients and Methods: The study group comprised 21 patients who received at least two courses of treatment. Intravenous docetaxel was administered with dose escalation from 20-45 mg/m2 depending on the dose-limiting toxicity (DLT) on days 1 and 15, and oral S-1 (BSA < 1.25 m2, 80 mg/day; 1.25 < or = BSA < 1.50 m2, 100 mg/day; 1.50 m2 < or = BSA, 120 mg/day) was administered on days 1-7 and 15-21., Results: The maximum tolerated dose of docetaxel was 45 mg/m2 and the DLT was defined as neutropenia. The recommended docetaxel dose was identified as 40 mg/m2. The response rate (including partial responses) was 57.1%. Five cases showed no change and four showed progressive disease after two courses of treatment. The mean survival rate was 15 months., Conclusion: A phase II clinical trial is required to confirm these results.

Objectives: A phase 2 trial of S-1 combined with cisplatin was conducted for unresectable pancreatic cancer., Patients and Methods: S-1 was administered for 28 days followed by a rest of 14 days. Cisplatin was infused on days 1-5, 8-12, 15-19 and 22-26 of the first course. After the second course, S-1 was administered as maintenance chemotherapy., Results: Thirty patients were enrolled and the responses observed were 0 complete response, 5 partial response, 22 stable disease and 3 progressive disease, with an overall response rate of 17% (95% confidence internal (CI), 6-35%). Toxicity was tolerable, with grade 3 toxicities observed for leukocytopenia (10%), neutropenia (7%), anemia (3%), thrombocytopenia (3%), anorexia (13%), and nausea and vomiting (7%). The median survival time (MST) and the 1-year survival rate were 9.0 months (95% CI, 6.0-14.5 months) and 35.7% (95% CI, 19-55%), respectively., Conclusion: S-1 with low-dose cisplatin is well tolerated and effective for advanced pancreatic cancer.

Unlabelled: THE AIM of this study was to compare the efficacy and toxicity of S-1 to an oral combination regimen of tegafur and uracil (UFT) with leucovorin (LV) in metastatic colorectal carcinoma (CRC) patients., Patients and Methods: Fifty-two patients were treated with either S-1 (80 mg/m2/d), administered for 28 days every 42 days, or UFT (300 mg/m2/d) and LV (90 mg/d), administered for 28 days every 35 days. The clinical results were compared retrospectively., Results: There were no statistically significant differences in overall response between the two patient groups. The overall response rate was 11.8% in the S-1 group, and 11.1% in the UFT/LV group. No statistically significant difference in-time- to progression (TTP) or survival time was observed between the treatments. The median survival time was 29 months with S-1 and 12 months with UFT/LV., Conclusion: The oral S-1 provided similar safety and efficacy, compared to UFT/LV for metastatic CRC.

Background: We have reported the efficacy and safety of S-1 combined with low-dose consecutive cisplatin therapy for advanced and recurrent gastric cancer, but the regimen was difficult because daily cisplatin administration was necessary. We have already confirmed that cisplatin of 6 mg/m2 twice-weekly maintained the same protein-bound Pt concentration as that of 3 mg/m2 of cisplatin daily. In the present study, the efficacy and safety of a combination of S-1 and low-dose twice-weekly cisplatin were investigated., Patients and Methods: The participants were 32 patients treated at our hospital, and all were admitted for the first 2 weeks of therapy. S-1 at 80 mg/m2 daily was administered orally in two divided doses. Cisplatin at 6 mg/m2 was administered by intravenous drip infusion over 30 minutes on 2 days each week, day 1 and day 4. Each treatment cycle consisted of 4 weeks of drug administration followed by a 2-week drug-free period (6 weeks in total)., Results: A total of 146 cycles were administered, with a median of three cycles (range: 1-24) per patient. The results were rated as a complete response in 1 case, partial response in 24 cases and stable disease in 5 cases. The response rate was 78.1% (25/32) and the median survival time was 12.0 months (95% confidence interval (CI) 8.9-15.1 months). The response rate did not differ between previously treated and untreated patients. The one-year survival rate was 48.2% (95% CI 30.3-66.0%). The major adverse reactions were myelosuppression and gastrointestinal symptoms. The total incidence of grade 3 or greater adverse reactions was 15.6% (5/32)., Conclusion: The combination of S-1 and low-dose twice-weekly cisplatin therapy appears to be highly efficacious and safe and shows promise as a useful treatment strategy, even in outpatient clinics.

