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Chemotherapy in relapsed colorectal cancer patients treated with oxaliplatin as adjuvant chemotherapy is under debate. REACT study aimed to investigate the efficacy of reintroducing modified FOLFOX6 (mFOLFOX6) or CAPOX with or without bevacizumab in recurrent colorectal cancer patients after oxaliplatin adjuvant chemotherapy. Patients that participated in this trial had a medical history of adjuvant chemotherapy, including oxaliplatin with a cumulative dose greater than 400 mg/m2, and recurrence that was diagnosed more six months post adjuvant chemotherapy. Primary endpoints were response rate (RR) and disease control rate (DCR), while key secondary endpoints were time to treatment failure (TTF), progression-free survival (PFS), overall survival (OS), and safety. A total of 31 patients were enrolled between October 2012 and October 2016. Of the 29 eligible patients, 7 received mFOLFOX6 and 22 received CAPOX. The RR was 62.1% (95% confidence interval 42.3–79.3) and the DCR was 82.8% (95% confidence interval 64.2–94.2). The RR for oxaliplatin-free interval was 100.0% in months 6–12 and 56.0% after 12 months. Median TTF, PFS, and OS were 6.3, 10.8, and 28.7 months, respectively. Grade 3 or worse peripheral sensory neuropathy developed in 6.5%. Allergic reactions occurred in 12.9% of the patients, with one (3.2%) grade 3 episode. There were no other severe treatment-related adverse events. Reintroduction of oxaliplatin was feasible and achieved high RR or DCR in patients after more than 6 months post oxaliplatin adjuvant chemotherapy.

Background Among patients with colorectal cancer (CRC) treated with oxaliplatin (L-OHP)-based chemotherapy, delayed chemotherapy-induced nausea and vomiting (CINV) have not been well controlled. Methods We pooled data from two prospective observational studies in Japan and one phase III clinical trial to assess whether delayed CINV could be controlled with a combination of three antiemetics adding a neurokinin-1 receptor antagonist and identified individual risk factors, using an inverse probability treatment-weighted analysis. Results A total of 661 patients were evaluable in this study (median age: 64 years; 391 male, and 270 female). 3 antiemetics controlled delayed nausea (33.18% vs. 42.25%; p = 0.0510) and vomiting (4.15% vs. 16.08%; p p = 0.0012; 2 antiemetics—OR: 1.485; 95% CI: 1.000–2.204; p = 0.0498) and delayed vomiting (female—OR: 2.735; 95% CI: 1.410–5.304; p = 0.0029; 2 antiemetics—OR: 4.551; 95% CI: 2.116–9.785; p = 0.0001). Conclusions Identifying individual risk factors can facilitate personalized treatments for delayed CINV. We recommend a 3-antiemetic combination prophylaxis for CRC patients treated with L-OHP-based chemotherapy, especially for female patients.

Background Fluorouracil (5-FU), leucovorin (LV) and oxaliplatin (FOLFOX) plus panitumumab therapy is a commonly used first-line chemotherapy for metastatic colorectal cancer (mCRC). However, the long-term administration of oxaliplatin is associated with peripheral neuropathy (PN). We investigated whether the planned discontinuation of oxaliplatin after FOLFOX plus panitumumab therapy can maintain efficacy and reduce PN incidence. Patients and methods Chemotherapy-naive patients with RAS wild-type mCRC, aged ≥20 years, were enrolled and received six cycles of modified FOLFOX6 (mFOLFOX6) plus panitumumab as induction therapy. Patients who completed induction therapy without progression were randomised to mFOLFOX6 plus panitumumab (group A) or to 5-FU/LV plus panitumumab (group B). The primary end-point was the progression-free survival (PFS) rate at 9 months after randomisation. The secondary end-points were PFS, overall survival (OS), time to treatment failure (TTF), response rate (RR) and safety. Results In total, 164 patients were enrolled; of whom, 113 patients were then randomised (group A, n = 56; group B, n = 57). The median follow-up after randomisation was 19.6 months. The PFS rates at 9 months and median PFS were 46.4% (80% confidence interval [CI], 38.1–54.9) and 9.1 months (95% CI, 8.6–11.1) in group A, compared with 47.4% (80% CI, 39.1–55.8) and 9.3 months (95% CI, 6.0–13.0) in group B, respectively. RR, OS and TTF were also similar in both groups. Grade ≥2 PN incidence was lower in group B (9.3%) than in group A (35.7%). Conclusion Planned discontinuation of oxaliplatin after six cycles of mFOLFOX6 plus panitumumab is a potential treatment option in patients with mCRC, achieving similar efficacy while reducing oxaliplatin-associated PN compared with mFOLFOX6 plus panitumumab. Trial registration number NCT02337946

Introduction Oxaliplatin-induced peripheral neuropathy (OIPN) is a common adverse events that can limit a patient's quality of life during/after chemotherapy. However, no appropriate methods have been established yet for monitoring the risk of progression of OIPN. Methods A simple assessment tool using gem clips, the CLIP test, was established and its performance in predicting the risk of progression to ≥grade 2 peripheral sensory neuropathy (CTCAE ver. 4.0) was investigated in patients receiving chemotherapy with oxaliplatin. Results Among 101 patients included in this study, 71 patients developed CTCAE ≥grade 1 peripheral neuropathy (grade 1, n = 67; grade 2, n = 4) at a median of 63 (range, 14-259) days after the start of treatment. Of the 67 patients with grade 1 peripheral neuropathy, 17 showed progression to ≥grade 2 neuropathy after a median interval of 84 (range, 21-246) days. Of these patients, 27 showed a positive result of the CLIP test at a median of 91 (range, 14-224) days, excluding one patient who already showed a positive result of the test at the baseline. Therefore, the risk ratio for the development of CTCAE ≥grade 2 peripheral neuropathy was 8.3 in the patients who showed a positive result on the CLIP test. Multivariate analysis confirmed that a positive results on the CLIP test was significantly correlated with the risk of future development of CTCAE ≥grade 2 peripheral neuropathy (odds ratio, 9.37; P = 0.002). Conclusion A positive result on the CLIP test predict is predictive of the risk of progression of OIPN during chemotherapy with oxaliplatin.

A 74-year-old man underwent distal gastrectomy for gastric cancer(CY1, fStage Ⅳ). About 18 months after surgery, abdominal CT scans revealed multiple lymph node metastases along the portal vein. Systemic chemotherapy was administered comprising a capecitabine/oxaliplatin(CAPOX)regimen. After 4 courses of chemotherapy, an adverse reaction of Grade 2 diarrhea and peripheral neuropathy occurred, although regression of the lymph node metastasis was confirmed. Ramucirumab was administered as the second-line regimen, but CT imaging revealed lymph node progression after several courses. Although irinotecan(CPT-11)was selected as the third-line chemotherapy, the lymph node progression remained uncontrolled. Nivolumab was selected as the fourth-line chemotherapy. After 23 courses, nivolumab immunotherapy induced a partial response to the lymph node metastasis. Nivolumab immunotherapy continues to be administered until now, 5 years after the operation. We experienced a case of lymph node metastasis from gastric cancer successfully treated with nivolumab chemotherapy.

