The efficiency of 18F-FDG-PET/CT in the assessment of tumor response to preoperative chemoradiation therapy for locally recurrent rectal cancer.

BACKGROUND: Locally recurrent rectal cancer (LRRC) remains a major problem after curative resection of primary rectal cancer. A noninvasive, prognostic biomarker with which to accurately evaluate disease status and assess the treatment response is critically needed to optimize treatment plans. This study assesses the effectiveness of PET/CT evaluation of preoperative chemoradiation therapy (CRT) in patients with LRRC. METHODS: Since 2004, we have been performing preoperative CRT to improve local tumor control and survival. Between 2004 and 2013, 40 patients with LRRC underwent preoperative CRT (radiation: 50 Gy/25 fractions; chemotherapy: irinotecan plus UFT [tegafur and uracil]/leucovorin) and radical surgery, and underwent 18F-FDG-PET/CT before and 3 weeks after the completion of CRT. The maximum standardized uptake values (SUVmax) of the pre-CRT scan (Pre-SUV) and the post-CRT scan (Post-SUV) were measured. The predictive value of the 18F-FDG-PET and CT/MRI response assessments was evaluated. RESULTS: The mean Pre-SUV was significantly higher than the Post-SUV (8.2 ± 6.1, vs. 3.8 ± 4.0; P < 0.0001). Following CRT, 17/40 patients (42.5%) were classified as responders according to the Mandard tumor regression grade (TRG1-2). The mean Post-SUV was significantly lower in responders than in nonresponders (2.0 ± 1.7 vs. 5.1 ± 3.9; P = 0.0038). Pathological response was not correlated with the response as evaluated by CT (P > 0.9999) or MRI (P > 0.9999). Multivariate regression analysis identified Post-SUV as an independent predictor of local re-recurrence-free survival (P = 0.0383) and for overall survival (P = 0.0195). CONCLUSIONS: PET/CT is useful in assessing tumor response to preoperative CRT for LRRC and predicting prognosis after surgery.

S-1 or gemcitabine adjuvant therapy in resected pancreatic cancer: a cost-effectiveness analysis based on the JASPAC-01 trial.

Purpose: This study aimed to investigate the cost-effectiveness of adjuvant treatments in resected pancreatic cancer.Methods: A Markov model was developed to mimic the disease process of postoperative pancreatic cancer, encompassing three health states (relapse-free survival, recurrent disease, and death). Health outcomes and utility scores were derived from the phase III trial and available literature. Cost data were calculated using standard fee data from the West China Hospital for 2017. One-way sensitivity analyses and probabilistic sensitivity analyses were developed to explore model uncertainty.Results: Treatment with S-1 was estimated to yield 1.61 quality-adjusted life-years (QALYs) at a cost of $25,696, whereas treatment with gemcitabine yielded 1.27 QALYs at a cost of $28,930. The incremental cost-effectiveness ratio of S-1 versus gemcitabine was $-9,490 per QALY. Based on the willingness-to-pay threshold of $25,841 per QALY, the net monetary benefit (NMB) was $15,786 for S-1 and $3,727 for gemcitabine, generating the incremental NMB of $12,059. A probabilistic sensitivity analysis revealed that the probabilities of S-1 and gemcitabine being cost-effective were 92% and 8%, respectively. Results were robust to changes in parameters.Conclusion: Adjuvant therapy using S-1 is a cost-effective alternative compared to gemcitabine in patients with postoperative pancreatic cancer from the Chinese societal perspective.

Cost minimization comparison of oral UFT/leucovorin versus 5-fluorouracil/leucovorin as adjuvant therapy for colorectal cancer in Taiwan.

AIM: Oral uracil-tegafur/leucovorin (UFT/LV) and intravenous 5-fluorouracil (FU)/LV are common adjuvant therapies for Stages II and III colorectal cancer. This study aims to determine the most cost-effective treatment alternative between UFT/LV and 5-FU/LV in Stages II and III colorectal cancer from Taiwan's National Health Insurance perspective. PATIENTS & METHODS: The costs were referenced directly from the National Health Insurance reimbursement price. Chemotherapy regimen considered for the cost analysis calculation was adapted from NSABP-C-06 study, and, a time saving calculation was also included. In addition, we compare the treatment outcome. RESULT: A total cost saving of US$3620.80-$3709.16 per patient per treatment was achieved with the UFT/LV treatment. UFT/LV provides the comparable outcome to 5-FU/LV. CONCLUSION: UFT/LV was the more cost-effective treatment as adjuvant chemotherapy.

