Background: Uracil-tegafur (UFT) has been reported to have broad antitumor activity in a variety ... more Background: Uracil-tegafur (UFT) has been reported to have broad antitumor activity in a variety of malignancies. However, its activity in biliary tract carcinoma has not been fully evaluated. The aim of this study was to evaluate the antitumor activity and toxicity of UFT in chemotherapy-naive patients with advanced biliary tract carcinoma. Methods: Nineteen patients with advanced biliary tract carcinoma that was histologically confirmed as adenocarcinoma were enrolled in this phase II trial of UFT. A dose of 360 mg/ m 2 /day of UFT was administered orally if there was no evidence of tumor progression or there was unacceptable toxicity. Results: Of the 19 patients evaluable for response, one patient (5%) achieved a partial response with a duration of 2.0 months. Six patients (32%) showed no change and the remaining 12 (63%) had progressive disease. The median survival, 6-month survival rate and 1-year survival rate for all patients were 8.8 months, 52.6 and 21.1%, respectively. The chemotherapy was well tolerated, because grades 3 or 4 toxicity were not observed. Conclusion: UFTappears to have little activity as a single agent in treating patients with advanced biliary tract carcinoma. These findings do not support its use in practice, and further trials with this regimen in patients with biliary tract carcinoma are not recommended.
Objective: The purpose of this study was to identify prognostic factors in patients with gemcitab... more Objective: The purpose of this study was to identify prognostic factors in patients with gemcitabine-refractory pancreatic cancer and to determine criteria for selecting candidates for second-line treatment. Methods: The records of 74 patients who were treated with gemcitabine (GEM) and followed up until disease progression were reviewed retrospectively. Sixteen clinical variables at the time of disease progression after GEM chemotherapy were chosen for analysis in this study. Univariate and multivariate analyses were conducted to identify prognostic factors associated with survival. Results: At the time of analysis, 71 patients had died because of tumor progression. The overall median survival time was 5.1 months after first-line chemotherapy with GEM was initiated. Median survival time after disease progression was 2.0 months. Three factors, performance status, peritoneal dissemination and C-reactive protein level, were identified as independent prognostic factors in multivariate analysis. Median survival time in the good prognosis group ( patients with performance status 0 or 1, no peritoneal dissemination and C-reactive protein ,5.0 mg/dl) was 3.4 months. Conclusions: Performance status, serum level of C-reactive protein and peritoneal dissemination were identified as important prognostic factors in patients with GEM-refractory pancreatic cancer. These factors should be considered in determining the treatment following first-line chemotherapy in patients with advanced pancreatic cancer.
Background: Despite the high complete necrosis rate of radiofrequency ablation (RFA), tumor recur... more Background: Despite the high complete necrosis rate of radiofrequency ablation (RFA), tumor recurrence, either local tumor recurrence or new tumor formation, remains a significant problem. Purpose of this study is to evaluate the pattern and risk factors for intrahepatic recurrence after percutaneous RFA for hepatocellular carcinoma (HCC). Methods: We studied 40 patients with 48 HCCs ( 3.5 cm) who were treated with percutaneous RFA. The mean follow-up period was 24.1 + 15.7 months. We evaluated the cumulative disease-free survival of overall intrahepatic recurrence, local tumor progression (LTP) and intrahepatic distant recurrence (IDR). Thirty host, tumoral and therapeutic risk factors were reviewed for significant tie-in correlation with recurrence: age; gender; whether RFA was the initial treatment for HCC or not; severity of liver disease; cause of liver cirrhosis; contact of tumor to major hepatic vessels and liver capsule; degree of approximation of tumor to the liver hilum; ablation time; degree of benign pre-ablational enhancement; sufficient safety margin; tumor multinodularity; tumor histological differentiation; tumor segmental location; maximum tumor diameter; degree of tumor pre-ablational enhancement at arterial phase CT, MRI or CT-angiography; and laboratory markers pre-and post-ablation (AFP, PIVKA II, TP, AST, ALT, ALP and TB). Results: The incidence of overall recurrence, LTP and IDR was 65, 23 and 52.5%, respectively. The cumulative disease-free survival rates were 54.6, 74.8 and 78.3% at 1 year, 27.3, 71.9 and 46.3% at 2 years and 20, 71.9 and 29.4 at 3 years, respectively. Univariate and multivariate analysis showed that the significant risk factors for LTP were: tumor size 2.3 cm, insufficient safety margin, multinodular tumor, tumors located at segments 8 and 5, and patient's age . 65 years (P , 0.05). No significant risk factor relationship for IDR could be detected. Conclusion: Our results would have clinical implications for advance warning and appropriate management of patients scheduled for RFA. Patients at risk of LTP should be closely monitored in the first year. Furthermore, regular long-term surveillance is essential for early detection and eradication of IDR.
Gastrointestinal hemorrhage from hepatocellular carcinoma invading the duodenum is very rare. A 6... more Gastrointestinal hemorrhage from hepatocellular carcinoma invading the duodenum is very rare. A 60-year-old man with multiple hepatocellular carcinoma was admitted to our hospital because of massive melena and hematemesis. We succeeded in hemostasis of an esophageal variceal rupture by endoscopic varicial ligation. The duodenum could not be observed endoscopically due to extramural compression to the stomach from the liver tumor. Massive gastrointestinal hemorrhage occurred again and the patient died of hepatic failure. The postmortem examination revealed that the liver tumor had invaded the second portion of the duodenum and perforated into the lumen.