Fluorouracil monotherapy, instead of the FOLFOX or FOLFIRI regimen, is administered to patients intolerant to oxaliplatin or irinotecan because of their adverse effects. A prospective clinical trial was designed to evaluate the efficacy and safety of fluorouracil monotherapy combined with panitumumab administered to patients with KRAS wild-type (WT) metastatic colorectal cancer (mCRC) intolerant to oxaliplatin and irinotecan. Screening for potential serum biomarkers to predict early therapeutic responses was conducted. This single-arm, open-label multicenter phase II trial recruited patients with KRAS WT mCRC from 16 institutes between January 2012 and October 2014. Panitumumab (6 mg/kg) was intravenously administered every 2 weeks, combined with fluorouracil monotherapy, in 2-week cycles. The primary objective was overall response rate, and secondary endpoints included disease-control rate, progression-free survival, overall survival, toxicity, and blood-test data. Forty patients (male, 65.0%; median age, 74 years; colon cancer, 72.5%) met eligibility criteria and received 7 cycles (median) of fluorouracil chemotherapy combined with panitumumab. There were no treatment-related deaths. Median time to treatment failure was 3.2 months. 23 (57.5%) patients experienced at least one adverse effect ≥ grade 3. The response rate was 10.0% (95% confidence interval 2.8–23.7%). Median progression-free survival and overall survival were 4.3 and 11.3 months, respectively. Total lactase dehydrogenase (LDH) levels and those of LDH-4 and LDH-5, quickly changed with disease reduction or progression. Fluorouracil monotherapy combined with panitumumab was safely administered to patients with KRAS WT mCRC intolerant to oxaliplatin and irinotecan. Serum LDH levels may predict early responses.

We aimed to determine the recommended dose for bi-weekly XELIRI plus bevacizumab for second-line chemotherapy and examined its safety and efficacy in patients with metastatic colorectal cancer resistant to oxaliplatin-based first-line chemotherapy. Irinotecan and bevacizumab were administered as a continuous intravenous infusion on Day 1 at 150 mg/mm2 and 5 mg/kg, respectively. Capecitabine was orally administered in two divided doses on Days 2–8. Each 2-week treatment cycle was defined as a single course of treatment. During Phase I, we determined the recommended dose for capecitabine. In Phase II trials, efficacy and treatment safety was verified (UMIN000003934). The recommended dose of capecitabine was determined to be 2000 mg/m2. Median progression-free survival was 7.8 months [95% confidence interval (CI) 6.1–10.9 months], and median overall survival was 18.9 months (95% CI 11.6–28.4 months). Response rate was 17.4% (95% CI 6.4–28.3%). The most common Grade ≥3 hematotoxic adverse events were anemia (10.9%), neutropenia (10.9%), and leukopenia (8.7%), while the occurrence rate of Grade ≥3 non-hematotoxic adverse events was relatively low (

A70s man was admitted to our hospital complaining of chest discomfort. Endoscopic examination showed mucosal erythema and irregularity and an area unstained by iodine in the middle esophagus 21 to 41 cm from the incisors. The biopsy specimen showed moderately differentiated squamous cell carcinoma. An abdominal computed tomographic(CT)scan revealed swelling of the lymph nodes along the celiac artery and abdominal aorta. The patient was diagnosed with unresectable advanced esophageal cancer(cT2N4M0, cStage Ⅳa). Systemic chemotherapy was initiated using a regimen of 5-FU and cisplatin(FP). After 2 courses of chemotherapy, an abdominal CT scan showed reduction of the lymph node swelling along the abdominal aorta, but the lymph node swelling remained along the celiac artery. Therefore, chemoradiotherapy(CRT; FP plus RT 60 Gy/30 Fr at the main tumor and the swelling of lymph nodes along the celiac artery)was administered. An abdominal CT scan showed reduced swelling of the lymph nodes along the abdominal aorta and the celiac artery after CRT. In addition, FP chemotherapy was also administered. APET -CT scan showed no increased FDG up take in the main tumor and swollen lymph nodes after 2 courses of chemotherapy. The complete response(CR)has been maintained for 30 months without therapy.

We report a case of chemotherapy with FOLFOXIRI plus cetuximab for liver metastasis of sigmoid colon cancer. The patient was a 40's man who was diagnosed with sigmoid colon cancer with liver metastasis. Colonoscopy revealed a type 2 tumor with stenosis in the sigmoid colon. He underwent sigmoidectomy under laparotomy, and after the operation, received 7 courses of chemotherapy with FOLFOXIRI plus cetuximab. The liver tumor was sufficiently reduced, and laparotomy and liver right lobectomy were performed. Histopathology revealed a modified, Grade 2 tumor regression. He has been followed for 1 year 4months after the operation.

The patient was a 66-year-old man. Total abdominal gastrectomy and D2 dissection were performed for gastric cancer (cT3N0M0P0CYXH0, cStage II A). Pathological examination confirmed a diagnosis of Stage III C mucinous adenocarcinoma (pT4pN3pM0, pStage III C). He underwent adjuvant chemotherapy with TS-1(120mg/body). One year after adjuvant chemotherapy, anastomotic stricture was caused. Although it was not possible to point out recurrent lesions on the CT image, we strongly suspected that extrinsic compression around the anastomotic portion was due to peritoneal dissemination recurrence because of symptoms and marked tumor elevation. Therefore, TS-1(120mg/body)plus cisplatin(CDDP 60mg/m2)were administered as first-line therapy for advanced gastric cancer. TS-1 plus CDDP(SP)chemotherapy resulted in marked tumor reduction and improved symptoms. However, after 33 courses of SP chemotherapy, renal function was worse due to cisplatin; thus, docetaxel(DTX 70mg/m2)was administered as second line therapy. After 8 courses of DTX, peritoneal dissemination recurrence was diagnosed, and the patient was treated with irinotecan(CPT-11 150mg/m / 2), ramucirumab(RAM 8 mg/kg) plus paclitaxel(PTX 80mg/m2 day 1, 8, 15). However, the disease worsened. The side effect of SP therapy was renal dysfunction. Nonetheless, we experienced that long-term disease control could be achieved by administering chemotherapy under strict follow-up.

Introduction The oral neurokinin-1 antagonist aprepitant is recommended in several guidelines for preventing chemotherapy-induced nausea & vomiting (CINV) due to highly emetogenic cancer chemotherapy. Little is known about the feasibility and safety of aprepitant in patients treated with oxaliplatin. Methods In this multicentre, open label, randomised, phase 3 trial, we recruited patients with colorectal cancer who underwent an oxaliplatin-based chemotherapy. Patients were centrally randomised in a 1:1 ratio to the control group (5-HT 3 -receptor antagonist+dexamethasone) or aprepitant group (5-HT 3 -receptor antagonist+dexamethasone+aprepitant or fosaprepitant) in the first course. All patients were treated with aprepitant/fosaprepitant therapy in the second course. The primary end-point was the proportion of patients with no emesis. Results A total of 413 patients entered this clinical trial from 25 centres in Japan. Significantly more patients in the aprepitant group achieved no vomiting overall and delayed phase than those in the control group (95.7% versus 83.6%, and 95.7% versus 84.7%, respectively). The aprepitant group also had statistically significantly higher percentages of no significant nausea, complete response and complete protection than the control group overall. In the control group, the percentages of no vomiting were higher in the second cycle than in the first cycle. The incidence of vomiting occurred day 7 or later was significantly higher in the control group compared with the aprepitant group. Other adverse events were not significant between the groups. Conclusion The aprepitant therapy was more effective than the control therapy for prevention of CINV in colorectal cancer patients receiving an oxaliplatin-based regimen.

