[Show abstract][Hide abstract] ABSTRACT: Background:
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.
International Journal of Clinical Oncology 10/2015; DOI:10.1007/s10147-015-0911-7 · 2.13 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: 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 m(2), 100 mg/day for 1.25-1.5 m(2), or 60 mg/day for > 1.5 m(2)). 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.
BMC Cancer 06/2015; 15(1):452. DOI:10.1186/s12885-015-1476-6 · 3.36 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The efficacy of chemotherapy for advanced or recurrent gastric cancer in patients who were aged over 75 years was investigated.
Progression free survival(PFS)and overall survival(OS)of advanced gastric cancer patients who received first-line chemotherapy with TS-1 plus cisplatin or TS-1 in our hospital from 2009 to 2013 were determined. The patients were divided into two groups: H and L. H group patients were aged over 75 years, and L group patients were aged less than 75 years.
Median PFS and median OS of patients in the H and L groups who received TS-1 plus cisplatin chemotherapy were not significantly different. PFS was 77[range, 13-211]days and 139[range, 53-211]days for the H and L groups, respectively(p=0.141), while OS was 523[range, 22-1,030]days and 402[range, 322-623]days, respectively(p=0.620). Similarly, median PFS and median OS of patients who received TS-1 chemotherapy were not significantly different between the H and L groups. PFS was 103[range, 51-156]days and 152.5[range, 85-278]days for the H and L groups, respectively(p=0.230), while OS was 414[range, 224-714]days and 605[range, 452-1,077]days, respectively( p=0.1337).
PFS and OS were not significantly different in younger patients with advanced gastric cancer who received TS-1 plus cisplatin or TS-1 chemotherapy compared to that in similarly treated elderly patients with advanced gastric cancer.
Gan to kagaku ryoho. Cancer & chemotherapy 11/2014; 41(12):2248-50.
[Show abstract][Hide abstract] ABSTRACT: A regimen of capecitabine plus oxaliplatin(XELOX)has becomeoneof thestandard postoperativeadjuvant chemotherapies for colon cancer. However, few tolerability studies have been conducted in Japan. In this study, we retrospectively examined treatment continuation and the adverse events that occurred during 8 courses of postoperative adjuvant chemotherapy with XELOX in 21 patients with colorectal cancer who had undergone curative resection. The completion rate for 8 courses of treatment with XELOX was 71.4%, while the median relative dose intensities of capecitabine and oxaliplatin were 85.0% and 75.0%, respectively. Although the incidence of subsequent Grade 3 or higher hand-foot syndromewas 14.3%, therateof peripheral neuropathy was 0%. Our hospital had a high rate of XELOX treatment continuation, suggesting that XELOX adjuvant chemotherapy would be well tolerated in clinical practice as well.
Gan to kagaku ryoho. Cancer & chemotherapy 06/2014; 41(6):743-747.
[Show abstract][Hide abstract] ABSTRACT: Cetuximab shows activity in KRAS (Kirsten rat sarcoma viral oncogene homolog) wild-type metastatic colorectal cancer (mCRC). Recent studies have demonstrated that cetuximab induces antibody-dependent cell-mediated cytotoxicity (ADCC) in mCRC. We investigated the associations of FcγR (fragment C γ receptor) and EGFR (epidermal growth factor receptor) polymorphisms with the outcome of mCRC patients treated with cetuximab and FOLFIRI (folic acid/5-fluorouracil/irinotecan) as second-line therapy in the FLIER (Cetuximab Plus Folinic Acid/5-Fluorouracil/Irinotecan in KRAS Wild-Type Metastatic Colorectal Cancer as a Second-Line Treatment) study.
A total of 57 patients were evaluated in this study. The association of each polymorphism with the response rate, progression-free survival, and overall survival was analyzed.
A tendency for longer overall survival was observed in patients with the EGFR CA repeat ≥36 genotype than in those with the ≤35 genotype (600 versus 483 days, P = 0.051). The haplotype containing the 131H and 158V alleles was associated with a lower response rate than the other haplotypes (P = 0.018). These results are contrary to previously published results.