Cost-effectiveness analysis of the introduction of S-1 therapy for first-line metastatic breast cancer treatment in Japan: results from the randomized phase III SELECT BC trial.

BACKGROUND: This study evaluated the cost-effectiveness of replacing standard intravenous therapy (taxane) with oral S-1 therapy for first-line metastatic breast cancer treatment. METHODS: This cost-effectiveness analysis was based on data from a randomized phase III trial (SELECT BC). As cost-effectiveness was a secondary endpoint of the SELECT BC trial, some of the randomized patients participated in an EQ-5D survey (N = 391) and health economic survey (N = 146). The EQ-5D responses, claims, and prescription data were collected for as long as possible until death. The expected quality-adjusted life years (QALY) obtained from each treatment were calculated using patient-level EQ-5D data, and the expected cost was calculated using patient-level claim data. The analysis was performed from the perspective of public healthcare payers. RESULTS: The estimated EQ-5D least-square means and 95% CI up to 48 months were 0.764 (95% CI, 0.741-0.782) and 0.742 (95% CI, 0.720-0.764) in the S-1 and taxane arms, respectively. The expected QALY was 2.11 for the S-1 arm and 2.04 for the taxane arm, with expected costs of JPY 5.13 million (USD 46,600) and JPY 5.56 million (USD 50,500), respectively. These results show that S-1 is cost-saving. According to probabilistic sensitivity analysis, S-1 was dominant with a probability of 63%. When the willingness to pay (WTP) value was JPY 5 million (USD 45,500) per QALY, the probability of being cost-effective was 92%. CONCLUSIONS: Our results show that the introduction of oral S-1 therapy for metastatic breast cancer is highly likely to be cost-effective. TRIAL REGISTRATION: UMIN CTR C000000416 . Registered on May 10, 2006.

Adjuvant S-1 chemotherapy after curative resection of gastric cancer in Chinese patients: assessment of treatment tolerability and associated risk factors.

INTRODUCTION: The use of adjuvant chemotherapy with S-1 (tegafur, gimeracil, and oteracil potassium) has been shown to improve the outcome of patients with gastric cancer. There are limited data on the tolerability of S-1 in Chinese patients. In this multicentre retrospective study, we assessed the toxicity profile in local patients. METHODS: Patients with stage II-IIIC gastric adenocarcinoma who had undergone curative resection and who had received S-1 adjuvant chemotherapy were included in the study. Patient demographics, tumour characteristics, chemotherapy records, as well as biochemical, haematological, and other toxicity profiles were extracted from medical charts. Potential factors associated with grade 2-4 toxicities were identified. RESULTS: Adjuvant S-1 was administered to 30 patients. Overall, 19 (63%) patients completed eight cycles. The most common grade 3-4 adverse events included neutropaenia (10%), anaemia (6.7%), septic episode (16.7%), diarrhoea (6.7%), hyperbilirubinaemia (6.7%), and syncope (6.7%). Dose reductions were made in 22 (73.3%) patients and 12 (40.0%) patients had dose delays. Univariate analyses showed that patients who underwent total gastrectomy were more likely to experience adverse haematological events (P=0.034). Patients with nodal involvement were more likely to report adverse non-haematological events (P=0.031). Patients with a history of regular alcohol intake were more likely to have earlier treatment withdrawal (P=0.044). Lower body weight (P=0.007) and lower body surface area (P=0.017) were associated with dose interruptions. CONCLUSIONS: The tolerability of adjuvant S-1 in our patient population was similar to that in other Asian patient populations. The awareness of S-1-related toxicities and increasing knowledge of potential associated factors may enable optimisation of S-1 therapy.

[Comparison of the Cost-Effectiveness of the SOX and COX Regimens in Patients with Unresectable Advanced and Recurrent Colorectal Cancer Using a Clinical Decision Analysis Approach].

