Hiroki Kawai

Aichi Cancer Center, Ōsaka, Ōsaka, Japan

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Publications (36)108.06 Total impact

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    ABSTRACT: Although there appears to be incomplete cross-resistance between docetaxel and paclitaxel in several types of malignancies, to our best knowledge there have been no available data on this for advanced gastric cancer. We retrospectively evaluated the efficacy and safety of docetaxel in patients with paclitaxel-resistant advanced gastric cancer. Docetaxel was administered at 50-60 mg/m2 every 3 weeks. Twenty-one patients were evaluated. All patients had received 2 or more previous chemotherapy regimens. Among the 12 patients with measurable lesions, apparent tumor shrinkage was seen in 1 patient for an overall response rate of 8. 3% and a disease control rate of 33. 3%. Median progression free survival and overall survival of all patients were 2. 6 months and 6. 7 months, respectively. There were no correlations between the progression free survival of docetaxel and the progression free survival of previous paclitaxel and between the progression free survival of docetaxel and taxane-free interval(Spearman's correlation coefficients of ρ=-0. 14 and ρ=-0. 02, respectively). Grade 3/4 neutropenia developed in 8 patients(38%)and Grade 3 febrile neutropenia in 1 patient(4. 8%). Docetaxel showed modest activity in paclitaxel-resistant advanced gastric cancer patients, and no correlations between previous efficacy of paclitaxel or taxane-free interval were seen.
    Gan to kagaku ryoho. Cancer & chemotherapy 10/2012; 39(10):1511-5.
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    ABSTRACT: To evaluate the efficacy and safety of adjunctive mosapride citrate for bowel preparation before colonoscopy. We conducted a randomized, double-blind, placebo-controlled study with mosapride in addition to polyethylene glycol (PEG)-electrolyte solution. Of 250 patients undergoing colonoscopy, 124 were randomized to receive 2 L PEG plus 15 mg of mosapride citrate (mosapride group), and 126 received 2 L PEG plus placebo (placebo group). Patients completed a questionnaire reporting the acceptability and tolerability of the bowel preparation process. The efficacy of bowel preparation was assessed by colonoscopists using a 5-point scale based on Aronchick's criteria. The primary end point was optimal bowel preparation rates (scores of excellent/good/fair vs poor/inadequate). A total of 249 patients were included in the analysis. In the mosapride group, optimal bowel preparation rates were significantly higher in the left colon compared with the placebo group (78.2% vs 65.6%, P < 0.05), but not in the right colon (76.5% vs 66.4%, P = 0.08). After excluding patients with severe constipation, there was a significant difference in bowel preparation in both the left and right colon (82.4% vs 66.7%, 80.8% vs 67.5%, P < 0.05, P < 0.01). The incidence of adverse events was similar in both groups. Among the subgroup who had previous colonoscopy experience, a significantly higher number of patients in the mosapride group felt that the current preparation was easier compared with patients in the placebo group (34/72 patients vs 24/74 patients, P < 0.05). Mosapride citrate may be an effective and safe adjunct to PEG-electrolyte solution that leads to improved quality of bowel preparation, especially in patients without severe constipation.
    World Journal of Gastroenterology 05/2012; 18(20):2517-25. · 2.55 Impact Factor
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    ABSTRACT: The aim of this study was to prospectively evaluate the efficacy of combination irinotecan and cetuximab chemotherapy in patients with pretreated metastatic colorectal cancer harboring wild-type KRAS. Patients with metastatic colorectal cancer that had progressed after chemotherapy with irinotecan, oxaliplatin, and fluoropyrimidine were included. KRAS status was evaluated using the Cycleave PCR method; only patients without KRAS mutations were included. Cetuximab was administered initially at 400 mg/m² followed by weekly 250 mg/m² infusions. Irinotecan was administered biweekly. From October 2008 to April 2009, a total of 30 patients were enrolled. The objective response rate was 30.0% (95% confidence interval [CI], 14.7-49.4%) and the disease control rate (complete response, partial response, or stable disease) was 80.0% (95% CI, 61.4-92.3%). Among the 15 patients with stable disease, 11 patients experienced >10% tumor shrinkage. Median progression-free survival was 5.8 months (95% CI, 4.1-7.6). Median overall survival was not reached at a median follow-up of 10.1 months. Grade 2 skin toxicity was observed in 23 patients, while no grade 3 skin toxicity was observed. Combined irinotecan and cetuximab is effective for pretreated metastatic wild-type KRAS colorectal cancer.
