Search PubMed⌕ Search

Biomedical subjects

Keisuke Aiba

Publications and source records attributed to Keisuke Aiba.

14 recordsLinked to original sources
PubMed2006

Breast-conserving surgery after chemotherapy: value of MDCT for determining tumor distribution and shrinkage pattern.

OBJECTIVE: For this study, we investigated the usefulness of MDCT in assessing the extent of residual breast cancer after neoadjuvant chemotherapy. To ensure the success of breast-conserving surgery, we evaluated the usefulness of determining the tumor distribution before neoadjuvant chemotherapy and the shrinkage pattern after neoadjuvant chemotherapy. SUBJECTS AND METHODS: MDCT before and after neoadjuvant chemotherapy was performed in 46 consecutive patients with 47 locally advanced breast cancers. The distribution pattern of contrast enhancement on MDCT before neoadjuvant chemotherapy was classified into five categories: solitary lesion, grouped lesion (localized lesion with linear, spotty, or linear and spotty enhancement), separated lesion (multiple foci of contrast enhancement), mixed lesion (grouped lesion with multiple foci), and replaced lesion (diffuse contrast enhancement in whole quadrants). RESULTS: There was agreement between the MDCT assessment and pathologic findings in 44 (94%) of the 47 tumors. In the partial response group with nonreplaced lesions, MDCT revealed three shrinkage patterns: pattern 1a, concentric shrinkage without surrounding lesions; pattern 1b, concentric shrinkage with surrounding lesions; and pattern 2, shrinkage with residual multinodular lesions. Breast-conserving surgery was performed successfully in 14 patients including complete response cases that were detected on the basis of MDCT findings and partial response cases that were detected on the basis of observation of pattern 1 shrinkage. In all five patients with pattern 2 shrinkage, CT underestimated the residual tumor extent by more than 2 cm. CONCLUSION: MDCT classification of tumor distribution before neoadjuvant chemotherapy and of shrinkage patterns after neoadjuvant chemotherapy is important in the preoperative evaluation of patients undergoing breast-conserving surgery.

Adult↗
PubMed2005

[Current status and problems in the chemotherapy of our outpatient clinic in the department of clinical oncology].

The department of clinical oncology performed an analysis of the current situation and problems inherent to 4500 chemotherapies of the outpatient clinic for the last 20 months using a new department of the outpatient clinical treatment. Divided into primary organs and the application of chemotherapy are as follow: breast cancer 49%, and gastrointestinal cancer 47% (esophageal cancer 4%, stomach cancer 28%, colorectal cancer 15%) and others 4%. In terms of time consumed by chemotherapy, there were differences in the tumors, regimens and ages. Within one hour, 40% of all chemotherapies mainly included those of breast cancers. From one to two hours, 40% included half breast cancers and half gastro-intestinal cancers, two to three hours, 15% the same as one to two hours. Over 3 hours, 5% mainly include those of gastro-intestinal cancers. In outpatient clinical chemotherapy, there were no human errors such as the use of wrong drugs and wrong intravenous injections. There were a few patients with adverse effects of chemotherapy including high fever with bone marrow suppression and severe diarrhea, who had an emergency admission to the hospital. As we perform an outpatient clinical chemotherapy with safe, it is important to coordinate with family doctors. To decrease the patients' effort of outpatient clinic, we request the treatment of high fever and the dose of G-CSF for bone marrow suppression to family doctors. The outpatient clinical chemotherapy enables to offer the suitable tailor-made treatment for each individual and to control the adverse effects of any regimen. But, patients' waiting period is still longer due to lack of numbers of doctors. To improve these statuses, careful consideration will be required for the trusting relationship with paramedical staffs' in the Department of Clinical Oncology.

Adult↗
PubMed2004

Successful combination therapy with trastuzumab and Paclitaxel for adriamycin- and docetaxel-resistant inflammatory breast cancer.

We present a case of adriamycin-and docetaxel-resistant inflammatory breast cancer (IBC) in which partial response was achieved with combination therapy using trastuzumab and paclitaxel. A 48-year old woman noticed a lump in her right breast. She was diagnosed with IBC and the disease was staged as T4d N1 M0, stage III B. The patient was started on neoadjuvant chemotherapy with adriamycin (50 mg/m2) and docetaxel (60 mg/m2) administered every three weeks. Six courses were performed and the response was evaluated as no change. After one month, contralateral breast swelling indicated bilateral IBC. Bilatera1 mastectomy using the Halsted method was performed. The immunohistochemical results of the Hercep Test was strongly positive (3+). After the mastectomy, right pleural effusion appeared, and cytological examination revealed the cells to be classV(adenocarcinoma). To treat the clinically advanced breast cancer, combination therapy with trastuzumab (initially 4 mg/kg followed by two or more cycles of 2 mg/kg) and paclitaxel (80 mg/m2) were given intravenously every week for eight cycles and then every two weeks thereafter. A total of 32 courses of therapy were performed, the pleural effusion completely disappeared and partial response was maintained for a duration of 482 days. The adverse reactions were mild, and it was possible for her to be treated as an outpatient with high quality of life. This report suggests that weekly combination therapy of trastuzumab and paclitaxel was useful for treatment of adriamycin-and docetaxel-resistant metastatic breast cancer.