Our data suggest that FcγR and EGFR CA repeat polymorphisms may be associated with the outcome of mCRC patients treated with cetuximab and FOLFIRI, although further investigations will be needed to confirm the association of FcγR and EGFR polymorphisms with the efficacy of cetuximab.
[Show abstract][Hide abstract] ABSTRACT: 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.
Anticancer research 04/2014; 34(4):1967-73. · 1.83 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Mesh plug repair has been one of the common methods for inguinal hernia. We report a case with perforation of sigmoid colon due to mesh plug for the repair of inguinal hernia. The patient presented peritoneal abscess forming colocutaneous and colovesicle fistula. He had previously undergone repair of left inguinal hernia with mesh plug. After diverting colostomy in transverse colon, sigmoidectomy, fistulectomy in bladder as well as removal of the prostheses were carried out. The third surgery of stoma closure finalized these procedures. A little literature described intestinal perforation due to prosthesis including mesh plug, though its incidence is very rare.
Nihon Gekakei Rengo Gakkaishi (Journal of Japanese College of Surgeons) 01/2014; 39(2):228-233. DOI:10.4030/jjcs.39.228
[Show abstract][Hide abstract] ABSTRACT: The Glasgow Prognostic Score (GPS) is an inflammation-based cumulative prognostic score calculated from C-reactive protein (CRP) and albumin levels. The aim of the present study was to assess the value of the GPS as a prognostic tool in advanced esophageal cancer patients undergoing radiation therapy. The medical records of 90 patients with advanced esophageal cancer who had been treated with radiation therapy were reviewed retrospectively. Patients with both elevated CRP (>1.0 mg/dL) and hypoalbuminemia (
[Show abstract][Hide abstract] ABSTRACT: Purpose:
We investigated the background factors, histopathological results, and prognosis of patients with gastrointestinal neuroendocrine tumors.
Materials and methods:
The medical records of 42 patients with gastrointestinal neuroendocrine tumors who were diagnosed and treated at our hospital from 2002 to 2012 were collected and retrospectively reviewed.
The ratio of male to female patients was 29:13; the mean age was 66.1 years. The tumors were located in the esophagus( 2 patients), stomach( 13 patients), duodenum( 9 patients), colon( 1 patient), and rectum( 18 patients). Regarding the depth of the tumor, invasion of the submucosa( SM) was observed in 26 patients; invasion of the muscularis propria( MP), in 1 patient; invasion of the subserosa( SS), in 3 patients; penetration of the serosa( SE)( AD), in 1 patient, invasion of the adjacent structures( SI)( AI), in 3 patients; and the extent of tumor invasion was unknown in 1 patient. Patients who experienced relapse had a poor prognosis, and all the patients died.
Gan to kagaku ryoho. Cancer & chemotherapy 11/2013; 40(12):2448-50.
[Show abstract][Hide abstract] ABSTRACT: We report a case of advanced gastric cancer successfully treated with preoperative S-1/Lentinan (LTN)chemotherapy followed by curative gastrectomy. The patient was a 75-year-old man with right hypochondralgia. Endoscopic examination revealed a huge type 2 gastric cancer in the middle body of the stomach. Abdominal computed tomography (CT) revealed multiple perigastric lymph node metastases and bulky para-aortic lymph node metastases. The clinical diagnosis was cT 4N3M1( LYM) with cStage IV. We thought a complete resection would be difficult, so he was treated with S-1( 80 mg/m2 day 1-28/q6w) and LTN (2 mg weekly) in May 2010. After 3 courses, the primary lesion was markedly reduced, and gastric endoscopic biopsy showed no malignant lesion. After 4 courses, abdominal CT showed no lymph node swelling at the perigastric and para-aortic areas. After 5 courses, distal gastrectomy with D2 lymphadenectomy was performed. The histological diagnosis was ypT2( MP) N0M0, Stage IB. Histological features of the primary tumor and lymph nodes were judged to be Grade 2 and Grade 3, respectively. After surgery, S-1/LTN treatment was continued for 1 year. During this period, there were no serious adverse events. The patient has been in good health without recurrence for 28 months after surgery.