    Investigational New Drugs 08/2011; 29(4):688-93. · 3.50 Impact Factor
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    ABSTRACT: The aim of this study was to evaluate the association of sensitivity to previous irinotecan-based chemotherapy with efficacy of cetuximab plus irinotecan therapy in metastatic colorectal cancer (MCRC) patients with wild-type KRAS. We analysed a pooled data set consisting of data from 87 MCRC patients from two previous phase II studies (n=60) and a group given off-protocol treatment (n=27) following irinotecan-, oxaliplatin-, and fluoropyrimidine-based chemotherapy. Overall objective response rate to cetuximab plus irinotecan was 28.7%, median progression-free survival (PFS) was 5.3 months, and median overall survival was 12.2 months. Objective response rate did not significantly differ between patients with a favourable response to previous irinotecan (n=23), stable disease (n=38), or progressive disease (n=26), with observed rates of 29.2%, 31.6%, and 23.1%, respectively. Additionally, the non-parametric Spearman rank correlation coefficients (ρ) between the PFS of previous irinotecan-based chemotherapy and that of cetuximab plus irinotecan were quite low (ρ=0.067 and 0.057 in patients with previous irinotecan as first- and second-line therapies, respectively). Although exploratory nature and small sample size may be limitations of this study, these findings indicate that the efficacy of irinotecan plus cetuximab in MCRC patients with wild-type KRAS did not differ by previous sensitivity to irinotecan.
    European journal of cancer (Oxford, England: 1990) 06/2011; 47(18):2673-80. · 4.12 Impact Factor
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    ABSTRACT: We conducted a multicenter, retrospective study to determine the anatomical distribution and prognostic factors of gastrointestinal (GI) follicular lymphoma (FL). This study included 125 patients with stage I and II(1) GI-FL. Of the 125 patients, the small intestine was examined in 70 patients, with double-balloon endoscopy and/or capsule endoscopy. The most frequently involved GI-FL site was the duodenal second portion (DSP) (81%), followed by the jejunum (40%); 85% of patients with involvement of the DSP also had jejunal or ileal lesions. The absence of abdominal symptoms and macroscopic appearance of multiple nodules were significantly present in the DSP-positive group. During a median follow up of 40 months, six patients showed disease progression. Patients with involvement of the DSP had better progression-free survival (PFS) than those without such involvement (P = 0.001). A multivariate analysis revealed that male sex, the presence of abdominal symptoms, and negative involvement of the DSP were independently associated with poor PFS. In conclusion, most patients with GI-FL have duodenal lesions associated with multiple jejunal or ileal lesions. Gastrointestinal follicular lymphomas involving the DSP might be a distinct entity showing a favorable clinical course.
    Cancer Science 05/2011; 102(8):1532-6. · 3.48 Impact Factor
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    ABSTRACT: Based on several phase III studies, oral S-1-based chemotherapy has become the standard for treatment of advanced gastric cancer in Japan. However, these studies included patients able to maintain sufficient oral intake, and the effectiveness of chemotherapy for patients unable to eat remained unclear. We retrospectively analyzed the effect of chemotherapy on patients with advanced gastric cancer who presented with inability to eat. We defined 'inability to eat' as requirement for daily intravenous fluids or hyperalimentation and 'improvement of oral intake' as no such requirement >1 week. Among the 777 patients who received first-line chemotherapy, 100 patients (12.8%) were considered unable to eat and required daily intravenous fluids or hyperalimentation. Performance status was 0-1 in 26 patients and ≥ 2 in the other 74 patients. Seventy-eight patients (78%) had peritoneal metastasis and 62 patients (62%) had ascites. First-line chemotherapy with 5-fluorouracil-based regimens was used in 46 patients, taxane-based chemotherapy in 34 patients, oral fluoropyrimidine-based therapy in 19 patients, and irinotecan-cisplatin combination treatment in 2 patients. Median survival time was 5.0 months (95% confidence interval, CI, 3.9-6.6). Improvement in oral intake with duration for >1 week was achieved in 40 patients (40%) with the median duration of nutritional-support-free time of 3.1 months (95% CI 2.5-4.6). Chemotherapy is moderately effective in improving oral intake in patients with advanced gastric cancer with inability to eat. Further study is required to improve its prognosis.