Chemotherapy is of limited value in the treatment of hepatocellular carcinoma (HCC), since there ... more Chemotherapy is of limited value in the treatment of hepatocellular carcinoma (HCC), since there are no established chemotherapeutic regimens proven to be effective. The aim of the present study was to determine predictive factors for tumor response to systemic chemotherapy in HCC patients. The relationship between patients' characteristics and tumor response was examined in 147 previously untreated HCC patients receiving systemic chemotherapy. Ten patients showed partial response (PR) and none showed complete response (CR). The response rate for all single anticancer agents was less than 10% and the overall response rate was 6.8%. The response rate in patients with unilateral HCC was significantly higher than in those with bilateral HCC. However, there were no responders among patients with a performance status of 2-3, ascites, a tumor occupying more than 50% of the entire liver, tumor thrombus in the main portal trunk or a serum bilirubin level of more than 2.0 mg/dl. There was a close relationship between patients' characteristics and tumor response. It is concluded that patients with fairly advanced HCC and/or poor hepatic reserve should not be given systemic chemotherapy.
The vast majority of pancreatic cancer patients have advanced disease at the time of diagnosis an... more The vast majority of pancreatic cancer patients have advanced disease at the time of diagnosis and they eventually become so emaciated that death primarily occurs from cancer cachexia. Cancer cachexia may be mediated by certain cytokines such as interleukin-6. In this study, we measured serum interleukin-6 levels in 55 patients with histologically proven pancreatic cancer and investigated theirrelationships to the clinical status of pancreatic cancer. A control population of 20 normal healthy adults and 25 chronic pancreatitis patients with comparable gender and agedistribution characteristics wasalso studied. Serum interleukin-6 levels were measured using a quantitative sandwich enzyme-linked immunosorbent assay. Thirty pancreatic cancer patients (54.5°,/0) had detectable levels, although interleukin-6 levels were detectable inonlyonehealthy control and in two chronic pancreatitis patients. The specificity of serum interleukin-6 in this population was 93.3°,/0, resulting in high diagnostic accuracy (72.0°,/0). Among the pancreatic cancer patients, the detection rates of serum interleukin-6 levels increased significantly with the disease extent (p < 0.01). Moreover, a significant difference wasalso found in the detection rates between the 30 pancreatic cancer patients with bodyweight loss (76.7%) and the remaining 25 patients without weight loss (28.00/0, p < 0.01). These results may provide new insight into both diagnosis and treatment of pancreatic cancer, because the diagnostic accuracy of serum interleukin-6 was high and because anti-interleukin-6 therapeutics could improve symptoms in pancreatic cancer patients with high interleukin-6Ievels.
Objective: The aim was to determine the recommended dose of combined chemotherapy with mitoxantro... more Objective: The aim was to determine the recommended dose of combined chemotherapy with mitoxantrone and uracil/tegafur (Phase I part) and to clarify its efficacy and safety in patients with advanced hepatocellular carcinoma at the recommended dose (Phase II part). Methods: Patients eligible had histologically confirmed, chemo-naive advanced hepatocellular carcinoma and were amenable to established forms of treatment. The therapy consisted of mitoxantrone administered intravenously at one of three dosages (6, 8 and 10 mg/m 2 /day) on day 1 and uracil/tegafur administered orally at 300 mg/m 2 from day 1 through day 21. The treatment was repeated every 4 weeks until evidence of tumor progression or unacceptable toxicity. Results: A total of 25 patients were enrolled. In the Phase I part, dose-limiting toxicities occurred in all three patients, given mitoxantrone at the dosage of 10 mg/m 2 /day, and the recommended mitoxantrone dosage was determined to be 8 mg/m 2 /day. Among 19 patients administered the drug at the recommended dosage, 1 patient (5.3%) showed partial response, 8 patients (42.1%) showed stable disease and 10 patients (52.6%) showed progressive disease. The median survival and median progression-free survival were 8.4 and 2.5 months, respectively. The most common toxicities were Grade 3 -4 leukopenia (63.2%) and neutropenia (68.4%). Conclusions: Mitoxantrone at 8 mg/m 2 combined with uracil/tegafur at 300 mg/m 2 /day was determined to be the recommended regimen. Although this regimen was generally well tolerated, it appeared to have little activity against advanced hepatocellular carcinoma. These findings do not support the use of this combination regimen in practice.
Undifferentiated carcinoma of the liveris very rare. A 54-year-old manwasadmitted to our hospital... more Undifferentiated carcinoma of the liveris very rare. A 54-year-old manwasadmitted to our hospital for a detailed examination of multiple liver tumors. These tumors were high or low echoic on ultrasonography, but not enhanced by contrast medium in dynamic computed tomography. A fine-needle aspiration biopsy specimen of the tumor showed undifferentiated carcinoma. The serum level of neuron-specific enolase was high (357 ng/ml) and the immunohistochemical stain of the biopsy specimen was positive for synaptophysin. We diagnosed the patient as having undifferentiated carcinoma of the liverwith neuroendocrine features. The patient was treated with combined systemic chemotherapy: etoposide 100 mg/m 2/day for three days plus cisplatin 80 mg/m 2/day on day one. He achieved a partial response, the duration of which was 7+ months. The serum neuron-specific enolase levels were decreased to the normal range after chemotherapy. Primary liver carcinoma with neuroendocrine features is extremely rare, but in a suspicious case it is important to measure the serum levels of neuroendocrine markers and make a histological confirmation, because chemotherapy may be effective for this disease.