Purpose Oxaliplatin-induced peripheral neurotoxicity (OPN) is frequent and potentially severe, but successful treatment of this condition is still an unmet clinical need. We aimed to determine whether treatment with goshajinkigan (TJ-107), a traditional Japanese medicine, is better than placebo in preventing OPN in patients with advanced or recurrent colorectal cancer patients treated with standard FOLFOX regimens. Methods In this phase 2, randomized, double-blind, placebo-controlled study, patients undergoing oxaliplatin-based chemotherapy were randomized to receive either oral TJ-107 (7.5 g) or matching placebo daily. The severity of OPN was assessed according to the Common Toxicity Criteria for Adverse Events at baseline, every 2 weeks until the 8th cycle, and every 4 weeks thereafter until the 26th week. The primary endpoint was the incidence of grade 2 or greater OPN until the 8th cycle of chemotherapy. Results Analyses were done by intention to treat. Eighty-nine patients were randomly assigned to receive either TJ-107 (n = 44) or placebo (n = 45) between May 2009 and March 2010. The incidence of grade 2 or greater OPN until the 8th cycle was 39 and 51 % in the TJ-107 and placebo groups, respectively (relative risk (RR), 0.76; 95 % CI, 0.47–1.21). The incidence of grade 3 OPN was 7 % (TJ-107) vs. 13 % (placebo) (0.51, 0.14–1.92). No concerns regarding toxicity emerged with TJ-107 treatment. Conclusions TJ-107 appears to have an acceptable safety margin and a promising effect in delaying the onset of grade 2 or greater OPN without impairing FOLFOX efficacy.

An 82-year-old man underwent anterior resection for rectal cancer in 2006. Local recurrence was diagnosed 5 years and 4 months after the operation. He could not undergo intensive chemotherapy because of his age and health status(a history of tubercular and pancytopenia due to chronic hepatitis C). sLV5FU2 chemotherapy was initiated. The CEA level decreased immediately after chemotherapy, and a complete response was observed on CT. After 18 courses, chemotherapy was discontinued. A complete response was detected for 1 year after the chemotherapy holiday began. For patients who experience difficulty tolerating intensive chemotherapy, good outcomes have been achieved even if relatively light regimens are used. For elderly patients or those with several complications, we suggest selecting a regimen based on the QOL.

We previously studied hypoxic tumor cells from hepatic metastases of colorectal cancer (CRC) and determined several potential prognostic factors, including expression of ephrin-A1 (EFNA1), which was highly induced by hypoxia. Here, we further evaluated the prognostic impact of EFNA1 expression. Samples from a total of 366 CRC patients from 11 institutes were analyzed by either microarray (n=220) or quantitative reverse-transcriptase polymerase chain reaction (n=146). EFNA1 was an independent prognostic factor for CRC (p

The efficacy of bevacizumab combined with infusional 5-fluorouracil/leucovorin (5-FU/LV) plus irinotecan (FOLFIRI) as the second-line treatment for metastatic colorectal cancer (mCRC) has not been fully clarified, although bevacizumab combined with infusional 5-FU/LV plus oxaliplatin (FOLFOX) in the second-line setting has demonstrated a survival benefit. We investigated the efficacy of bevacizumab plus FOLFIRI in mCRC patients who failed oxaliplatin-containing regimens without bevacizumab. Patients who received bevacizumab plus FOLFIRI or bevacizumab plus FOLFOX as second-line chemotherapy between July 2007 and March 2008 were registered (trial registration: UMIN000001547). Patient background data and progression-free survival (PFS), overall survival (OS), response, and bevacizumab-related adverse events were prospectively collected every 6 months. A total of 195 patients were enrolled from 26 institutions. Among them, 115 patients received bevacizumab plus FOLFIRI after failure of oxaliplatin and fluoropyrimidine (FOLFIRI+BV after OX/FU group), and 45 patients received bevacizumab plus FOLFOX after failure of irinotecan and fluoropyrimidine (FOLFOX+BV after IRI/FU group). Median PFS was 8.3 months (95% confidence interval [CI], 6.7–9.9) for the FOLFIRI+BV after OX/FU group and 7.8 months (95% CI, 5.8–9.7) for the FOLFOX+BV after IRI/FU group. Median OS was 21.6 months (95% CI, 17.6–25.6) and 16.5 months (95% CI, 11.8–21.2), respectively. Overall response rates were 25 and 29%, respectively. The most common grade ≥3 bevacizumab-related adverse events were hypertension (5.0%) and bleeding (3.8%). FOLFIRI+BV after OX/FU showed comparable efficacy to FOLFOX+BV after IRI/FU.

Postoperative antimicrobial therapy is generally administered as standard prophylaxis against postoperative infection, despite a lack of sufficient evidence for its usefulness. This study was a phase II study to evaluate the necessity of postoperative antibiotic prophylaxis in patients undergoing a colectomy. Patients received 1 g cefmetazole or flomoxef immediately after anesthetic induction, every 3 h during surgery, and then later once again on the next day. They were randomly assigned to receive either cefmetazole or flomoxef. Ninety-one patients were enrolled in the study. A surgical site infection (SSI) occurred in 7.7% (7/91) of patients. All cases were superficial incisional infections. When comparing the two drugs, SSI occurred in 8.3% (4/48) of patients treated with cefmetazole and in 7.0% (3/43) treated with flomoxef, showing no significant difference (P > 0.99). Antimicrobial prophylaxis was well tolerated when used on the day of a colectomy and once again on the next day.

Objective: This is a feasibility trial of oral uracil/tegafur (UFT)/oral leucovorin (LV) and irinotecan (TEGAFIRI) with maximum dose confirmed in Japan. To document the toxicity and define the objective response rate (RR); and determine progression-free and overall survival. Methods: Patients with advanced or metastatic colorectal cancer (CRC) received: UFT 300 mg/m 2 , LV 75 mg/body and CPT-11 150 mg/m 2 (UFT and LV given on days 1 –1 4, and CPT-11 on day 1, every 3 weeks). Eligibility: ECOG performance status (PS) 0–1, adequate bone marrow/liver function and serum creatinine level less than institutional normal value. Results: Eighteen patients enrolled, 17 evaluable for toxicity and response and 1 patients recalled chemotherapy upon registration. Characteristics: 61% male, median age 63.5 years (51–71). Seventy-two per cent PS 0, 50% first line. One hundred and eighty-six cycles have been delivered. The common Grade 3 –4 toxicities were neutropenia (35.3%), leukopenia (29.4%), diarrhea (5.9%), anorexia (5.9%), vomiting (5.9%) and dizziness (5.9%). There was no episode of febrile neutropenia. No death occurred on treatment: Overall RR was 41.2% [7/ 17: 1 complete response (CR) þ 6 partial response (PR)]. Progression-free survival (PFS) is 6.9 months, median survival time (MST) is 25.1 months and 1-year survival rate is 70.6%, whereas PFS 15.0 months, MST 43.6þ months and 1-year survival rate 100% in cases with CR or PR. Conclusions: Approved dose of CPT-11 is 150 mg/m 2 in Japan. As is lower dose with CPT11, TEGAFIRI for patients with advanced or metastatic CRC in Japan seems to have the similar effect with that reported in aboard and indicates prolonged PFS and MST in cases with CR or PR.