Antibodies, Monoclonal↗
PubMed2004

Phase I and pharmacokinetic study of KW-2170, a novel pyrazoloacridone compound, in patients with malignant tumors.

PURPOSE: The primary purposes of this study were to determine the dose-limiting toxicity (DLT) and maximum tolerated dose (MTD), to recommend a dose for phase II studies, and to analyze the pharmacokinetics of KW-2170. A secondary purpose was to assess tumor response to KW-2170. EXPERIMENTAL DESIGN: KW-2170 was given as a 30-min i.v. infusion every 4 weeks. Doses were escalated from 1.0 mg/m2 according to a modified Fibonacci method. RESULTS: A total of 45 cycles of KW-2170 were delivered to 41 patients at doses ranging from 1.0 to 53.0 mg/m2. The primary DLT was neutropenia which was observed in two of six patients treated at 32.0 mg/m2 and in two of two patients treated at 53.0 mg/m2; therefore, the MTD was 53.0 mg/m2. Although no patients showed a complete response (CR)or partial response (PR), 15 patients were evaluated a shaving freedom from progression at the 1-month time-point, with two demonstrating slight tumor shrinkage in their metastatic lesions. None of the patients experienced significant cardiotoxicity. The plasma concentration of KW-2170 declined in a triphasic manner. The half-life, total clearance (CLtot) and volume of distribution (Vdss) were nearly constant and independent of dose, and showed a relatively small interpatient variability. A linear relationship was observed between dose and maximum plasma concentration (Cmax) and area under the concentration-time curve (AUC 0-infinity). In addition, there was a good correlation between neutropenia and AUC 0- infinity. This suggests that toxicity may be dependent on systemic exposure to the drug. Two oxi-dative metabolites were observed in the patients' plasma and urine. CONCLUSIONS: The primary DLT of KW-2170 in this study was neutropenia, with a MTD of 53 mg/m2.A significant linear relationship was observed between neutropenia and AUC 0- infinity. We estimate the recommended dose for phase II studies to be 41.0 mg/m2.

Acridines↗
PubMed2004

[Chemotherapy].

Cancer chemotherapy in the treatment of colorectal cancer has been evolving so extensively than ever. 5-fluorouracil (5-FU) has been a pivotal and a single active agent in the treatment of colorectal cancer. Reproducing and consistent better response rate has been shown since the introduction of the concept of biochemical modulation of 5-FU by leucovorin, a reduced folate, to the clinic and a combination chemotherapy of 5-FU and leucovorin (FL) has enable us to obtain a response rate around 20-30% and a median survival time ranging from 10 to 12 months. IFL regimen combing CPT-11 with FL showed a better MST ranging from 14 to 15 months, but now serious toxicity precludes general use outside of clinical trials. In the Europe, de Gramont regimen, an unique dose and schedule of 5-FU using a combination of continuous intravenous infusion of 5-FU with leucovorin over two days and bolus infusion of 5-FU twice over the same period, has been developed and shown improved antitumor activity and toxic profiles. FOLFOX 4, a combination chemotherapy of de Gramont regimen and oxaliplatin which is a third generation of cisplatin and a uniqe toxic profile with neuropathy, has demonstrated improved MST over a year and acceptable toxic profiles. Now FOLFOX 4 is considered to be a standard chemotherapy for the patients with advanced colorectal cancer, since a large phase III randomized study has shown that FOLFOX 4 was the most active and less toxic treatment regimen among active regimens such as IFL and IROX (CPT-11 and oxaliplatin). More recently, a combination of IFL and bevacizumab which is one of the molecular target agents and a antibody agent against vascular endothelial growth factor (VEGF), has demonstrated better MST reaching 20 months. Future large scale trials will attempt to develop more active regimen incorporating so-called molecular target agents.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2003

Severe infusion reaction induced by trastuzumab: a case report.

We report a case of a severe infusion reaction caused by trastuzumab. A 59-year-old woman with metastatic breast cancer was treated with trastuzumab. During the first infusion, initial symptoms such as severe headache and general fatigue developed. Blood pressure fell 90 minutes after these initial symptoms. A collapsed lung was demonstrated by chest X-ray and computed tomography. Steroid therapy was successfully used for these reactions. Careful monitoring of vital signs, examination of the respiratory system, and the use of steroids are recommended for severe infusion reaction.