The incidence of pancreatic or biliary tract cancer is increasing in our aging population, but li... more The incidence of pancreatic or biliary tract cancer is increasing in our aging population, but little is known of treatment outcomes in elderly patients with pancreatic or biliary tract cancer. Patients with pancreatic or biliary tract cancer who received chemotherapy in our institute between September 2007 and August 2009 were retrospectively reviewed to compare treatment outcomes between the elderly (aged 75 years or older) and the younger patients. Data were collected of patient backgrounds, adverse events and dose intensity within the first two cycles and overall survival time. Of the 102 who met the inclusion criteria, 19 were elderly who were introduced to full dose chemotherapy. Medication for their comorbidities was required in 15 (79%) of the 19 elderly patients and in 27 (33%) of 83 younger patients. The frequencies of haematological adverse events of grades 3 or 4 were 42% and 39%, and those of non-haematological adverse events were 21% and 16%, for the elderly and younger, respectively. Similar dose intensities were delivered to the elderly and younger. Also, similar proportions of elderly and younger received dose reductions. There was no difference in overall survival between the elderly and the younger. No clear difference in treatment outcomes was seen between the elderly and the younger patients who received gemcitabine alone. Gemcitabine chemotherapy appears to be safe and the same treatment effect was seen even in older patients with pancreatic or biliary tract cancer.
The Hepatobiliary and Pancreatic Oncology Group of the Japan Clinical Oncology Group (JCOG) was c... more The Hepatobiliary and Pancreatic Oncology Group of the Japan Clinical Oncology Group (JCOG) was constituted in April 2008 to develop new standard treatments for hepatobiliary and pancreatic cancer. In pancreatic cancer, the Hepatobiliary and Pancreatic Oncology Group focuses on establishing standard chemotherapy or chemoradiotherapy for unresectable locally advanced disease. The JCOG 0506 study was a Phase II study of gemcitabine alone to examine its efficacy and safety in patients with locally advanced disease. The results in survival significantly exceeded expectations, and gemcitabine monotherapy has come to be regarded as the provisional standard therapy by our group. Following JCOG 0506, the JCOG 1106 study, which is currently under investigation, is a randomized Phase II study to evaluate the efficacy of induction chemotherapy with gemcitabine in combination with S-1 chemoradiotherapy and select a candidate therapeutic agent in a Phase III study comparing with gemcitabine alone. The JCOG 0805 study was a randomized Phase II study comparing S-1 monotherapy with gemcitabine plus S-1 combination therapy for unresectable biliary tract cancer. As a result, gemcitabine plus S-1 combination therapy was considered the more promising candidate in comparison with the gemcitabine plus cisplatin combination therapy in a subsequent Phase III trial. The Hepatobiliary and Pancreatic Oncology Group is planning a Phase III study to compare gemcitabine plus S-1 combination therapy with gemcitabine plus cisplatin combination therapy (JCOG PC1113 study). No standard postoperative adjuvant treatment has been established. We plan to conduct a Phase III study to compare S-1 as adjuvant therapy after surgery with surgery alone in patients with biliary tract cancer (JCOG PC1202).
Objective: To clarify the prognostic factors for patients with obstructive jaundice due to advanc... more Objective: To clarify the prognostic factors for patients with obstructive jaundice due to advanced colorectal and gastric cancers who had undergone percutaneous transhepatic biliary drainage. Methods: Baseline variables and clinical outcomes were evaluated for 92 consecutive patients treated with percutaneous transhepatic biliary drainage. Results: Of the 92 patients, 32 (35%) had colorectal cancer and the remaining 60 (65%) had gastric cancer. Percutaneous transhepatic biliary drainage was successfully achieved in 74 (80%) patients, and 39 of them could receive subsequent chemotherapy. The median survival after percutaneous transhepatic biliary drainage was 273 days in the 39 patients who had undergone successful percutaneous transhepatic biliary drainage and subsequent chemotherapy, 65 days in 35 patients who had undergone successful percutaneous transhepatic biliary drainage but who had not received subsequent chemotherapy and 34 days in the remaining 18 patients who had undergone unsuccessful percutaneous transhepatic biliary drainage (P , 0.001). Multiple liver metastases and hepatic hilar bile duct stricture were independently associated with unsuccessful percutaneous transhepatic biliary drainage. Poor performance status, multiple liver metastases, presence of ascites, multiple prior chemotherapy administrations, undifferentiated type histology and high serum CA19-9 level were independently associated with a poor prognosis. A prognostic index calculated based on the number of these six factors was used to classify the patients into a good-risk group (index 2) (n ¼ 56) and a poor-risk group (index 3) (n ¼ 36). The median survival time and 2-month survival rate for the two groups were 163 and 44 days, respectively, and 85.7 and 33.3%, respectively (P , 0.001). Conclusions: As regards the introduction of percutaneous transhepatic biliary drainage in patients with obstructive jaundice due to colorectal and gastric cancers, careful patient selection might be necessary. A prognostic model seems to be useful for making decisions as to whether percutaneous transhepatic biliary drainage is indicated for particular patients.