Phase III clinical trials have comfirmed that the S-1 plus oxaliplatin(SOX)is inferior to the capecitabine plus oxaliplatin (COX)regimen in the treatment of metastatic colorectal cancer.On the basis of these findings, we compared, using a clinical decision analysis-based approach, the cost-effectiveness of the SOX and COX regimens.Herein, we simulated the expected effects and costs of the SOX and COX regimens using the markov model.Clinical data were obtained from Hong's 2012 report.The cost data comprised the costs for pharmacist labor, material, inspection, and treatment for adverse event, as well as the total cost of care at the advanced stage.The result showed that the expected cost of the SOX and COX regimen was 1,538,330 yen, and 1,429,596 yen, respectively, with an expected survival rate of 29.18 months, and 28.63 months, respectively.The incremental cost-effectiveness ratio of the SOX regimen was 197,698 yen/month; thus, the SOX regimen was found to be more cost-effective that the COX regimen.

Assessment of Adrenal Function and Health-Related Quality of Life in Advanced Gastric Cancer Patients Who Received First-Line Chemotherapy.

OBJECTIVE: We performed this prospective study to identify both the incidence of adrenal insufficiency (AI) and health-related quality of life (HRQOL) in advanced gastric cancer (AGC) patients who were treated with the S-1 plus cisplatin (SP) regimen as a first-line palliative chemotherapy. METHODS: We assessed adverse events (AEs) observed in 52 patients who received the SP regimen for AGC between January 2009 and June 2010 using the Common Toxicity Criteria Adverse Events (CTCAE) version 3.0. Adrenal function was assessed at baseline and 12 weeks after chemotherapy using the low-dose adrenocorticotropic hormone stimulation test. HRQOL was assessed using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire version 3.0 (EORTC-QLQ C30). RESULTS: The incidence of AI was 30.8% (n = 16) and of AE observed 55% (n = 29) among 52 patients after 12 weeks of chemotherapy. Of 29 patients with AE, 34.4% (n = 10) were diagnosed with AI, and of 23 patients without AE, 26.1% (n = 6) were diagnosed with AI. CONCLUSION: The incidence of secondary AI in AGC patients was not rare and was not correlated with the presence of nonspecific AEs. Although patients diagnosed with AI did not show any related symptoms, they are at risk of potentially life-threatening consequences. Thus, the evaluation of AI could be suggested for patients who received chemotherapy.

Study protocol of the TRICOLORE trial: a randomized phase III study of oxaliplatin-based chemotherapy versus combination chemotherapy with S-1, irinotecan, and bevacizumab as first-line therapy for metastatic colorectal cancer.

BACKGROUND: Metastatic colorectal cancer carries a poor prognosis and cannot be cured by currently available therapy. Chemotherapy designed to prolong survival and improve the quality of life (QOL) of patients is the mainstay of treatment. Standard regimens of FOLFOX/bevacizumab and CapeOX/bevacizumab can cause neurotoxicity, potentially disrupting treatment. The results of 3 phase II studies of combination therapy with S-1, irinotecan, and bevacizumab showed comparable efficacy to mFOLFOX6/bevacizumab and CapeOX/bevacizumab, without severe neurotoxicity. Therefore, the establishment and evaluation of S-1-containing irinotecan-based regimens for first-line treatment are expected to become more important. METHODS: The TRICOLORE trial is a multicenter, randomized, open-label, controlled phase III study which aims to evaluate the non-inferiority of combination therapy with S-1/irinotecan/bevacizumab (a 3-week regimen [SIRB] or 4-week regimen [IRIS/bevacizumab]) to oxaliplatin-based standard treatment (mFOLFOX6/bevacizumab or CapeOX/bevacizumab) in patients with metastatic colorectal cancer who had not previously received chemotherapy. Patients will be randomly assigned to either the control group (mFOLFOX6/bevacizumab or CapeOX/bevacizumab) or study group (SIRB or IRIS/bevacizumab). The target sample size is 450 patients. The primary endpoint is progression-free survival (PFS), and the secondary endpoints are overall survival (OS), response rate (RR), time to treatment failure (TTF), relative dose intensity (RDI), the incidence and severity of adverse events, quality of life (QOL), quality-adjusted life years (QALY), health care costs, and relations between biomarkers and treatment response (translational research, TR). DISCUSSION: The results of this study will provide important information that will help to improve the therapeutic strategy for metastatic colorectal cancer, and we believe that this study is very meaningful from the perspective of comparative effectiveness research. TRIAL REGISTRATION: UMIN000007834.

