s-1-(combination) and Rectal-Neoplasms

Chemotherapy that targets metastatic colorectal cancer originally developed in Europe and the US, and was introduced to Japan in April, 2005, where it has since headed toward full scale clinical applications. This event created an opportunity to re-evaluate the role of postoperative adjuvant chemotherapy in Japan. In Europe and the US, adjuvant therapy has centered on the intravenous administration of leucovorin/fluorouracil, while in Japan, it has been long-term continuous administration of oral fluoropyrimidine preparations. Despite this difference in historical background,guidelines created in 2005 recommend both LV/5-FU and LV/UFT regimens and there has been increased application of evidence-based adjuvant chemotherapy. The benefits of postoperative adjuvant chemotherapy in stage II and III (high risk of recurrence) colorectal cancer patients have also come to be recognized. Examination of a new survey of 100 medical specialists on the current state of adjuvant chemotherapy for colorectal cancer in Japanese clinical settings revealed that for stage III patients, there is a tendency to choose treatment based on evidence gathered from both home and abroad. In contrast, a solid majority (60%) of stage II patients are treated exclusively with oral fluoropyrimidine despite a lack of, or limited evidence of efficacy. At the same time, half of the physicians who treated stage II patients with adjuvant chemotherapy initially attempted to identify those with a high risk of cancer recurrence and treat them accordingly; which was a breakthrough in the clinical treatment approach. While ongoing comparative Japanese clinical studies that use adjuvant chemotherapy for the treatment of colorectal cancer were noted, consideration was also given to the desired future direction clinical research should take.

Topics: Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Chemotherapy, Adjuvant; Colonic Neoplasms; Combined Modality Therapy; Drug Administration Schedule; Drug Combinations; Europe; Evidence-Based Medicine; Fluorouracil; Humans; Irinotecan; Japan; Leucovorin; Neoplasm Staging; Oxonic Acid; Practice Guidelines as Topic; Rectal Neoplasms; Tegafur; United States; Uracil

Recently, the demand for more useful therapies for cancer patients has increased. We describe in this paper a therapeutic modality based on a self-rescuing concept (SRC), and which features dual activity, i.e., an effect-enhancing activity and an adverse reaction-reducing activity. We present the theory and practice of S-1, a novel oral fluoropyrimidine anticancer agent designed to enhance anticancer activity and reduce gastrointestinal toxicity through the deliberate combination of the following components: the oral fluoropyrimidine agent tegafur; a DPD inhibitor (CDHP) which is more potent than uracil, which is used in UFT; and an ORTC inhibitor (Oxo) which localizes in the gastrointestinal tract. S-1 is a combination drug with a molar ratio of 1:0.4:1 in FT, CDHP, and Oxo, respectively. A clinical pharmacology study was conducted to examine blood concentrations of 5-FU after twice-a-day administration of S-1 at a dose of 40 mg/m2. Blood concentrations of 5-FU were found to be 60 to 200 ng/ml in all twelve patients examined. The overall response rate was 44.6% (45/101). In addition, the incidence of adverse reactions judged to be grade 3 or higher was 10% or less. We have also reported a combination therapy with 5-FU (civ) (5-FU: 250 to 350 mg/body, 24-hour cvi, consecutive days) and low-dose cisplatin (CDDP: 3 to 5 mg/body, i.v., 5 days/week), in which CDDP was used as a modulator of 5-FU. Low-dose FP therapy provided response rates as high as 40 to 60% in 163 patients with various gastrointestinal cancers other than pancreas cancer. The incidence of the adverse reactions of nausea and vomiting which were judged to be grade 3 or higher was 2.5% (4/163). The incidences of other adverse reactions were 1% or less. In line with the theory and practice of combination therapy with 5-FU (cvi) 24 hr cvi; 5-FU: 750 to 1,000 mg/body/day on Monday, Wednesday, and Friday (withdrawal on Tuesday, Thursday, Saturday and Sunday) intermittent administration and low-dose CDDP (3 to 5 mg/body/day day 1-5/w) consecutive administration was utilized in which there was a difference in cell cycle between gastrointestinal mucosal cell and tumor cell, or between bone marrow cell and tumor cell. Few adverse reactions, e.g., diarrhea and stomatitis, were observed despite the overall response rate being as high as 52.4% (22/42). The incidence of adverse reaction judged to be grade 3 or higher was as low as 9.3% (5/54), with an incidence of 9.3% (5/54) in Grade 3 or higher myelotox

Topics: Administration, Oral; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Colonic Neoplasms; Drug Administration Schedule; Drug Combinations; Esophageal Neoplasms; Fluorouracil; Humans; Infusions, Intravenous; Oxonic Acid; Pancreatic Neoplasms; Pyridines; Rectal Neoplasms; Tegafur

Preoperative chemoradiotherapy (CRT), the current standard of care for locally advanced rectal cancer (LARC), is associated with many radiotherapy (RT)-related side effects. We aimed to evaluate whether S-1 and oxaliplatin (SOX) or folinic acid, 5-FU, and oxaliplatin (mFOLFOX6) can be as effective as neoadjuvant chemotherapy (NAC) regimens for LARC without RT.. Patients with untreated resectable LARC were randomly assigned to receive SOX or mFOLFOX6. The NAC protocol period was 3 months. The primary endpoint was 3-year disease-free survival (DFS), and the secondary endpoints included pathological effects, surgical completion rate, 3-year survival, and safety.. From September 2013 to October 2015, 56 and 54 patients were enrolled in the SOX and mFOLFOX6 arms, respectively. The 3-year DFS rates were 69.4% (95% confidence interval [CI] 54.9-83.6) and 73.4% (95% CI 58.7-83.6) in the SOX and mFOLFOX6 arms, respectively; no significant differences were found between the arms (log-rank test; P = 0.5315, hazard ratio: 0.808, 95% CI 0.414-1.578). The 3-year survival rates were 92.3 and 91.8% in the SOX and mFOLFOX6 arms, respectively. The surgical completion rate was 98.1% overall, 100% in the SOX arm, and 96.0% in the mFOLFOX6 arm. The incidences of pathological response rates ≥grade 1b were 41.5 and 43.8% in the SOX and mFOLFOX6 arms, respectively. Both treatments were manageable and tolerable.. We demonstrated the effectiveness and safety of SOX and mFOLFOX6, both of which may be new neoadjuvant treatment candidates in previously untreated LARC cases.. Date of enrolment of the first participant to the trial: 3rd Oct 2013; This study was registered in the UMIN clinical trials registry on 14th Aug, 2013. (Prospectively registered, UMIN-CTR number UMIN000011486). https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr.cgi?function=brows&recptno=R000013441&language=J.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Drug Combinations; Female; Fluorouracil; Follow-Up Studies; Humans; Leucovorin; Male; Middle Aged; Neoadjuvant Therapy; Oxaliplatin; Oxonic Acid; Prognosis; Rectal Neoplasms; Survival Rate; Tegafur

Preventing distant recurrence and achieving local control are important challenges in rectal cancer treatment, and use of adjuvant chemotherapy has been studied. However, no phase III study comparing adjuvant chemotherapy regimens for rectal cancer has demonstrated superiority of a specific regimen. We therefore conducted a phase III study to evaluate the superiority of S-1 to tegafur-uracil (UFT), a standard adjuvant chemotherapy regimen for curatively resected stage II/III rectal cancer in Japan, in the adjuvant setting for rectal cancer.. The ACTS-RC trial was an open-label, randomized, phase III superiority trial conducted at 222 sites in Japan. Patients aged 20-80 with stage II/III rectal cancer undergoing curative surgery without preoperative therapy were randomly assigned to receive UFT (500-600 mg/day on days 1-5, followed by 2 days rest) or S-1 (80-120 mg/day on days 1-28, followed by 14 days rest) for 1 year. The primary end point was relapse-free survival (RFS), and the secondary end points were overall survival and adverse events.. In total, 961 patients were enrolled from April 2006 to March 2009. The primary analysis was conducted in 480 assigned to receive UFT and 479 assigned to receive S-1. Five-year RFS was 61.7% [95% confidence interval (CI) 57.1% to 65.9%] for UFT and 66.4% (95% CI 61.9% to 70.5%) for S-1 [P = 0.0165, hazard ratio (HR): 0.77, 95% CI 0.63-0.96]. Five-year survival was 80.2% (95% CI 76.3% to 83.5%) for UFT and 82.0% (95% CI 78.3% to 85.2%) for S-1. The main grade 3 or higher adverse events were increased alanine aminotransferase and diarrhea (each 2.3%) in the UFT arm and anorexia, diarrhea (each 2.6%), and fatigue (2.1%) in the S-1 arm.. One-year S-1 treatment is superior to UFT with respect to RFS and has therefore become a standard adjuvant chemotherapy regimen for stage II/III rectal cancer following curative resection.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Colonic Neoplasms; Disease-Free Survival; Drug Combinations; Drug-Related Side Effects and Adverse Reactions; Female; Humans; Japan; Male; Middle Aged; Neoplasm Recurrence, Local; Neoplasm Staging; Oxonic Acid; Rectal Neoplasms; Tegafur; Uracil

Preoperative 5-fluorouracil-based chemoradiotherapy is a standard treatment for locally advanced lower rectal cancer (LALRC). We performed a phase I study to develop a new regimen combining irinotecan and S-1.. Patients with LALRC (T3-4, N0-2) were studied. The radiation dose was 45Gy in 25 fractions. S-1 (80mg/m(2)/day) was administered on days 1-5, 8-12, 22-26, and 29-33. Irinotecan was administered on days 1, 8, 22, and 29. The dose of irinotecan was initially 60mg/m(2) (level 1). Surgery was performed 6-10weeks after the chemoradiotherapy.. Twenty patients were enrolled, of whom 18 patients were analyzed. Dose-limiting toxicity (DLT) did not occur in the first 3 patients treated with irinotecan at 80mg/m(2) (level 2), but developed in 3 of the 6 patients who received irinotecan at 90mg/m(2) (level 3). Then DLT occurred in 3 other patients at level 2. At level 2 or 3, DLT comprised neutropenia, thrombocytopenia, and diarrhea. Level 2 was designated as the maximum tolerated dose, and level 1 as a recommended dose (RD). The pathological complete response rate was 28%, and the down-staging rate was 56%.. Our results suggested that the RD of irinotecan when combined with preoperative S-1 and pelvic radiation was 60mg/m(2).

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Chemoradiotherapy; Diarrhea; Drug Administration Schedule; Drug Combinations; Female; Humans; Irinotecan; Magnetic Resonance Imaging; Male; Maximum Tolerated Dose; Middle Aged; Neoadjuvant Therapy; Oxonic Acid; Radiotherapy Planning, Computer-Assisted; Rectal Neoplasms; Tegafur; Tomography, X-Ray Computed

The purpose of this phase I study of the dose escalation of oxaliplatin in combination with oral S-1 and pelvic radiation preoperatively for poor-risk lower rectal cancer was to determine the dose-limiting toxicity (DLT) and recommended dose of oxaliplatin.. Patients with cT4 and lateral pelvic lymph node metastasis, and without distant metastasis (cM0), were treated with weekly oxaliplatin, oral S-1 40 mg/m(2) twice daily for 5 days a week, and radiation. A total of 5 weekly doses of oxaliplatin were planned. RT was administered to a total dose of 50.4 Gy in 28 fractions.. We enrolled 11 patients between December 2009 and January 2012. DLTs were observed at dose level 1 (50 mg/m(2)) in two patients, one of whom experienced grade 3 aspartate aminotransferase elevation and a grade 3 alanine aminotransferase increase, and the other developed grade 4 hypokalemia and a grade 3 alanine aminotransferase increase. Five patients at dose level 2 (60 mg/m(2)) showed no DLTs. The hematological toxicities in all patients were mild and reversible. One patient showed distant metastasis after chemoradiation. Ten of the 11 patients achieved R0 resection by mesorectal resection and lateral lymph node dissection; three of the 10 underwent combined resection of the other organs.. This phase I trial of preoperative S-1 in combination with oxaliplatin and radiation for lower rectal cancer with T4 and lateral pelvic lymph node metastasis revealed that the recommended dose of oxaliplatin was 60 mg/m(2) weekly.

Topics: Adenocarcinoma; Adult; Aged; Alanine Transaminase; Antineoplastic Combined Chemotherapy Protocols; Aspartate Aminotransferases; Chemoradiotherapy, Adjuvant; Diarrhea; Dose Fractionation, Radiation; Drug Combinations; Female; Humans; Lymph Node Excision; Lymphatic Metastasis; Male; Middle Aged; Neoadjuvant Therapy; Neoplasm Staging; Neutropenia; Organoplatinum Compounds; Oxaliplatin; Oxonic Acid; Pelvis; Preoperative Care; Rectal Neoplasms; Tegafur; Vomiting

This phase I study was performed to determine the maximum tolerated dose (MTD), recommended dose (RD), and dose-limiting toxicities (DLTs) of oxaliplatin combined with preoperative chemoradiotherapy with S-1, oxaliplatin, and bevacizumab in locally advanced rectal cancer.. Eligible patients had a newly diagnosed clinical stage T1-4 N0-3 M0 rectal adenocarcinoma within 12 cm of the anal verge suitable for curative resection. Conformal radiation therapy was given (4 fields, 2 Gy daily fractions, 5 days/week, total dose 40 Gy) with concurrent S-1 (80 mg/m(2)/day orally, days 1-5, 8-12, 15-19, and 22-26), bevacizumab (90 min continuous intravenous infusion at 5 mg/kg, days 1 and 15), and oxaliplatin (120 min continuous intravenous infusion, days 1, 8, 15, and 22). The initial oxaliplatin dose (40 mg/m(2)/day) was gradually increased to determine the MTD and RD. Surgery was performed 6 weeks after completion of preoperative chemoradiotherapy.. 11 patients were enrolled. The MTD of oxaliplatin was considered to be 60 mg/m(2), because three of five patients developed DLTs such as diarrhea and hives. The recommended dose of oxaliplatin was set at 50 mg/m(2). Of the patients who received oxaliplatin at ≤ RD, 5 (83.3%) had a clinical response [four pathological responses and one pathological complete response (Grade 3)].. With this new regimen, the MTD of oxaliplatin was 60 mg/m(2), and the RD for phase II studies was 50 mg/m(2). This new regimen appears to provide worthwhile outcomes for locally advanced rectal cancer and merits a phase II study.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Chemoradiotherapy; Dose-Response Relationship, Drug; Drug Combinations; Female; Humans; Male; Maximum Tolerated Dose; Middle Aged; Neoadjuvant Therapy; Organoplatinum Compounds; Oxaliplatin; Oxonic Acid; Radiotherapy, Conformal; Rectal Neoplasms; Rectum; Tegafur

A single-arm phase II clinical trial was conducted to evaluate the safety and efficacy of preoperative chemoradiotherapy (CRT) with concurrent S-1, bevacizumab, and radiation in patients with locally advanced rectal cancer (LARC).. Fifty-two patients with LARC were enrolled. A total dose of 45 Gy was delivered in 25 fractions over 5 weeks, S-1 was administered orally twice a day on days 1-14 and 22-35, and bevacizumab was administered on days 1, 15, and 29. Surgical resection was scheduled 8 weeks (6-10 weeks) after completing the CRT.. All 52 patients underwent R0 radical surgery. Sphincter preservation was possible in 38 (73.1%) patients. A pathologic complete response was obtained in 10 (19.2%) patients, a pathologic downstaging was achieved in 37 (71.2%) patients, and the tumor shrinkage rate was 77.1%. The only grade 3 adverse events were leukopenia and rash in 1 (1.9%) patient. The rate of postoperative complications was 28.8%. Anastomotic leakage occurred in 9 (23.7%) of the 38 patients who underwent sphincter-preserving surgery. Perineal wound dehiscence developed in 2 (14.3%) of the 14 patients who received an abdominoperineal resection.. Adding bevacizumab to S-1 clearly increased the incidence of wound-related complications, with no distinct enhancement of tumor response.