Background SM-11355 is a platinum complex developed to treat hepatocellular carcinoma (HCC) via a... more Background SM-11355 is a platinum complex developed to treat hepatocellular carcinoma (HCC) via administration into the hepatic artery as a sustained-release suspension in iodized oil. We conducted a multicenter phase II trial in patients with HCC to evaluate the efficacy and safety of SM-11355, using a Zinostatin stimalamer suspension in iodized oil as a reference. Methods Patients with unresectable HCC were randomized 2:1 to receive administration of the SM-11355 or Zinostatin stimalamer suspension into the hepatic artery. A second injection was given 4-12 weeks later. Efficacy was evaluated by CT 3 months after treatment and categorized as therapeutic T. Okusaka (effect (TE) V to I, where TE V was defined as disappearance or 100% necrosis of all treated tumors. Results A total of 122 patients were evaluated for efficacy and toxicity (SM-11355, n083; Zinostatin stimalamer, n039). Baseline characteristics were similar in the two groups. The TE V rates were 26.5% (22/83) and 17.9% (7/39) in the SM-11355 and Zinostatin stimalamer groups, respectively. In the SM-11355 group,the most frequent drug-related adverse events (AEs) of≥grade 3 were elevated AST, elevated ALT, thrombocytopenia, and hyperbilirubinemia. The AEs with the largest difference between the two groups (SM-11355 vs. Zinostatin stimalamer) were hepatic vascular injury (0 vs. 48.4%) and eosinophilia (84.3 vs. 41.0%). The 2-year and 3year survival rates were 75.9% vs. 70.3% and 58.4% vs. 48.7%, respectively. Conclusions The results suggest that SM-11355 in iodized oil has similar efficacy to Zinostatin stimalamer and that repeated dosing of SM-11355 is possible without hepatic vascular injury in cases of relapse.
Abbreviations & Acronyms mTOR = mammalian target of rapamycin RCC = renal cell carcinoma Abstract... more Abbreviations & Acronyms mTOR = mammalian target of rapamycin RCC = renal cell carcinoma Abstract: A 55-year-old Japanese man was admitted to Oita University Hospital (Oita, Japan) for pyrexia, malaise and dyspnea, and abnormal shadows on chest radiographs. He had started receiving sunitinib (37.5 mg a day for 3 weeks, followed by a 3-week break before beginning the next dosing cycle) for metastatic renal cell carcinoma after the improvement of temsirolimus-induced interstitial pneumonia. Sunitinib is a multiple tyrosine kinase receptor inhibitor approved for the treatment of metastatic renal cell carcinoma, and the most common clinical adverse effects of sunitinib are diarrhea, mucositis, stomatitis, hypertension, rashes and altered taste. We herein report a rare case of sunitinib-related interstitial pneumonia after treatment with temsirolimus for metastatic renal cell carcinoma. This case suggests the possibility of recall phenomenon of drug-induced pneumonia during the administration of additional chemotherapy.
International Journal of Radiation Oncology*Biology*Physics, 2013
S-1 is the first single anticancer agent to be judged non-inferior to gemcitabine in a large-scal... more S-1 is the first single anticancer agent to be judged non-inferior to gemcitabine in a large-scale, randomized, phase III trial for advanced pancreatic cancer, and it can also act as a radiosensitizer. S-1 with concurrent radiation therapy showed very favorable activity, with mild toxicity in patients with Purpose: The aim of this trial was to evaluate the efficacy and toxicity of S-1 and concurrent radiation therapy for locally advanced pancreatic cancer (PC). Methods and Materials: Locally advanced PC patients with histologically or cytologically confirmed adenocarcinoma or adenosquamous carcinoma, who had no previous therapy were enrolled. Radiation therapy was delivered through 3 or more fields at a total dose of 50.4 Gy in 28 fractions over 5.5 weeks. S-1 was administered orally at a dose of 80 mg/m 2 twice daily on the day of irradiation during radiation therapy. After a 2-to 8-week break, patients received a maintenance dose of S-1 (80 mg/m 2 /day for 28 consecutive days, followed by a 14-day rest period) was then administered until the appearance of disease progression or unacceptable toxicity. The primary efficacy endpoint was survival, and the secondary efficacy endpoints were progression-free survival, response rate, and serum carbohydrate antigen 19-9 (CA19-9) response; the safety endpoint was toxicity. Results: Of the 60 evaluable patients, 16 patients achieved a partial response (27%; 95% confidence interval [CI], 16%-40%). The median progression-free survival period, overall survival period, and 1-year survival rate of the evaluable patients were 9.7 months (95% CI, 6.9-11.6 months), International Journal of biology physics www.redjournal.org locally advanced pancreatic cancer. 16.2 months (95% CI,, and 72% (95%CI, 59%-82%), respectively. Of the 42 patients with a pretreatment serum CA19-9 level of !100 U/ml, 34 (81%) patients showed a decrease of greater than 50%. Leukopenia (6 patients, 10%) and anorexia (4 patients, 7%) were the major grade 3-4 toxicities with chemoradiation therapy. Conclusions: The effect of S-1 with concurrent radiation therapy in patients with locally advanced PC was found to be very favorable, with only mild toxicity. Ó 2013 Elsevier Inc.