Gan to kagaku ryoho. Cancer & chemotherapy 11/2013; 40(12):2200-2.
[Show abstract][Hide abstract] ABSTRACT: We report the case of a patient with paclitaxel (PTX) -resistant recurrent gastric cancer who was effectively treated with S-1 plus docetaxel( DOC). A 62-year-old woman underwent total gastrectomy for Stage IV advanced gastric cancer (type 4, por 2>sig, pT4a (SE), pN3a, pP1, CY1) in 2009. Although S-1 was administered as first-line chemotherapy, recurrent peritoneal metastasis was diagnosed 22 months after surgery. S-1 plus irinotecan (CPT-11) was administered as second-line chemotherapy, and this was followed by weekly PTX (80 mg/m2) as third-line chemotherapy. However, computed tomography (CT) showed increased ascites and peritoneal wall thickening in the pelvis. As the tumor proved resistant to PTX, making the treatment ineffective, S-1( 80 mg/m2, day 1-14, q3w) plus DOC( 40 mg/m2, day 1, q3w) was initiated. Two months later, the ascites and peritoneal wall thickening in the pelvis disappeared. Twelve months after initiation of S-1 plus DOC chemotherapy, no sign of recurrence has been noted.
Gan to kagaku ryoho. Cancer & chemotherapy 11/2013; 40(12):2259-61.
[Show abstract][Hide abstract] ABSTRACT: Purpose:
Public knowledge-based application for paclitaxe(l PAC) has been approved for advanced or recurrent esophageal cancer. We investigated the feasibility of weekly PAC chemotherapy as a second-line or subsequent regimen for metastatic or recurrent esophageal cancer.
Materials and methods:
Patients received PAC( 100 mg/m2 intravenously) on days 1, 8, 15, 22, 29, and 36 of each 8-week period. We analyzed the toxicity and efficacy in 6 patients treated with the weekly PAC chemotherapy.
Grade 3-4 toxicities were neutropenia, leukopenia, and anemia. Two patients had stable disease and 2 had progressive disease.
By managing the side effects, weekly PAC therapy is considered a feasible regimen that can be administered on an outpatient basis.
Gan to kagaku ryoho. Cancer & chemotherapy 11/2013; 40(12):2118-20.
[Show abstract][Hide abstract] ABSTRACT: We report a case of human epidermal growth factor receptor(HER)2-positive advanced gastric cancer successfully treated with a combination of capecitabine, cisplatin(CDDP), and trastuzumab as first-line chemotherapy. A 66-year-old woman diagnosed as having advanced gastric cancer underwent chemotherapy after abdominal computed tomography (CT)revealed multiple metastases to the liver, lung, lymph nodes, and peritoneum. Histopathological examination indicated a type 3, tub1, cT3(SS), N3, H1, P1, M1(LYM, PUL), cStage IV gastric tumor. Because overexpression of HER2 protein was observed in primary tumor immunostaining, combination therapy of capecitabine+CDDP+trastuzumab was administered as first-line chemotherapy. After 4 courses, CT scans revealed decreased primary tumor size, liver lesion, lymph nodes, and elimination of the lung lesion, thereby suggesting a partial response(PR). The grade 3 adverse events were neutropenia, anemia, and anorexia. After discontinuation of CDDP because of elevation of serum creatinine levels, combination therapy with capecitabine and trastuzumab was continued.
Gan to kagaku ryoho. Cancer & chemotherapy 11/2013; 40(12):2253-5.
[Show abstract][Hide abstract] ABSTRACT: Objective:
Based on the results of the X-ACT study, capecitabine has become one of the standard postoperative adjuvant chemotherapies for colon cancer. However, few studies of tolerability have been conducted in Japan.