Topics: Adenocarcinoma; Adult; Aged; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Chemoradiotherapy; Drug Combinations; Female; Humans; Male; Middle Aged; Oxonic Acid; Postoperative Complications; Rectal Neoplasms; Tegafur

The objective of this phase I study was to determine the maximum tolerated dose (MTD) and recommended dose (RD) of preoperative chemoradiotherapy (CRT) with S-1 plus oxaliplatin in patients with locally advanced rectal cancer.. Patients received radiotherapy in a total dose of 50.4 Gy in 28 fractions. Concurrent chemotherapy consisted of a fixed oral dose of S-1 (80 mg/m(2)/day) on days 1-5, 8-12, 22-27, and 29-33, plus escalated doses of oxaliplatin as an intravenous infusion on days 1, 8, 22, and 29. Oxaliplatin was initially given in a dose of 40 mg/m(2)/week to three patients. The dose was then increased in a stepwise fashion to 50 mg/m(2)/week and the highest dose level of 60 mg/m(2)/week until the MTD was attained.. Thirteen patients were enrolled, and 12 received CRT. Dose-limiting toxicity (DLT) occurred in two of six patients (persistent grade 2 neutropenia, delaying oxaliplatin treatment by more than 3 days) at dose level 3; there were no grade 3 or 4 adverse events defined as DLT. The RD was 60 mg/m(2)/week of oxaliplatin on days 1, 8, 22, and 29. Twelve patients underwent histologically confirmed R0 resections, and two out of six patients (33%) given dose level 3 had pathological complete responses.. The RD for further studies is 80 mg/m(2) of S-1 5 days per week plus 60 mg/m(2) of oxaliplatin on days 1, 8, 22, and 29 and concurrent radiotherapy. Although our results are preliminary, this new regimen for neoadjuvant chemoradiotherapy is considered safe and active.. This trial was registered with Clinicaltrials.gov (identifier: NCT01227239 ).

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Chemoradiotherapy; Drug Combinations; Female; Follow-Up Studies; Humans; Male; Maximum Tolerated Dose; Middle Aged; Neoplasm Staging; Organoplatinum Compounds; Oxaliplatin; Oxonic Acid; Pelvis; Prognosis; Rectal Neoplasms; Remission Induction; Tegafur; Young Adult

Postoperative adjuvant chemotherapy for patients with stage III Colorectal cancer (CRC) is now internationally accepted as standard care for improving patient outcomes. The Adjuvant Chemotherapy Trial of S-1 for Colorectal Cancer (ACTS-CC) confirmed the non-inferiority of S-1 to tegafur/urcail/leucovorin in terms of overall survival and disease-free survival in patients with stage III CRC after curative surgery. However, the 6-month completion rate of S-1 treatment was 76.5% in the ACTS-CC. Therefore, treatment completion remains an unresolved problem.. A randomized phase II trial was designed to evaluate the efficacy and safety of oral daily administration and alternate-day administration of S-1 as adjuvant chemotherapy in curatively resected stage III CRC. Enrolled patients were assigned to either S-1 daily administration (Arm A) or alternate-day S-1 administration (Arm B). Assigned treatment will start within 8 weeks after surgery. In both arms, S-1 dosing (oral) will be based on body surface area (80 mg/day for body surface area<1.25 m2, 100 mg/day for 1.25-1.5 m2, or 60 mg/day for >1.5 m2). In Arm A, S-1 will be administered orally for 28 days, followed by a 14-day rest. Administration will be conducted for 24 weeks from the date of therapy start. In Arm B, S-1 will be administered orally on alternate days for 28 weeks from the date of the start of therapy. After treatment, all patients will be observed without additional therapy unless recurrent lesions or other cancer lesions occur. The primary endpoint is treatment completion rate. Secondary endpoints include 3-year disease-free survival, compliance, and adverse events.. Previously, S-1 alternate-day intake maintained the efficacy of chemotherapy while reducing adverse effects for patients with R0-resected stage II/III gastric cancer. Improvement of chemotherapy completion rate for patients with colorectal cancer will lead to an improved patient prognosis. Therefore, a randomized phase II trial has been designed to examine the efficacy of alternate-day versus current standard daily S-1 administration as adjuvant chemotherapy for R0-resected stage III colorectal cancer.. This study was registered on 18 February 2014 with University Hospital Medical Information Network Clinical Trials Registry: UMIN000013185.

Topics: Adenocarcinoma; Administration, Oral; Adult; Aged; Aged, 80 and over; Antimetabolites, Antineoplastic; Body Surface Area; Chemotherapy, Adjuvant; Colonic Neoplasms; Disease-Free Survival; Drug Administration Schedule; Drug Combinations; Drug Dosage Calculations; Humans; Medication Adherence; Middle Aged; Oxonic Acid; Rectal Neoplasms; Research Design; Tegafur; Young Adult

The purpose of this study was to evaluate the rate of pathologic complete response (pCR) in patients with locally advanced rectal cancer (LARC) treated with neoadjuvant chemoradiation therapy (CRT) with leucovorin (FL) versus irinotecan/S-1 (IS).. Patients with resectable LARC (clinical stage T3/4, lymph node positive, or both) were randomly assigned to receive preoperative radiation (45-50.4 Gy in 25 to 28 daily fractions) and concomitant chemotherapy either with a bolus injection of FL (400 mg/m(2)/day 5-fluorouracil and 20 mg/m(2)/day leucovorin) for 3 consecutive days every 4 weeks for 2 cycles (FL group) or with 40 mg/m(2) irinotecan on days 1, 8, 15, 22, and 29, and 35 mg/m(2) S-1 twice on the day of irradiation (IS group). Curative surgery was performed approximately 4 to 8 weeks after the completion of CRT. The postoperative chemotherapy regimen was FL with a primary endpoint of a pCR rate evaluation.. One hundred forty-two eligible patients were randomly assigned, and the median follow-up duration was 43.8 months (95% confidence interval, 40.8-46.8 months). One hundred thirty-three patients (93.7%) of 142 underwent total mesorectal excision; pCR was achieved in 11 (16.7%) of 66 patients in the FL group and 17 (25.8%) of 67 patients in the IS group (P=.246). When good responders were defined as patients with Mandard grades 1 and 2, the rate of good responders was significantly higher in the IS group than in the FL group (54.6% vs 36.4%, respectively, P=.036). The preoperative rates of grade 3 and 4 toxicities were higher in the IS group (7.0%) than in the FL group (1.4%, P=.095). The 3-year disease-free survival was not significantly different between the 2 groups (79.7% vs 76.6%, respectively, P=.896).. IS-based preoperative CRT did not increase pCR rate, but it did increase acute toxicities compared with standard 5-FU treatment. Therefore, further investigation is needed.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Chemoradiotherapy, Adjuvant; Chi-Square Distribution; Confidence Intervals; Disease-Free Survival; Drug Administration Schedule; Drug Combinations; Female; Fluorouracil; Humans; Induction Chemotherapy; Irinotecan; Leucovorin; Male; Middle Aged; Neoadjuvant Therapy; Oxonic Acid; Rectal Neoplasms; Tegafur

To assess the long-term outcomes of patients with rectal cancer who received neoadjuvant chemoradiation therapy (NCRT) with concurrent S-1 and irinotecan (S-1/irinotecan) therapy.. The study group consisted of 115 patients with clinical stage T3 or T4 rectal cancer. Patients received pelvic radiation therapy (45 Gy) plus concurrent oral S-1/irinotecan. The median follow-up was 60 months.. Grade 3 adverse effects occurred in 7 patients (6%), and the completion rate of NCRT was 87%. All 115 patients (100%) were able to undergo R0 surgical resection. Twenty-eight patients (24%) had a pathological complete response (ypCR). At 60 months, the local recurrence-free survival was 93%, disease-free survival (DFS) was 79%, and overall survival (OS) was 80%. On multivariate analysis with a proportional hazards model, ypN2 was the only independent prognostic factor for DFS (P=.0019) and OS (P=.0064) in the study group as a whole. Multivariate analysis was additionally performed for the subgroup of 106 patients with ypN0/1 disease, who had a DFS rate of 85.3%. Both ypT (P=.0065) and tumor location (P=.003) were independent predictors of DFS. A combination of these factors was very strongly related to high risk of recurrence (P<.0001), which occurred most commonly in the lung.. NCRT with concurrent S-1/irinotecan produced high response rates and excellent long-term survival, with acceptable adverse effects in patients with rectal cancer. ypN2 is a strong predictor of dismal outcomes, and a combination of ypT and tumor location can identify high-risk patients among those with ypN0/1 disease.

Topics: Adult; Aged; Aged, 80 and over; Agranulocytosis; Analysis of Variance; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Chemoradiotherapy; Diarrhea; Disease-Free Survival; Dose Fractionation, Radiation; Drug Administration Schedule; Drug Combinations; Female; Fluorouracil; Humans; Irinotecan; Leucovorin; Leukopenia; Male; Middle Aged; Neoadjuvant Therapy; Neoplasm Staging; Organoplatinum Compounds; Oxonic Acid; Rectal Neoplasms; Tegafur; Treatment Outcome

The purpose of this phase I trial of S-1 chemotherapy in combination with pelvic radiotherapy for locally recurrent rectal cancer was to determine the maximum tolerated dose (MTD), recommended dose (RD), and dose-limiting toxicity (DLT) of S-1.. We enrolled 9 patients between April 2005 and March 2009. Radiotherapy (total dose, 60 Gy in 30 fractions) was given to the gross local recurrent tumor and pelvic nodal metastases using three-dimensional radiotherapy planning. We administered oral S-1 twice a day on days 1-14 and 22-35 during radiotherapy. The dose of S-1 was initially 60 mg/m(2)/day and was increased to determine the MTD and RD for this regimen.. DLT appeared at dose level 2 (70 mg/m(2)/day) in 2 patients, who experienced grade 3 enterocolitis and consequently required suspension of S-1 administration for longer than 2 weeks. Hematological toxicity was mild and reversible. At the initial evaluation, complete regression and partial regression were seen in 1 patient (11%) and 2 patients (22%), respectively.. This phase I trial of S-1 chemotherapy with pelvic radiotherapy for locally recurrent rectal cancer revealed that the MTD for S-1 was 70 mg/m(2)/day and the RD was 60 mg/m(2)/day.

Topics: Aged; Combined Modality Therapy; Drug Combinations; Female; Humans; Male; Maximum Tolerated Dose; Middle Aged; Neoplasm Recurrence, Local; Oxonic Acid; Radiation Dosage; Rectal Neoplasms; Tegafur

A phase II study of preoperative chemoradiation (CRT) with S-1 plus oxaliplatin in patients with locally advanced rectal cancer was conducted. The total radiotherapy dose was 50.4 Gy. Chemotherapy consisted of oxaliplatin 50 mg/m(2) on days 1, 8, 22 and 29 and S-1 80 mg/m(2) per day on days 1-14 and 22-35. The tumor apparent diffusion coefficient (ADC) was measured using diffusion-weighted magnetic resonance imaging (DW-MRI) before and after CRT. Total mesorectal excision was performed within 6 ± 2 weeks. The primary end-point was the pathological complete response (pCR) rate. A total of 38 patients were enrolled. The pCR rate was 22.9% (8/35; 95% CI, 10.9-42.1), and 10 (28.6%) patients showed near-total tumor regression. There was no grade 4 adverse event, and grade 3 adverse events included leukopenia (5.4%), diarrhea (5.4%), anorexia (2.7%) and nausea (2.7%). The tumor ADC was calculated in 38 patients (including those who participated in the phase I study). The post-CRT ADC (P = 0.037) and the percentage change in ADC (P = 0.026) were significantly correlated with pathological response. In conclusion, preoperative CRT with S-1 plus oxaliplatin showed promising results in pathological responses and favorable toxicity profiles.

Topics: Adult; Aged; Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Chemoradiotherapy; Drug Combinations; Female; Humans; Male; Middle Aged; Organoplatinum Compounds; Oxaliplatin; Oxonic Acid; Rectal Neoplasms; Tegafur; Treatment Outcome

In Western countries, the standard treatment for locally advanced rectal cancer is preoperative chemoradiotherapy followed by total mesorectal excision. However, in Japan, the treatment results without preoperative chemoradiotherapy are by no means inferior; therefore, extrapolation of the results of preoperative treatment in Western countries to Japan is controversial. We consider that survival may be improved by preoperative chemoradiotherapy with new anticancer agents as they are expected not only to decrease the local recurrence rate but also to prevent distant metastases. We are conducting a multicentre Phase II study to evaluate the safety and efficacy of neoadjuvant chemoradiotherapy using S-1 in patients with locally advanced rectal cancer. The primary endpoint is the rate of complete treatment of neoadjuvant chemoradiotherapy. Secondary endpoints are the response rate of neoadjuvant chemoradiotherapy, short-term clinical outcomes, rate of curative resection and pathological evaluation. The short-term clinical outcomes are adverse events of neoadjuvant chemoradiotherapy and surgery-related complications. Thirty-five patients are required for this study.

Topics: Antimetabolites, Antineoplastic; Chemoradiotherapy; Clinical Protocols; Drug Combinations; Feasibility Studies; Humans; Neoadjuvant Therapy; Oxonic Acid; Rectal Neoplasms; Tegafur

To perform a Phase I study of preoperative chemoradiation (CRT) with S-1, a novel oral fluoropyrimidine, plus oxaliplatin in patients with locally advanced rectal cancer, to determine the maximum tolerated dose and the recommended dose.. Radiotherapy was delivered to a total of 45 Gy in 25 fractions and followed by a coned-down boost of 5.4 Gy in 3 fractions. Concurrent chemotherapy consisted of a fixed dose of oxaliplatin (50 mg/m2/week) on Days 1, 8, 22, and 29 and escalated doses of S-1 on Days 1-14 and 22-35. The initial dose of S-1 was 50 mg/m2/day, gradually increasing to 60, 70, and 80 mg/m2/day. Surgery was performed within 6±2 weeks.. Twelve patients were enrolled and tolerated up to Dose Level 4 (3 patients at each dose level) without dose-limiting toxicity. An additional 3 patients were enrolled at Dose Level 4, with 1 experiencing a dose-limiting toxicity of Grade 3 diarrhea. Although maximum tolerated dose was not attained, Dose Level 4 (S-1 80 mg/m2/day) was chosen as the recommended dose for further Phase II studies. No Grade 4 toxicity was observed, and Grade 3 toxicities of leukopenia and diarrhea occurred in the same patient (1 of 15, 6.7%). Pathologic complete responses were observed in 2 of 15 patients (13.3%).. The recommended dose of S-1 was determined to be 80 mg/m2/day when combined with oxaliplatin in preoperative CRT, and a Phase II trial is now ongoing.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Combined Modality Therapy; Diarrhea; Drug Administration Schedule; Drug Combinations; Female; Humans; Male; Maximum Tolerated Dose; Middle Aged; Nausea; Neutropenia; Organoplatinum Compounds; Oxaliplatin; Oxonic Acid; Preoperative Care; Radiotherapy Dosage; Rectal Neoplasms; Tegafur; Thrombocytopenia; Vomiting

We aimed to validate our hypothesis that a preoperative chemoradiotherapy regimen with S-1 plus irinotecan is feasible, safe, and active for the management of locally advanced rectal cancer in a single-arm Phase II setting.. Eligible patients had previously untreated, locally advanced rectal adenocarcinoma. Radiotherapy was administered in fractions of 1.8 Gy/d for 25 days. S-1 was administered orally in a fixed daily dose of 80 mg/m2 on Days 1 to 5, 8 to 12, 22 to 26, and 29 to 33. Irinotecan (80 mg/m2) was infused on Days 1, 8, 22, and 29. Four or more weeks after the completion of the treatment, total mesorectal excision with lateral lymph node dissection was performed. The primary endpoint was the rate of completing treatment in terms of feasibility. The secondary endpoints were the response rate and safety.. We enrolled 43 men and 24 women in the study. The number of patients who completed treatment was 58 (86.6%). Overall, 46 patients (68.7%) responded to treatment and 24 (34.7%) had a complete histopathologic response. Three patients had Grade 3 leukopenia, and another three patients had Grade 3 neutropenia. Diarrhea was the most common type of nonhematologic toxicity: 3 patients had Grade 3 diarrhea.. A preoperative regimen of S-1, irinotecan, and radiotherapy to the rectum was feasible, and it appeared safe and effective in this nonrandomized Phase II setting. It exhibited a low incidence of adverse events, a high rate of completion of treatment, and an extremely high rate of pathologic complete response.