Cost-effectiveness analysis of gemcitabine, S-1 and gemcitabine plus S-1 for treatment of advanced pancreatic cancer based on GEST study.

Gemcitabine (GEM) alone, S-1 alone and gemcitabine plus S-1 (GS) have shown a marginal clinical benefit for the treatment of advanced pancreatic cancer. However, there is no clearly defined optimal cost-effectiveness treatment. The objective of this study was to assess the cost-effectiveness of GEM alone, S-1 alone and GS for the treatment of advanced pancreatic cancer based on GEST study for public payers. A decision model compared GEM alone, S-1 alone and GS. Primary base case data were identified using the GEST study and the literatures. Costs were estimated from West China Hospital, Sichuan University, China, and incremental cost-effectiveness ratios (ICERs) were calculated. Survival benefits were reported in quality-adjusted life-months (QALMs). Sensitive analyses were performed by varying potentially modifiable parameters of the model. The base case analysis showed that the GEM cost $21,912 and yielded survival of 6.93 QALMs, S-1 cost $19,371 and yielded survival of 7.90 QALMs and GS cost $22,943 and yielded survival of 7.46 QALMs in the entire treatment. The one-way sensitivity analyses showed that the ICER of S-1 was driven mostly by the S-1 group utility score of stable state compared with GEM, and the GEM group utility score of progressed state played a key role on the ICER of GS compared with GEM. S-1 represents an attractive cost-effective treatment for advanced pancreatic cancer, given the favorable cost per QALM and improvement in clinical efficacy, especially the limited available treatment options.

Clinical Benefit and Health-Related Quality of Life Assessment in Patients Treated with Cisplatin/S-1 Versus Cisplatin/5-FU: Secondary End Point Results From the First-Line Advanced Gastric Cancer Study (FLAGS).

PURPOSE: Patient-reported outcomes (PRO) of health-related quality of life (HRQoL) and time to worsening of clinical benefit parameters were evaluated as secondary end points in the phase 3 first-line advanced gastric cancer study (FLAGS) trial of cisplatin/S-1 versus cisplatin/5-fluorouracil (5-FU) in patients with previously untreated advanced gastric cancer. METHODS: The primary PRO end point was the Trial Outcome Index of the Functional Assessment of Cancer Therapy-Gastric (FACT-Ga). FACT-Ga was completed at the beginning of the first 4 cycles, cycle 6, and then every 3 cycles thereafter. The Chemotherapy Convenience and Satisfaction Questionnaire (CCSQ) was administered before the first 4 cycles; clinical benefit parameters (performance status, weight loss, and anorexia) were assessed at baseline, prior to study drug administration on day 1 of each cycle after cycle 1, and at the end of study treatment. RESULTS: Compliance to questionnaire fulfillment was more than 80 % through cycle 9. Significantly, fewer patients treated with cisplatin/S-1 reported worsened physical well-being (PWB) scores (45.1 versus 51.7 %, p = 0.044) and experienced significantly longer time to worsening in PWB scores, with a median of 4.5 months (95 % confidence interval (CI), 3.1-5.1) compared to 3.0 months (2.8-4.6) with cisplatin/5-FU (CF) (p = 0.01). Patients receiving cisplatin/S-1 also reported significantly higher best and worst score of PWB as well as CCSQ scores and a longer median time to worsening in clinical benefit parameters. CONCLUSIONS: Differences in secondary end points of PWB, CCSQ scores, and clinical benefit parameters favoring the cisplatin/S-1 arm provide further evidence for considering this combination a standard therapeutic option for first-line treatment of advanced gastric cancer.

Assessment of the value of carcinoembryonic antigen reduction ratio as a prognosis factor in rectal cancer.