Objective: No salvage treatment had been established for metastatic colorectal cancer (mCRC) with mutated KRAS before the emergence of the new drugs regorafenib and TAS-102. We performed a phase II study of third-line chemotherapy with combined bevacizumab and S-1 for mCRC. Methods: Subjects were mCRC patients with mutated KRAS who showed disease aggravation even after two regimens with oxaliplatin and irinotecan. Bevacizumab was given intravenously every 2 weeks, and S-1 was administered orally on days 1-28 of a 42-day cycle. The primary endpoint was disease control rate (DCR). Results: In total, 31 subjects were enrolled between August 2009 and June 2011. Three subjects in whom antitumor effects could not be evaluated were excluded. The median follow-up period was 8.6 months. The DCR was 67.9%, the response rate 0%, median progression-free survival 3.7 months, and overall survival 8.6 months. In 30 subjects evaluated for safety, there was no treatment-related death. The most common adverse events were anorexia (grade ≥3, 20%), diarrhea (grade 3, 10%), and decreased hemoglobin (grade ≥3, 17%). Conclusions: The results suggest that third-line chemotherapy with combined bevacizumab and S-1 is safe and may delay the progression of mCRC resistant to oxaliplatin and irinotecan with mutated KRAS.

Recently, self-expanding metallic stent (SEMS) have been found to be useful for treatment of intestinal obstruction by colorectal cancer, either as a bridge to surgery or terminal treatment. When SEMS are used for patients in the terminal stage with obstruction due to colorectal cancer, re-obstruction is a severe problem. We report 2 cases of re-insertion of SEMS for obstruction of colon cancer after the first insertion of SEMS. No major problems occurred in either the 2 cases. In the first case, the patient suffered from re-obstruction of colon cancer 6 months after the first SEMS treatment and died 9 months after the second SEMS treatment. In the second case, the patient suffered from re-obstruction of colon cancer 5 months after the first SEMS treatment and died 7 months after the second SEMS treatment. Re-insertion of SEMS for a second obstruction due to colorectal cancer after SEMS treatment is useful for terminal treatment for maintaining QOL.

For patients with Stage Ⅳ colorectal cancer, primary site resection improves survival and relieves symptoms of bleeding and obstruction by the primary lesion. Laparoscopic surgery is thought to be useful for Stage Ⅳ colorectal cancer because of its low aggressiveness and the short recovery time. We examined the usefulness of laparoscopic resection of primary lesions for Stage Ⅳ colon cancer patients. Forty-one cases of Stage Ⅳ colorectal cancer treated by resection of the primary lesion were investigated, and we compared the group of patients with laparoscopic surgery (LAC) to the group of patients with open laparotomy (OP). The LAC Group was superior to the OP Group from the viewpoint of blood loss, days of hospitalization, and length of time from operation to start of chemotherapy. For Stage Ⅳ colorectal cancer, laparoscopic resection of the primary lesion is thought to be a useful method to reduce the invasiveness of treatment.

Background The clinical benefit of cetuximab combined with oxaliplatin-based chemotherapy remains under debate. The aim of the present multicenter open-label Phase II study was to explore the efficacy and safety of biweekly administration of cetuximab and mFOLFOX-6 or XELOX as first-line chemotherapy in patients with metastatic colorectal cancer. Methods Sixty-two patients with previously untreated KRAS/BRAF wild-type metastatic colorectal cancer were recruited to the study between April 2010 and May 2011. Patients received one of two treatment regimens, either cetuximab plus mFOLFOX-6 (FOLFOX + Cmab) or cetuximab plus biweekly XELOX (XELOX + Cmab), according to their own preference. Treatment was continued until disease progression or the appearance of intolerable toxicities. The primary endpoint was response rate; secondary endpoints were progression-free survival, overall survival, disease control rate, dose intensity, conversion rate to surgical resection, and safety. Results The response rates in the FOLFOX + Cmab (n = 37) and XELOX + Cmab (n = 25) groups were 64.9 % (24/37) and 72.0 % (18/25), respectively. The median PFS in the FOLFOX + Cmab and XELOX + Cmab groups was 13.1 months (95 % confidence interval [CI] 12.1–17.5) and 13.4 months (95 % CI 10.1–17.9), respectively. Neutropenia was the most frequent grade 3/4 adverse event in both groups (33.9 %), followed by anorexia, acneiform eruption, skin fissure and paronychia. A waterfall plot of tumor diameter showed prominent shrinkage of the tumors in 88.7 % of patients. Conclusions The results of the present study indicate that biweekly cetuximab plus mFOLFOX-6/XELOX is an effective and tolerable treatment regimen. Biweekly administration of cetuximab requires only one hospital visit every 2 weeks, and may become a convenient treatment option for patients with KRAS/BRAF wild-type metastatic colorectal cancer. Trial registration This study is registered with University Hospital Medical Information Network (UMIN 000003253). Registration date is 02/24/2010. Electronic supplementary material The online version of this article (doi:10.1186/s12885-015-1685-z) contains supplementary material, which is available to authorized users.

Background Although number of elderly patients with metastatic colorectal cancer (mCRC) is rapidly increasing, this population is often underrepresented in clinical trials. Recently, a phase II trial demonstrated that capecitabine and oxaliplatin (XELOX) combined with bevacizumab XELOX plus bevacizumab was effective and well tolerated by elderly patients with mCRC who reside in Western countries. The aim of this study was to evaluate the safety and efficacy of XELOX plus bevacizumab for Japanese patients aged ≥75 years with mCRC. Methods This prospective, open-label phase II trial recruited patients aged ≥75 years with previously untreated mCRC between March 2010 and January 2012. Treatment consisted of 7.5 mg/kg of intravenous bevacizumab and 130 mg/m2 of oxaliplatin on day 1 of each cycle combined with 2000 mg/m2 of oral capecitabine per day on days 1–14 of each cycle. Treatment was repeated every 3 weeks until disease progression or termination of the study. The primary endpoint was progression-free survival; the secondary endpoints were toxicity, overall response rate, time-to-treatment failure, and overall survival. Results Thirty-six patients (male 58 %; median age 78 years; colon cancer 67 %) met all eligibility criteria and received at least one course of the planned treatment. The median time-to-treatment failure was 7.0 months. Twelve patients (33.3 %) experienced adverse effects (AEs) ≥ grade 3 and frequent AEs ≥ grade 3, including neutropenia (22.2 %) and neuropathy (13.9 %). Hypertension was the most frequent AE ≥ grade 3 associated with bevacizumab (11.1 %). Low baseline creatinine clearance associated significantly with the incidence of AEs ≥ grade 3. Response and disease control rates were 55.6 and 91.7 %, respectively. Median progression-free and overall survival times were 11.7 months (95 % confidence interval, 8.0–13.4 months) and 22.9 months, respectively. Conclusion XELOX combined with bevacizumab was well tolerated by selected Japanese patients aged ≥75 years with mCRC patients, and controlled clinical trials are now required to determine the survival benefit. Electronic supplementary material The online version of this article (doi:10.1186/s12885-015-1712-0) contains supplementary material, which is available to authorized users.

