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Biomedical subjects

Tsuneo Sasaki

Publications and source records attributed to Tsuneo Sasaki.

At least 19 recordsLinked to original sources

[Management of chemotherapy-induced mucositis and diarrhea].

Mucositis is a common complication of cytoreductive cancer chemotherapy. Stomatitis is associated with a higher risk of bacterial infection and treatment-related death. Basic oral care is recommended to reduce the incidence and severity of stomatitis. Recently, new effective prophylaxis against stomatitis has been developed such as human keratinocyte growth factor and AES-14. Gastritis can sometimes cause severe bleeding,and it may be life-threatening. It has been shown that prophylactic H2 blockers or proton pump inhibitors can reduce the incidence and severity of gastric mucosal injury. The risk for chemotherapy-induced diarrhea is significantly greater for chemotherapeutic regimens that contain irinotecan. Intestinal alkalization and Hangeshasin-to a Chinese herbal product are applied in clinical practice in Japan to prevent or reduce irinotecan-induced diarrhea,but careful monitoring,early detection and rapid cure are most important to prevent treatment-related death.

Allopurinol↗

[The present state and future of home care for gastric cancer patients].

Recently, cancer treatment has been shift from inpatient chemotherapy to outpatient chemotherapy, because of various medical circumstances. In chemotherapy of gastric cancer, outpatient chemotherapy was not spread in the last decade, because the chemotherapy protocol of gastric cancer was not fit for outpatient chemotherapy. But the development of new drugs as TS-1 make outpatient chemotherapy more frequent. So home care of patients has been important for management of gastric cancer. Various symptoms due to obstruction at primary lesion or other lesion prevent patients from living at home in gastric cancer. But recently, technical development and spread of home parenteral nutrition make a possible home care of patients with gastric cancer. It is necessary to make a system that supports patient life at home.

Adult↗

[Clinicopathological characteristics of gastric cancer in elderly patients].

Careful consideration must be given to the efficacy of treatment for elderly patients with advanced gastric cancer. Thirty-two elderly patients, 75 years of age or older with gastric cancer, were treated in Tokyo Metropolitan Komagome Hospital,Department of Chemotherapy, between January, 1993 to December, 2002. We analyzed the data of these patients retrospectively. The male/female ratio was 13:3, and 90.6% of the patients developed complications. Some 29 patients were treated with 5-FU regimen. The response rate was 17.2%, median survival time was 201 days, and 5 PR pts had 421 days' survival time. Patients with good PS had long survival times. A comparative study was conducted between 15 cases treated with cisplatin (CDDP) regimen and 14 cases without CDDP. Among them, 13 pts were given a low dose and 16 pts a full dose of chemotherapy (5-FU+/-CDDP). No differences were found between the two groups in overall survival time. No patients showed a severe adverse effect and some exhibited improvement by the chemotherapy. Therefore, the choice of chemotherapy for an elderly gastric cancer patient mostly depends on the patient' s general condition. Elderly patients can develop many complications, so the organ function test should be carefully evaluated. Development of an oral anticancer drug for gastric cancer is in progress and promises to show good results in the near future. Chemotherapy appears able to preserve good "Quality of Life" and will play an important role in the treatment of gastric cancer in elderly patients.

Adenocarcinoma↗

A multicenter and open label clinical trial of zoledronic acid 4 mg in patients with hypercalcemia of malignancy.

BACKGROUND: Hypercalcemia of malignancy is a serious complication of cancer. The objective of this study was to investigate the efficacy and safety of zoledronic acid, a new-generation bisphosphonate and the most potent inhibitor of bone resorption identified to date, for hypercalcemia of malignancy in Japanese patients. METHODS: Patients with hypercalcemia of malignancy, defined as an albumin-corrected serum calcium level > or =12.0 mg/dl, were treated with a single dose of zoledronic acid, 4 mg, by 15 min infusion. Clinical end-points included the proportion of patients with complete response, which was defined as a decrease of corrected serum calcium < or =10.8 mg/dl by day 10, and time to relapse, which is defined as the duration in days between the date of infusion and last available corrected serum calcium <11.6 mg/dl. RESULTS: Twenty-seven patients were enrolled in this study and 25 patients were evaluable for the efficacy of zoledronic acid. The mean corrected serum calcium level decreased from 14.5 to 9.6 mg/dl by day 10. The complete response rate was 84%. The median time to relapse was 23 days, ranging from 0 to 56 days. The most frequently observed adverse event was fever (< or =38 degrees C). Electrolyte abnormalities suspected to be drug related including grade 3 or 4 hypocalcemia, hypophosphatemia and hypokalemia were observed in 11 patients; however, all patients were asymptomatic. No serious adverse events associated with renal toxicity were reported. CONCLUSIONS: Zoledronic acid is well tolerated and is effective for hypercalcemia of malignancy in Japanese patients.