Background: Uracil-tegafur (UFT) has been reported to have broad antitumor activity in a variety ... more Background: Uracil-tegafur (UFT) has been reported to have broad antitumor activity in a variety of malignancies. However, its activity in biliary tract carcinoma has not been fully evaluated. The aim of this study was to evaluate the antitumor activity and toxicity of UFT in chemotherapy-naive patients with advanced biliary tract carcinoma. Methods: Nineteen patients with advanced biliary tract carcinoma that was histologically confirmed as adenocarcinoma were enrolled in this phase II trial of UFT. A dose of 360 mg/ m 2 /day of UFT was administered orally if there was no evidence of tumor progression or there was unacceptable toxicity. Results: Of the 19 patients evaluable for response, one patient (5%) achieved a partial response with a duration of 2.0 months. Six patients (32%) showed no change and the remaining 12 (63%) had progressive disease. The median survival, 6-month survival rate and 1-year survival rate for all patients were 8.8 months, 52.6 and 21.1%, respectively. The chemotherapy was well tolerated, because grades 3 or 4 toxicity were not observed. Conclusion: UFTappears to have little activity as a single agent in treating patients with advanced biliary tract carcinoma. These findings do not support its use in practice, and further trials with this regimen in patients with biliary tract carcinoma are not recommended.
Objective: The purpose of this study was to identify prognostic factors in patients with gemcitab... more Objective: The purpose of this study was to identify prognostic factors in patients with gemcitabine-refractory pancreatic cancer and to determine criteria for selecting candidates for second-line treatment. Methods: The records of 74 patients who were treated with gemcitabine (GEM) and followed up until disease progression were reviewed retrospectively. Sixteen clinical variables at the time of disease progression after GEM chemotherapy were chosen for analysis in this study. Univariate and multivariate analyses were conducted to identify prognostic factors associated with survival. Results: At the time of analysis, 71 patients had died because of tumor progression. The overall median survival time was 5.1 months after first-line chemotherapy with GEM was initiated. Median survival time after disease progression was 2.0 months. Three factors, performance status, peritoneal dissemination and C-reactive protein level, were identified as independent prognostic factors in multivariate analysis. Median survival time in the good prognosis group ( patients with performance status 0 or 1, no peritoneal dissemination and C-reactive protein ,5.0 mg/dl) was 3.4 months. Conclusions: Performance status, serum level of C-reactive protein and peritoneal dissemination were identified as important prognostic factors in patients with GEM-refractory pancreatic cancer. These factors should be considered in determining the treatment following first-line chemotherapy in patients with advanced pancreatic cancer.
Background: Despite the high complete necrosis rate of radiofrequency ablation (RFA), tumor recur... more Background: Despite the high complete necrosis rate of radiofrequency ablation (RFA), tumor recurrence, either local tumor recurrence or new tumor formation, remains a significant problem. Purpose of this study is to evaluate the pattern and risk factors for intrahepatic recurrence after percutaneous RFA for hepatocellular carcinoma (HCC). Methods: We studied 40 patients with 48 HCCs ( 3.5 cm) who were treated with percutaneous RFA. The mean follow-up period was 24.1 + 15.7 months. We evaluated the cumulative disease-free survival of overall intrahepatic recurrence, local tumor progression (LTP) and intrahepatic distant recurrence (IDR). Thirty host, tumoral and therapeutic risk factors were reviewed for significant tie-in correlation with recurrence: age; gender; whether RFA was the initial treatment for HCC or not; severity of liver disease; cause of liver cirrhosis; contact of tumor to major hepatic vessels and liver capsule; degree of approximation of tumor to the liver hilum; ablation time; degree of benign pre-ablational enhancement; sufficient safety margin; tumor multinodularity; tumor histological differentiation; tumor segmental location; maximum tumor diameter; degree of tumor pre-ablational enhancement at arterial phase CT, MRI or CT-angiography; and laboratory markers pre-and post-ablation (AFP, PIVKA II, TP, AST, ALT, ALP and TB). Results: The incidence of overall recurrence, LTP and IDR was 65, 23 and 52.5%, respectively. The cumulative disease-free survival rates were 54.6, 74.8 and 78.3% at 1 year, 27.3, 71.9 and 46.3% at 2 years and 20, 71.9 and 29.4 at 3 years, respectively. Univariate and multivariate analysis showed that the significant risk factors for LTP were: tumor size 2.3 cm, insufficient safety margin, multinodular tumor, tumors located at segments 8 and 5, and patient's age . 65 years (P , 0.05). No significant risk factor relationship for IDR could be detected. Conclusion: Our results would have clinical implications for advance warning and appropriate management of patients scheduled for RFA. Patients at risk of LTP should be closely monitored in the first year. Furthermore, regular long-term surveillance is essential for early detection and eradication of IDR.
Gastrointestinal hemorrhage from hepatocellular carcinoma invading the duodenum is very rare. A 6... more Gastrointestinal hemorrhage from hepatocellular carcinoma invading the duodenum is very rare. A 60-year-old man with multiple hepatocellular carcinoma was admitted to our hospital because of massive melena and hematemesis. We succeeded in hemostasis of an esophageal variceal rupture by endoscopic varicial ligation. The duodenum could not be observed endoscopically due to extramural compression to the stomach from the liver tumor. Massive gastrointestinal hemorrhage occurred again and the patient died of hepatic failure. The postmortem examination revealed that the liver tumor had invaded the second portion of the duodenum and perforated into the lumen.