Purpose: We reported in a retrospective study that the presence of micrometastasis in lymph nodes, when assessed by carcinoembryonic antigen (CEA)-specific RT-PCR, is a significant prognostic factor in stage II colorectal cancer. The aim of this study was to clarify the clinical value of micrometastasis in a prospective multicenter trial. Experimental Design: From November 2001 to December 2005, a total of 419 colorectal cancer cases were preoperatively registered at a central data center. Of them, 315 node-negative stage II colorectal cancer cases were enrolled. After RNA quality check, 304 colorectal cancer cases were analyzed for CEA mRNA in lymph nodes by both conventional RT-PCR (a band method) and quantitative RT-PCR. Long-term prognosis of the patients was determined by each method. Results: A positive band for CEA mRNA was detected in 73 (24.0%) of 304 patients. Postoperative adjuvant chemotherapy was applied in 31 CEA band-positive cases with an oral 5-fluorouracil derivative HCFU (1-hexylcarbamoyl-5-fluorouracil) for 1 year, whereas chemotherapy was not administered to CEA band-negative group. Multivariate Cox regression analyses revealed that a high micrometastasis volume (high MMV, n = 95) was an independent poor prognostic factor for 5-year disease-free survival (DFS; P = 0.001) and 5-year overall survival (OS; P = 0.016). Conclusions: This prospective clinical trial demonstrates that micrometastasis volume is a useful marker in identifying patients who are at high or low risk for recurrence of stage II colorectal cancer. Clin Cancer Res; 22(13); 3201–8. ©2016 AACR.

The aim of this multicenter, open-label, randomized phase II trial was to evaluate the efficacy of a dose-dense capecitabine and oxaliplatin (XELOX) regimen in patients with metastatic colorectal cancer (mCRC) for whom reintroduction of oxaliplatin had been planned as a third- or later-line regimen.The patients with mCRC who had received prior chemotherapy including oxaliplatin and were scheduled for reintroduction of oxaliplatin were randomized to capecitabine (1,000 mg/m(2)) twice daily on days 1-14 and oxaliplatin (130 mg/m(2)) on day 1 every 21 days (Q3W group) or capecitabine (2,000 mg/m(2)) twice daily on days 1-7 and oxaliplatin (85 mg/m(2)) on day 1 every 14 days (Q2W group). The primary endpoint was the time-to-treatment failure (TTF). Other endpoints included overall survival (OS), progression-free survival (PFS) and other adverse events (AEs).A total of 46 patients were enrolled in the trial-22 patients were randomly assigned to the Q3W group and 23 to the Q2W group. The median TTF was 3.4 months in both groups (hazard ratio [HR] 1.053; p = 0.880). The median PFS and OS were 3.3 and 9.2 months in the Q2W group and 4.3 and 12.1 months in the Q3W group, respectively (HR 1.15; p = 0.153 and 0.672; p = 0.836). The most common grade 3-4 AEs in the Q3W and Q2W groups were fatigue (27.3 vs 21.7), neuropathy (9.1 vs 0 %) and diarrhea (9.1 vs 0 %), respectively.There was no significant inter-group difference in any of the efficacy and safety endpoints, including TTF, OS, RFS and AEs. The results of this clinical trial were convincingly negative.

A 60-year-old man presented to our hospital with melena. A submucosal tumor (24 mm) was found via magnetic resonance imaging between the prostate and the rectum (Rb). A gastrointestinal stromal tumor (GIST) that displaced the prostate ventrally was diagnosed via histopathology. Preoperative imatinib treatment was initiated to reduce the tumor size and prevent extensive surgery. Approximately 33% of the tumor was reduced using chemotherapy. First, laparoscopic rectal dissection and mobilization were performed reaching the pelvic floor. Then, we performed perineal partial rectal resection. There has been no recurrence.

A 74-year-old man was diagnosed with unresectable HER2-positive gastric cancer due to metastases to distant lymph nodes. Paclitaxel combined with trastuzumab was administered as third-line chemotherapy. After 4 courses of therapy, the metastases to distant lymph nodes disappeared with no evidence of progressive disease. Downstaging by chemotherapy made curative treatment feasible and he underwent distal gastrectomy. The patient has been free from recurrent disease 13 months after surgery.

Ileus due to colon cancer often develops from a timing and the method of the operation and perioperative care, comparing with ordinary cases. The use of self-expanding metallic stent (SEMS) was first authorized by insurance and became available nationwide in Japan in 2012. Insertion of SEMS for ileus due to colorectal cancer is useful as a bridge to surgery (BTS) approach and releases stenosis as palliative care. Here we report 5 successful cases of anastomosis performed during a laparoscopic operation for ileus due to colorectal cancer after BTS using SEMS. Successful SEMS insertion for colon cancer ileus enables observation of the proximal side. Because the decompression efficiency with SEMS is high, laparoscopic surgery becomes possible. SEMS insertion as a BTS is useful for ileus due to colorectal cancer.

Background/Objective: Oral tegafur/uracil and leucovorin (UFT/LV) therapy is effective and safe for elderly patients with advanced or metastatic colorectal cancer (CRC). However, there are few studies on the combination of bevacizumab with UFT/LV. This clinical study evaluated the efficacy and safety of UFT/LV plus bevacizumab as a first-line therapy for elderly patients with advanced or metastatic CRC. Methods: Forty patients with advanced or metastatic CRC aged ≥75 years were enrolled in this multicenter, open-label, single-arm phase II study. All patients received oral UFT (300-600 mg) and LV (50 mg) twice daily on days 1-21 and intravenous bevacizumab (5 mg/kg) on days 1 and 15 of a 4-week cycle (University Hospital Medical Information Network No. UMIN000003447). Results: The median follow-up period was 14.7 months. The response rate was 20.0% [95% confidence interval (CI): 9.1-35.6], median progression-free survival was 8.9 months (95% CI: 5.3-11), and median overall survival was 21.7 months (95% CI: 13.7-23.4). The only grade 3 hematological toxicity was neutropenia (3.0%), and the incidence rates of grade 3 nonhematological toxicity were low at ≤10%. Conclusion: UFT/LV plus bevacizumab is a promising first-line regimen for elderly patients with advanced or metastatic CRC. The combination is well tolerated and efficacious.

This phase II trial was performed to evaluate the efficacy and tolerability of tegafur/uracil (UFT) and oral leucovorin (LV) in elderly patients with advanced or metastatic colorectal cancer who had not received prior chemotherapy.Patients agedor = 70 years were eligible. UFT and LV were taken orally on days 1-28 of the cycle at doses of 300 mg/m2/day and 75 mg/m2/day, respectively. Treatment was administered on an outpatient basis every 35 days and consisted of at least two cycles until disease progression.A total of 30 patients were enrolled in this study. The median age of the patients was 81.5 years (range: 74-88 years). The observed overall response rate was 17.9%. The estimated median overall survival time was 23.5 months. Two patients (7%) experienced toxicities with a worst grade of 3, and one patient (4%) experienced toxicities with a worst grade of 4. There were no treatment-related deaths. No patients experienced grade 3 or 4 hematological adverse events.Although the response rate to UFT/LV was moderate, a favorable survival time was observed. Lower hematological adverse event rate of UFT/LV may introduce second line therapy safely to elderly colorectal cancer patients and contribute longer survival.