Adult↗

Nonmyeloablative allogeneic stem cell transplantation for patients with unresectable pancreatic cancer.

OBJECTIVES: To clarify whether nonmyeloablative allogeneic stem cell transplantation (NST) can produce the graft versus tumor (GVT) effect in patients with pancreatic cancer. METHODS: A pilot trial of NST was conducted in 5 patients with unresectable pancreatic cancer. Preparative conditioning consisted of administration of 60 mg/kg cyclophosphamide on days 6 and 7 before transplantation, followed by 25 mg fludarabine per square meter of body surface on each of the last 5 days prior to transplantation. Cyclosporine was started 4 days before transplantation. Peripheral blood stem cells from the patients' HLA-identical siblings were transfused into the patients. RESULTS: Complete donor T-cell chimerism in peripheral blood was obtained in 4 patients on day 15 after transplantation. NST resulted in tumor reduction in 2 patients as determined by CT, decreasing levels of tumor markers in 2 patients, pain relief in 2 patients, and a decrease in pleural fluid in 1 patient. Two patients developed acute graft versus host disease (GVHD) of grade II or III and 2 had chronic GVHD involving skin and/or liver. Administration of immunosuppressive drugs for the treatment of GVHD resulted in the elevation of tumor marker levels. CONCLUSION: These findings are the first to suggest that NST induces a GVT effect on pancreatic cancer.

Adult↗

Randomized comparative study of surgical adjuvant chemotherapy using 5-fluorouracil and dl-leucovorin with CDDP, 5-FU and dl-leucovorin for advanced colorectal cancer.

BACKGROUND: 5-fluorouracil (5-FU) is the most useful chemotherapeutic agent for colorectal carcinoma. Recently, the effectiveness of multidrug therapy in modifying the anticancer activity of 5-FU for advanced cases was clarified. We conducted a randomized comparative study of surgical adjuvant chemotherapy comparing cis-diamminedichloroplatinum (CDDP), 5-FU and dl-leucovorin (LV) (PFL therapy) with dl-LV and 5-FU (FL therapy) in patients who underwent curative resection of stage II and III colorectal carcinoma. METHODS: Thirty-one patients, 13 ungergoing PFL therapy and 18 undergoing FL therapy, completed the scheduled administration, while 20 dropped out. Administration schedules were as follows: PFL therapy consisted of 13 mg/m2 CDDP, 300 mg/m2 5-FU and 30 mg/body weight LV for 5 consecutive days. The FL therapy consisted of 300 mg/m2 5-FU and 30 mg/body weight LV for 5 consecutive days in hospital. Both regimens were followed by biweekly administration of the same dosages of LV and 5-FU in an outpatient setting. RESULTS: Seven of 23 patients in the PFL therapy group and five of 28 patients in the FL therapy group experienced recurrence of colorectal carcinomas. Regarding prognosis of stage II patients, both groups showed similar results in 5-year disease specific survival and disease-free survival. However, stage III patients obtained better prognostic results in the FL therapy group than in the PFL therapy group. Major toxicities in these regimens were vomiting and leukopenia, both being more frequent in the PFL therapy group. Symptoms of toxicity resolved completely in all patients. CONCLUSION: From the present study we found that PFL therapy brought no benefit for stage II and III colorectal carcinoma compared with FL therapy. We should search for more appropriate adjuvant therapy, increasing the therapeutic effect of 5-FU + LV for stage II and III colorectal carcinoma.