Chemotherapy is of limited value in the treatment of hepatocellular carcinoma (HCC), since there ... more Chemotherapy is of limited value in the treatment of hepatocellular carcinoma (HCC), since there are no established chemotherapeutic regimens proven to be effective. The aim of the present study was to determine predictive factors for tumor response to systemic chemotherapy in HCC patients. The relationship between patients' characteristics and tumor response was examined in 147 previously untreated HCC patients receiving systemic chemotherapy. Ten patients showed partial response (PR) and none showed complete response (CR). The response rate for all single anticancer agents was less than 10% and the overall response rate was 6.8%. The response rate in patients with unilateral HCC was significantly higher than in those with bilateral HCC. However, there were no responders among patients with a performance status of 2-3, ascites, a tumor occupying more than 50% of the entire liver, tumor thrombus in the main portal trunk or a serum bilirubin level of more than 2.0 mg/dl. There was a close relationship between patients' characteristics and tumor response. It is concluded that patients with fairly advanced HCC and/or poor hepatic reserve should not be given systemic chemotherapy.
The vast majority of pancreatic cancer patients have advanced disease at the time of diagnosis an... more The vast majority of pancreatic cancer patients have advanced disease at the time of diagnosis and they eventually become so emaciated that death primarily occurs from cancer cachexia. Cancer cachexia may be mediated by certain cytokines such as interleukin-6. In this study, we measured serum interleukin-6 levels in 55 patients with histologically proven pancreatic cancer and investigated theirrelationships to the clinical status of pancreatic cancer. A control population of 20 normal healthy adults and 25 chronic pancreatitis patients with comparable gender and agedistribution characteristics wasalso studied. Serum interleukin-6 levels were measured using a quantitative sandwich enzyme-linked immunosorbent assay. Thirty pancreatic cancer patients (54.5°,/0) had detectable levels, although interleukin-6 levels were detectable inonlyonehealthy control and in two chronic pancreatitis patients. The specificity of serum interleukin-6 in this population was 93.3°,/0, resulting in high diagnostic accuracy (72.0°,/0). Among the pancreatic cancer patients, the detection rates of serum interleukin-6 levels increased significantly with the disease extent (p < 0.01). Moreover, a significant difference wasalso found in the detection rates between the 30 pancreatic cancer patients with bodyweight loss (76.7%) and the remaining 25 patients without weight loss (28.00/0, p < 0.01). These results may provide new insight into both diagnosis and treatment of pancreatic cancer, because the diagnostic accuracy of serum interleukin-6 was high and because anti-interleukin-6 therapeutics could improve symptoms in pancreatic cancer patients with high interleukin-6Ievels.
Objective: The aim was to determine the recommended dose of combined chemotherapy with mitoxantro... more Objective: The aim was to determine the recommended dose of combined chemotherapy with mitoxantrone and uracil/tegafur (Phase I part) and to clarify its efficacy and safety in patients with advanced hepatocellular carcinoma at the recommended dose (Phase II part). Methods: Patients eligible had histologically confirmed, chemo-naive advanced hepatocellular carcinoma and were amenable to established forms of treatment. The therapy consisted of mitoxantrone administered intravenously at one of three dosages (6, 8 and 10 mg/m 2 /day) on day 1 and uracil/tegafur administered orally at 300 mg/m 2 from day 1 through day 21. The treatment was repeated every 4 weeks until evidence of tumor progression or unacceptable toxicity. Results: A total of 25 patients were enrolled. In the Phase I part, dose-limiting toxicities occurred in all three patients, given mitoxantrone at the dosage of 10 mg/m 2 /day, and the recommended mitoxantrone dosage was determined to be 8 mg/m 2 /day. Among 19 patients administered the drug at the recommended dosage, 1 patient (5.3%) showed partial response, 8 patients (42.1%) showed stable disease and 10 patients (52.6%) showed progressive disease. The median survival and median progression-free survival were 8.4 and 2.5 months, respectively. The most common toxicities were Grade 3 -4 leukopenia (63.2%) and neutropenia (68.4%). Conclusions: Mitoxantrone at 8 mg/m 2 combined with uracil/tegafur at 300 mg/m 2 /day was determined to be the recommended regimen. Although this regimen was generally well tolerated, it appeared to have little activity against advanced hepatocellular carcinoma. These findings do not support the use of this combination regimen in practice.
Undifferentiated carcinoma of the liveris very rare. A 54-year-old manwasadmitted to our hospital... more Undifferentiated carcinoma of the liveris very rare. A 54-year-old manwasadmitted to our hospital for a detailed examination of multiple liver tumors. These tumors were high or low echoic on ultrasonography, but not enhanced by contrast medium in dynamic computed tomography. A fine-needle aspiration biopsy specimen of the tumor showed undifferentiated carcinoma. The serum level of neuron-specific enolase was high (357 ng/ml) and the immunohistochemical stain of the biopsy specimen was positive for synaptophysin. We diagnosed the patient as having undifferentiated carcinoma of the liverwith neuroendocrine features. The patient was treated with combined systemic chemotherapy: etoposide 100 mg/m 2/day for three days plus cisplatin 80 mg/m 2/day on day one. He achieved a partial response, the duration of which was 7+ months. The serum neuron-specific enolase levels were decreased to the normal range after chemotherapy. Primary liver carcinoma with neuroendocrine features is extremely rare, but in a suspicious case it is important to measure the serum levels of neuroendocrine markers and make a histological confirmation, because chemotherapy may be effective for this disease.