Unlabelled: Anticancer drugs may frequently induce host immunosuppression and symptomatic toxicities. Once symptomatic toxicity occurs, the patient's quality-of-life (QOL) is reduced. Since little is known of the relationship between host immunity and the toxicity of chemotherapy, the host immunity before and after chemotherapy was compared to assess whether it is related to symptomatic toxicity during chemotherapy., Patients and Methods: Fourteen patients with colorectal cancer underwent leucovorin /5-fluorouracil (LV/5-FU) treatment, or S-1/irinotecan (CPT-11). Host immunity (cytokine production of peripheral blood mononuclear cell (PBMC), serum soluble interleukin-2 receptor (sIL-2R) levels and phenotypic analyses of PBMC were measured before and after the first chemotherapy., Results: An increase of sIL-2R, CD4+CD25+ T-cells and the CD4/8 ratio in patients with symptomatic adverse reactions were found. These changes in the first chemotherapy were significantly different (p = 0.0211, p = 0.0087, p = 0.0234)., Conclusion: The current study indicated that there are some parameters correlated with toxicity during chemotherapy which effect QOL. In such patients, negative influences on host immunity, such as an increase of sIL-2R and regulatory T-cells, and a decrease of cytotoxic T-cells could occur.

Background: The primary objective of this study was to determine the maximum tolerated dose (MTD), the toxicity profile and the recommended dose (RD) for phase II of a combination of S-1 and weekly administration of docetaxel., Patients and Methods: Patients with histologically diagnosed recurrent or unresectable locally advanced gastric cancer were enrolled. A fixed oral dose of 80 mg/m2 S-1 was given for 3 weeks. Docetaxel was infused intravenously on day 1, 8 and 15, repeated every 5 weeks. A pharmacokinetic study was also performed., Results: A total of 14 patients were enrolled. One dose-limiting toxicity (DLT) (grade 3 diarrhea with febrile neutropenia) occurred at level 2. DLTs occurred in 3/5 patients at level 3, (grade 3 stomatitis, with febrile neutropenia or continuous grade 4 neutropenia). The pharmacokinetic study suggested no drug interactions. Overall response and disease control rates were 20% and 80%, respectively. The response rate at the RD (level 2) was 50%. Overall survival was 9.4 months., Conclusion: RD was level 2 (80 mg/m2 of S-1 for 3 weeks and 20 mg/m2 of docetaxel on day 1, 8 and 15, every 5 weeks). Dose intensities of S-1 and docetaxel were 48 mg/m2/week and 12 mg/m2/week, respectively. This regimen showed promising activity for advanced gastric cancer.

Unlabelled: A phase I study of chemotherapy was planned with S-1 and nedaplatin to find the optimal dose for patients with recurrent head and neck cancer., Materials and Methods: Oral administration of S-1 (days 1-14) and intravenous nedaplatin (day 8) were tested for patients with recurrent head and neck cancer in a phase-I setting. The dose of S-1 was fixed and the dose of nedaplatin was escalated from 80 mg/m2, with an increase of 10 mg/m2 per step, to find the maximum tolerated dose., Results: Nine patients were recruited in this trial. The maximum tolerated dose (MTD) of nedaplatin was 90 mg/m2. At this dose level, dose-limiting toxicity (DLT) was observed in two out of three patients. One experienced grade 4 thrombocytopenia and febrile grade 3 neutropenia, while the other suffered myelosuppression causing more than a two-week delay of the second chemotherapy cycle. Myelosuppression was the DLT of this regimen., Conclusion: The recommended phase II dose of nedaplatin combined with oral S-1 was identified as 80 mg/m2.