    Oncology 03/2011; 79(3-4):211-8. · 2.17 Impact Factor
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    ABSTRACT: Endoscopic ultrasound-guided choledochoduodenostomy (EUS-CDS) has recently been reported as an alternative to percutaneous transhepatic biliary drainage (PTBD) in cases of biliary obstruction, when endoscopic biliary drainage (EBD) is unsuccessful. However, prospective studies of EUS-CDS have not yet been performed. We conducted a prospective study to evaluate the safety, feasibility, and efficacy of EUS-CDS in patients with malignant lower biliary tract obstruction. A prospective study to confirm the safety of EUS-CDS was carried out in 6 patients, followed by a trial to evaluate the feasibility and efficacy of EUS-CDS in 12 additional patients. We placed a plastic stent from the duodenal bulb into the extrahepatic bile duct under EUS guidance using an oblique viewing echoendoscope, needle knife, guidewire, and biliary dilators. The site of extrahepatic bile duct puncture was the common hepatic duct in 15 patients and the common bile duct in 3 patients. Mean diameter of the punctured extrahepatic bile ducts was 10 mm (range: 6-20 mm). Technical and functional success rates were 94% (17/18) and 100% (17/17), respectively. Median procedure time was 30 min (range: 10-52 min). Median duration to first oral intake after the procedure was 1 day (range: 1-3 days). Early complications were encountered in three (17%) patients, including focal peritonitis in two patients and hemobilia in one patient. During the follow-up period (median: 163 days; range: 46-484 days), 12 stent occlusion events were observed in nine patients. Re-intervention with exchange of the occluded stent was successful in 8 of 12 (66%) times. Severe early and late complications were not encountered in any patients in this study. Median duration of stent patency by Kaplan-Meier analysis was 272 days. EUS-CDS is safe, feasible, and effective as an alternative to PTBD and EBD in cases of malignant distal biliary tract obstruction. Prospective randomized studies are needed to compare the safety and efficacy of various kinds of endoscopic devices used in EUS-CDS and to compare EUS-CDS with PTBD or EBD.
    The American Journal of Gastroenterology 03/2011; 106(7):1239-45. · 7.55 Impact Factor
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    ABSTRACT: Endoscopic ultrasonography (EUS) represents the combination of endoscopy and intraluminal ultrasonography. This allows use of a high-frequency transducer (5-20 MHz) that, due to the short distance to the target lesion, provides ultrasonographic images of higher resolution than those obtained from other imaging modalities, including multiple-detector-row-computed tomography, magnetic resonance imaging, and positron emission tomography. EUS is now a widely accepted modality for diagnosing pancreatic diseases. However, the most important limitation of EUS has been the lack of specificity in differentiating between benign and malignant changes. In 1992, EUS-guided fine needle aspiration (FNA) of lesions in the pancreas head was introduced into clinical practice, using a curved linear-array echoendoscope. Since then, EUS has evolved from EUS imaging to EUS-FNA and wider applications. Interventional EUS for pancreatic cancer includes EUS-FNA, EUS-guided fine needle injection, EUS-guided biliary drainage and anastomosis, EUS-guided celiac neurolysis, radiofrequency ablation, brachytherapy, and delivery of a growing number of anti-tumor agents. This review focuses on interventional EUS, including EUS-FNA and therapeutic EUS for pancreatic cancer.
    World journal of clinical oncology. 02/2011; 2(2):108-14.
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    ABSTRACT: Although fluoropyrimidines, platinum agents, taxanes, and irinotecan are used in the treatment of advanced gastric cancer (AGC), it remains unclear whether these agents in any line of chemotherapy are associated with overall survival (OS) in these patients. We retrospectively analyzed 704 patients with AGC. To avoid possible lead-time bias, we applied time-varying covariate analysis for chemotherapy with four agents in any line. Median OS was 12.3 months. The frequency of exposure to each agent class during all lines of treatment was 92.6% for FU (5-fluorouracil or oral fluoropyrimidine), 48.2% for platinum agents, 65.1% for taxanes, and 39.1% for irinotecan. According to a multivariate Cox model with exposure to each agent class as a time-varying covariate, the hazard ratios (HRs) of death were 0.41 (95% confidence interval [CI], 0.27-0.57; p < 0.001) for FU, 0.71 (95% CI, 0.58-0.84; p < 0.001) for platinum agents, 0.51 (95% CI, 0.41-0.63; p < 0.001) for taxanes, and 0.53 (95% CI, 0.43-0.65; p < 0.001) for irinotecan. Although other agents were used in 18.6% of the patients, they did not affect survival. Each of the four agent classes (FU, platinum agents, taxanes, and irinotecan) appears to be independently associated with improved OS in patients with AGC regardless of timing. This result suggests the importance of developing strategies which make these active agents available to all patients with AGC to prolong OS.