The incidence of pancreatic or biliary tract cancer is increasing in our aging population, but li... more The incidence of pancreatic or biliary tract cancer is increasing in our aging population, but little is known of treatment outcomes in elderly patients with pancreatic or biliary tract cancer. Patients with pancreatic or biliary tract cancer who received chemotherapy in our institute between September 2007 and August 2009 were retrospectively reviewed to compare treatment outcomes between the elderly (aged 75 years or older) and the younger patients. Data were collected of patient backgrounds, adverse events and dose intensity within the first two cycles and overall survival time. Of the 102 who met the inclusion criteria, 19 were elderly who were introduced to full dose chemotherapy. Medication for their comorbidities was required in 15 (79%) of the 19 elderly patients and in 27 (33%) of 83 younger patients. The frequencies of haematological adverse events of grades 3 or 4 were 42% and 39%, and those of non-haematological adverse events were 21% and 16%, for the elderly and younger, respectively. Similar dose intensities were delivered to the elderly and younger. Also, similar proportions of elderly and younger received dose reductions. There was no difference in overall survival between the elderly and the younger. No clear difference in treatment outcomes was seen between the elderly and the younger patients who received gemcitabine alone. Gemcitabine chemotherapy appears to be safe and the same treatment effect was seen even in older patients with pancreatic or biliary tract cancer.
The Hepatobiliary and Pancreatic Oncology Group of the Japan Clinical Oncology Group (JCOG) was c... more The Hepatobiliary and Pancreatic Oncology Group of the Japan Clinical Oncology Group (JCOG) was constituted in April 2008 to develop new standard treatments for hepatobiliary and pancreatic cancer. In pancreatic cancer, the Hepatobiliary and Pancreatic Oncology Group focuses on establishing standard chemotherapy or chemoradiotherapy for unresectable locally advanced disease. The JCOG 0506 study was a Phase II study of gemcitabine alone to examine its efficacy and safety in patients with locally advanced disease. The results in survival significantly exceeded expectations, and gemcitabine monotherapy has come to be regarded as the provisional standard therapy by our group. Following JCOG 0506, the JCOG 1106 study, which is currently under investigation, is a randomized Phase II study to evaluate the efficacy of induction chemotherapy with gemcitabine in combination with S-1 chemoradiotherapy and select a candidate therapeutic agent in a Phase III study comparing with gemcitabine alone. The JCOG 0805 study was a randomized Phase II study comparing S-1 monotherapy with gemcitabine plus S-1 combination therapy for unresectable biliary tract cancer. As a result, gemcitabine plus S-1 combination therapy was considered the more promising candidate in comparison with the gemcitabine plus cisplatin combination therapy in a subsequent Phase III trial. The Hepatobiliary and Pancreatic Oncology Group is planning a Phase III study to compare gemcitabine plus S-1 combination therapy with gemcitabine plus cisplatin combination therapy (JCOG PC1113 study). No standard postoperative adjuvant treatment has been established. We plan to conduct a Phase III study to compare S-1 as adjuvant therapy after surgery with surgery alone in patients with biliary tract cancer (JCOG PC1202).
Objective: To clarify the prognostic factors for patients with obstructive jaundice due to advanc... more Objective: To clarify the prognostic factors for patients with obstructive jaundice due to advanced colorectal and gastric cancers who had undergone percutaneous transhepatic biliary drainage. Methods: Baseline variables and clinical outcomes were evaluated for 92 consecutive patients treated with percutaneous transhepatic biliary drainage. Results: Of the 92 patients, 32 (35%) had colorectal cancer and the remaining 60 (65%) had gastric cancer. Percutaneous transhepatic biliary drainage was successfully achieved in 74 (80%) patients, and 39 of them could receive subsequent chemotherapy. The median survival after percutaneous transhepatic biliary drainage was 273 days in the 39 patients who had undergone successful percutaneous transhepatic biliary drainage and subsequent chemotherapy, 65 days in 35 patients who had undergone successful percutaneous transhepatic biliary drainage but who had not received subsequent chemotherapy and 34 days in the remaining 18 patients who had undergone unsuccessful percutaneous transhepatic biliary drainage (P , 0.001). Multiple liver metastases and hepatic hilar bile duct stricture were independently associated with unsuccessful percutaneous transhepatic biliary drainage. Poor performance status, multiple liver metastases, presence of ascites, multiple prior chemotherapy administrations, undifferentiated type histology and high serum CA19-9 level were independently associated with a poor prognosis. A prognostic index calculated based on the number of these six factors was used to classify the patients into a good-risk group (index 2) (n ¼ 56) and a poor-risk group (index 3) (n ¼ 36). The median survival time and 2-month survival rate for the two groups were 163 and 44 days, respectively, and 85.7 and 33.3%, respectively (P , 0.001). Conclusions: As regards the introduction of percutaneous transhepatic biliary drainage in patients with obstructive jaundice due to colorectal and gastric cancers, careful patient selection might be necessary. A prognostic model seems to be useful for making decisions as to whether percutaneous transhepatic biliary drainage is indicated for particular patients.