Topics: Administration, Oral; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Diarrhea; Drug Administration Schedule; Drug Combinations; Feasibility Studies; Female; Humans; Irinotecan; Japan; Leukopenia; Lymph Node Excision; Male; Middle Aged; Neoadjuvant Therapy; Neutropenia; Oxonic Acid; Rectal Neoplasms; Tegafur

To assess the maximum tolerability of a combination of S-1 and preoperative radiotherapy and to evaluate the feasibility and activity in patients with locally advanced rectal cancer.. Patients (n = 30) with adenocarcinoma of the middle or lower rectum were enrolled in a phase I (n = 9) and/or phase II (n = 21) trial. A total dose of 45 Gy was delivered in 25 fractions over 5 weeks, and S-1 was orally administered twice a day on days 1-14 and 22-35. Surgical resection was scheduled 4-8 weeks after the completion of chemoradiation.. In phase I, the recommended dose (RD) of S-1 was 80 mg/m(2)/day, and the maximum-tolerated dose was never reached. A total of 27 cases, including the 6 RD cases in phase I, were enrolled in phase II. In phase II, a pathological complete response (pCR) was observed in 6/27 patients (22%), pathological downstaging was observed in 21/27 patients (78%), and a tumor volume reduction of 69 ± 22% was obtained. These results were similar to the previously reported pCR rates of 16-18%, pathological downstaging rates of 49-59%, and tumor volume reduction of 68% after chemoradiotherapy with capecitabine. Grade 3 adverse events consisted of one case of leukopenia (4%), 2 cases of anemia (7%) and 3 cases of diarrhea (11%). Overall, the adverse events were very mild. Hand-foot syndrome was not observed.. The efficacy of chemoradiotherapy with S-1 seems to be equivalent to the efficacy reported for chemoradiotherapy with capecitabine, but the adverse events were much milder, although further study is warranted.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Antimetabolites, Antineoplastic; Chemoradiotherapy; Combined Modality Therapy; Drug Combinations; Female; Humans; Male; Maximum Tolerated Dose; Middle Aged; Neoadjuvant Therapy; Oxonic Acid; Postoperative Complications; Radiotherapy Dosage; Rectal Neoplasms; Tegafur; Tumor Burden

The aim of this study is to evaluate the efficacy and safety of preoperative radiation therapy combined with S-1 and irinotecan (SI) in LARC.. Patients were considered LARC if they had a T3/T4 lesion or node positive. Weekly doses of 40 mg/m(2) irinotecan were intravenously administered once per week during weeks 1-5 of radiotherapy. S-1 (70 mg/m(2)) was given from Monday to Friday in all weeks of radiotherapy. 3-D conformal radiotherapy was given at daily fractions of 1.8Gy for 5days for a total dose of 50.4 (45+5.4)Gy. Surgery was performed 4-6 weeks following the completion of chemoradiation.. Between June 2006 and November 2007, 43 pts were enrolled. The stage was: cT3 24 patients, cT4 6 patients; 28 patients were cN+. Forty-one patients completed the chemoradiation and 42 patients underwent operation: a low anterior resection was performed in 36 patients, a total colectomy in 1 patient, and an abdominal perineal resection in 5 patients. T downstaging was observed in 50%; 23 N+ patients became N- (55%). The complete pathological response was observed in 9 patients (21%). The 3-year locoregional failure rate, distant failure rate, disease-free survival, and overall survival were 9.5%, 18.6%, 72.1%, and 94.3%, respectively. Only three patients experienced G3 diarrhea; one had G3 sepsis and two had septic shock. Hematological toxicity (G3-G4) was observed in five patients.. This study demonstrated the efficacy of preoperative CRT with S-1 and irinotecan with 21% of complete response. However, prompt recognition and management of infection is needed to use it in patients with locally advanced rectal cancer.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Combined Modality Therapy; Disease-Free Survival; Drug Combinations; Female; Humans; Irinotecan; Male; Middle Aged; Oxonic Acid; Rectal Neoplasms; Tegafur

The aim of this study was to determine the maximum tolerated dose, recommended dose and dose-limiting toxicities of irinotecan (CPT-11) plus S-1 in advanced colorectal cancer.. S-1 was administered orally at 80 mg/m(2) per day for 14 consecutive days followed by a 2-week rest. CPT-11 was given intravenously on days 1 and 15 of each course, at an initial dose of 80 mg/m(2) per day, stepping up to 100, 120 or 150 mg/m(2) per day. Courses were repeated every 4 weeks, unless disease progression or severe toxicities were observed.. A total of 21 patients were entered in this study. The maximum tolerated dose of CPT-11 was considered to be 150 mg/m(2), because 2 of 3 patients developed dose-limiting toxicities such as leukopenia, neutropenia, diarrhea and anorexia. The recommend dose of CPT-11 was set at 120 mg/m(2). Tumor response rate was 42.8% and median progression-free survival time was 10 months (95% confidential interval, 6.0-14.0 months).. A combination of S-1 and CPT-11 showed a good safety profile and can be recommended for further phase II studies in patients with colorectal cancer.

Topics: Administration, Oral; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Colonic Neoplasms; Colorectal Neoplasms; Disease Progression; Dose-Response Relationship, Drug; Drug Combinations; Female; Humans; Injections, Intravenous; Irinotecan; Male; Middle Aged; Oxonic Acid; Rectal Neoplasms; Tegafur

S-1 is a novel, oral fluoropyrimidine and a known radiosensitizer. We conducted a phase I trial to establish a schedule of S-1/irinotecan with standard pelvic radiotherapy as a preoperative treatment of locally advanced rectal cancer. Our findings suggest that this new combination is feasible and well tolerable.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Agents, Phytogenic; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Combined Modality Therapy; Drug Combinations; Female; Humans; Irinotecan; Male; Maximum Tolerated Dose; Middle Aged; Neoadjuvant Therapy; Oxonic Acid; Radiation-Sensitizing Agents; Radiotherapy Dosage; Radiotherapy, High-Energy; Rectal Neoplasms; Tegafur

To determine the maximum tolerated dose (MTD) and recommended dose (RD) of irinotecan combined with preoperative chemoradiotherapy with S-1 in patients with locally advanced rectal cancer.. We gave preoperative radiotherapy (total dose, 45 Gy) to 23 patients with locally advanced (T3/T4) rectal cancer. Concurrently, S-1 was given orally at a fixed dose of 80 mg/m2/day on Days 1-5, 8-12, 22-26, and 29-33, and irinotecan was given as a 90-min continuous i.v. infusion on Days 1, 8, 22, and 29. The dose of irinotecan was initially 40 mg/m2/day and gradually increased to determine the MTD and RD of this regimen.. Among the 4 patients who received 90 mg/m2 irinotecan, 2 had Grade 4 neutropenia and 1 had Grade 3 diarrhea. Because dose-limiting toxicity (DLT) occurred in 3 of the 4 patients, 90 mg/m2 irinotecan was designated as the MTD. Consequently, 80 mg/m2 irinotecan was given to 7 additional patients, with no DLT, and this was considered the RD. Of the patients who received irinotecan at the RD or lower doses, 6 (31.6%) had a complete pathologic response (Grade 3) and 9 (47.4%) underwent sphincter-preserving surgery.. With our new regimen, the MTD of irinotecan was 90 mg/m2, and the RD of irinotecan for Phase II studies was 80 mg/m2. Although our results are preliminary, this new neoadjuvant chemoradiotherapy was considered safe and active, meriting further investigation in Phase II studies.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Drug Combinations; Female; Humans; Irinotecan; Male; Maximum Tolerated Dose; Middle Aged; Neoadjuvant Therapy; Neoplasm Staging; Oxonic Acid; Rectal Neoplasms; Tegafur

We are conducting a prospective randomized trial to evaluate the survival benefit of adjuvant chemotherapy with S-1 (tegafur, gimeracil, oteracil potassium) and UFT (uracil-tegafur) after curative surgery for patients with Stage II and III rectal cancer. Patients are randomized to either administration of UFT (control) or S-1. UFT was orally administered for 5 days (400 mg/m2/day) followed by two days rest for a year. S-1 was orally administered for 4 weeks (80 mg/m2/day) followed by two weeks rest for a year. The primary endpoint is relapse-free survival (RFS) rate, and the secondary endpoints are overall survival time (OS) and frequency or level of adverse events. We aim to include 400 patients in each of the treatment groups and assume that the registration period will last until 2009.

Topics: Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Combined Modality Therapy; Drug Administration Schedule; Drug Combinations; Endpoint Determination; Female; Humans; Lymph Node Excision; Male; Neoplasm Staging; Oxonic Acid; Proportional Hazards Models; Prospective Studies; Rectal Neoplasms; Survival Rate; Tegafur; Uracil

In developing a new anticancer agent, it is most important to balance the antitumor activity and toxicity of the agent. S-1 was designed to achieve high activity and low toxicity. In it tegafur, a prodrug of 5-FU, is combined with two classes of modulators. CDHP, an inhibitor of 5-FU degradation in the liver, and Oxo, an inhibitor of 5-FU phosphoribosylation in the digestive tract. In both early and late Phase II studies, S-1 was effective against advanced or recurrent gastrointestinal cancer. Toxicities were generally mild, and there were no toxic deaths.

Topics: Administration, Oral; Antimetabolites, Antineoplastic; Colonic Neoplasms; Drug Administration Schedule; Drug Combinations; Female; Humans; Male; Middle Aged; Oxonic Acid; Pyridines; Rectal Neoplasms; Remission Induction; Stomach Neoplasms; Tegafur

Preoperative chemoradiotherapy with capecitabine or 5-fluorouracil is a standard treatment for locally advanced rectal cancer (LARC). S-1, a prodrug of 5-fluorouracil, is a candidate for this chemoradiotherapy regimen in Japan; however, treatment outcomes after S-1 treatment alone are not clear. This study aimed to assess the efficacy and tolerability of preoperative chemoradiotherapy with S-1 alone for LARC. We retrospectively evaluated 54 LARC patients who underwent preoperative chemoradiotherapy with S-1 alone in our institution between 2005 and 2017. The clinical tumor stage was cT2-3 in 31 patients and cT4 in 23 patients, and lymph node metastases were clinically evident in 31 patients. S-1, at a dose of 80 mg/m2/day, was orally administered during radiotherapy. A total dose of 45-50.4 Gy was delivered in 25-28 fractions (median: 50.4 Gy). Surgical resections were scheduled 6-10 weeks after chemoradiotherapy completion. The 3- and 5-year overall survival rates were 92.4 and 72.8%, respectively, with a median follow-up time of 51 months. The 3- and 5-year local control rates were 96.2 and 85.9%, respectively. A pathological complete response was observed in 7 patients (13.0%) at the time of surgery. Ten patients (18.5%) had grade 3 acute toxicities and 5 patients (9.3%) had grade 3 late toxicities. No grade 4 or 5 toxicities were observed. Preoperative chemoradiotherapy with S-1 alone followed by total mesorectal excision resulted in a low incidence of toxicities and comparable clinical results. Therefore, S-1 alone can be a treatment option for preoperative chemoradiotherapy in LARC patients.

Topics: Adult; Aged; Aged, 80 and over; Chemoradiotherapy; Disease-Free Survival; Drug Combinations; Female; Humans; Male; Middle Aged; Neoplasm Staging; Oxonic Acid; Prognosis; Rectal Neoplasms; Survival Rate; Tegafur; Treatment Outcome

To explore the efficacy and safety of Transcatheter rectal arterial chemoembolization with oxaliplatin and S-1 concurrent chemoradiotherapy as neoadjuvant therapy for locally advanced rectal cancer.. This s a prospective, monocentric, non-randomized clinical study, a total of 95 patients were enrolled and assigned to two groups: an investigational group (n = 50) receiving transcatheter rectal arterial chemoembolization (TRACE) with oxaliplatin and preoperative radiotherapy plus S-1 concurrent chemotherapy (NATRACE-CRT), followed by surgery, a control group (n = 45) receiving standard fluorouracil-based combined modality treatment, consisting of preoperative radiotherapy plus capecitabine based chemotherapy (NA-CRT), followed by surgery. The primary endpoint was postoperative pathological regression rate which evaluated by tumor regression grade (TRG) according to the 7th edition of the American Joint Committee on Cancer (AJCC) standard, and the secondary endpoints included objective response rate (ORR) and toxicity, as well as surgical complications, and postoperative tumor downstaging.. Compared with NA-CRT group (17.78% (95% confidence interval (CI): 6.2-29.4)), the TRG0 was 30% (95% CI 16.8-43.2) in the NATRACE-CRT group (P = 0.231). The TRG0 + 1 rate was 60% (95% CI: 45.9-74.1) and 33.33% (95% CI: 19-47.7) in NATRACE-CRT group and NA-CRT group, respectively (P = 0.013). The ORR of the NATRACE-CRT group was 84% and that of the NA-CRT group was 66.67% (p = 0.058). Incidence of preoperative toxic side effects and surgical complications was similar between the two groups.. TRACE with oxaliplatin plus concurrent S-1 chemoradiotherapy as a neoadjuvant therapy provided better pathological remission rate versus standard treatment with a similar safety profile.. NCT03601156.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Capecitabine; Chemoradiotherapy; Colorectal Surgery; Dose Fractionation, Radiation; Drug Combinations; Female; Humans; Male; Middle Aged; Neoadjuvant Therapy; Oxaliplatin; Oxonic Acid; Prospective Studies; Rectal Neoplasms; Tegafur; Treatment Outcome; Young Adult

A 60s man was diagnosed with rectal cancer and underwent low anterior resection of the rectum. The pathological diagnosis was mucinous adenocarcinoma, pT3(SS), pN0, pM0, pStage Ⅱ. Two years after the primary surgery, contrast-enhanced CT showed local recurrence on the oral side of the anastomosis. As the tumor had invaded the left seminal vesicle and coccygeus muscle, neoadjuvant chemoradiotherapy(NACRT)(S-1 80mg/m / 2 plus 45 Gy/25 Fr)was performed. After NACRT, abdominoperineal resection, including the left seminal vesicle, coccygeus muscle, and coccygeal bone, was performed. Pathological examination showed a histological response of Grade 2 and that R0 resection was achieved. Although the only radical treatment of locally recurrent rectal cancer is R0 resection, we performed R0 resection with Grade 2 histological response to NACRT.

Topics: Adenocarcinoma, Mucinous; Antimetabolites, Antineoplastic; Chemoradiotherapy; Drug Combinations; Humans; Male; Neoadjuvant Therapy; Neoplasm Recurrence, Local; Neoplasm Staging; Oxonic Acid; Rectal Neoplasms; Tegafur; Treatment Outcome

Preoperative chemoradiotherapy (CRT) using 5-fluorouracil (5-FU)-based chemotherapy is the standard of care for rectal cancer. The effect of additional chemotherapy during the period between the completion of radiotherapy and surgery remains unclear. Predictive factors for CRT may differ between combination chemotherapy with S-1 and with tegafur-uracil/leucovorin (UFT/LV).. The subjects were 54 patients with locally advanced rectal cancer who received preoperative CRT with S-1 or UFT/LV. The pathological tumor response was assessed according to the tumor regression grade (TRG). The expression levels of 18 CRT-related genes were determined using RT-PCR assay.. A pathological response (TRG 1-2) was observed in 23 patients (42.6%). In a multivariate logistic regression analysis for pathological response, the overall expression levels of four genes, HIF1A, MTHFD1, GGH and TYMS, were significant, and the accuracy rate of the predictive model was 83.3%. The effects of the gene expression levels of GGH on the response differed significantly according to the treatment regimen. The total pathological response rate of both high-GGH patients in the S-1 group and low-GGH patients in the UFT/LV group was 58.3%.. Additional treatment with 5-FU-based chemotherapy during the interval between radiotherapy and surgery is not beneficial in patients who have received 5-FU-based CRT. The expression levels of four genes, HIF1A, MTHFD1, GGH and TYMS, in tumor tissues can predict the response to preoperative CRT including either S-1 or UFT/LV. In particular, the gene expression level of GGH in tumor tissues may be a useful biomarker for the appropriate use of S-1 and UFT/LV in CRT.