Adenocarcinoma↗

[In regard to gastric cancer treatment guidelines--a revised edition].

The Japanese Gastric Cancer Association issued a revised edition of gastric cancer treatment guidelines in April 2004. Distinctive features of this revision are adopting newly published literatures after the first edition of the guidelines, laparoscopy-assisted gastrectomy and perioperative management, and illustrating evidence levels in the clinical study of chemotherapy. The treatment protocol of the phase III study is an actual example of this. Gastric cancer treatment in Japan leads the world when considering operation and endoscopic treatment. However, there are only few controlled randomized clinical trials in Japan, and many low quality literatures. On the other hand, an evaluation of the consensus of gastric cancer treatment indicates that it is a high evidence level. Furthermore, a revised edition of chemotherapy was the only one that could be able to show a high evidence level. According to a questionnaire investigation of the revised guidelines, more than 90% of the respondents (the members of Japanese Gastric Cancer Association) have used the guidelines. Hence, the role of the guidelines is important.

Chemotherapy, Adjuvant↗

[Combination chemotherapy for gastric cancer including LV/5-FU].

LV (l-LV)/5-FU therapy has been used broadly and is considered to be a standard treatment for large bowel cancer due to an enhancing therapeutic effect of 5-FU. According to recent clinical study reports on large bowel cancer in Europe and the United States, various administration methods of LV/5-FU with a combination of other drugs have been devised. It appeared that 5-FU used together in bolus and continuous infusions have yielded outstanding results. Although the basis of combination therapy for gastric cancer seemed to be LV/5-FU, there were many reports on TS-1 combined with other drugs because the oral medicine TS-1 was domestically available for the past one or two years. Currently, controlled randomized trials of LV/5-FU therapy and TS-1 have been ongoing. However, when patients cannot take oral intakes, LV/5-FU therapy is important. It seems that LV/5-FU therapy in combination with other drugs, in particular, CDDP, CPT-11, paclitaxel, docetaxel, oxaliplatin, and ETP will be given as candidates for the standard treatment of gastric cancer.

Antineoplastic Combined Chemotherapy Protocols↗

Current topics of S-1 at the 74th Japanese Gastric Cancer Congress.

S-1 (TS-1)-related studies presented at the 74th Japanese Gastric Cancer Congress are reviewed. Of the papers presented at this conference, 35 were related to S-1. In the panel discussion on the therapeutic significance of oral fluoropyrimidines in gastric cancer, 9 papers were related to S-1 (sensitivities to oral fluoropyrimidines, 2 papers; clinical results of treatment with S-1, 5 papers; and combination therapy with S-1, 2 papers). In the general presentations, there were 26 papers on S-1 related-subjects (clinical studies or clinical practice of S-1, 12 papers; case reports, 3 papers; basic studies on animal models of peritoneal metastasis, 2 papers; and combination therapy with S-1, 9 papers). Several studies showed that S-1 was basically as effective against tumors in postmarketing surveillance in clinical practice as in phase II studies at the time of its development, including a report of a patient with complete response to S-1. Some reports suggested the possibility of using S-1 in neoadjuvant chemotherapy and postoperative adjuvant chemotherapy. The usefulness of S-1 in combination chemotherapy was also suggested in several reports. These results indicate that S-1 is a key drug that can be used in first-line treatment of gastric cancer. It will be necessary to accumulate evidence based on data from clinical trials and clinical applications in the future.

Administration, Oral↗

A dose-finding study of glycosylated G-CSF (Lenograstim) combined with CHOP therapy for stem cell mobilization in patients with non-Hodgkin's lymphoma.