Anaphylaxis↗
PubMed2003

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↗
PubMed2003

[Globalization of clinical trials].

Based on reviews of the Japanese clinical trial situation in lung cancer, gastric cancer, prostate cancer and breast cancer, it was clear that much progress has been made in short time. There are considerable differences between Japan and the West and also differences between clinical areas in Japan. For regulatory purposes bridging studies have become increasingly important. Use of identical protocols are required for effective bridging. Participations in global phase III trials is the best way of achieving registration in Japan. For successful global trials in Japan it is important to include Japanese investigators in the preparation of the protocol and to recognise the challenges facing such a project. Clinical practice in diagnosis and treatment have many differences, thus it is recommended to have clear and detailed information in the protocol. Hard end points like survival are important since they are not biased by cultural differences. There are clear difficulties with HE or QOL outcomes. The emergence of focus on evidence based medicine is also happening in Japan and will help to harmonize documentation across the world. For large adjuvant or prevention cancer global trials are essential. To facilitate global studies further development of infrastructure is necessary in Japan. Use of electronic data capture web based communication etc. will help overcome communication difficulties. Other improvements that will make Japanese participation in global trials easier and better include establishment of clinical trial centre at each hospital, introduction of trial coordinators or study nurses and an improved collaboration with company staff. A critical issue that also need addressing is agreement of centre target recruitment. We need to introduce a new flexible system in Japan if participation in global trial is to be optimised. If we can address these issues Japanese investigators and collaborative groups should be able to initiate and lead global trials in the future.

Antineoplastic Agents↗
PubMed2003

[Adverse reactions of cancer chemotherapy and fluid replacement].

Clinical oncologists and physicians handling anticancer drugs need to be thoroughly aware of anticancer drug adverse reactions, and have all the necessary skills to deal with such events if they occur. This chapter discusses anticancer drug adverse reactions requiring fluid replacement. Adverse reactions that require fluid replacement are in general considered serious. Most are at least grade 3 events (serious/high toxicity) based on the NCI-CTC ver 2 classification and require immediate treatment. Here we discuss the general view of fluid replacement for dehydration caused by gastrointestinal toxicity, fluid replacement for nephrotoxicity, hemorrhagic cystitis, tumor lysis syndrome that sometimes requires substantial fluid replacement and SIADH that is a condition requiring a prudent approach to fluid therapy, including also specific methods of fluid replacement.

Antineoplastic Agents↗
PubMed2002

Irinotecan hydrochloride for the treatment of recurrent and refractory non-Hodgkin lymphoma: a single institution experience.

BACKGROUND: Irinotecan hydrochloride (CPT-11) has a broad range of antitumor activity and has demonstrated little cross-resistance with doxorubicin or vincristine. In the current study, the authors investigated the efficacy and adverse effects of irinotecan in the treatment of recurrent and refractory non-Hodgkin lymphoma, for which current therapies appear to be unsatisfactory. METHODS: Irinotecan was administered by intravenous infusion at a dose of 40 mg/m(2)/day for 3 days, and this regimen was repeated 2-3 times at weekly intervals, followed by 2 weeks off therapy. The subjects were 48 patients with recurrent or refractory non-Hodgkin lymphoma. The histologic classification (Working Formulation) was low grade in 8 patients, intermediate grade in 36 patients, high grade in 1 patient, and other (angiocentric lymphoma, Ki-1 lymphoma, and unidentified) in 3 patients. RESULTS: Forty-five patients were determined to be evaluable. Therapy resulted in a complete disease remission in 2 patients and a partial remission in 15 patients. The response rate was 37.8%. The median duration of response was 64 days and the median time to disease progression was 77 days. The median survival time was 422 days. Major adverse reactions included myelosuppression and gastrointestinal toxicity. Leukopenia, anemia, and thrombocytopenia of Grade 3 or 4 (according to the National Cancer Institute Common Toxicity Criteria) was observed in 63.0%, 30.4%, and 6.5% of the patients, respectively, and Grade 3 or 4 diarrhea occurred in 30.4% of patients. Treatment was withdrawn because of diarrhea in three patients. Because of myelosuppression and diarrhea, approximately 67% of the patients required changes to the regimen, including dose reduction, prolongation of the interval between treatments, and reducing the number of days of consecutive treatment. CONCLUSIONS: The results of the current study suggest the activity of irinotecan as salvage therapy for patients with recurrent and refractory non-Hodgkin lymphoma. However, the optimum dosing schedule remains to be determined.