Background SM-11355 is a platinum complex developed to treat hepatocellular carcinoma (HCC) via a... more Background SM-11355 is a platinum complex developed to treat hepatocellular carcinoma (HCC) via administration into the hepatic artery as a sustained-release suspension in iodized oil. We conducted a multicenter phase II trial in patients with HCC to evaluate the efficacy and safety of SM-11355, using a Zinostatin stimalamer suspension in iodized oil as a reference. Methods Patients with unresectable HCC were randomized 2:1 to receive administration of the SM-11355 or Zinostatin stimalamer suspension into the hepatic artery. A second injection was given 4-12 weeks later. Efficacy was evaluated by CT 3 months after treatment and categorized as therapeutic T. Okusaka (effect (TE) V to I, where TE V was defined as disappearance or 100% necrosis of all treated tumors. Results A total of 122 patients were evaluated for efficacy and toxicity (SM-11355, n083; Zinostatin stimalamer, n039). Baseline characteristics were similar in the two groups. The TE V rates were 26.5% (22/83) and 17.9% (7/39) in the SM-11355 and Zinostatin stimalamer groups, respectively. In the SM-11355 group,the most frequent drug-related adverse events (AEs) of≥grade 3 were elevated AST, elevated ALT, thrombocytopenia, and hyperbilirubinemia. The AEs with the largest difference between the two groups (SM-11355 vs. Zinostatin stimalamer) were hepatic vascular injury (0 vs. 48.4%) and eosinophilia (84.3 vs. 41.0%). The 2-year and 3year survival rates were 75.9% vs. 70.3% and 58.4% vs. 48.7%, respectively. Conclusions The results suggest that SM-11355 in iodized oil has similar efficacy to Zinostatin stimalamer and that repeated dosing of SM-11355 is possible without hepatic vascular injury in cases of relapse.
Abbreviations & Acronyms mTOR = mammalian target of rapamycin RCC = renal cell carcinoma Abstract... more Abbreviations & Acronyms mTOR = mammalian target of rapamycin RCC = renal cell carcinoma Abstract: A 55-year-old Japanese man was admitted to Oita University Hospital (Oita, Japan) for pyrexia, malaise and dyspnea, and abnormal shadows on chest radiographs. He had started receiving sunitinib (37.5 mg a day for 3 weeks, followed by a 3-week break before beginning the next dosing cycle) for metastatic renal cell carcinoma after the improvement of temsirolimus-induced interstitial pneumonia. Sunitinib is a multiple tyrosine kinase receptor inhibitor approved for the treatment of metastatic renal cell carcinoma, and the most common clinical adverse effects of sunitinib are diarrhea, mucositis, stomatitis, hypertension, rashes and altered taste. We herein report a rare case of sunitinib-related interstitial pneumonia after treatment with temsirolimus for metastatic renal cell carcinoma. This case suggests the possibility of recall phenomenon of drug-induced pneumonia during the administration of additional chemotherapy.
International Journal of Radiation Oncology*Biology*Physics, 2013
S-1 is the first single anticancer agent to be judged non-inferior to gemcitabine in a large-scal... more S-1 is the first single anticancer agent to be judged non-inferior to gemcitabine in a large-scale, randomized, phase III trial for advanced pancreatic cancer, and it can also act as a radiosensitizer. S-1 with concurrent radiation therapy showed very favorable activity, with mild toxicity in patients with Purpose: The aim of this trial was to evaluate the efficacy and toxicity of S-1 and concurrent radiation therapy for locally advanced pancreatic cancer (PC). Methods and Materials: Locally advanced PC patients with histologically or cytologically confirmed adenocarcinoma or adenosquamous carcinoma, who had no previous therapy were enrolled. Radiation therapy was delivered through 3 or more fields at a total dose of 50.4 Gy in 28 fractions over 5.5 weeks. S-1 was administered orally at a dose of 80 mg/m 2 twice daily on the day of irradiation during radiation therapy. After a 2-to 8-week break, patients received a maintenance dose of S-1 (80 mg/m 2 /day for 28 consecutive days, followed by a 14-day rest period) was then administered until the appearance of disease progression or unacceptable toxicity. The primary efficacy endpoint was survival, and the secondary efficacy endpoints were progression-free survival, response rate, and serum carbohydrate antigen 19-9 (CA19-9) response; the safety endpoint was toxicity. Results: Of the 60 evaluable patients, 16 patients achieved a partial response (27%; 95% confidence interval [CI], 16%-40%). The median progression-free survival period, overall survival period, and 1-year survival rate of the evaluable patients were 9.7 months (95% CI, 6.9-11.6 months), International Journal of biology physics www.redjournal.org locally advanced pancreatic cancer. 16.2 months (95% CI,, and 72% (95%CI, 59%-82%), respectively. Of the 42 patients with a pretreatment serum CA19-9 level of !100 U/ml, 34 (81%) patients showed a decrease of greater than 50%. Leukopenia (6 patients, 10%) and anorexia (4 patients, 7%) were the major grade 3-4 toxicities with chemoradiation therapy. Conclusions: The effect of S-1 with concurrent radiation therapy in patients with locally advanced PC was found to be very favorable, with only mild toxicity. Ó 2013 Elsevier Inc.
Social networks can leverage collective intelligence toward understanding complex problems such a... more Social networks can leverage collective intelligence toward understanding complex problems such as environmental sustainability, health and policy. This collective simulation relies on trustworthy systems that empower distributed and open investigation. We present a case study of the development of an application for the collective simulation of global product supply chains (Sourcemap. org).
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Papers by Hiroshi Ishii