BACKGROUND: Peripheral blood stem cell (PBSC) reinfusion has been widely used for hematopoietic reconstitution after high-dose chemotherapy. However, the optimal dose of granulocyte colony-stimulating factor (G-CSF) for PBSC mobilization in combination with chemotherapy for autograft remains unknown. METHODS: To find the optimal dose of glycosylated G-CSF (lenograstim) for PBSC mobilization in combination with chemotherapy for aggressive non-Hodgkin's lymphoma (NHL), we conducted a dose-finding study on 43 newly diagnosed patients who had unfavorable prognostic factors. They received four to six courses of cyclophosphamide, doxorubicin, vincristine and prednisolone combined with lenograstim every 2 weeks (biweekly CHOP therapy). PBSC apheresis was started after the third course of biweekly CHOP therapy. Lenograstim was given daily from day 3 until the day of the last apheresis. The optimum dose of lenograstim was assessed based on mobilization efficacy and safety profiles at a daily single dose of 2, 5 and 10 microg/kg for eight patients in each level. RESULTS: The collected number of CD34+ cells in the first apheresis products was higher in the 5 microg/kg group than in the 2 microg/kg group (median, 4.22 x 10(6) vs 2.49 x 10(6) CD34+ cells/kg, P = 0.051). The highest dose of 10 microg/kg (median, 2.99 x 10(6) CD34+ cells/kg) failed to show a dose dependence in PBSC mobilization. The efficacy and safety of the 5 microg/kg dose were further confirmed in an additional 19 patients. CONCLUSIONS: The present study suggests that the recommended dose of lenograstim for PBSC mobilization with CHOP therapy in untreated NHL is 5 microg/kg.

Adjuvants, Immunologic↗

Phase I dose-escalation trial of ZD9331 in Japanese patients with refractory, solid malignancies.

BACKGROUND: ZD9331 is a novel thymidylate synthase inhibitor that, unlike some other antifolates, does not require polyglutamation for activity. This phase I dose-escalation trial investigated the tolerability, efficacy and pharmacokinetics of ZD9331 in Japanese patients with refractory, solid malignancies. PATIENTS AND METHODS: The mean age of patients was 57.6 years, and the most common primary tumours were gastric and colorectal cancer. Most patients had received prior chemotherapy and/or surgery. ZD9331 (69, 108 and 130 mg/m2/day) was administered as a 30-min i.v. infusion on days 1 and 8 of a 3-week cycle. RESULTS: A total of 18 patients received ZD9331 treatment; six at each dose level. Patients received a median of 2 cycles of treatment ZD9331 demonstrated some antitumour activity, with one-third of patients showing no significant change in tumour size. ZD9331 was associated with non-dose-dependent myelosuppression, and dose-limiting toxicity was observed in one patient given 69 mg/m2/day and one patient given 130 mg/m2/day. The maximum plasma concentration and total area under the concentration-time curve increased with ZD9331 dose, whereas other pharmacokinetic parameters remained constant and independent of dose. Pharmacokinetic parameters were comparable following day 1 and 8 doses, with no accumulation of ZD9331 following the second dose. CONCLUSION: ZD9331 has a manageable toxicity profile and shows some evidence of activity in Japanese patients with refractory, solid malignancies. The pharmacokinetic profile of ZD9331 in Japanese patients is similar to that observed in Western patients.

Adult↗

[Discussion for gastric cancer treatment guidelines in Japan].

The Japan Gastric Cancer Association issued the first version of Gastric Cancer treatment guidelines in March 2001 and those for patients in December 2001. These guidelines aim to reduce differences in treatment selection by institutions and doctors by to provide standard indication for doctors and patients. This guidelines show treatment indications according to the clinical stages of disease. If doctors are planning to offer treatments different from those in the guidelines, they are expected to explain the reasons for this difference to patients. The advantages and disadvantages of the guidelines had been discussed in developing committee and symposium of Japanese gastric cancer association. In these guidelines for patients, [there is no evidence to prevent gastric cancer by Helicobacter pylori eradication.]. But, many studies have yielded a positive relationship between Helicobacter pylori and gastric cancer. These gastric cancer treatment guidelines are significant in every respect, especially medical care and informed consent. Treatment guidelines should be revised associated with developments in the treatment of gastric cancer.

Helicobacter Infections↗

[Hepatotoxicity of chemotherapy].

Patients who will receive chemotherapy require careful assessment of liver function prior to treatment to determine which drugs are not appropriate, and which drug need dose modification. Many medications, alcohol has their more or less hepatotoxic effect, so because of their immunocompromise state, some body are prone to liver infection, including viral hepatitis. Lamivudine is effective in treating hepatitis B reactivation during chemotherapy. Now, the increased use of high-dose regimens with bone marrow or stem-cell support has been shown the drugs toxicities complication more, which does not observed in with conventional doses. Clinical judgment and a high index of suspicion remain critical tool in preventing and treating hepatic manifestations of cancer chemotherapy.