BACKGROUND: Carcinoembryonic antigen (CEA) is the most widely used tumor marker for colorectal cancer. This study aimed to investigate the role of CEA reduction ratio after preoperative chemoradiotherapy (CRT). METHODS: We enrolled 284 patients who underwent preoperative CRT followed by radical surgical resection. Patients were divided into 3 groups: serum CEA levels before CRT (pre-CRT CEA) less than 5 ng/mL (group 1); pre-CRT CEA of 5 ng/mL or more with CEA reduction ratio of 50% or more (group 2); and pre-CRT CEA of 5 ng/mL or more with CEA reduction ratio less than 50% (group 3). RESULTS: The 5-year disease-free survival (DFS) rate was not different between groups 1 (71.8%) and 2 (69.4%) but was significantly lower in group 3 (49.5%). CEA group, lymph node status after CRT (ypN) stage, and histologic type were independent prognostic factors for DFS on multivariate analysis. CONCLUSIONS: CEA reduction ratio might be an independent prognostic factor for DFS in rectal cancer patients treated with preoperative CRT and radical surgery.

Validity of response assessment criteria in neoadjuvant chemotherapy for gastric cancer (JCOG0507-A).

BACKGROUND: Neoadjuvant chemotherapy may improve outcomes in gastric cancer. Tumor responses can be evaluated with RECIST, Japanese Classification of Gastric Carcinoma (JCGC), and histological criteria. These approaches have not yet been compared. METHODS: We analyzed two phase II trials of neoadjuvant chemotherapy using S-1 plus cisplatin. JCOG0210 included patients with linitis plastica and large ulcero-invasive tumors, whereas JCOG0405 comprised those with para-aortic or bulky lymph node metastases. Radiologic evaluations were conducted using RECIST in JCOG0405 and JCGC criteria in JCOG0210, because the latter included many patients without measurable lesions. A histological responder was defined as a patient in whom one third or more of the tumor was affected. The hazard ratios (HR) for death between responders and non-responders and response rate differences between short- and long-term survivors were estimated. RESULTS: In JCOG0210 (n = 49), HR was 0.54 in JCGC responders (P = 0.059) and 0.40 in histological responders (P = 0.005). The difference in response rates between short- and long-term survivors using histological criteria (34 %, P = 0.023) was greater than that using JCGC criteria (24 %, P = 0.15). In JCOG0405 (n = 51), HR was 0.67 in RECIST responders (P = 0.35) and 0.39 in histological responders (P = 0.030). In short- and long-term survivors, respectively, RECIST response rates were 62  and 67 % (P = 0.77), whereas histological response rates were 33  and 63 % (P = 0.048). CONCLUSIONS: Histological criteria showed higher response assessment validity than RECIST or JCGC criteria and yielded the best surrogate endpoint for overall survival.

[Assessment of the vulnerable elders survey as a predictive test for elderly patients with advanced or metastatic gastric cancer treated with combined S-1 and docetaxel therapy].

Ten patients aged 75 years or more with advanced or metastatic gastric cancer were prescribed S-1 plus docetaxel (DOC) combination therapy. None of the patients showed complete response, but 2 showed partial response and 4 showed stable disease. Grade 3 or 4 toxicities occurred in 3 patients. Three patients with performance status (PS) 1 achieved partial response or stable disease and were free of Grade 3 or 4 toxicities, whereas the response and occurrence of adverse events in 7 patients with PS 2 varied widely. In these patients, an investigation of the relationship between response to treatment and the Vulnerable Elders Survey (VES-13) score showed that VES-13 scores were higher in the non-response group than in the other patients and in patients who experienced adverse events than in those who did not. These findings suggest that VES-13 could be a useful screening tool for predicting response and the occurrence of adverse events in elderly patients undergoing combined S-1 plus DOC therapy for advanced or metastatic gastric cancer.

The European Medicines Agency review of Tegafur/Gimeracil/Oteracil (Teysuno™) for the treatment of advanced gastric cancer when given in combination with cisplatin: summary of the Scientific Assessment of the Committee for medicinal products for human use (CHMP).