Objective: The objective of this study was to determine the dose-limiting toxicity (DLT), the maximum tolerated dose (MTD), the recommended dose (RD) and the preliminary antitumor activity of S-1, oral dihydropyrimidine dehydrogenase inhibitory fluoropyrimide, in combination with cisplatin and paclitaxel for advanced gastric cancer., Patients and Methods: Paclitaxel was administered on day 1. A fixed dose of S-1 (70 mg/m2/day) was orally administered for 14 consecutive days from day 1 and a 24-h infusion of a fixed dose of cisplatin (60 mg/m2) was administered on day 14 of every 28-day cycle. Four dose escalation levels of paclitaxcel were studied (120, 140, 160 and 180 mg/m2)., Results: Twenty patients were enrolled. The toxicities were generally mild no grade 4 hematological toxicity or grade 3 non-hematological toxicity were observed. Level 4 was considered as the MTD because of a treatment delay of more than 2 weeks in 3 out of 6 patients. The RD of paclitaxcel was 160 mg/m2. The overall response rate was 75%., Conclusion: A triple combination chemotherapy consisting of S-1, cisplatin and paclitaxel showed a tolerable level of adverse reactions and favorable antitumor activity.

Background: The surgical outcome for advanced gastric cancer, even following curative surgery, is associated with a poor prognosis. A pilot study in advanced gastric cancer patients was carried out using pre-operative chemotherapy with S-1 and low-dose cisplatin (CDDP) (TSLD)., Patients and Methods: Twenty-one patients with stage IV gastric cancer were treated with TSLD as the initial treatment, after informed consent had been obtained. Surgery was performed when curative resection was deemed feasible in selected patients who showed improvement in their tumors. Other regimens including CPT-11 or taxanes were utilized as second-line chemotherapy when the tumor showed no change or progressive disease following TSLD therapy., Results: No patient had a complete response, while 11 had partial responses following TSLD therapy, yielding an overall response rate of 52.4%. Fifteen out of 21 (71.4%) underwent surgery following TSLD therapy, while curative surgery determined by histological investigation was performed in 10 out of 15 (47.6%) patients. No grade 4 toxicities or treatment-related deaths were observed. The following grade 3 toxicities were observed: neutropenia (6 patients), thrombocytopenia (1 patient) and anemia (1 patient). The other toxicities observed, including gastrointestinal toxicity, were grade 2 or less. The median survival time of all patients was 526 days, and 1- and 2-year survival rates were 64.9% and 41.7%, respectively., Conclusion: TSLD is a potent regimen with a low toxicity profile for highly advanced gastric cancer.

Background: S-1 is a novel oral fluorouracil antitumor drug that contains a combination of 3 pharmacological agents: tegafur (FT), a 5-fluorouracil (5-FU) prodrug, 5-chloro-2,4-dihydroxypyridine (CDHP), which inhibits the activity of dihydropyrimidine dehydrogenase (DPD), and potassium oxonate (Oxo), which reduces the gastrointestinal toxicity of 5-FU. S-1 and docetaxel have both been identified as effective agents for the treatment of gastric cancer. However, little is known about the effects and/or adverse effects of a combination of these drugs in the treatment of gastric cancer. The aim of this phase I study was to determine the maximum-tolerated dose (MTD) and the recommended dose of docetaxel with a fixed dose of S-1 in patients with advanced or recurrent gastric cancer., Patients and Methods: Patients with metastatic, recurrent, or unresectable gastric cancer received docetaxel at a starting dose of 25 mg/m2 by i.v. infusion over 1 h on days 1, 15 and 29, and S-1 at the full dose of 80 mg/m2 daily for 4 weeks of every 6 weeks. Nine patients were treated with increasing dosages of docetaxel as follows: (docetaxel/S-1, mg/m2): 25/80 (level 1), 30/80 (level 2) and 35/80 (level 3). All cases were assessable for drug safety and 7 were assessable for response. Colony-stimulating factor (CSF) was not used in this study. The adverse effects of treatment were analyzed according to NCI-CTC, version 2 and the response was assessed according to the Japanese Classification of Gastric Cancer, 13th Ed., Results: The MTD was reached at the 35/80 mg/m2 dose-level in 3 out of 3 patients. These patients experienced some dose-limiting toxicity (DLT) or grade 3 anemia. The reported DLTs included diarrhea, stomatitis and general fatigue. Due to these results, 3 additional patients were not enrolled at this dose-level. No hematological or non-hematological adverse effects (more severe than grade 2) were observed in any of the level 1 or 2 patients. However, among the level 1 patients, 66.7% developed grade 2 leukocytopenia and 33.3% developed grade 2 neutropenia. Among the level 2 patients, 33.3% developed grade 2 appetite loss, diarrhea and general fatigue. Partial responses were achieved in 3 (42.9%) out of the 7 patients with evaluable lesions. These results indicated that the appropriate doses of the 2 drugs in combination therapy are 30 mg/m2 for docetaxel and 80 mg/m2 for S-1., Conclusion: The S-1/docetaxel drug combination showed a good safety profile, with diarrhea and general fatigue being common, but manageable, adverse reactions. Moreover, the responses observed in this study suggest that the drug combination shows a high degree of efficacy in patients with advanced and/or recurrent gastric cancer.