Antineoplastic Agents↗

[Hepatotoxicity of chemotherapy].

Patients who will receive chemotherapy require careful assessment of liver function prior to treatment to determine which drugs are not appropriate, and which drugs need dose modification. However, if the hepatic parenchymal abnormalities are caused by an underlying neoplasm and the neoplasm is sensitive to the drugs, it may not be necessary to reduce the dose. Clearly, this is an area where clinical judgment must be used to assess the risk/benefit ratio. Treatment of chronic hepatitis B virus (HBV) involves either the nucleoside analogue lamivudine or interferon alpha. The advantage of lamivudine includes limited adverse effects and the fact that histological improvement has been documented in the majority of patients. Primary prophylaxis with lamivudine may be a well tolerated and effective method to reduce the frequency of chemotherapy-induced HBV reactivation in chronic HbsAg carriers. HbsAg screening is necessary before beginning chemotherapy for non Hodgkin's lymphoma patients. However, the main problem with long-term lamivudine therapy is the emergence of genotypic resistance because of base pair substitution at specific sites within the YMDD locus of the DNA polymerase gene. Significant hepatic dysfunction is uncommon among hepatitis C virus (HCV) infected patients treated with chemotherapy for hematological malignancies. However, infection with elevated AST levels is a significant risk factor for veno-occlusive disease after hematopoietic stem cell transplantation. Clinical judgment and a high index of suspicion remain critical tools in preventing and treating hepatic manifestations of cancer chemotherapy.

Antineoplastic Agents↗

[Rituximab].

CHOP has been the standard chemotherapy for aggressive non-Hodgkin's lymphoma (NHL). However, indolent NHL remains largely an incurable diseases, with nearly static overall survival, and only 40% of patients with aggressive NHL are cured by CHOP. Monoclonal antibodies are an exciting advance in the treatment of lymphoma. Rituximab is a mouse/human chimeric monoclonal antibody that targets the CD20 antigen found on the surface of malignant and normal cells of the B-cell lineage, but not on primitive stem cells or mature plasma cells. Rituximab is safe and well-tolerated, and exhibit little cross-resistance with conventional chemotherapeutic agents. Clinical trials with rituximab indicate that the drug has broad application to NHL, although further clarification is needed to determine its optimal use in many of these clinical settings. In indolent NHL, rituximab has shown useful response rates, both as first-line therapy in relapsed disease. In aggressive lymphomas, diffuse large B-cell lymphoma is the most common form, the addition of rituximab to CHOP chemotherapy significantly lengthens disease-free and overall survival compared to CHOP alone as first line therapy, at least in elderly patients. These included combination with chemotherapy, prolonged or increased dosing regimens, and maintenance therapy, in which rituximab is administered to patients in remission to eliminate minimal residual disease and reduce the risk of relapse. Rituximab in vivo purging and maintenance is also being evaluated in autologous transplantation setting. Newer agents, including radiolabelled antibodies, Immunotoxin-linked antibodies and antibodies against novel target antigens are being tested in on-going clinical trial.

Antibodies, Monoclonal↗

[Gastrointestinal cancer].

Ten patients with refractory gastrointestinal cancer received nonmyeloablative allogeneic stem-cell transplantation(NST) from HLA-identical sibling. The conditioning regimen consisted of cyclophosphamide and fludarabine. None of the patients rejected the allograft. Five patients developed grade II-III acute GVHD and 5 patients developed extensive chronic GVHD. Three patients achieved remarkable serum tumor marker regressions after the steroids were discontinued, which were attributed to graft-versus-tumor (GVT) effects. One patient achieved a partial response, and three patients had stable disease. At a median follow up of 155.5 days (52-349), 2 patients are alive and 8 patients died for progressive disease. NST for refractory gastrointestinal cancer was feasible. Although GVT effects against gastrointestinal cancer were observed, the effects were limited for highly progressive disease.

Adult↗