    Gastric Cancer 02/2011; 14(2):155-60. · 3.99 Impact Factor
  • Gastrointestinal Endoscopy - GASTROINTEST ENDOSCOP. 01/2011; 73(4).
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    ABSTRACT: We describe a 54-year old woman with oxaliplatin-induced autoimmune hemolytic anemia and review the clinical features of similar published cases. The present patient had metastatic colon cancer and was admitted to our hospital with a floating sensation and general malaise on day 4 after undergoing the last of 4 cycles of a 7th round of chemotherapy with XELOX. Laboratory data revealed 4.6g/dl hemoglobin and 8.77 mg/dl creatinine. Direct and indirect Coombs tests of a blood sample for blood transfusion were both positive. We diagnosed immune hemolysis with acute renal failure based on the clinical course and blood samples showing haptoglobin <10mg/dl. We treated her with hemodialysis, plasmapheresis and immune suppression with prednisolone, which improved the anemia and renal failure.
    Nippon Shokakibyo Gakkai zasshi The Japanese journal of gastro-enterology 01/2011; 108(10):1712-9.
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    ABSTRACT: A woman in her 60's presented with a tumor of the pancreatic body. Pan-hysterectomy had been performed under a diagnosis of uterine leiomyoma 11 years previously. A sample obtained by endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) revealed the histopathological proliferation of spindle-shaped bundles of atypical cells, and immunohistochemical staining demonstrated that these cells were positive for KIT. Therefore, distal pancreatectomy was performed under a diagnosis of pancreatic gastrointestinal stromal tumor (GIST). Immunohistochemical staining of surgical specimens demonstrated that the tumor cells were positive for desmin and negative for KIT and CD34. The low-grade leiomyosarcoma in pathological specimens of the uterine myoma obtained 11 years previously histologically resembled the pathological findings of the pancreatic specimens except for atypical nuclei and mitotic cells. Therefore, the final diagnosis was extremely rare metastatic leiomyosarcoma of the pancreas. Herein, we report metastasis of uterine leiomyosarcoma to the pancreas and discuss the usefulness and limitations of EUS-FNA.
    Nippon Shokakibyo Gakkai zasshi The Japanese journal of gastro-enterology 01/2011; 108(6):987-96.
  • Gastroenterology 01/2011; 140(5). · 12.82 Impact Factor
  • Gastroenterology 01/2011; 140(5). · 12.82 Impact Factor
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    ABSTRACT: Imatinib used to be the only effective treatment for advanced gastrointestinal stromal tumor. However, early clinical reports have shown that sunitinib has substantial anticancer activity in patients with advanced gastrointestinal stromal tumor after failure of imatinib. Eighteen Japanese patients with advanced gastrointestinal stromal tumor who were resistant or intolerant to previous treatment with imatinib were entered into this study. These patients were given sunitinib orally, once daily at a 50-mg starting dose, in 6-week cycles with 4 weeks on and 2 weeks off treatment. Tumor response and drug safety were then evaluated. Median time-to-treatment failure was 207 days. Overall, 5.6% (1/18) of patients achieved partial response, 38.9% (7/18) had stable disease and 44.4% (8/18) had progressive disease. The common adverse events were hand-foot syndrome, liver dysfunction, fatigue, anorexia and hypertension. Mild anemia, leukocytopenia and neutropenia were also noted. Nine patients required dose reduction or cessation because of adverse events. This study demonstrates that sunitinib may be an effective agent for advanced gastrointestinal stromal tumor after failure of imatinib in clinical practice.
    Japanese Journal of Clinical Oncology 01/2011; 41(1):57-62. · 1.90 Impact Factor
  • Gastrointestinal Endoscopy - GASTROINTEST ENDOSCOP. 01/2011; 73(4).