Adolescent↗
PubMed2002

[Globalization of anti-cancer therapies].

Based on short reviews of lung, gastric, colorectal, prostate, breast and ovarian cancer, there remain significant differences between Japan and the West in the therapeutic regimen for most cancers. Some of the differences are due to differences in stage of disease at diagnosis or historical factors affecting availability of products. In both Japan and the West, there are initiatives to prepare treatment guidelines based on published data. For Japan this initiative is limited by the lack of Japanese clinical trial data or even safety data. When guidelines are prepared from international data, many of the products have limited indications in Japan and therefore not reimbursed. Availability of the most appropriate therapies to Japanese patients will depend on a facilitation of clinical trials in both primary and additional indications. However, the experience in other countries is that, even where data and registration approval are available, guidelines are hard to agree and are not uniformly accepted by prescribers. The ICH E5 guideline on the use of bridging studies to interpolate Western data to Japanese regulatory dossiers provides an opportunity to accelerate availability of new medicines to Japanese prescribers and patients. The use of bridging studies has so far been limited for anti-cancer therapies. Where relevant pharmacodynamic endpoints can be measured, (e.g. aromatase inhibition) there can increase confidence in bridging. The newer types of agent which act to stabilise disease rather than tumour shrinkage present a special problem. In some cases surrogate markers can be valuable but in each case they need to be validated. As globalization continues, an alternative approach is to include a significant cohort of Japanese patients in Japanese patients but this depends on sufficient similarity in the patient population and background therapy. The most significant limitation to either large outcome studies in Japan or for Japanese centers to join international trials has been the environment for conduct of clinical trials. There have been some recent improvements and further progress is expected so that Japanese doctors can play a full role in the evaluation of new therapies.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2002

[Pancreatic islet cell carcinoma with multiple hepatic metastases successfully treated with a streptozocin/5-FU regimen--a case report].

A 53-year-old woman was hospitalized because of lientery and steatorrhea. CT scans revealed a pancreatic head tumor along with multiple liver tumors. The pancreatic head tumor had spread to the duodenum. Following tumor biopsy with gastrointestinal fiberscopy, we diagnosed a pancreatic malignant islet cell tumor with multiple liver metastases. Since there was no clinical evidence of recognized endocrinopathy, we diagnosed "nonfunctioning" tumor. At first we administered only 5-FU at a dose of 370 mg/m2/day continuously for two weeks. However, neither the pancreatic head tumor nor the metastatic liver tumors changed in size. We then administered streptozocin and 5-FU at doses of 1,000 mg/m2 and 370 mg/m2, respectively, every week. The patient received a total of 10 g/m2 of streptozocin. After this treatment, the enlarged metastatic liver tumors were reduced in size, with marked improvement in liver enzyme. Toxic reactions to this regimen were mild. Only grade 1 nausea and alopecia were observed during the treatment. No hematological toxicity was observed, nor, with sufficient diuresis, was nephrotoxicity, demonstrating that this regimen can be administered safely.

Antineoplastic Combined Chemotherapy Protocols↗
PubMedDate not supplied

Histologic breast cancer extent after neoadjuvant chemotherapy: comparison with multidetector-row CT and dynamic MRI.

PURPOSE: To evaluate the efficacy of dynamic multidetector-row CT (MDCT) in assessing residual cancer extent after neoadjuvant chemotherapy (NAC), and to compare MDCT results with those derived from dynamic three-dimensional MRI using the volumetric interpolated breath-hold examination (VIBE) sequence. MATERIALS AND METHODS: MDCT before and after NAC was performed in 19 consecutive patients with breast cancer. MRI was also performed before surgery. The early phase of MDCT and MRI was started 60 sec after commencing contrast injection. The late phase was started at a 4-min delay from the injection. The injection rate was 3 mL/sec. The distribution pattern of contrast enhancement (CE) by CT before NAC was classified into two groups: replaced lesion (diffuse CE in whole quadrants) and non-replaced lesion (localized CE). RESULTS: Pathological complete response (pCR) was obtained in one case. In replaced lesions, accuracy for the detection of tumor extent with a deviation of less than 2 cm in length was 0% (0/7) with early-phase CT/MRI and 100% (7/7) with late-phase CT/MRI. In non-replaced lesions, accuracy was 55% (6/11) with early-phase CT/MRI and 82% (9/11) with late-phase CT/MRI. One case of ductal carcinoma in situ (DCIS) could be detected only with late phase MRI. CONCLUSION: Late-phase images obtained by MDCT and MRI may be accurate in the diagnosis of residual cancer extent after NAC. The tumor distribution determined by MDCT before NAC is thought to be useful in the evaluation of shrinkage pattern following NAC.

Adult↗