This study was the first multicenter phase II study of cetuximab plus folinic acid/5-fluorouracil/irinotecan (FOLFIRI) in KRAS wild-type mCRC as a second-line treatment in Japan including BRAF and PIK3CA genotyping.Tumors of 112 pre-registered patients were genotyped for KRAS, BRAF, and PIK3CA. The primary study end-point was response rate, and secondary end-points were progression-free survival (PFS), overall survival (OS), and safety.Sixty-seven patients (59.8%) were EGFR-positive and KRAS wild-type. The mean age of the enrolled patients (n=60) was 62.6 years (range=37-82 years). The response rate was 31.7% and stable disease was observed in 53.3%. No objective response was observed in patients with BRAF or PIK3CA mutations. The median PFS and OS were 7.4 and 18.2 months, respectively. Grade-3/4 adverse events were leucopenia (26.7%), neutropenia (43.3%), paronychia (10.0%), fissure (10.0%) and acne-like rash (5.0%).Second-line cetuximab plus FOLFIRI was effective and well-tolerated.

A 49-year-old man was admitted to our hospital with back pain, appetite loss, and body weight loss in January 2009. Gastroduodenal endoscopy, abdominal computed tomography( CT), and magnetic resonance imaging( MRI) revealed type 4 advanced gastric cancer( signet-ring cell carcinoma) with multiple lymph node( No. 16 LNs), right adrenal gland, and multiple bone metastases. Between February 2009 and April 2011, 20 courses of S-1( 80 mg/m2) plus CDDP( 60 mg/m2) and zoledronic acid hydrate (4 mg/body) were administrated. Since May 2011, S-1 (70 mg/m2) and zoledronic acid hydrate( 4 mg/body) have been continued. The lymph node and adrenal gland metastases showed a complete response( CR), and the gastric tumor showed a partial response; however, the bone metastases did not show CR or progressive disease (PD) for 4 years after initiation of therapy. Chemotherapy with zoledronic acid hydrate is considered as a useful therapeutic option for advanced unresectable gastric cancer with multiple bone metastases.

We examined 11 gastric cancer patients undergoing gastroduodenal stent placement for the treatment of gastric outlet obstruction at our hospital, and assessed the significance and problems associated with stenting. None of the patients exhibited any complications associated with stenting, and the median post-stenting fasting period was 3 days(range, 1-7 days). Oral intake improved significantly in all the patients; in patients with nasogastric tubes, the tubes were removed after stenting. However, in patients with peritoneal dissemination, oral intake alone was not sufficient, and additional parenteral nutrition was required. In conclusion, gastroduodenal stenting is believed to be useful for palliative care in gastric cancer patients with pyloric stenosis.

The patient was a 54-year-old man who had undergone resection of the sigmoid colon for unresectable sigmoid colon cancer with multiple liver( H1), lymph node, and lung metastases at the previous hospital. Chemotherapy with 5-fuorouracil, Leucovorin, and oxaliplatin (mFOLFOX6) plus bevacizumab was initiated after surgery. The outcome was partial response. The patient was introduced to our hospital because he had relocated. Based on the findings of the patient's computed tomography( CT) and positron emission tomography( PET)-CT scans, we decided to perform radical resection. We performed partial hepatectomy( S7 and S8) and pancreatoduodenectomy for metastases to the hepatoduodenal ligament lymph node. After confirming that there was no recurrence, he underwent right partial pneumonectomy. Currently, the patient shows no signs of recurrence. The therapy for colon cancer should include aggressive radical surgery to control metastasis.

We evaluated the efficacy of laparoscopic palliative stoma creation for patients with malignant bowel obstruction (MBO).Twenty-four patients with MBO who underwent laparoscopic stoma creation between January 2009 and December 2012 were studied and their clinical outcome was evaluated retrospectively.Compared to the open approach, the laparoscopic approach led to significantly shorter operation times and a significantly lower incidence of surgical site infection( SSI). The rate of removal of the intestinal tube and intravenous drip after surgery was 100% and 88%, respectively, and the rate of oral intake was 100% after palliative stoma creation. The prognosis was 58% in 3 months and 29% in 1 year, and the median survival time was approximately 4 months.The quality of surgery by the laparoscopic approach was better than that by the open approach, and the quality of life( QOL) after stoma creation was better than that before surgery. Given the shorter operation time, lower incidence of SSI, and better QOL, laparoscopic stoma creation is a beneficial choice for palliative treatment in patients with MBO.

Trousseau's syndrome involves unexplained thrombotic events along with malignancy. We report the cases of 3 patients undergoing chemotherapy for gastric cancer in whom Trousseau's syndrome occurred. Case 1 involved a 43-year-old woman undergoing S-1/cisplatin( CDDP) combination therapy as first-line chemotherapy for type 4 remnant gastric cancer( cT4bN2M1P1/stage IV) who experienced left hemiplegia. Cerebral hemorrhage of the right parietal lobe was diagnosed by computed tomography( CT), and thrombosis from the upper sagittal sinus to the right sinus sigmoideus was diagnosed by magnetic resonance venography( MRV). Case 2 involved a 59-year-old man undergoing S-1/irinotecan (CPT-11) combination therapy as second-line chemotherapy for type 3 gastric cancer( cT3N1M0H1/stage IV) who experienced ataxic, stuttering, and left membrum inferius paralysis. Multiple cerebral infarction of the right parietal lobe was diagnosed by magnetic resonance imaging (MRI). Case 3 involved a 67-year-old woman undergoing S-1/CDDP combination therapy as preoperative chemotherapy for type 3 gastric cancer( cT4aN1M0/stage IIIA) who experienced right cerebellum incontinentia, nystagmus, and right facioplegia. Multiple cerebral infarction of the right cerebellum and pedunculus cerebellaris medius was diagnosed by MRI. An anticoagulant was administered orally for stroke, and chemotherapy for gastric cancer was resumed after activities of daily living( ADL) improved in all 3 patients. Recurrent stroke was not diagnosed in any of the 3 patients. Patients with malignancy often exhibit hypercoagulability associated with cancer. Accordingly, periodic blood tests for coagulation should be performed and dehydration should be prevented to prevent strokes in cancer patients.

A 71-year-old man presented at a clinic with fever and melena. Capsule endoscopy revealed ulcers accompanied by bleeding in the central part of the jejunum. Blood tests revealed a high level of soluble interleukin-2 receptor( sIL-2R). A malignant lymphoma of the small intestine was suspected. A biopsy was performed using double-balloon enteroscopy. We diagnosed a malignant lymphoma, peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS). There was a large amount of ascites and we determined that it was stage IIE according to the Lugano International Conference classification. The patient was hospitalized to receive pirarubicin hydrochloride, cyclophosphamide, vincristine sulfate, and prednisolone (THP-COP) therapy. One day after the fourth chemotherapy cycle, the patient complained of abdominal pain. Perforative peritonitis was diagnosed by abdominal computed tomography and emergency laparotomy was performed. A 3.5×2.0 cm perforation was detected in the jejunum, 180 cm from the ligament of Treitz. Approximately 20 cm of the small intestine was resected, and functional end-to-end anastomosis was performed. Histology showed that there were no malignant cells around the perforation site. We believe that the malignant lymphoma had disappeared rapidly because of the effective chemotherapy, and fibrosis could not adequately cover the space from which the tumor had disappeared. Although pancytopenia was observed and granulocyte colony-stimulating factor (G-CSF) was administered to the patient, the postoperative course was uneventful. He received the fifth course of chemotherapy on postoperative day 21.