The product Teysuno™ (S-1) contains tegafur, a prodrug of 5-fluorouracil (5-FU), and two modulators of 5-FU metabolism, gimeracil and oteracil. The main clinical study in this application was a randomized controlled study comparing S-1 plus cisplatin with 5-FU plus cisplatin. In this study, median overall survival times of 8.6 months and 7.9 months for S-1 plus cisplatin and 5-FU plus cisplatin, respectively, were observed (hazard ratio, 0.92; 95% confidence interval, 0.80-1.05). The Committee for Medicinal Products for Human Use of the European Medicines Agency concluded that S-1 in combination with cisplatin (75 mg/m²) was noninferior to 5-FU plus cisplatin (100 mg/m²) in patients with advanced gastric cancer and adopted a positive opinion recommending the marketing authorization for this product for the treatment of advanced gastric cancer when given in combination with cisplatin. The recommended dose of S-1 is 25 mg/m² (expressed as tegafur content) twice a day, for 21 consecutive days followed by 7 days rest (one treatment cycle), in combination with 75 mg/m² cisplatin i.v. administered on day 1. This treatment cycle is repeated every 4 weeks. The most common side effects reported in the pivotal study were anemia, neutropenia, vomiting, diarrhea, abdominal pain, weight decrease, anorexia, and fatigue. The objective of this paper is to summarize the scientific review of the application leading to approval in the EU. The full scientific assessment report and the summary of product characteristics are available on the European Medicines Agency website (http://www.ema.europa.eu).

[Assessment of quality of life by questionnaires between S-1/CPT-11 and mFOLFOX6 in patients with advanced colorectal cancer].

UNLABELLED: Injectable combination chemotherapy with 5-fluorouracil (5-FU)/Leucovorin (LV), oxaliplatin (OHP), and irinotecan (CPT-11) has been a standard treatment for advanced colorectal cancer (CRC). An oral fluoropyrimidine, S-1 (tegafur, gimeracil, and oteracil), has been developed recently, and a combination of S-1/CPT-11 demonstrated effects comparable to FOLFIRI for the treatment of advanced CRC. Being without continuous infusion lasting for days, combination chemotherapy with oral fluoropyrimidine may limit inconvenience and improve the quality of life (QOL) of patients. There have been few studies evaluating chemotherapy with oral fluoropyrimidine in terms of patient QOL and convenience. PATIENTS AND METHODS: We assessed the patients' QOL by questionnaire, comparing experiences of those treated with S-1/CPT-11 to those treated with mFOLFOX6 in patients with advanced CRC. The questionnaire, selected from EORTC QLQ, FACT-G, and FACT/GOG-Ntx, consisted of six categories: moving activity, willingness, pain and numbness, gastrointestinal symptoms, daily life, and convenience. The questionnaire had 5 questions in each category and a total of 30 questions. RESULTS: Patients' background and characteristics were similar. No significant difference was observed in response rates and time to progression between the groups. As for adverse effects, there was a case of fatigue (grade 2), five cases of neurotoxicites (grade 1 and 2) in mFOL-FOX6, and a case of diarrhea (grade 3) in S-1/CPT-11. No difference between the two groups was observed in responses to the questionnaire asking about moving activity, willingness, gastrointestinal symptoms, and daily life. As for neurotoxicity and convenience, however, S-1/CPT-11 showed significantly better results than mFOLFOX6. CONCLUSION: The present results suggest that questionnaires are useful for assessing patients' QOL with advanced CRC treated chemotherapy. Combination chemotherapy with oral fluoropyrimidine S-1 could provide similar response rates, limit inconvenience, and improve QOL.

[European Organization for Research and Treatment of Cancer QLQ-C30 and functional assessment of cancer therapy- general for measurement of quality of life in colorectal cancer patients who received adjuvant chemotherapy- a comparison].

Quality of life (QOL) was measured prospectively using the European Organization for Research and Treatment of Cancer QLQ-C30 (QLQ-C30) and Functional Assessment of Cancer Therapy-General (FACT-G) in 94 colorectal cancer patients who received adjuvant chemotherapy with oral uracil/tegafur plus leucovorin. Two QOL questionnaires were then compared with reference to corresponding scales. The post-treatment assessments changed significantly from the baseline values and favored post-treatment for all scales except social well-being of the FACT-G. All scales except social well-being in patients with Grade 0-1 toxicities were better than those with Grade 2-3 toxicities. Social well-being in patients with Grade 2-3 toxicities were worse than those with Grade 0-1. When corresponding scales between the two QOL questionnaires were compared, a high correlation for physical domain or emotional domain was found, whereas no correlation was noticed for social domain. In conclusion, the social domain of the two QOL questionnaires may evaluate different aspects of QOL.