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    ABSTRACT: Neutropenia during chemotherapy has been reported to be a predictor of better survival in patients with several types of cancers, although there are no reports in pretreated patients. We retrospectively analyzed 242 patients with advanced gastric cancer (AGC) who received weekly paclitaxel (Taxol) as second-line chemotherapy. Background characteristics and neutropenia as time-varying covariates (TVCs) were analyzed as prognostic factors. Of the 242 patients, mild neutropenia (grades 1-2) occurred in 101 patients (41.7%) and severe neutropenia (grades 3-4) occurred in 63 patients (26.0%). The other 78 patients (32.2%) did not experience neutropenia. According to a multivariate Cox model with neutropenia as a TVC, hazard ratios of death were 0.61 [95% confidence interval (CI) 0.43-0.85; P = 0.004] for patients with mild neutropenia and 0.61 (95% CI 0.41-0.88; P = 0.009) for those with severe neutropenia. Among the patients in landmark analysis (landmark of 2.5 months; median time to treatment failure of paclitaxel), mild and severe neutropenia remained significant prognostic factors. Our results indicate that neutropenia during chemotherapy is associated with improved survival in patients with AGC who received weekly paclitaxel as second-line chemotherapy. Prospective trials are required to assess whether dosing adjustments based on neutropenia may improve chemotherapy efficacy.
    Annals of Oncology 12/2010; 21(12):2403-9. · 7.38 Impact Factor
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    ABSTRACT: The aim of this study is to prospectively evaluate the efficacy of combination chemotherapy with every second week cetuximab and irinotecan in patients with pretreated metastatic colorectal cancer harboring wild-type KRAS. Patients with wild-type KRAS metastatic colorectal cancer that had progressed after chemotherapy with irinotecan, oxaliplatin, and fluoropyrimidine were included. Cetuximab was administered at 500 mg/m(2) biweekly with irinotecan. The primary endpoint was response rate. The pharmacokinetics of cetuximab was also evaluated in 5 patients. From May 2009 to February 2010, a total of 31 patients were enrolled from five institutions. One patient was not eligible. Among the 30 patients who were treated with biweekly cetuximab plus irinotecan, partial response was observed in 9 patients. The objective response rate was 30.0% (95% confidence interval [CI], 14.7%-49.4%) and the disease control rate (complete response, partial response, or stable disease) was 76.7% (95% CI, 57.7%-90.0%). The median progression-free survival was 5.3 months and median overall survival was 10.8 months. Grade 3 skin toxicity was observed in 3 patients (10.0%) and one treatment related death due to pneumonia was observed. Combination chemotherapy with biweekly cetuximab and irinotecan was effective for pretreated metastatic colorectal cancer with wild-type KRAS.
    Investigational New Drugs 12/2010; 30(2):787-93. · 3.50 Impact Factor
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    ABSTRACT: Endoscopic ultrasonography (EUS) combines endoscopy and intraluminal ultrasonography, and allows imaging with a high-frequency transducer over a short distance to generate high-resolution ultrasonographic images. EUS is now a widely accepted modality for diagnosing pancreatobiliary diseases. EUS-guided fine-needle aspiration (EUS-FNA) using a curved linear-array echoendoscope was initially described more than 20 years ago, and since then many researchers have expanded its indications to sample diverse lesions and have also used it for various therapeutic purposes. EUS-guided biliary drainage (EUS-BD) is one of the therapeutic procedures that has been developed using a curved linear-array echoendoscope. Technically, EUS-BD includes rendezvous techniques via transesophageal, transgastric, and transduodenal routes, EUS-guided choledochoduodenostomy (EUS-CDS), and EUS-guided hepaticogastrostomy (EUS-HGS). Published data have demonstrated a high success rate, albeit with a comparatively high rate of nonfatal complications for EUS-CDS and EUS-HGS, and a comparatively low success rate with a low complication rate for the rendezvous technique. At present, these procedures represent an alternative to surgery or percutaneous transhepatic biliary drainage (PTBD) for patients with obstructive jaundice when endoscopic biliary drainage (EBD) has failed. However, these procedures should be performed in centers with extensive experience in linear EUS and therapeutic biliary ERCP. Large prospective studies are needed in the near future to establish standardized EUS-BD procedures as well as to perform controlled comparative trials between EUS-BD and PTBD, between rendezvous techniques and direct-access techniques (EUS-CDS and EUS-HGS), and between EBD and EUS-BD.
    Gut and liver 09/2010; 4 Suppl 1:S67-75. · 1.31 Impact Factor
  • Endoscopy 01/2010; 42 Suppl 2:E27-8. · 5.74 Impact Factor