We report the case of a 64-year-old man who had early submucosal invasive colorectal cancer with synchronous multiple liver metastases. The patient underwent endoscopic resection for a type Isp polyp of the sigmoid colon. The pathological diagnosis was well-differentiated adenocarcinoma with submucosal layer( sm3) invasion and lymphatic infiltration (ly2). A positive vertical margin was suspected. Abdominal computed tomography revealed multiple tumors at the S2/3, S5, and S8 segments of the liver and a small gastric submucosal tumor. The patient underwent sigmoid colon resection with D3 lymphadenectomy, left lateral hepatic segmentectomy, partial hepatectomy in the S5 and S8 segments, and partial gastrectomy. Histological examination showed lymph node metastasis but no residual cancer in the sigmoid colon. The histological findings from the liver were similar to those found in primary colorectal carcinoma. The gastric submucosal tumor was confirmed to be a gastrointestinal stromal tumor with a low risk grade. As the present case is considered rare, we herein review our previous report on a case of early colorectal cancer with synchronous multiple liver metastases.

Hand-foot syndrome( HFS) has been reported to be the most common adverse effect of capecitabine, with an incidence of more than 50%. AboundTM, containing β-hydroxy-β-methyl butyric acid( HMB), L-glutamine, and L-arginine is effective in the treatment of decubitus ulcers and in wound healing; however, whether AboundTM is efficacious for HFS caused by capecitabine is not clear. This study aimed at evaluating the effectiveness of AboundTM in the recovery from HFS caused by capecitabine. Capecitabine administration was discontinued in 6 patients with more than grade 2 HFS, and AboundTM was administered. The time to recovery was examined. The median time to recovery to less than grade 1 HFS was 10 days( range, 4-14 days). The grade of HFS decreased following the administration of AboundTM. The findings of this study suggest that AboundTM is effective against HFS caused by capecitabine.

We previously reported that the antitumor effect of OK-432, a streptococcal preparation, was markedly augmented when this agent was injected into tumors together with fibrinogen. In order to elucidate the effect of this treatment on the spleen, we assessed splenic function in gastric cancer patients receiving preoperative local immunotherapy with OK-432 and fibrinogen. Immunohistochemical studies of the spleen at 7 days after intratumoral injection therapy revealed numerous macrophages phagocytizing OK-432 in the splenic sinuses. Phenotypic analysis of splenocytes by flow cytometry revealed an increase in the CD4/CD8 ratio and in the expression of HLA-DR, CD25, and Leu M3 by splenic T cells of the patients treated with OK-432 plus fibrinogen when compared to patients treated with OK-432 alone or untreated patients. Splenic T cells from patients treated with OK-432 plus fibrinogen showed significantly higher cytotoxicity against Daudi and K562 cells than T cells from control patients (p

We recently showed that liver metastatic tissue from patients with colorectal cancer (CRC) was a useful model for identifying novel, hypoxia-inducible genes and prognostic markers. We showed that the expression of secretoglobin, family 2A, member 1 (SCGB2A1) was a potential prognostic factor for CRC. Here, we further evaluated the prognostic impact and function of SCGB2A1 in 222 patients with CRC. The impact of SCGB2A1 expression on disease-free survival (DFS) and overall survival (OS) was assessed with mRNA expression profiling. The function of SCGB2A1 was analyzed by evaluating mRNA expression profiles in cells derived from patients with CRC and by testing the effects of transfecting SCGB2A1 into different CRC-derived cell lines. We evaluated the effects of SCGB2A1 on proliferation, chemosensitivity, radiation sensitivity and sphere formation. Univariate and multivariate analyses indicated that the expression of SCGB2A1 was an independent prognostic factor for CRC (p

We retrospectively examined the feasibility and outcome of S-1 adjuvant chemotherapy for 18 patients with gastric cancer treated based on the liaison-clinical pathway (liaison group), and compared them with those of 26 patients treated before the induction of the liaison-clinical pathway (non-liaison group). The persistent rate of S-1 adjuvant chemotherapy for one year except for recurrence, the relative performance (RP) value of cases who had received S-1 for one year, and Grade 3/4 adverse events in non-liaison group/liaison group, were 88.5/87.5% (p = 0.93), 87.0/92.9% (p = 0.56), and 26.9/5.6% (p = 0.07), respectively. This did not show a significant difference. The rate of patients administered medication for coexistent diseases in our hospital in the non-liaison group/liaison group was 53.8/0% (p = 0.0002), which reflected the accomplishment of the transfer of medical care for coexistent disease from a hospital to a clinic on the liaison-clinical pathway. Furthermore, a neighboring clinic could be arranged to accommodate 9 (64.3%) of 14 patients living quite far from the hospital in the liaison group. In conclusion, S-1 adjuvant chemotherapy for patients with gastric cancer treated based on the liaison-clinical pathway was feasible, led to the effective practice of sharing between hospital and clinic, and the shorter trip for treatment at a neighboring clinic by patients living far from a hospital.

Objective: Combined chemotherapy with S-1 and irinotecan (IRIS) for metastatic colorectal cancer has been reported to be effective and safe. However, there are only a few studies on the effects of adding bevacizumab to IRIS. We conducted a clinical study to evaluate the efficacy and safety of IRIS plus bevacizumab as first-line therapy for metastatic colorectal cancer. Methods: Forty metastatic colorectal cancer patients were enrolled in this phase II study. All patients received irinotecan (80 mg/m2) and bevacizumab (7 mg/kg) on days 1 and 15 and S-1 (40-60 mg twice daily) on days 1-21 of a 5-week repeated cycle. Results: The response rate was 47.4% [95% confidence interval (CI) 31.5-63.2], progression-free survival was 11.9 months (95% CI 9.4-16.8), and overall survival was 23.4 months (95% CI 19.0-inf). The only grade 3 hematological toxicity was neutropenia (16%) and the incidences of grade 3 nonhematological toxicity were low at Conclusion: In this clinical study, we revealed IRIS plus bevacizumab to be a promising first-line regimen for metastatic colorectal cancer with a low incidence of serious toxicities, in which favorable response rates and extension of survival time can be expected.

We report a case of methicillin-resistant Staphylococcus aureus(MRSA) surgical site infection successfully treated with linezolid. A 66-year-old man had undergone total gastrectomy for gastric cancer after neoadjuvant chemotherapy. Three days after the operation, he was diagnosed with deep incisional surgical site infection due to MRSA, and wound care was started. After discharge, he received adjuvant chemotherapy and wound care, but the wound had not healed in 10 months. We started treatment with oral linezolid and nutritional support, and the wound was fully healed 12 months after the operation. Antibiotic treatment with oral linezolid may be effective for refractory deep incisional surgical site infection due to MRSA in outpatients.