[Therapeutic outcome and prognosis in S-1+CDDP chemotherapy for advanced gastric cancer--postoperative histopathological assessment].

UNLABELLED: The efficacy and prognosis with neoadjuvant chemotherapy(NAC)for advanced gastric cancer were assessed by histopathological examination of resected tumors. The subjects consisted of cases (< or =75 y.o.) having type 4/large type 3 (diameter> or = 8 cm) gastric cancer curable by resection based on preoperative imaging diagnostics. The NAC regimen consisted of oral S-1 at 80-120 mg/body on Days 1-21 and CDDP at 60 mg/m2 on Day 8. After two courses, gastrectomy with D2 or more extended lymph node dissection was performed. Based on histopathological effect grading of resected tumors, patients were classified into responder(grade 2 or above)or nonresponder(grade 1b or below)and analyzed for TS and OPRT gene expressions and prognosis. There were 5 responders and 6 nonresponders. High OPRT expression was mainly associated with responders. On the other hand, high TS expression with low OPRT expression was more frequently associated with nonresponders. At a median follow-up of more than 56 months (minimum follow-up, 54 months; maximum follow-up, 60 months), the 4-year overall survival was 36. 4%. Compared to nonresponders, responders showed a longer survival (p=0. 0864) and relapse-free period (p=0. 0414). CONCLUSION: These results suggest that NAC with S-1+CDDP is promising against resectable advanced gastric cancer; however, its true value will only emerge after completion of the ongoing phase III study of NAC plus surgery and postoperative chemotherapy for resectable large type 3/type 4 advanced gastric cancer (JCOG0501).

[The assessment of chemoradiation therapy with CDDP/S-1 for advanced gastric cancer that was actively bleeding].

In the management of inoperable patients with advanced gastric cancer, it is important to control a tumor bleeding actively and to make sure that the patient can take meals through the stenotic cardia for the purpose of keeping the patients' quality of life well. We treated five gastric cancer patients with chemoradiation therapy consisting of CDDP (6 mg/m2) and S-1 (100 mg/body). In the treatment results, we have never seen an active tumor bleeding and anemic state, which required a blood transfusion after the treatment. In all of the 5 cases, a total quantity of taking meals increased due to a cardia stenosis improvement by tumor. We thought this treatment was useful for patients with cardia stenosis and actively bleeding in advanced gastric cancer.

[Assessment of chemoradiation therapy for advanced rectal cancer invaded the pelvic organ].

We assess the effect of chemoradiation therapy for four cases of advanced rectal cancer. The radiation therapy consisted of 40-50 Gy delivered in fraction of 2 Gy/day. A treatment of 5-fluorouracil (500 mg/body) with l-leucovorin (100 mg/body) intravenously once a week, or oral S-1 (100 mg/day/body) for four weeks, was given during radiation therapy. Efficacy for primary carcinoma was evaluated as partial response in all four cases. We performed a curative operation in two cases. Histological efficacy for primary tumors was diagnosed as Grade 2 and Grade 3. Grade 3 adverse effect for neutropenia occurred in one patient, and Grade 3 adverse effect for appetite loss occurred in 2 patients. All cases survived without a recurrence for a period of 4 months-5 years and 3 months. Chemoradiation therapy was safe and an effective treatment prior to curative operation for advanced rectal cancer which invaded the pelvic organ.

[A case of recurrent rectal cancer with multiple lung metastases successfully treated with S-1 and CPT-11 combination chemotherapy].

We report a case of recurrent rectal cancer with multiple lung metastases successfully treated with S-1 and CPT-11 combination chemotherapy. Rectal amputation was carried out on the rectal cancer patient, a 63-year-old man. CT scan revealed multiple lung metastases after 20 months of surgery. The patient was treated with S-1 and CPT-11 combination chemotherapy. S-1(100mg/body/day)was orally administered for 2 weeks followed by a 1-week interval, and CPT-11 (120 mg/body on day 1)was simultaneously administered. After completion of 8 courses, CT scan showed no lung metastases, and the patient was judged to have achieved a complete response (CR). The CR interval was maintained for twelve months until 20 courses of chemotherapy had been completed. This chemotherapy was expected to have a potent therapeutic efficacy for recurrent rectal cancer, considering the convenience, cost benefit and no severe adverse event.