Topics: Adenocarcinoma; Adult; Aged; Antidotes; Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Chemoradiotherapy; Combined Modality Therapy; Drug Combinations; Female; Fluorouracil; gamma-Glutamyl Hydrolase; Gene Expression Regulation, Neoplastic; Humans; Leucovorin; Male; Middle Aged; Oxonic Acid; Rectal Neoplasms; Reproducibility of Results; Tegafur; Treatment Outcome

We report a case of locally advanced rectal cancer, treated effectively with chemotherapy consisting of mFOLFOX6 combined with radiotherapy. A 63-year-old man was admitted to our hospital in March 2012 for diarrhea and anal and perineal pain. Advanced rectal cancer with invasion ofthe right perineum was diagnosed based on computer tomography(CT) findings. Surgery was performed; however, the rectal cancer was unresectable. A sigmoid colostomy was performed, and a central venous port was implanted. In April 2012, the patient was treated with chemotherapy using 3 courses ofmFOLFOX6 and concurrent radiotherapy. Radiotherapy at 2 Gy/day was administered 25 times(total dose, 50 Gy). After chemoradiotherapy, the patient underwent 3 courses ofmFOLFOX6 as an additional therapy. By June 2012, CT showed resolution ofthe tumor in the right perineum and a marked decrease in the size ofthe primary rectal cancer. Because the patient refused surgery, we started treatment with combination chemotherapy using oral S-1 and intravenous CPT-11 in August 2012. After 18 courses, the treatment was changed to oral administration ofS -1 alone, which was continued for 1 year. The patient remained well without recurrence for 54 months since the original diagnosis. Therefore, chemoradiotherapy with mFOLFOX6 is a possible option for the management of advanced rectal cancer.

Topics: Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Chemoradiotherapy; Drug Combinations; Fluorouracil; Humans; Irinotecan; Leucovorin; Male; Middle Aged; Organoplatinum Compounds; Oxonic Acid; Rectal Neoplasms; Tegafur; Treatment Outcome

To investigate the clinicopathological outcomes of patients with T4 lower rectal cancer treated using preoperative chemoradiotherapy with S-1 plus Irinotecan.. Between 2005 and 2011, 35 patients with T4M0 lower rectal cancer, diagnosed initially as T4a in 12 and as T4b in 23, were treated with 45 Gy of radiotherapy concomitantly with S-1 plus Irinotecan. The median follow-up period was 50.6 months (range 2-123 months).. A total of 32 patients (91.4 %) completed the radiotherapy and 26 (74.3 %) completed the full chemotherapy regimen. Radical surgery was then performed in 33 (94.3 %) of the 35 patients after the exclusion of two patients, who had macroscopic residual disease. The pathological diagnosis was downstaged from T4a to ypT0-3 in all 12 of those patients (100 %) and from T4b to ypT0-4a in 20 of those 23 patients (87.0 %). The tumor regression grade of 1a/1b/2/3 (complete response) was 10/8/15/2, respectively. In terms of long-term survival, the 5-year local relapse-free survival rate was 74.8 % and the recurrence-free survival rate was 52.0 %.. This regimen may result in favorable downstaging. Moreover, in this series, pathological evidence of involvement of adjacent organs was rare following preoperative chemoradiotherapy, in the patients with disease diagnosed as T4b at the initial staging.

Topics: Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Chemoradiotherapy, Adjuvant; Digestive System Surgical Procedures; Drug Combinations; Female; Follow-Up Studies; Humans; Irinotecan; Male; Middle Aged; Neoplasm Staging; Oxonic Acid; Preoperative Period; Rectal Neoplasms; Survival Rate; Tegafur; Time Factors; Treatment Outcome

To evaluate the safety and efficacy of induction SOX (S-1 + oxaliplatin) ± cetuximab chemotherapy followed by short-course chemoradiotherapy and surgery in patients with poor-risk locally advanced rectal cancer.. We enrolled eligible patients with poor-risk rectal cancer defined as T3 lower rectal cancer with mesorectal fascia involvement, T4a or T4b tumors or cases with lateral lymph node swelling. The primary endpoint was a pathological complete response (pCR), and the secondary endpoints were the objective response rate (ORR) and the pathological high response rate (Grade 2 plus 3).. Twenty eligible patients were enrolled. The majority (75.0 %, 15/20) of the patients completed four cycles of induction chemotherapy, and all patients completed the radiotherapy (25 Gy/10 fractions/5 days). The global rate of Grade 3-4 toxicities was 30.0 % (6/20 patients). The ORRs were 85.0 % (17/20) and 95.0 % (19/20) in the patients who underwent R0 and R1 resection, respectively. The pathological high response rate was 70.0 % (14/20) and the pCR was 10.0 % (2/20).. The regimen of induction SOX (S-1 + oxaliplatin) ± cetuximab chemotherapy followed by short-course chemoradiotherapy is safe and is associated with good tumor regression in patients with poor-risk locally advanced rectal cancer.

Topics: Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Cetuximab; Chemoradiotherapy; Combined Modality Therapy; Drug Combinations; Female; Humans; Induction Chemotherapy; Male; Middle Aged; Neoplasm Staging; Organoplatinum Compounds; Oxaliplatin; Oxonic Acid; Rectal Neoplasms; Risk; Tegafur; Time Factors; Treatment Outcome

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Colitis; Drug Combinations; Escherichia coli Infections; Escherichia coli O157; Female; Humans; Lung Neoplasms; Organoplatinum Compounds; Oxaliplatin; Oxonic Acid; Rectal Neoplasms; Tegafur; Tomography, X-Ray Computed

This study was aimed to assess the feasibility and short-term outcomes of adjuvant systemic chemotherapy with either S-1/oxaliplatin (SOX) or mFOLFOX6 (FOLFOX)after curative resection of distant metastases from colorectal cancer. We retrospectively examined 16 patients who underwent R0 resection of colorectal metastases, including the liver (n=6), lung (n=5), lymph node (n=3), and peritoneum (n=2), followed by chemotherapy with SOX (n=7) or FOLFOX (n=9) until disease progression. The mean recurrence-free survival was 13.2 months in the SOX group and 16.9 months in the FOLFOX group. The mean overall survival was 17.9 and 22.9 months, respectively. The number of given courses were 6.5 and 11.0, respectively. Although sensory neuropathy was observed in 38% of the patients, relative dose intensity was higher than 80%. Adjuvant chemotherapy with SOX or FOLFOX was feasible and effective. Further randomized prospective trials are warranted to confirm these results.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Colonic Neoplasms; Drug Combinations; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Neoplasm Metastasis; Organoplatinum Compounds; Oxaliplatin; Oxonic Acid; Rectal Neoplasms; Recurrence; Retrospective Studies; Tegafur

We report the case of a patient with advanced rectal cancer who achieved a pathological complete response to preoperative chemoradiotherapy (CRT). A 65-year-old man was diagnosed as having a two-thirds circumferential well-to moderately differentiated tumor (Rb-P, type 2). To control local recurrence, we treated the patient with CRT. Radiotherapy was administered in fractions of 2 Gy/day (total, 40 Gy). Concurrently, S-1 was administered orally at a fixed daily dose of 80 mg/m2 for 20 days. Withdrawal and/or dose reduction of S-1 was not necessary in spite of Grade 1 or 2 toxic effects, including diarrhea and periproctitis, occurring on day 7. Laparoscopic abdominoperineal resection was performed 6 weeks after the final dose of chemotherapy was administered. The histopathological regression grade was Grade 3. No recurrence was detected on enhanced CT more than 5 years after surgery. This case suggests that the regimen was both effective and tolerated, and that preoperative chemoradiotherapy may be effective for tumor suppression to prevent local recurrence.

Topics: Aged; Antimetabolites, Antineoplastic; Biopsy; Chemoradiotherapy; Drug Combinations; Humans; Male; Neoplasm Staging; Oxonic Acid; Rectal Neoplasms; Tegafur; Treatment Outcome

The aim of the study was to identify biomarkers capable of predicting response to preoperative chemoradiotherapy (CRT) including S-1 or UFT for rectal cancer using biopsy specimens obtained before CRT (Pre-samples) and 7 days after the start of CRT (Day-7 samples).. Preoperative CRT including S-1 or UFT was performed in 82 patients with locally advanced rectal cancer. The expression levels of 18 genes related to 5-fluorouracil, folate, and radiation in the Pre-samples and the Day-7 samples were evaluated using reverse transcription polymerase chain reaction (RT-PCR) assay.. The gene expression levels of hypoxia inducible factor 1 alpha subunit (HIF1A), dihydropyrimidine dehydrogenase (DPYD) and thymidine phosphorylase (TYMP) were found significantly increased in Day-7 samples compared to Pre-samples in responders, but not in non-responders.. Increases in gene expression levels of TYMP, DPYD, and HIF1A in tumor tissues at 7 days after the start of CRT may be useful for predicting the efficacy of CRT including S-1 or UFT.

Topics: Adult; Aged; Chemoradiotherapy; Dihydrouracil Dehydrogenase (NADP); Drug Combinations; Female; Gene Expression Regulation, Neoplastic; Humans; Hypoxia-Inducible Factor 1, alpha Subunit; Male; Middle Aged; Oxonic Acid; Rectal Neoplasms; Reverse Transcriptase Polymerase Chain Reaction; Tegafur; Thymidine Phosphorylase; Uracil

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.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Capecitabine; Colonic Neoplasms; Cost-Benefit Analysis; Decision Support Techniques; Drug Combinations; Female; Humans; Male; Middle Aged; Organoplatinum Compounds; Oxaliplatin; Oxonic Acid; Rectal Neoplasms; Recurrence; Tegafur

We report a case of pathological complete response after neoadjuvant chemotherapy(NAC)(S-1 plus oxaliplatin)for rectal cancer. The patient was a 50-year-old man who had type 3 circumferential rectal cancer. An abdominal CT scan revealed locally advanced rectal cancer(cT3N2H0P0M0, cStage III b)with severe stenosis and oral-side intestinal dilatation. The patient was treated with NAC after loop-ileostomy. After 3 courses of chemotherapy, a CT scan revealed significant tumor reduction. Laparoscopic low anterior resection and bilateral lymph node dissection were performed 5 weeks after the last course of chemotherapy. The pathological diagnosis was a pathological complete response(no residual cancer cells). This case suggests that laparoscopic low anterior resection after NAC with S-1 plus oxaliplatin for locally advanced rectal cancer is a potentially effective procedure.

Topics: Antineoplastic Combined Chemotherapy Protocols; Drug Combinations; Humans; Intestinal Obstruction; Laparoscopy; Male; Middle Aged; Neoadjuvant Therapy; Organoplatinum Compounds; Oxaliplatin; Oxonic Acid; Rectal Neoplasms; Tegafur; Treatment Outcome

A 50-year-old woman with a chief complaint of bloody stools was diagnosed with rectal cancer via colonoscopy. Laparoscopic rectal anterior resection with D3 lymph node dissection was performed in June 2014. The pathological diagnosis was pStage III a(Ra, pT3, N1)cancer, and the patient received 8 courses of XELOX as postoperative adjuvant chemotherapy. During follow-up at 12 months after surgery, chest computed tomography revealed a mass in the left lingular segment measuring 25mm in diameter and multiple small nodules in both the lungs, indicating lung metastases. We found several subcutaneous nodules with a maximum diameter of 10mm in her abdomen and the back of head. We removed 3 subcutaneous nodules for the purpose of diagnosis and treatment in June of 2015. The pathological findings were consistent with cutaneous metastases of rectal cancer. The patient received a 1 course of IRIS and 5 courses of IRIS plus bevacizumab. Subsequently, the lung metastases disappeared and no new skin lesions were detected. We suggest that this case could be a good reference in determining the appropriate treatment for rectal cancer having lung or cutaneous metastases.

Topics: Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Camptothecin; Chemotherapy, Adjuvant; Drug Combinations; Female; Humans; Irinotecan; Lung Neoplasms; Middle Aged; Oxonic Acid; Rectal Neoplasms; Skin Neoplasms; Tegafur; Treatment Outcome

A woman in her 70's presented with the predominant complaint of bloody stools. She was diagnosed with rectal cancer, and bilateral lymph node and pulmonary metastases were detected on computed tomography(CT). The patient was diagnosed with cT3N3M1a, cStage IV disease. After undergoing a colostomy, the patient was treated with S-1 plus oxaliplatin (SOX), and bevacizumab(Bev). A second CT scan obtained after completion of 7 courses of chemotherapy revealed that the lung metastases had significantly reduced or disappeared. Approximately 7 months after initial treatment, the patient underwent a laparoscopic Hartmann procedure to remove the tumor. The patient is currently under observation while being administered postoperative adjuvant chemotherapy as an outpatient in our department. There is currently no evidence of the safety of laparoscopic-assisted rectal cancer surgery for first-time Stage IV cases. However, when tumor regression has been achieved with chemotherapy, it may be an effective option.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Colostomy; Drug Combinations; Female; Humans; Laparoscopy; Lung Neoplasms; Organoplatinum Compounds; Oxaliplatin; Oxonic Acid; Rectal Neoplasms; Tegafur

We report a case of rectal metastasis of gastric cancer associated with dermatomyositis showing paraneoplastic syndrome. The patient was a 70-year-old man who had undergone curative total gastrectomy for Stage III Agastric cancer in March 2005. He was diagnosed with dermatomyositis and treated with prednisolone after gastrectomy. In April 2006, erythema of his face relapsed, and his serum CPK level was abnormally elevated. He experienced muscle weakness and dysphagia, and was treated with increased doses of prednisolone and gamma-globulin. At this time, endoscopic examination and computed tomography(CT)revealed a rectal tumor with hepatic metastasis. We performed Hartmann's operation in July 2006. The rectal tumor was predominantly submucosal, was 7 cm in diameter, involved #251 lymph node, and had positive peritoneal lavage cytology. The histopathological findings of the rectal tumor were comparable with those of gastric cancer, and we therefore diagnosed metastatic adenocarcinoma of gastric cancer. After surgery, we could control the patient's dermatomyositis with prednisolone at a reduced dose. However, chemotherapy with S-1 was ineffective and the patient died 8 months postoperatively.

Topics: Adenocarcinoma; Aged; Antimetabolites, Antineoplastic; Dermatomyositis; Drug Combinations; Fatal Outcome; Humans; Male; Oxonic Acid; Rectal Neoplasms; Stomach Neoplasms; Tegafur

5-Fluorouracil-based chemotherapy is considered to be a radiosensitizer; however, conventional short-course radiotherapy combined with chemotherapy is generally thought to not be feasible because of the prevalence of side effects.. The aim of this study was to evaluate the feasibility of modified short-course radiotherapy combined with a chemoradiosensitizer for T3 rectal cancer.. This study was retrospective in nature and used a prospectively collected database.. Patients with T3 rectal cancer located below the peritoneum reflection were selected.. A total dose of 25 Gy of radiotherapy was administered in 10 fractions of 2.5 Gy each for 5 days. Radiotherapy was performed with S-1 as a radiosensitizer from day 1 to day 10. Surgery was targeted to be performed 4 weeks after radiotherapy.. The morbidity, sphincter-preserving rate, anal function, and long-term outcomes were assessed.. All patients (n = 170) completed the radiotherapy regimen and 166 (97.6%) completed the combination regimen with chemotherapy. A total of 149 patients (87.6%) had sphincter-preserving surgery (double stapling technique (DST), 58 patients; intersphincteric resection (ISR), 91 patients), and postoperative complications were relatively mild (anastomotic leakage, 15.4%; intra-abdominal infection, 8.2%). Among those undergoing sphincter preserving surgery, the 5-year local relapse-free survival rate was 94.3% in the DST group, and 89.8% in the ISR group. With respect to the anal function, the Wexner score the first year after stoma closure for the double-stapling technique group was 6 and that for intersphincteric resection was 15; however, the score for the intersphincteric resection group was improved to 8 at 4 years after stoma closure.. This study had limitations because it was an uncontrolled, 1-arm, retrospective review with a small sample size.. Modified short-course radiotherapy combined with chemoradiosensitizer is a feasible approach for treating T3 rectal cancer. With the use of the short-course approach, efforts to reduce the incidence of side effects by appropriately prolonging the waiting period enable the administration of combination treatment with short-course radiotherapy and chemotherapy.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Anal Canal; Antimetabolites, Antineoplastic; Chemoradiotherapy; Databases, Factual; Dose Fractionation, Radiation; Drug Combinations; Feasibility Studies; Fecal Incontinence; Female; Humans; Male; Middle Aged; Neoadjuvant Therapy; Neoplasm Staging; Organ Sparing Treatments; Oxonic Acid; Postoperative Complications; Radiation-Sensitizing Agents; Rectal Neoplasms; Rectum; Retrospective Studies; Tegafur; Treatment Outcome

A 56-year-old man who underwent a radical operation and adjuvant chemotherapy for recurrent rectal cancer had been followed-up and had no recurrence for one and a half years. Thereafter, CT and upper endoscopy showed a submucosal tumor with a central recess developing in the stomach wall. It was suspected that the gastric tumor was either a metastasis of rectal cancer or a submucosal tumor-like gastric cancer. We performed a radical operation to remove the lesion. In the resected specimen, immunohistopathological findings including HER2 status suggested that the gastric tumor was a primary gastric cancer resembling a submucosal tumor.