S-1/cisplatin(CDDP) combination therapy(SP therapy)(S-1: 80 mg/m2/day, day 1-21, CDDP: 60 mg/m2, day 8, q35 days) is a standard regimen for advanced gastric cancer in Japan. Hydration under hospitalization is necessary for CDDP administration to prevent renal toxicity; nevertheless, ambulatory chemotherapy has recently become commonly used. Therefore CDDP administration using a short hydration regimen for gastric cancer outpatients undergoing SP therapy has been performed in our institute. Between August 2009 and November 2011, 23 patients who were treated with SP therapy as a first line therapy and began CDDP treatment in the outpatient setting were examined, and monitored for adverse events, response rate[best objective response rate(ORR)], time to treatment failure(TTF) and overall survival. A short hydration regimen means 2,550 mL of fluid in 4 h and 55 min, and the necessity of an oral intake of more than 1,000 mL liquid per day on day 7 to 9 was explained to the patients. Grade 1/2 serum creatinine elevation occurred in 5 patients (22%), but there were no incidences of grade 3/4 serum creatinine elevation or heart failure. The best ORR was 69%, median time to treatment failure(mTTF) was 11.5 months, the 1-year survival rate was 77.8%, and the 2-year survival rate was 44.7%.CDDP administration using a short hydration regimen for gastric cancer outpatients undergoing SP therapy was considered to be feasible.

A man is his 50s experienced epigastric discomfort and body weight loss from 60 to 56 kg over 3 months. A lesion was diagnosed as type 3 advanced gastric cancer (group 5, tub2) with para-aortic lymph node and multiple liver metastases. Pretreatment hemoglobin(Hb), albumin(Alb), and C-reactive protein(CRP) levels were 11.0 mg/dL, 3.0 g/dL, and 2.40 mg/dL, respectively. S-1+cisplatin (CDDP) combined chemotherapy (S-1 120 mg/day, day 1-21, CDDP 60 mg/ m2, day 8, q35 days) with nutritional supportive care using enteral nutrition (EN) agent (Prosure) enriched with eicosapentaenoic acid (EPA) was initiated. After 6 weeks, body weight, Hb, Alb, and CRP improved to 60 kg, 13.6 mg/dL, 4.6 g /dL, and 0.14 mg/dL, respectively. Moreover, a marked reduction in para-aortic lymph node and multiple liver metastases was seen on computed tomography (CT) scans 12 weeks after treatment initiation. Accordingly, nutritional supportive care using EN agent enriched with EPA during chemotherapy might be an effective treatment for patients with gastric cancer who show increased CRP and decreased albumin levels.

We report a case of low anterior resection that led to a pathological complete response of locally recurrent rectal cancer to neoadjuvant chemoradiotherapy. A 57-year-old male patient underwent low anterior resection for rectal cancer pathologically diagnosed as type 2, tub2tub1,pSS,INF b,int,ly2,v2,pPM0,pDM0,no,M0,H0,P0, and fStage II. After 2 years and 11 months, local recurrence of his rectal cancer was identified by colon fiberscopy. Neoadjuvant chemoradiotherapy was conducted with CPT-11, UFT/LV, and radiation(50 Gy),and this recurrent lesion exhibited a partial response to the chemoradiotherapy regimen according to magnetic resonance imaging findings. Then, we performed total pelvic exenteration, and the pathological examination revealed a pathological complete response.

A number of clinical trials, including the FIRIS study, have shown that S-1 plus irinotecan (IRIS) is safe and effective in patients with colorectal cancer. Several different treatment protocols for IRIS are commonly used in Japan, besides the one used in the FIRIS study. This study was designed to evaluate the feasibility of a 5-week cycle of IRIS. Between January 2005 and February 2008, a total of 55 patients with metastatic colorectal cancer were enrolled at nine centers in Japan. All patients received irinotecan intravenously (80 mg/m2) on days 1 and 15 and S-1 orally (40–60 mg twice daily, according to body surface area) on days 1–21 of a 5-week repeated cycle. The overall response rate was 29.1 %. The response rate was 43.8 % in patients who received IRIS as first-line therapy and 23.1 % in those who received IRIS as second-line or subsequent therapy. The median survival time was 678 days (22.6 months). Adverse events of Grade 3 or higher that occurred at an incidence of ≥10 % were neutropenia (12.7 %) and diarrhea (10.9 %). Our efficacy and safety data suggest that a 5-week cycle of IRIS is an effective alternative to used currently regimens.

After Adjuvant Chemotherapy Trial of S-1 for Gastric Cancer(ACTS-GC), adjuvant chemotherapy with S-1 is a standard treatment for stage II or III gastric cancer patients. In this study, we retrospectively examined factors that influence the continuity of S-1 adjuvant chemotherapy. We analyzed the clinical documentation of 27 gastric cancer patients being treated with S-1 adjuvant chemotherapy. Patients who completed the treatment without reduction dose were classified into a complete group(n=14), and those for whom S-1 was discontinued or reduced due to adverse reactions were classified into a reduced/discontinuation group(n=13). First, we examined the background factors at baseline between these two groups. Univariate logistic regression analysis revealed that the operative procedure, leukocyte count, and serum creatinine level at baseline were identified as factors that influence the continuity of S-1 chemotherapy. Next, we investigated the hematological and nutritional conditions of these patients during the treatment period. The loss of body mass index(BMI)during the treatment period was remarkable in the reduced/discontinuation group regardless of the operative procedure. This result suggests that an early nutritional intervention might be important for gastric cancer patients undergoing S-1 adjuvant chemotherapy.

A 70-year-old man was diagnosed as thyroid medullary carcinoma with multiple bone metastases. He underwent total thyroidectomy and cervical lymph node dissection. After one year, the pain from his bone lesions was becoming severe. To relieve the pain, he was administered opioids and external-beam radiation therapy. However, he continued to have substantial multiple bone pain. We used combination therapy of strontium-89 chloride for the treatment of widespread multiple bone pain and external-beam radiation therapy for localized pain. That combination therapy was effective and improved the QOL of the patient. We used strontium-89 chloride four times within one year, and no serious side effects occurred during therapy. Our thoroughly investigated case suggests that strontium-89 therapy is one of the effective and safe therapies for patients with painful bone metastases of thyroid medullary carcinoma.

We investigated the efficacy of gastrojejunostomy followed by S-1-based chemotherapy for unresectable gastric cancer with pyloric stenosis. We performed gastrojejunostomy and S-1-based chemotherapy in 14 unresectable gastric cancer patients with gastric outlet obstructions between April 2006 and June 2010. Although there were two complications after surgery, no treatment-related deaths were observed. The response rate of the S-1-based chemotherapy was 41.7%, and the median survival after surgery was 12.3 months. All patients were tolerating a regular diet and a significant improvement in oral intake lasted for at least 6 months. In conclusion, gastrojejunostomy followed by chemotherapy with S-1 appears to be an effective treatment modality for unresectable gastric cancer with pyloric stenosis. It enables us to practice S-1-based standard chemotherapy for advanced gastric cancer and improve the quality of life of patients.