In this study, we retrospectively examined treatment continuation, and the adverse events that occurred during eight courses of postoperative adjuvant chemotherapy with capecitabine, in 34 patients with colon cancer who had undergone curative resection.
The completion rate for eight courses of treatment with capecitabine was 79. 4%(27 of 34 subjects), the median relative dose intensity was 94. 4%(13% to 106%), and the proportion of subjects with relative dose intensity B 60% was 82. 4%(28 of 34 subjects). The following Grade 3 or higher adverse events were reported: hand-foot syndrome, in 11. 8%(4 of 34 subjects); mucositis oral, in 2. 9%(1 of 34 subjects); diarrhea, in 2. 9%(1 of 34 subjects); and glans penis ulcer, in 2. 9%(1 of 34 subjects).
In our hospital, a high rate of capecitabine treatment continuation comparable to that reported in the X-ACT study was obtained, suggesting that capecitabine adjuvant chemotherapy would be well tolerated in clinical practice as well.
Gan to kagaku ryoho. Cancer & chemotherapy 03/2013; 40(3):327-330.
[Show abstract][Hide abstract] ABSTRACT: There is no standard therapy for advanced gastric cancer patients who had already failed treatment with major anti-cancer drugs including fluoropyrimidine, cisplatin, taxans, and irinotecan. We report the results of treatment with capecitabine and cisplatin(XP)after the failure of all other conventional therapies. A total of five advanced gastric cancer patients were treated. The median age was 59 years(range, 46-76); there were 3male and 2 female patients; performance status was 0/1/2: 2/2/ 1 patients, respectively. The median duration from start of first-line chemotherapy to XP was 653 days(range, 372-1,107). Three patients were treated after fourth-line therapy and two patients after fifth-line therapy. All of the patients had received S-1, cisplatin, irinotecan, paclitaxel, and docetaxel previously. Patients received 80mg/m2 of cisplatin intravenously on day 1, and 1,000mg/m2 of capecitabine orally twice a day from day 1 to day 14 followed by a 7-day rest period. Treatment courses were between 2 to 5. Median time to progression was 107 days. Median overall survival was 245 days. One PR and one SD were reported. All reported adverse events were manageable. XP is considered one of the effective regimens for advanced gastric cancer after all conventional therapies have failed.
Gan to kagaku ryoho. Cancer & chemotherapy 01/2013; 40(1):57-60.
[Show abstract][Hide abstract] ABSTRACT: Hangeshashinto (TJ-14, a Kampo medicine), which reduces the level of prostaglandin E2 and affects the cyclooxygenase activity, alleviates chemotherapy-induced oral mucositis (COM). We conducted a double-blind, placebo-controlled, randomized comparative trial to investigate whether TJ-14 prevents and controls COM in patients with colorectal cancer.
Ninety-three patients with colorectal cancer who developed moderate-to-severe COM (WHO grade ≧1) during any cycle of chemotherapy using FOLFOX, FOLFIRI, and/or XELOX treatment were randomly assigned to receive either TJ-14 (n = 46) or placebo (n = 47). Patients received the administration of placebo or TJ-14 for 2 weeks at the start of the next course of chemotherapy. Patients were assessed three times per week for safety and for COM incidence and its severity using the WHO grading.
Ninety eligible patients (TJ-14; 43, placebo; 47) per protocol set analysis were included in the analysis after the key-opening. Although the incidence of grade ≧2 oral mucositis was lower for patients treated with TJ-14 compared to those treated with placebo, there was no significant difference (48.8 vs. 57.4 %; p = 0.41). The median duration of grade ≧2 mucositis was 5.5 versus 10.5 days (p = 0.018). No difference in other treatment toxicity was observed between the two groups, and patients exhibited high compliance in dosing administration.
The present study results did not meet the primary endpoint. However, TJ-14 demonstrated a significant effect in the treatment of grade ≧2 mucositis in patients with colorectal cancer compared to the placebo.
Annals of Cancer Research and Therapy 01/2013; 21(1):26-30. DOI:10.4993/acrt.21.26