Topics: Antimetabolites, Antineoplastic; Drug Combinations; Gastric Mucosa; Humans; Male; Middle Aged; Neoplasms, Second Primary; Oxonic Acid; Rectal Neoplasms; Stomach Neoplasms; Tegafur

A 72-year-old woman was admitted to our hospital with bloody stools and constipation. She was diagnosed with advanced lower rectal cancer with multiple liver and pulmonary metastases. Because the rectal cancer was located 2 cm from the anal verge, we suggested she undergo an abdominoperineal resection(Miles operation), but she refused to undergo a colostomy. Then, 6 courses of chemotherapy with S-1/oxaliplatin(SOX)were administered, and the local tumor, liver metastases, and pulmonary metastases were all significantly decreased in size(reduction rate 60%). After chemotherapy, she chose to undergo low anterior resection(LAR), D2. Postoperative recovery was uneventful, and she currently has stable disease with adjuvant SOX chemotherapy. Induction SOX chemotherapy was considered to be useful for maintaining the quality of life(QOL) in a patient with advanced rectal cancer.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Colostomy; Drug Combinations; Female; Humans; Liver Neoplasms; Lung Neoplasms; Neoplasm Staging; Organoplatinum Compounds; Oxaliplatin; Oxonic Acid; Rectal Neoplasms; Tegafur; Treatment Outcome

A 51-year-old man presented with a chief complaint of constipation. Rectal cancer was detected up to 13 cm proximal to the anal verge. The cancer was a fully circumferential type II tumor that was accompanied by prostate invasion and lymph node metastasis. After sigmoid colostomy, preoperative chemoradiotherapy with S-1/irinotecan (CPT-11; total 50 Gy) was administered, resulting in tumor volume reduction. However, because of residual invasion in some parts of the prostate, therapy with capecitabine and oxaliplatin (XELOX) plus bevacizumab was added to avoid pelvic exenteration. Because magnetic resonance imaging revealed no invasion prostate after 7 courses of the therapy, abdominoperineal resection of the rectum was performed. Pathological examination revealed no residual tumor cells, and a pathological complete response was thus confirmed. The addition of chemotherapy to preoperative chemoradiotherapy was considered to be an effective strategy for locally advanced rectal cancer in this case.

Topics: Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Camptothecin; Capecitabine; Chemoradiotherapy; Deoxycytidine; Drug Combinations; Fluorouracil; Humans; Irinotecan; Male; Middle Aged; Neoplasm Staging; Oxaloacetates; Oxonic Acid; Rectal Neoplasms; Tegafur

A 60-year-old man with advanced rectal cancer and urinary bladder fistula received preoperative chemoradiotherapy with S-1(120mg/m / 2day)on weekdays and concurrent radiotherapy(65 Gy). After chemoradiotherapy, the clinical symptoms resolved and the tumor shrunk, as observed on endoscopic and radiologic examinations. However, remnant cancer was suspected; therefore, modified oxaliplatin, 5-fluorouracil, and Leucovorin(mFOLFOX6)therapy was initiated, although it was stopped after 3 cycles because of numbness in the lower extremities. Finally, clinical and pathological complete response(CR) was achieved by administering additional doses of S-1 for approximately 1 year after treatment initiation; CR was confirmed by using endoscopy and computed tomography(CT), and there has been no recurrence for 6 years. This case suggests that treatment without surgery is a viable alternative for advanced rectal cancer with pathological CR after chemoradiotherapy.

Topics: Antimetabolites, Antineoplastic; Chemoradiotherapy; Drug Combinations; Humans; Male; Middle Aged; Oxonic Acid; Rectal Neoplasms; Remission Induction; Tegafur; Time Factors; Urinary Bladder Fistula

The purpose of this study was to analyze the influence of variations in clinical practice regarding the timing of surgery with short-course chemoradiotherapy with delayed surgery (SCRT-delay) for lower rectal cancer.. A total of 171 patients with T3 N0-2 lower rectal cancer treated with SCRT-delay (25 Gy/10 fractions/5 days (S-1); days 1-10) were retrospectively evaluated. The median waiting period of 30 days was used as a discriminator (group A: waiting period, ≤30 days; group B: waiting period, ≥31 days). Preoperative treatment responses and oncological outcomes were analyzed.. The mean waiting periods for groups A and B were 24.4 ± 5.3 and 41.4 ± 12.3 days, respectively. There were no statistically significant differences between the two groups in any of the clinical variables. The clinicopathological outcomes were as follows: T downstaging (43.5 vs 37.2 %; p = 0.400), negative yp N (67.1 vs 75.6 %; p = 0.218), pCR (7.1 vs 1.2 %; p = 0.119). The 5-year local recurrence-free survival (89.3 vs 87.6 %; p = 0.956), the recurrence-free survival (82.2 vs 78.8 %; p = 0.662), and the overall survival (88.5 vs 84.4 %; p = 0.741), all of which were similar between the two groups.. The longer waiting period did not increase the tumor downstaging and not improve the oncological outcomes for T3 lower rectal cancer treated with SCRT-delay. In addition, considering that the impaired leukocyte response occurred during the sub-acute period, any time after the sub-acute period (day 12) up to 30 days after radiotherapy would be a suitable waiting period.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Antimetabolites, Antineoplastic; Chemoradiotherapy; Disease-Free Survival; Drug Combinations; Female; Humans; Male; Middle Aged; Neoplasm Staging; Oxonic Acid; Postoperative Complications; Rectal Neoplasms; Retrospective Studies; Tegafur; Time Factors

The aim of this paper was to compare the efficacy and safety of S-1-based and capecitabine-based preoperative chemoradiotherapy regimens in patients with locally advanced rectal cancer through a retrospective matched-pair analysis.. Between Jan 2010 and Mar 2014, 24 patients with locally advanced rectal cancer who received preoperative radiotherapy concurrently with S-1 were individually matched with 24 contemporary patients with locally advanced rectal cancer who received preoperative radiotherapy concurrently with capecitabine according to clinical stage (as determined by pelvic magnetic resonance imaging and computed tomography) and age (within five years). All these patients performed mesorectal excision 4-8 weeks after the completion of chemoradiotherapy.. The tumor volume reduction rates were 55.9±15.1% in the S-1 group and 53.8±16.0% in the capecitabine group (p = 0.619). The overall downstaging, including both T downstaging and N downstaging, occurred in 83.3% of the S-1 group and 70.8% of the capecitabine group (p = 0.508). The significant tumor regression, including regression grade I and II, occurred in 33.3% of S-1 patients and 25.0% of capecitabine patients (p = 0.754). In the two groups, Grade 4 adverse events were not observed and Grade 3 consisted of only two cases of diarrhea, and no patient suffered hematologic adverse event of Grade 2 or higher. However, the incidence of diarrhea (62.5% vs 33.3%, p = 0.014) and hand-foot syndrome (29.2% vs 0%, p = 0.016) were higher in capecitabine group. Other adverse events did not differ significantly between two groups.. The two preoperative chemoradiotherapy regimens were effective and safe for patients of locally advanced rectal cancer, but regimen with S-1 exhibited a lower incidence of adverse events.

Topics: Capecitabine; Chemoradiotherapy; Deoxycytidine; Drug Combinations; Female; Fluorouracil; Humans; Male; Matched-Pair Analysis; Middle Aged; Neoplasm Staging; Oxonic Acid; Postoperative Care; Preoperative Care; Rectal Neoplasms; Tegafur; Treatment Outcome

Colorectal cancer (CRC) is among the most common cancers worldwide, but marked epidemiological differences exist between Asian and non-Asian populations. Hence, a consensus meeting was held in Hong Kong in December 2012 to develop Asia-specific guidelines for the management of metastatic CRC (mCRC). A multidisciplinary expert panel, consisting of 23 participants from 10 Asian and 2 European countries, discussed current guidelines for colon or rectal cancer and developed recommendations for adapting these guidelines to Asian clinical practice. Participants agreed that mCRC management in Asia largely follows international guidelines, but they proposed a number of recommendations based on regional 'real-world' experience. In general, participants agreed that 5-fluorouracil (5-FU) infusion regimens in doublets can be substituted with UFT (capecitabine, tegafur-uracil) and S1 (tegafur, 5-chloro-2,4-dihydroxypyridine and oxonic acid), and that the monoclonal antibodies cetuximab and panitumumab are recommended for KRAS wild type tumors. For KRAS mutant tumors, bevacizumab is the preferred biological therapy. FOLFOX (folinic acid, 5-FU, and oxaliplatin) is preferred for initial therapy in Asian patients. The management of mCRC is evolving, and it must be emphasized that the recommendations presented here reflect current treatment practices and thus might change as more data become available.

Topics: Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Asia; Bevacizumab; Camptothecin; Capecitabine; Cetuximab; Colonic Neoplasms; Combined Modality Therapy; Deoxycytidine; Drug Combinations; ErbB Receptors; Fluorouracil; Guideline Adherence; Humans; Leucovorin; Liver Neoplasms; Lung Neoplasms; Magnetic Resonance Imaging; Metastasectomy; Neoplasm Staging; Organoplatinum Compounds; Oxaloacetates; Oxonic Acid; Panitumumab; Practice Guidelines as Topic; Proto-Oncogene Proteins; Proto-Oncogene Proteins p21(ras); ras Proteins; Rectal Neoplasms; Tegafur; Tomography, X-Ray Computed

A 54-year-old man presented with an enlarged left (lt) lateral lymph node (LLN), which was detected by magnetic resonance imaging (MRI) and positron emission tomography/computed tomography (PET-CT). Endoscopic examination of the colon revealed the presence of a type 1 tumor, 20mm in diameter, in the lower rectum; the tumor was diagnosed as a well-differentiated adenocarcinoma (tub1). The patient received combined neoadjuvant chemoradiotherapy (nCRT)with S- 1 for treatment of the rectal cancer and LLN metastasis (MP, T2N3M0, Stage IIIb). S-1 was administered orally at a dose of 120 mg/day on days 1-14, and 22-35; a total dose of 45 Gy was delivered (1.8 Gy/day, for 25 days). Upon nCRT, there was a remarkable reduction in the tumor size, the primary tumor receded, and the LLN decreased from 16 mm to 8 mm in diameter. The maximum standardized uptake value (SUVmax) also decreased from 3.8 to 1.9 on PET-CT. Six weeks after nCRT, ultralow anterior resection and bilateral lymph node dissections were performed. Histopathological examination showed a partial presence of cancer cells in the scarred primary tumor; however, no viable cancer cells were observed in the lt. LLN.

Topics: Adenocarcinoma; Antineoplastic Combined Chemotherapy Protocols; Chemoradiotherapy; Drug Combinations; Humans; Lymphatic Metastasis; Male; Middle Aged; Neoadjuvant Therapy; Oxonic Acid; Rectal Neoplasms; Tegafur

A 63-year-old woman underwent a low anterior resection for rectal cancer in 2002.A n anastomotic recurrence was diagnosed in July 2011.S he rejected the possibility of colostomy as radical surgery.Chemotherapy consisting of capecitabine+ oxaliplatin (XELOX) or folinic acid, fluorouracil, and oxaliplatin (FOLFOX6) + bevacizumab were not possible because of high costs. In view of the lower costs and the potential for ambulation, S-1 monotherapy was started. After 3 months, a reduction in the recurrent lesion was observed.After 19 months, the recurrent lesion revealed a scar, which was judged by biopsy to be Group 1.We had achieved a pathological complete response (CR).The standard treatment for recurrent colon cancer is surgical resection or multidrug chemotherapy. However, in view of a patient's quality of life (QOL), S-1 monotherapy may be considered as a potential therapy.

Topics: Antimetabolites, Antineoplastic; Drug Combinations; Female; Humans; Middle Aged; Neoplasm Recurrence, Local; Oxonic Acid; Quality of Life; Rectal Neoplasms; Remission Induction; Tegafur

In recent years, with the increase in the adoption of anus-preserving surgery, understanding of residual lower rectal cancer distribution to the anal side after chemoradiotherapy (CRT) has become an increasingly important issue. We aimed to clarify the pathological safe distal resection margin for lower rectal cancer after preoperative CRT. This study included 36 patients with lower third rectal cancer, who underwent preoperative CRT. We classified the gross tumor appearance as type 0-II like, Borrmann type 2, and Borrmann type 5. Whole-mount sections were used for pathological examination. We examined all slides and measured the extent of residual cancer spread. In many cases, residual cancer was observed in the deeper layers of the lesion, and in none of the cases was the cancer limited to the superficial layer. With regard to lateral distribution, tumors with a type 0-II like appearance showed a wider extent of lateral cancer spread from the optimal margin. In conclusion, although CRT contributes to tumor reduction, attention should be paid to both circumferential and lateral residual cancer spread. Our results suggest that the lateral distribution of residual cancer spread could be predicted by gross tumor appearance. This is an ongoing study.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Chemoradiotherapy; Drug Combinations; Female; Humans; Irinotecan; Male; Middle Aged; Oxonic Acid; Postoperative Complications; Rectal Neoplasms; Tegafur

The purpose of this study was to evaluate S-1 plus oxaliplatin( SOX) as neoadjuvant chemotherapy for the treatment of patients with locally advanced rectal cancer. The clinical features and management of 10 patients with this disease seen at the Hirosaki University Hospital between 2011 and 2013 were examined. Of these patients, 30% were treated with bevacizumab, and the mean number of courses was 3.3. There were no adverse events of severity greater than Grade 3, and no patient required treatment interruption because of toxicity. SOX administered every 3 weeks was associated with a partial response rate of 40% and a tumor control rate of 100%; progressive disease was not observed. Curative resection was performed in all patients except in 1 with liver metastasis. With regard to the pathological findings, 2 cases were of Grade 0; 4 cases, of Grade 1a; and 2 cases, of Grade 2. Postoperative complications such as anastomotic leakage were observed in 80% of the patients. Thus, SOX administration without a central venous drug injection port was very useful because most patients could receive SOX treatment on an outpatient basis. However, the frequency of postoperative complications associated with this treatment is increasing, and therefore, it is important to accumulate more evidence.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Drug Combinations; Female; Humans; Male; Middle Aged; Neoadjuvant Therapy; Neoplasm Staging; Organoplatinum Compounds; Oxaliplatin; Oxonic Acid; Rectal Neoplasms; Tegafur