Background: The aim of this multicentric trial was to determine the clinical toxicities and antitumor effects of a chemotherapy regimen of S-1 combined with cisplatin in patients with inoperable locally or metastatic advanced gastric cancer., Patients and Methods: Forty-two patients were entered into the study. S-1 (80 mg/m2) was administered orally daily for 14 consecutive days and 24-h infusion of cisplatin (70 mg/m2) was administered on day 8 of every 28-day cycle., Results: The overall response rate was 50% and complete response rate was 5%. The most common adverse event was leucopenia, which occurred with grade 3 in 7 patients (16.6%) and grade 4 in 2 patients (4.8%). Non-hematological adverse events were generally mild. The median survival time was 342 days. The 2-year survival rate was 22.9%., Conclusion: This combination chemotherapy is active, convenient and well tolerated in patients with high-grade advanced gastric cancer.

Background: S-1, an oral fluorouracil antitumor drug, and docetaxel have both been identified as effective agents for the treatment of gastric cancer. The two drugs have incompletely overlapping principal toxicities, which constitute the rationale for evaluating the effects of a combination of S-1 and docetaxel in this phase I study. The aim of this phase I study was to determine the maximum-tolerated dose (MTD) and the recommended dose of docetaxel with a fixed dose of S-1 in patients with advanced or recurrent gastric cancer., Patients and Methods: The pharmacokinetics of both drugs were evaluated on Day 1 of treatment. Patients with a performance status (PS) of 0 to 2 received docetaxel at the starting dose of 40 mg/m2 by i.v. infusion over 1 hour on Day 1 and S-1 at the fill dose of 80 mg/m2 daily for two weeks every three weeks. Nine patients were treated with increasing dose levels of docetaxel as follows: (docetaxel/S-1, mg/m2): 40/80 (Level 1), 50/80 (Level 2) and 60/80 (Level 3) and all the cases were found to be assessable for drug safety, while 7 were assessable for response. Colony-stimulating factor (CSF) was not used in this study. The adverse effects of the treatment were analyzed according to NCI-CTC version 2, and the response was assessed according to the Japanese Classification of Gastric Cancer, 13th Ed., Results: The MTD was reached at the 50/80 mg/m2 dose level in three patients out of six, who experienced a dose-limiting toxicity (DLT). The DLTs were neutropenia and allergic reactions. No hematological or non-hematological adverse effects (nore severe than Grade 2) were observed in any of the Level 1 patients. However among the Level 2 patients, 50% developed neutropenia (more severe than Grade 2), 33% developed loss of appetite, 17% developed diarrhea, 33% developed stomatitis and 17% developed allergic reactions. On the other hand, partial response was achieved in 5 (71.4%) of the 7 patients with evaluable lesions. The pharmacokinetics of docetaxel were not altered as compared to that in the historical controls by the administration of S-1. These results indicate that the recommended doses of the two drugs in the combination therapy would be 40 mg/m2 for docetaxel and 80 mg/m2 for S-1., Conclusion: The drug combination showed a good safety profile, with neutropenia being a common but manageable adverse reaction. Moreover, the responses observed in the study suggest that the drug combination shows a high degree of efficacy in patients with advanced and or recurrent gastric cancer.