Preoperative chemoradiation therapy (CRT) significantly decreases local recurrence in locally advanced rectal cancer. Various biomarkers in biopsy specimens obtained before CRT have been proposed as predictors of response. However, reliable biomarkers remain to be established.. The study group comprised 101 consecutive patients with locally advanced rectal cancer who received preoperative CRT with oral uracil/tegafur (UFT) or S-1. We evaluated histologic findings on hematoxylin and eosin (H&E) staining and immunohistochemical expressions of Ki67, p53, p21, and apoptosis in biopsy specimens obtained before CRT and 7 days after starting CRT. These findings were contrasted with the histologic response and the degree of tumor shrinkage.. In biopsy specimens obtained before CRT, histologic marked regression according to the Japanese Classification of Colorectal Carcinoma (JCCC) criteria and the degree of tumor shrinkage on barium enema examination (BE) were significantly greater in patients with p21-positive tumors than in those with p21-negative tumors (P=.04 and P<.01, respectively). In biopsy specimens obtained 7 days after starting CRT, pathologic complete response, histologic marked regression according to both the tumor regression criteria and JCCC criteria, and T downstaging were significantly greater in patients with apoptosis-positive and p21-positive tumors than in those with apoptosis-negative (P<.01, P=.02, P=.01, and P<.01, respectively) or p21-negative tumors (P=.03, P<.01, P<.01, and P=.02, respectively). The degree of tumor shrinkage on both BE as well as MRI was significantly greater in patients with apoptosis-positive and with p21-positive tumors than in those with apoptosis-negative or p21-negative tumors, respectively. Histologic changes in H&E-stained biopsy specimens 7 days after starting CRT significantly correlated with pathologic complete response and marked regression on both JCCC and tumor regression criteria, as well as with tumor shrinkage on BE and MRI (P<.01, P<.01, P<.01, P<.01, and P=.03, respectively).. Immunohistochemical expressions of p21 and apoptosis together with histologic changes on H&E-stained biopsy specimens obtained 7 days after starting CRT are strong predictors of the response to CRT.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Antimetabolites, Antineoplastic; Apoptosis; Biomarkers, Tumor; Biopsy; Chemoradiotherapy; Cyclin-Dependent Kinase Inhibitor p21; Drug Combinations; Female; Humans; Ki-67 Antigen; Male; Middle Aged; Oxonic Acid; Rectal Neoplasms; Rectum; Tegafur; Time Factors; Treatment Outcome; Tumor Burden; Tumor Suppressor Protein p53

FOLFOX or FOLFIRI are commonly used as first- or second-line chemotherapy for unresectable colorectal cancer or its metastases.Recently, it had become a trend to add bevacizumab or cetuximab(Cmab)limited to the K-ras wild-type or panitumumab(Pmab)limited to the K-ras wild-type.At the present time, a common third-line chemotherapy is CPT-11 plus Cmab limited to the K-ras wild-type, or Cmab/Pmab.However, the results are unsatisfactory.With Cmab plus S-1 we treated a case of remnant liver metastases from rectal cancer which was a K-ras wild-type, after treating 5-FU, L-OHP and CPT-11. The tumor marker dropped and 7 focuses of liver metastases disappeared after 6 courses of treatment(complete response: CR in)and CR was achieved after 9 courses treatment.After 10 courses of treatment, a new lesion appeared on S5 of the liver and we performed percutaneous radiofrequency ablation.

Topics: Aged; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Cetuximab; Combined Modality Therapy; Drug Combinations; Fluorouracil; Humans; Irinotecan; Liver Neoplasms; Male; Mutation; Organoplatinum Compounds; Oxaliplatin; Oxonic Acid; Proto-Oncogene Proteins; Proto-Oncogene Proteins p21(ras); ras Proteins; Rectal Neoplasms; Recurrence; Salvage Therapy; Tegafur; Tomography, X-Ray Computed

A total of 37 patients treated with chemoradiotherapy between 2008 and 2011 were analyzed. Radiotherapy was administered in fractions of 1.8 Gy/day for 25 days. S-1 was administered orally in a fixed daily dose of 80 mg/m2 on days 1-5, 8-12, 22-26, and 29-33. Irinotecan(CPT-11 80 mg/m2) was infused on days 1, 8, 22, and 29. Curative surgery was performed 6-8 weeks later. The clinical downstaging rate was 40%. During the median follow-up time of 664 days, 37 patients survived. Recurrence was found in 8 patients. Local recurrence (pelvic lymph node metastasis) was only observed in 1 patient. Grade 3-4 toxic effects, including interstitial pneumonia, occurred in 27% of the patients. Neoadjuvant chemoradiotherapy may result in excellent local control with acceptable morbidity. However, longer follow up is required to assess neoadjuvant chemoradiotherapy for locally advanced rectal cancers.

Topics: Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Chemoradiotherapy; Drug Combinations; Female; Humans; Irinotecan; Male; Middle Aged; Neoadjuvant Therapy; Neoplasm Staging; Oxonic Acid; Rectal Neoplasms; Tegafur

We report a rare case of a patient with multiple liver metastases of gastric and rectal cancers after laparoscopic sigmoidectomy, who responded completely to S-1 therapy followed by open gastrectomy. A 72-year-old man with a chief complaint of occult blood in the feces was referred to our hospital and was diagnosed with rectal cancer by colonoscopy. In addition, we found concomitant gastric cancer by gastrointestinal fiberscopy. Abdominal plain computed tomography showed no liver metastasis. In August 2010, we performed laparoscopic resection of the rectal cancer. However, at the time of discharge, abdominal enhanced computed tomography showed multiple liver metastases. Then, we administered 4 courses of S-1 therapy. In December 2010, abdominal enhanced computed tomography showed no liver metastasis. In March 2011, because no other lesion without residual gastric cancer was detected, the patient underwent gastrectomy followed by S-1 therapy. As of January 2012, the patient is alive and disease free. S-1 therapy with laparoscopic resection for rectal cancer and gastrectomy may help prolong the survival of patients with multiple liver metastases of gastric and rectal cancers.

Topics: Aged; Antimetabolites, Antineoplastic; Colectomy; Combined Modality Therapy; Drug Combinations; Gastrectomy; Humans; Laparoscopy; Liver Neoplasms; Male; Neoplasms, Multiple Primary; Oxonic Acid; Rectal Neoplasms; Stomach Neoplasms; Tegafur

The patient is a 47-year-old female. She had undergone abdominoperineal resection for rectal cancer at 39 years of age. Two years and 9 months after surgery, she was diagnosed with a vagina invasion. Radiation therapy and chemotherapy (UFT/ LV) were performed. After 4 courses of UFT/LV, a complete response (CR) was noted. Four years and 3 months after surgery, she was diagnosed with a sacrum metastasis. Chemotherapy with S-1 was performed. After 2 courses of S-1, a CR was noted. There has been no recurrence sign to date.

Topics: Antimetabolites, Antineoplastic; Bone Neoplasms; Drug Combinations; Female; Humans; Magnetic Resonance Imaging; Middle Aged; Oxonic Acid; Rectal Neoplasms; Remission Induction; Sacrum; Tegafur

A 62-year-old male was admitted to our hospital because of anal pain and bloody stool. After careful examination, a locally advanced rectal cancer was found, and an invasion of the prostate was suspected. The prevention of pelvic recurrence and downstaging for S-1/oxaliplatin (SOX), combined with preoperative chemoradiation (CRT) make, PR decision (reduction rate 70%), and surgery (APR+central D3) were performed. The postoperative course was uneventful and the patient was discharged 18 hospital days after surgery. The outpatient is receiving the adjuvant chemotherapy by single S-1 now. Advanced lower rectal cancer S-1/oxaliplatin (SOX), combined with preoperative chemoradiation (CRT), have fewer adverse events and are considered to be useful.

Topics: Antineoplastic Combined Chemotherapy Protocols; Biopsy; Combined Modality Therapy; Drug Combinations; Humans; Male; Middle Aged; Neoplasm Staging; Organoplatinum Compounds; Oxaliplatin; Oxonic Acid; Rectal Neoplasms; Tegafur

A 66-year-old man with a 39-year history of anal fistula was admitted to our hospital for anal pain and bleeding. Fistulectomy was carried out for anal fistula. Histological examination of the specimen revealed carcinoma associated with anal fistula. A computed tomography showed that the tumor had invaded the prostate. Therefore, preoperative chemoradiotherapy(S-1 plus radiation 40 Gy/body)for locally advanced cancer was performed. Magnetic resonance imaging showed that the boundary between the tumor and the prostate was unclear, but we performed an abdominoperineal resection and the prostate was fully preserved. Histopathologically, no cancer cell existed on the surgical margin. The histological effect of chemoradiotherapy was judged as grade 2. This case suggested that surgical treatment combined with preoperative chemoradiotherapy may be effective for locally advanced carcinoma associated with anal fistula, in which preservation of adjacent organs is considered to be difficult.

Topics: Antimetabolites, Antineoplastic; Combined Modality Therapy; Drug Combinations; Humans; Magnetic Resonance Imaging; Male; Oxonic Acid; Rectal Fistula; Rectal Neoplasms; Tegafur; Tomography, X-Ray Computed

A 66-year-old man was referred to our hospital with obstructive jaundice. Computed tomography(CT)scan showed thickening of the gallbladder wall, invasion into the liver bed, and thickening of the rectal wall. Colonoscopy revealed a type 2 rectal cancer, in which adenocarcinoma was identified by endoscopic biopsy. He was diagnosed with double-cancer of the gallbladder and rectum. Because his gallbladder cancer was more life threatening than his rectal cancer, gemcitabine was administered at 1, 000 mg/m2 on days 1, 8, and 15 of a 28-day course. After 3 courses of gemcitabine, the CT scan showed that the lymph nodes in the hepatoduodenal ligament had been enlarged, and duodenal stenosis had occurred as a result of gallbladder cancer invasion. S-1 was administered orally at doses of 120 mg/day twice daily on days 1-28 of a 42-day course. Partial response was confirmed by CT scan. After 8 courses of S-1, the gallbladder cancer had progressed and liver metastases had appeared. He subsequently died of disease progression. He survived for 17 months after the first course of chemotherapy, and the progression-free survival with S-1 was 10 months. Therefore, S-1 could be an effective agent for synchronous double cancer of the gallbladder and rectum.

Topics: Aged; Antimetabolites, Antineoplastic; Combined Modality Therapy; Drug Combinations; Fatal Outcome; Gallbladder Neoplasms; Humans; Male; Neoplasms, Multiple Primary; Oxonic Acid; Rectal Neoplasms; Salvage Therapy; Tegafur; Tomography, X-Ray Computed

We reviewed the patients with neoadjuvant chemoradiotherapy (CRT) with S-1 to evaluate the feasibility and effectiveness for locally advanced lower rectal cancer. The CRT regimen consisted of pelvic irradiation (45 Gy in fractions of 1.8 Gy), five days a week. A treatment of oral S-1 (80 mg/m2 per day) on days 1-14 and 22-35 was given during radiotherapy. Patients underwent a curative resection with lateral lymph node resection at 6-8 weeks intervals after neoadjuvant CRT. The response rate on pathological study was 60% (all were grade 2), and no patients had lateral lymph node metastases. Grade 1 or 2 adverse effects occurred in all patients during CRT, but the CRT was achieved in all patients. We found two patients had surgical complications with wound infection and one patient with anastomotic leakage. All complications were improved by conservative treatment. The neoadjuvant CRT was feasible and effective treatment for all patients with locally advanced rectal cancer. We have started a phase II study of the neoadjuvant CRT.

Topics: Aged; Antimetabolites, Antineoplastic; Chemoradiotherapy; Drug Combinations; Female; Humans; Male; Middle Aged; Neoadjuvant Therapy; Oxonic Acid; Rectal Neoplasms; Tegafur

A 52-year-old woman diagnosed with lower rectal cancer was referred to our hospital for the operation of anal sphincter preservation. Rectal examination and colonoscopy showed a type 2 semicircular tumor on the posterior wall at 4 .5-7 cm from anal verge with incomplete mobility (cT3). She was diagnosed as the moderately differentiated tubular adenocarcinoma by biopsy. Computed tomography and magnetic resonance imaging showed no sign of invasion to the surrounding organs and metastasis to lymph nodes or the other organs (cN0, cM0). We performed a preoperative chemoradiotherapy (CRT) combined with S-1 and CPT-11. Radiation (1.8 Gy) was administered a total of 45 Gy( day 1-5, 8-12, 15-19, 22-26, 29-33). S-1 was taken orally( 100 mg/day: day 1-5, 8-12, 22-26, 29-33), and CPT-11 was administered intravenously (60 mg/m²: day 1, 8, 22, 29). Endoscopy after CRT showed a reduction of the tumor size (from semicircular to quarter-circular) and lowering of marginal wall. Rectal examination revealed an improvement of tumor mobility. Eight weeks after CRT, the patient underwent ISR with partial ESR and covering ileostomy pathological examination demonstrated no residual cancer cell in the primary lesion and lymph node (Grade 3, pCR). Preoperative CRT can be a promising tool for locally advanced rectal cancer.

Topics: Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Chemoradiotherapy; Drug Combinations; Female; Humans; Irinotecan; Middle Aged; Neoplasm Staging; Oxonic Acid; Rectal Neoplasms; Tegafur

We report a long-term survival case of rectal cancer that was initially thought unresectable treated with chemoradiotherapy (CRT). The patient was a 50s female with advanced rectal cancer and liver metastasis. The primary tumor was expanded locally and made abscess around the rectum. We evaluated the primary lesion as unresectable, and we performed CRT after colostomy. After radiation therapy (total 60 Gy) and chemotherapy with S-1 (3 courses), the primary tumor was remarkably reduced. The liver metastasis showed a progressive growth in size but not in number. She underwent complete resection of rectal tumor and partial resection of metastatic liver tumor. Postoperative course was uneventful, and she is alive without a recurrence for 5 years after the surgery.

Topics: Antimetabolites, Antineoplastic; Chemoradiotherapy; Drug Combinations; Female; Humans; Liver Neoplasms; Middle Aged; Oxonic Acid; Rectal Neoplasms; Remission Induction; Tegafur; Time Factors; Tomography, X-Ray Computed

To evaluate the safety of focal dose escalation to regions with standardized uptake value (SUV) >2.0 using intensity-modulated radiation therapy (IMRT) by comparison of radiotherapy plans using dose-volume histograms (DVHs) and normal tissue complication probability (NTCP) for postoperative local recurrent rectal cancer. First, we performed conventional radiotherapy with 40 Gy/20 fr. (CRT 40 Gy) for 12 patients with postoperative local recurrent rectal cancer, and then we performed FDG-PET/CT radiotherapy planning for those patients. We defined the regions with SUV > 2.0 as biological target volume (BTV) and made three boost plans for each patient: 1) CRT boost plan, 2) IMRT without dose-painting boost plan, and 3) IMRT with dose-painting boost plan. The total boost dose was 20 Gy. In IMRT with dose-painting boost plan, we increased the dose for BTV+5 mm by 30% of the prescribed dose. We added CRT boost plan to CRT 40 Gy (summed plan 1), IMRT without dose-painting boost plan to CRT 40 Gy (summed plan 2) and IMRT with dose-painting boost plan to CRT 40 Gy (summed plan 3), and we compared those plans using DVHs and NTCP.. D(mean) of PTV-PET and that of PTV-CT were 26.5 Gy and 21.3 Gy, respectively. V50 of small bowel PRV in summed plan 1 was significantly higher than those in other plans ((summed plan 1 vs. summed plan 2 vs. summed plan 3: 47.11 +/- 45.33 cm3 vs. 40.63 +/- 39.13 cm3 vs. 41.25 +/- 39.96 cm3 (p < 0.01, respectively)). There were no significant differences in V30, V40, V60, D(mean) or NTCP of small bowel PRV.. FDG-PET-guided IMRT can facilitate focal dose-escalation to regions with SUV above 2.0 for postoperative local recurrent rectal cancer.

Topics: Antimetabolites, Antineoplastic; Dose-Response Relationship, Radiation; Drug Combinations; Fluorodeoxyglucose F18; Humans; Neoplasm Recurrence, Local; Oxonic Acid; Positron-Emission Tomography; Radiopharmaceuticals; Radiotherapy Planning, Computer-Assisted; Radiotherapy, Intensity-Modulated; Rectal Neoplasms; Tegafur

A 70-year-old man was referred to our hospital with bowel obstruction because of rectal cancer. High anterior resection of rectum and lymph node dissection was performed. The rectal cancer was in stage III, and the patient selected no adjuvant chemotherapy. At 1-year follow-up, the CEA level was 17. 6 ng/mL, and CT revealed multiple lung metastases and paraaortic and parailiac lymph node metastases. S-1, 100 mg/body, was administered for 4 weeks followed by 2 drug-free weeks. After 3 courses, the CEA level was 4. 5 ng/mL, and metastatic lesions were remarkably reduced in the CT findings. After 10 courses, the CEA level was hovering around 6 ng/mL, and CT showed no recurrent foci. The effect of S-1 treatment was PR, and no severe side effect was observed throughout the treatment.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Drug Combinations; Humans; Lung Neoplasms; Lymphatic Metastasis; Male; Oxonic Acid; Rectal Neoplasms; Tegafur; Tomography, X-Ray Computed

Although neoadjuvant chemoradiotherapy (CRT) is the standard treatment for advanced rectal cancer (RC), markers to predict the treatment response have not been fully established. In 73 patients with advanced RC who underwent CRT in a neoadjuvant setting, we retrospectively examined the associations between the clinical effects of CRT and blood cell counts before and after CRT. Clinical or pathological complete response (CR) was observed in 10 (14%) cases. The CR rate correlated significantly with the size and the circumferential extent of the tumor. Hemoglobin level, white blood cell (WBC) count and platelet count before CRT did not show a significant difference between CR and non-CR cases. Interestingly, however, lymphocyte ratio in WBC was significantly higher (p = 0.020), while neutrophil ratio tended to be lower (p = 0.099), in CR cases, which was shown to be an independent association by multivariate analysis. When all the blood data obtained in the entire treatment period were evaluated, circulating lymphocyte count was most markedly decreased in the CRT period and gradually recovered by the time of surgery, while the numbers of neutrophils and monocytes were comparatively stable. Moreover, the lymphocyte percentage in samples obtained from CR patients was maintained at a relatively higher level than that from non-CR patients. Since tumor shrinkage is known to be dependent not only on the characteristics of tumor cells but also on various host conditions, our data raise the possibility that a lymphocyte-mediated immune reaction may have a positive role in achieving complete eradication of tumor cells. Maintenance of circulating lymphocyte number may improve the response to CRT in rectal cancer.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Combined Modality Therapy; Drug Combinations; Female; Fluorouracil; Follow-Up Studies; Humans; Leucovorin; Lymphocyte Count; Male; Middle Aged; Neoadjuvant Therapy; Neoplasm Staging; Oxonic Acid; Radiotherapy, Adjuvant; Rectal Neoplasms; Retrospective Studies; Survival Rate; Tegafur; Treatment Outcome; Uracil

In patients with advanced rectal cancer, preoperative chemoradiotherapy is superior to postoperative chemoradiotherapy because of causing less toxicity and achieving higher rates of sphincter preservation and curative resection. We treated a patient who had advanced rectal cancer with preoperative chemotherapy using S-1 and concurrent radiotherapy. S-1 was orally administered at a dose of 100 mg/day during the first cycle (two-week on and one week off). During the third cycle, radiotherapy was initiated concurrently and a total dose of 45 Gy was given. The most severe adverse event was grade 3 leukopenia during the third cycle. On day 42 after completing radiotherapy, low anterior resection with diverting colostomy was performed. Histological examination found no viable cancer cells in the resected specimens, including the primary tumor site and lymph nodes. Thus, a pathological complete response was achieved. Postoperatively, anastomotic leakage occurred, but it was resolved with transanal drainage. Preoperative chemoradiotherapy using S-1 contributed to sphincter preservation and curative resection in this patient. This regimen was both effective and well-tolerated, suggesting that it could be useful for advanced rectal cancer.

Topics: Adult; Antimetabolites, Antineoplastic; Chemotherapy, Adjuvant; Colostomy; Drug Combinations; Female; Humans; Lymphatic Metastasis; Magnetic Resonance Imaging; Neoplasm Staging; Oxonic Acid; Radiotherapy, Adjuvant; Rectal Neoplasms; Tegafur

The patient was a 65-year-old male, who underwent low anterior resection for rectal cancer. The pathological diagnosis showed mucinous adenocarcinoma, pSS, and pN0. He complained of diarrhea and melena 4 months after the surgery. Abdominal computed tomography and colonofiberscopy showed a local recurrence of rectal cancer. Because the tumor was diagnosed as unresectable, combined chemotherapy of S-1 (100 mg/day, per os, 4 weeks of treatment and 2 weeks of rest) and PSK (3 g/day, per os, the same schedule as S-1) was started. After the 2 courses of chemotherapy, computed tomography and colonofiberscopy showed a complete disappearance of the tumor. The chemotherapy was continued until the 9th course and then stopped. Five years and 4 months since the induction of a complete response, the patient is still alive without disease recurrence. Combined chemotherapy of S-1 and PSK may be one of useful choices for recurrent colorectal cancer.

Topics: Adenocarcinoma, Mucinous; Aged; Antibiotics, Antineoplastic; Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Drug Combinations; Humans; Male; Neoplasm Recurrence, Local; Oxonic Acid; Proteoglycans; Rectal Neoplasms; Tegafur; Treatment Outcome

Combined chemotherapy including 5-FU plus radiation treatment resulted in a synergistic effect has been reported. S-1 enhances a radiation response of colon cancer cell line xenografts. Also the effectiveness of S-1 + radiation therapy has been reported. A 66-year-old man underwent a low anterior resection for lower rectal cancer. Adjuvant chemotherapy was not performed due to Stage II rectal cancer. Twenty months after the operation, solitary sacral bone metastasis was found during the postoperative work-up. S-1 (120 mg/day) combined with radiotherapy was performed on days 1-14 and 21-35. Radiation (3 Gy) was administered a total of 45 Gy on days 1-5, 7-12 and 35-40. Moreover, the reduction was judged as complete response after 11 courses of mFOLFOX 6. There has been no sign of recurrence for 44 months. It suggested that local control therapy (S-1 + radiation) plus systemic chemotherapy (mFOLFOX6) was one of the promising effective therapies for single sacral bone metastasis of rectal cancer.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Bone Neoplasms; Combined Modality Therapy; Drug Combinations; Fluorouracil; Humans; Leucovorin; Male; Organoplatinum Compounds; Oxonic Acid; Radiotherapy Dosage; Rectal Neoplasms; Sacrum; Tegafur

A 42-year-old man with advanced rectal cancer underwent a low anterior resection with TME and pelvic lateral lymph-node and paraaortic lymph-node dissections. Pathological examination revealed as Type 2, 84 × 70 mm, tub 2 > por, A-SE, int, INF b, ly3, v1, pN3 (35/68), M1 (No. 216: 24/37), Stage IV (Cur B) by Japanese Classification of Colorectal Carcinoma. Three kinds of chemotherapy, 3 courses of irinotecan and bolus fluorouracil plus Leucovorin (IFL), 4 courses of irinotecan and S-1 (IRIS), and one-year of S-1 were administered sequentially. After 5 years from the operation, the patient survived and showed no sign of recurrence. Aggressive lymph-node dissection for rectal cancer patients with massive lymph-node metastasis followed by intensive chemotherapy may result in long-term survival.

Topics: Adult; Antimetabolites, Antineoplastic; Antineoplastic Agents, Phytogenic; Antineoplastic Combined Chemotherapy Protocols; Aorta, Abdominal; Camptothecin; Combined Modality Therapy; Disease-Free Survival; Drug Administration Schedule; Drug Combinations; Fluorouracil; Humans; Irinotecan; Leucovorin; Lymph Node Excision; Lymphatic Metastasis; Male; Oxonic Acid; Pelvis; Rectal Neoplasms; Tegafur; Vitamin B Complex

The patient was an 80-year-old woman who was diagnosed with locally advanced low rectal cancer. It was unresectable and we performed chemoradiotherapy combined with S-1 (S-1 80 mg/m2, RT 1.8 Gy × 25, total 45 Gy). An effective reduction of primary region resulted in curative resection (super low anterior resection, D3 lymph node dissection, covering ileostomy) with preserving the anal sphincter. Histopathologically, therapeutic efficacy was Grade 2. Preoperative chemoradiation has been a standard therapy in Western countries and would control local recurrence. This case indicated that CRT could improve a rate of curative resection in patients with locally advanced rectal carcinomas.

Topics: Aged, 80 and over; Antimetabolites, Antineoplastic; Combined Modality Therapy; Drug Combinations; Female; Humans; Lymph Node Excision; Oxonic Acid; Radiotherapy Dosage; Rectal Neoplasms; Rectum; Tegafur

We report a case of local recurrent colorectal cancer that has been treated successfully with low-dose oral chemotherapeutic agent. An 80-year-old man underwent a low anterior resection for rectal cancer. Two years and nine months later, a recurrent tumor was revealed in the vicinity of the anastomotic region by colonoscopy. Additional examination by enhanced CT elucidated the tumor infiltrated the sacrum. For this reason, we planned an abdominoperineal resection of rectum with sacrum excision for treatment. However, we considered that he could not overcome the burden of operation for his complication. As a result of informed consent with the patient and his family, we decided a conservative treatment, and started chemotherapy using S-1. The tumor has been diminished slowly on enhanced CT and colonoscopy. The chemotherapy using S-1 has been continued with good quality of life for over five years. S-1 is expected to be an effective choice for the patient of colorectal cancer who cannot be taken the standard treatment for various reasons.

Topics: Administration, Oral; Aged, 80 and over; Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Drug Combinations; Humans; Male; Neoplasm Recurrence, Local; Oxonic Acid; Rectal Neoplasms; Tegafur; Uracil

The patient was a 70-year-old male with advanced cancers of stomach and rectum and multiple metastatic hepatic tumors. No resectability was detected. The origin of metastatic hepatic tumors was unknown, so the combination of S- / 1 and CPT-11 as a treatment regimen was selected. S-1, 80 mg m(2), was administered on 14 consecutive days followed / by a 14-day rest period, and CPT-11, 100 mg/m(2), was administered on day 1 and day 15. One cycle was defined as 4 weeks, and cycles were repeated. CR was achieved as long as metastatic hepatic tumors after completion of 5 cycles. When we encounter a case of simultaneous double cancers with metastatic sites which has no respectability, generally speaking, it is difficult to determine the strategy for chemotherapy. This case suggests that the combination of S-1 and CPT-11 may be an effective regimen for the treatment of simultaneous advanced cancers of stomach and rectum with multiple hepatic metastases.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Biopsy; Camptothecin; Carcinoembryonic Antigen; Drug Combinations; Endoscopy, Gastrointestinal; Humans; Irinotecan; Liver Neoplasms; Male; Neoplasms, Multiple Primary; Oxonic Acid; Rectal Neoplasms; Stomach Neoplasms; Tegafur; Tomography, X-Ray Computed; Treatment Outcome

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.

Topics: Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Drug Combinations; Humans; Irinotecan; Lung Neoplasms; Male; Middle Aged; Oxonic Acid; Rectal Neoplasms; Recurrence; Tegafur; Tomography, X-Ray Computed; Treatment Outcome

A 78-year-old female underwent an abdomino-perineal resection for lower rectal cancer with para-aortic, right iliac artery and left inguinal lymph node metastasis. Two weeks later, an enlargement of para-aortic and right iliac artery lymph node metastasis was detected by CT. S-1 (100 mg/day for 2 weeks followed by a 1-week rest period) + CPT-11 (120 mg/m2, day 1)treatment was initially administered. However, the patient developed grade 2 anorexia so this treatment regimen was terminated. After complete recovery from the adverse reaction, the regimen was converted to S-1 administration at 100mg/day S-1 for 2 weeks followed by a 1-week rest period. Eventually, this schedule was modified to 100mg/day for 1 week followed by a 1-week rest period. A year after the operation, CT revealed the lymph node metastasis to have disappeared, and no relapse occurred for 32 months. This was a successful case in which S-1 yielded an extended complete response for advanced rectal cancer. Treatment with S-1 is an effective choice for patients who for various reasons can not tolerate the standard treatment for unresectable advanced colorectal cancer. Moreover, randomized controlled trials have to be started to evaluate the efficacy of S-1 treatment for advanced rectal cancer as soon as possible.

Topics: Aged; Antimetabolites, Antineoplastic; Antineoplastic Agents, Phytogenic; Camptothecin; Drug Combinations; Female; Humans; Irinotecan; Lymphatic Metastasis; Oxonic Acid; Rectal Neoplasms; Tegafur

The patient was a 42-year-old female who had advanced rectal cancer(Ra, type 2)with liver metastasis. The preoperative diagnosis was T2N1H2, but the liver tumor was unresectable for hepatic vein invasion in September, 2004. She underwent low anterior resection for primary rectal cancer at first after she was given S-1 80 mg/day(14 days)for a histological effect judgment. The pathological diagnosis was moderately-differentiated adenocarcinoma, ss, n1, and the histological effect was Grade 1a. Because CT showed reduction of liver metastasis after the operation, she was treated with 2 courses of chemotherapy using S-1. Radiographic examination showed reduction of liver metastasis(36%)and improvement of hepatic vein invasion. In January, 2005, she underwent hepatectomy and the pathological diagnosis was moderately-differentiated adenocarcinoma, metastasis and the histological effect was Grade 1a. There has not been any recurrence for 48 months after hepatectomy. We experienced this case in which preoperative S-1 proved effective for liver metastasis from rectal cancer.

Topics: Adenocarcinoma; Adult; Antimetabolites, Antineoplastic; Drug Combinations; Female; Hepatectomy; Humans; Liver Neoplasms; Neoadjuvant Therapy; Oxonic Acid; Rectal Neoplasms; Tegafur

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.

Topics: Adenocarcinoma, Mucinous; Aged; Aged, 80 and over; Antimetabolites, Antineoplastic; Combined Modality Therapy; Drug Combinations; Female; Fluorouracil; Humans; Male; Oxonic Acid; Pelvis; Rectal Neoplasms; Tegafur

The patient was a 58-year-old man who had been performed a low anterior resection for an advanced upper rectal cancer (T3N0M0, Stage II). At fourteen months after primary operation, follow-up CT scan, MRI and FDG-PET showed a pelvic recurrence located at upper presacral region. Following radiotherapy combined with S-1, we performed a curative surgical resection. Pathologically, an extensive fibrosis was shown without a tumor cell. Complete surgical removal of the recurrent disease remains the best chance of cure after a local recurrence. But in the case of recurrent tumor located in upper presacral region and extended to the pelvic side-wall, it is very difficult to achieve negative resection margins. So selection of patients is very important to reduce the risk of positive surgical margins. We experienced a resected case of pathologically complete response of a pelvic recurrence from rectal cancer after chemoradiotherapy with S-1. This case suggests the neoadjuvant chemoradiotherapy has potential to improve management of locally recurrent rectal cancer.

Topics: Antimetabolites, Antineoplastic; Drug Combinations; Humans; Male; Middle Aged; Neoadjuvant Therapy; Neoplasm Recurrence, Local; Oxonic Acid; Pelvis; Rectal Neoplasms; Tegafur

We describe a case of locally recurrent rectal cancer that was successfully treated with radiation and chemotherapy with S-1; this treatment resulted in long-term survival of the patient with a good performance status. A 51-year-old man underwent Hartmann's operation for advanced rectal cancer. At 6 months after the surgery, a pelvic computed tomography (CT) scan showed a local recurrence of the rectal cancer. The patient's serum CA19-9 level had increased to 3,200 U/mL. The tumor was unresectable, so that radiation therapy was administered to the pelvic region at a total dose of 56 Gy, followed by oral chemotherapy with S-1 for 2 years. After these treatments, the serum CA19-9 level returned to normal. No signs of tumor recurrence were observed as of 3 years and 5 months after the confirmation of local recurrence. A combination of radiation therapy and oral administration of S-1 could be a useful treatment for unresectable locally recurrent rectal cancer.

Topics: Antimetabolites, Antineoplastic; Combined Modality Therapy; Drug Combinations; Humans; Male; Middle Aged; Neoplasm Recurrence, Local; Oxonic Acid; Rectal Neoplasms; Tegafur

A 68-year-old man lost in unconscious and was diagnosed as ruptured hepatocellular carcinoma (HCC) in a local emergency hospital. He was treated by transcatheter arterial embolization, and further investigation revealed simultaneous cancer in rectum. He was referred to our institute, and admitted in June 2005. He underwent lateral segment and S8 partial resection of the liver, cholecystectomy, anterior resection of rectum, and D3 lymphadenectomy in August 2005. Multiple HCC recurrences in the remnant liver appeared in December 2005. He was subsequently treated with transcatheter chemoembolization four times. In May 2006, CT scan revealed multiple metastatic nodules in bilateral lungs with remarkably elevated serum AFP and PIVKA-II. The nodules were diagnosed as lung metastasis of the HCC. Because the lesions grew larger, S-1 was started in February 2007. Diagnostic imaging and tumor markers showed a marked improvement 2 months after S-1 administration, and no recurrence has been found since then. This case illustrates that S-1 may be an effective treatment for HCC with extrahepatic metastasis.

Topics: Aged; Antimetabolites, Antineoplastic; Carcinoma, Hepatocellular; Drug Combinations; Hepatectomy; Humans; Liver Neoplasms; Lung Neoplasms; Male; Neoplasm Recurrence, Local; Neoplasms, Multiple Primary; Oxonic Acid; Rectal Neoplasms; Tegafur

We reviewed 7 cases of clinical record with preoperative chemo-radiotherapy to evaluate the clinical effectiveness of the chemo-radiotherapy for T4 rectal cancer. The preoperative radiation therapy consisted of 40-45 Gy delivered in fractions of 1.8-2.0 Gy per day, five days a week. A treatment of 5-fluorouracil, 500 mg/body per day intravenously, or oral UFT-E (300 mg/m2) with l-leucovorin (75 mg) per day, or oral S-1 (80 mg/m2) per day five days a week, was given during radiotherapy. Grade 1 or 2 adverse effects occurred in 3 patients during chemo-radiotherapy, but the completion of chemo-radiotherapy was achieved in all of the 7 patients. Tumor invasion identified by CT and MRI to other organs in the pelvis disappeared in four cases with complete or partial response after a month of chemo-radiotherapy. Although the other organs were also removed during surgery in 4 patients, curative surgery was performed in 5 patients. There was no histological invasion seen to other organs in 4 patients, and one patient had histological complete disappearance of tumor. Although complications after surgery were found in all of the patients, they were improved by conservative treatment. One of 4 patients with curative surgery had liver and local recurrence, but others survived without recurrence. Preoperative chemo-radiotherapy was expected to be a safe and effective treatment to improve the resection rate and prognosis for T4 rectal cancer.

Topics: Antineoplastic Agents; Drug Combinations; Fluorouracil; Humans; Male; Middle Aged; Neoadjuvant Therapy; Neoplasm Staging; Oxonic Acid; Rectal Neoplasms; Tegafur

A 64-year-old man was admitted to general practitioner because of dyschezia. He was diagnosed with lower rectal cancer by colonoscopy and referred to our hospital for therapy. At first, in spite of multiple liver metastases, we tried a resection of primary lesion in order to control of breeding, dyschezia and pain. However, we had to give up the resection, so we made sigmoid colostomy only. One month after the operation, a combination chemo-radiotherapy using S-1 was performed for controlling of local symptom. S-1 (120 mg/day) was administered on days 1-14, and 21-35. Radiation (2 Gy) was administered on days 1-5, 7-12, 14-19, 21-26, 28-33, and 35-40, a total of 60 Gy. One month after this therapy, the tumor was remarkably reduced and the reduction was judged as partial response. Moreover after 6 courses of FOLFIRI, the reduction was judged as complete response. Local control therapy (S-1+chemo-radiation) plus systemic therapy (FOLFIRI) is one of the promising effective therapies for advanced rectal cancer.

Topics: Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Camptothecin; Drug Combinations; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Neoplasm Staging; Oxonic Acid; Proctoscopy; Rectal Neoplasms; Remission Induction; Tegafur; Tomography, X-Ray Computed

We report a case of a 72-year-old man with advanced rectal cancer who refused an operation for cancer therapy. We underwent radiation therapy (40 Gy) for the purpose of suppressing tumor bleeding. Consequently, we administered S-1 (100 mg/day) orally. As a result, the tumor has disappeared by radiation therapy and chemotherapy with S-1 for 2 years. We have recognized no side effects. This therapy seemed to be an effective treatment for poor-risk elderly patients.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Colonoscopy; Combined Modality Therapy; Drug Combinations; Humans; Male; Neoplasm Staging; Oxonic Acid; Rectal Neoplasms; Tegafur

The patient was a 44-year-old male in whom low anterior resection of the rectum, partial pneumonectomy, and liver biopsy were performed because of suspicion of synchronous liver and pulmonary metastases of rectal cancer which caused familial adenomatous polyposis. Because anticancer drug sensitivity testing by the HDRA method performed on tissue collected from the cancer immediately postoperatively revealed sensitivity to 5-FU and CPT-11, and measurement of nucleic acid metabolizing enzymes showed a high level of DPD, a 5-FU metabolizing enzyme, combination therapy with TS-1 and CPT-11 was started. TS-1, 120 mg/body, was administered on 14 consecutive days followed by a 7-day rest period, and CPT-11, 120 mg/body, was administered on day 1 and day 8. One cycle was defined as 3 weeks,and cycles were repeated. Grade 2 diarrhea occurred, but the CPT-11 dose was reduced to 100 mg/body, and treatment was continued. CR was achieved when the 4th course had been completed. Thoracic and abdominal CT was performed after 4 courses, but no recurrent foci were detected in the residual lung tissue, and all of the metastatic liver foci had resolved. To date 6 courses have been completed, and no relapses have been detected by thoracic CT. We report a case in which it was possible to predict efficacy as a result of treatment based on anticancer drug sensitivity testing and measurements of nucleic acid metabolizing enzymes.

Topics: Adenomatous Polyposis Coli; Adult; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Combined Modality Therapy; Diabetes Complications; Diabetes Mellitus, Type 2; Drug Administration Schedule; Drug Combinations; Humans; Irinotecan; Liver Neoplasms; Lung Neoplasms; Male; Neoplasms, Multiple Primary; Oxonic Acid; Rectal Neoplasms; Remission Induction; Tegafur

A 77-year-old male patient who had been receiving doxifluridine (5'-DFUR) for about a year after surgery for rectal cancer, was newly prescribed TS-1, because tumor markers were elevated and abdominal ultrasonography documented liver metastasis. However, the patient took TS-1 concomitantly with 5'-DFUR, which is contraindicated to TS-1, and experienced a severe drug interaction. This inadvertent drug interaction was caused by a combination of the newly prescribed drug and the unused drug remaining at the patient's home. This type of medication error has not been reported previously. Health professionals should be aware of such drug interactions which may be caused by newly prescribed drugs plus unused drugs remaining in the patient's home. Furthermore, health professionals should instruct patients on the nature of drug interactions as well as explaining their diagnosis and treatment. Although the severity of such drug interaction may vary, health professionals must be alerted to such incidents, which could happen frequently.

Topics: Aged; Contraindications; Drug Combinations; Floxuridine; Humans; Male; Medication Errors; Oxonic Acid; Rectal Neoplasms; Self Medication; Tegafur

We report a case of advanced rectal cancer successfully treated with a combination of S-1 and CPT-11 as neoadjuvant chemotherapy. The patient, a 61-year-old man, had a rectal cancer with pelvic viscera invasion and severe stenosis. After colostomy for removing stenosis, he was treated with a combination of S-1 and CPT-11 (S-1 120 mg/body day on day 1-14, CPT-11 120 mg/body/day on day 1 and day 15, every 4 weeks). Seven courses of treatment resulted in a marked reduction of the primary tumor and disappearance of invasion. Subsequently, rectal amputation for curative intent was done. No surgical complication was observed. On microscopic examination, only a few tumor cells were detected in the granulation tissue of the resected rectum and no tumor cells in dissected LNs. This case demonstrates the effectiveness and safety in a neoadjuvant setting of a combination of S-1 and irinotecan for rectal cancer.

Topics: Antimetabolites, Antineoplastic; Antineoplastic Agents, Phytogenic; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Chemotherapy, Adjuvant; Drug Combinations; Humans; Irinotecan; Male; Middle Aged; Neoadjuvant Therapy; Neoplasm Invasiveness; Oxonic Acid; Rectal Neoplasms; Tegafur

An 80-year-old female visited our hospital with a chief complaint of anal pain and bleeding. The patient was diagnosed by colonoscopy to have rectal cancer which invaded the perineal region. A pelvic CT also revealed metastases to the lymph node located in the femoral artery. Miles operation was performed and a curative resection was successfully achieved. The pathological findings were poorly differentiated adenocarcinoma with pMP and pN2. Adjuvant chemotherapy was refused by the patient. Paraaortic lymph node metastasis was diagnosed by abdominal CT 6 months after the surgery. The patient was treated with S-1 combined with CPT-11. The S-1 (80 mg/m2) was orally administered for 2 weeks followed by a 2-week interval and CPT-11 (100 mg/m2) was also simultaneously administered biweekly. One cycle of chemotherapy was 28 days. The patient experienced grade 2 leukocytopenia, neutropenia, diarrhea and grade 1 alopecia. Abdominal CT revealed a partial response after 2 cycles. After 10 cycles, the patient continued to demonstrate a partial response. The S-1 combined with CPT-11 regimen for elderly patients was thus found to be very feasible and convenient, and we obtained a good compliance. As a result, this regimen was thus found to be promising for unresectable or recurrent colorectal cancer in elder patients. In the future, the efficacy and safety of this regimen should be verified in phase II clinical trial for elderly patients.

Topics: Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Colonoscopy; Drug Combinations; Female; Humans; Irinotecan; Lymphatic Metastasis; Neoplasm Recurrence, Local; Oxonic Acid; Rectal Neoplasms; Tegafur; Tomography, X-Ray Computed

A 63-year-old woman was referred to our hospital with complaints of anal pain, constipation and abdominal distention caused by a rectal tumor. After examinations, she was diagnosed as rectal cancer with multiple liver metastases. The CEA level was 70.0 ng/ml and the CA19-9 level was more than 5,000 U/ml at admission. To prevent bowel obstruction, low anterior resection of the rectum was performed. At 34 days after operation, TS-1 chemotherapy was started as outpatient treatment (each course consisted of daily oral administration of 100 mg TS-1 for 4 weeks followed by 2 drug-free weeks). After the first course, the CEA level was reduced to 3.3 ng/ml and the CA19-9 level to 15 U/ml, both under the normal value. After the second course, administration was discontinued due to diarrhea, and restarted as a daily oral administration of 80 mg TS-1. After the five courses, the CEA level was 4.0 ng/ml and the CA19-9 level was 4 U/ml, both under the normal value. Multiple liver metastases had remarkably reduced in the CT findings. The patient continues to undergo outpatient treatment with good QOL.

Topics: Adenocarcinoma; Ambulatory Care; Antimetabolites, Antineoplastic; Biomarkers, Tumor; CA-19-9 Antigen; Carcinoembryonic Antigen; Drug Administration Schedule; Drug Combinations; Female; Humans; Liver Neoplasms; Middle Aged; Oxonic Acid; Rectal Neoplasms; Tegafur

The patient, a 40-year-old woman, underwent total gastrectomy and excision of the pancreatic tail, spleen and gallbladder for gastric cancer in September 2000. The lesion was judged to be P1, SE, H0, N2 and Stage IV and the patient was managed on a regular schedule as an outpatient. In September 2004, she passed blood-stained feces and rectal palpation detected a hard nodule at the anterior rectal wall. A fiber optic examination of the sigmoid colon detected an ulcerous lesion with a hemorrhage at the anterior rectal wall. A biopsy revealed the lesion to be Group V poorly differentiated adenocarcinoma. Starting in October 2004, 100 mg/day of TS-1 was administered for 3 weeks; intravenous drip infusion of 100 mg/body of CDDP was conducted in the second week for a period of 24 hours. After 3 courses of this regimen, a fiber optic examination of the colon conducted in February 2005 no longer detected the rectal tumor, leaving only a cicatrix. Upon a CT examination, the para-aortic lymph nodes that had been enlarged were notably reduced in size and an improvement was eminent in the hypertrophic rectal wall. The patient no longer experienced constipation or melena. Her clinical course is being observed while an oral administration of 100 mg/day of TS-1 continues.

Topics: Adenocarcinoma; Adult; Antimetabolites, Antineoplastic; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Cholecystectomy; Cisplatin; Constriction, Pathologic; Drug Combinations; Female; Gastrectomy; Humans; Oxonic Acid; Pancreatectomy; Pyridines; Rectal Diseases; Rectal Neoplasms; Splenectomy; Stomach Neoplasms; Tegafur

A 50-year-old woman visited our hospital with a chief complaint of lower abdominal mass. The patient was diagnosed with rectal cancer using colonoscopy and also diagnosed with unresectable rectal cancer because abdominal CT revealed metastases to the liver, lung and lymph node located porta hepatis. The patient was treated with TS-1 combined with CPT-11. The TS-1 (80 mg/m2) was orally administered for 2 weeks and followed by a 2 week interval, and CPT-11 (80 mg/m2) was simultaneously administered biweekly. One cycle of chemotherapy was 28 days. The patient experienced grade 1 leukocytopenia and neutropenia. Abdominal CT revealed partial response after 2 cycles. After 6 cycles, the patient was subjected to curative operation. Pathological efficacy was Grade 1a at lymph node metastasis and Grade 3 at liver metastasis. TS-1 combined with CPT-11 regimen was very feasible and convenient, and obtained a good compliance. So this regimen was promising for unresectable colorectal cancer. In the future, this regimen will be verified in phase III clinical trial and compared with FOLFIRI and FOLFOX regimens.

Topics: Adenocarcinoma; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Drug Administration Schedule; Drug Combinations; Female; Humans; Irinotecan; Middle Aged; Oxonic Acid; Preoperative Care; Pyridines; Rectal Neoplasms; Tegafur

We report a patient with multiple pulmonary metastases from rectal cancer effectively treated with TS-1 and low-dose CDDP combination chemotherapy. The patient was a 61-year-old man with rectal cancer and multiple pulmonary metastases. He had undergone abdominoperineal excision of the rectum at another hospital before this hospitalization. After the operation, we treated the patient by the combination chemotherapy of TS-1 and low-dose CDDP during his hospital stay and in the outpatient clinic after hospital discharge. After the chemotherapy was started, tumor markers decreased, and finally were in the normal range. The pulmonary metastatic lesions were remarkably reduced on CT, and the effect of this therapy was PR. No severe side effect was observed throughout the treatment. This combination chemotherapy is considered to be an effective therapy for colorectal cancer with good QOL.

Topics: Adenocarcinoma; Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Cisplatin; Combined Modality Therapy; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Combinations; Humans; Lung Neoplasms; Male; Middle Aged; Oxonic Acid; Pyridines; Rectal Neoplasms; Remission Induction; Tegafur

TS-1 is an oral anticancer drug that produces biochemical modulation. TS-1 is composed of FT (tegafur), CDHP (gimestat), and Oxo (ostat potassium), in a molar ratio of 1:0.4:1. We administered TS-1 to a patient with liver and pulmonary metastasis of rectal cancer (phase II study). Each treatment course consisted of a four-week administration followed by two drug-free weeks. The daily dose was 120-150 mg/day. Before the administration, hepatic metastasis was 30 x 20 mm. After 2 courses, it was reduced to 20 x 15 mm (reduction rate: 50%). Three pulmonary metastases that were recognized in chest radiographs before the administration tended to reduction after 3 courses. The reduction rate after 4 courses was 42.5%. The reduction was judged PR for the hepatic metastasis and MR for pulmonary metastases. There was no side effect and hospitalization was not required during the treatment. Thus, the administration of TS-1 enhanced the quality of life of this patient.

Topics: Adenocarcinoma; Administration, Oral; Antimetabolites, Antineoplastic; Drug Administration Schedule; Drug Combinations; Humans; Liver Neoplasms; Lung Neoplasms; Male; Middle Aged; Oxonic Acid; Pyridines; Rectal Neoplasms; Tegafur