Satoru Iwase

Bevacizumab in the treatment of five patients with breast cancer and brain metastases: Japan Breast Cancer Research Network-07 trial

Background Brain metastases from breast cancer occur in 20%–40% of patients, and the frequency has increased over time. New radiosensitizers and cytotoxic or cytostatic agents, and innovative techniques of drug delivery are still under investigation. Methods Five patients with brain metastases who did not respond to whole-brain radiotherapy and then received bevacizumab combined with paclitaxel were identified using our database of records between 2011 and 2012. The clinicopathological data and outcomes for these patients were then reviewed. Results The median time to disease progression was 86 days. Of five patients, two (40%) achieved a partial response, two had stable disease, and one had progressive disease. In addition, one patient with brain metastases had ptosis and diplopia due to metastases of the right extraocular muscles. However, not only the brain metastases, but also the ptosis and diplopia began to disappear after 1 month of treatment. The most common treatment-related adverse events (all grades) were hypertension (60%), neuropathy (40%), and proteinuria (20%). No grade 3 toxicity was seen. No intracranial hemorrhage was observed. Conclusion We present five patients with breast cancer and brain metastases, with benefits from systemic chemotherapy when combined with bevacizumab.

Single center experience of cell-free and concentrated ascites reinfusion therapy in malignancy related ascites.

Cell‐Free and Concentrated Ascites Reinfusion Therapy (CART) is expected to improve patients’ symptoms related to ascites. Use of a patients own proteins in ascites might reduce the risk of infection. However, several reports have described that reinfusion of concentrated ascites might elevate body temperature. The aim of this study is to examine the safety and efficacy of the CART system performed exclusively on patients with malignancies. In this retrospective cohort observational study, we examined 81 CART processes performed on 24 patients with malignancies. Data were collected from medical records and records during processing of ascites. We investigated the effectiveness and adverse events during the procedures. The amount of ascites processed was 2.6 ± 1.4 L on average. The concentration ratio was 9.31 ± 5.45 on average. We found an increase in the urine volume after the procedure, which was significantly related to the amount of reinfused protein. The body temperature increased by 0.44°C. Systolic blood pressure decreased by 4 mm Hg after paracentesis, but no significant difference was found between the pressure before paracentesis and after reinfusion. In platelet counts, no significant change was observed. After all, no clinically significant adverse event was confirmed during CART procedures. Results show that CART can be performed safely even on patients with malignancy‐related ascites and that the procedure might improve diuresis.

Physician-Reported Corticosteroid Therapy Practices in Certified Palliative Care Units in Japan: A Nationwide Survey

BACKGROUND Although corticosteroids are commonly used for symptom relief in the treatment of patients with advanced cancer, few studies have addressed nationwide physician-reported practices and attitudes toward corticosteroid therapy in palliative care settings. DESIGN AND SUBJECTS To clarify physician-reported practices and attitudes toward corticosteroid therapy for anorexia, fatigue, and dyspnea, a 15-item questionnaire was mailed to all 178 certified palliative care units in Japan. RESULTS In total, 124 physicians returned questionnaires (response rate of 70%). The median percentage receiving corticosteroids among all terminally ill cancer inpatients was 80% (fatigue, 80%; anorexia, 80%; dyspnea, 80%). Physicians reported varying methods and attitudes regarding corticosteroid use in palliative care settings. Regarding withdrawal when patient death was imminent, 46% of respondents usually abruptly ceased corticosteroid use, while 33% reduced but did not stop administration, and 21% neither stopped nor reduced corticosteroids. As for dosage, 47% of physicians selected a minimum daily dose for fatigue <2 mg, while 51% chose 2-4 mg. As for administration period, 50% started administering corticosteroids for dyspnea regardless of the prognosis, while 30% regarded a predicted survival of less than 3 months to be an indication for corticosteroid treatment. For side effect management, 48% did not principally prescribe corticosteroids for patients with hyperactive delirium, while 44% cautiously prescribed corticosteroids. CONCLUSION The use of corticosteroids is very common in Japanese palliative care units, but physicians reported varying practices and attitudes regarding administration protocols. Future studies are needed to determine the standard treatment protocol for corticosteroid use in the terminally ill.

Preliminary statistical assessment of intervention by a palliative care team working in a Japanese general inpatient unit.

The effectiveness of intervention by the palliative care team at the University of Tokyo Hospital was assessed using the Support Team Assessment Schedule. During the study, 316 consecutive patients with malignant tumor disease were referred to the palliative care team, which assessed 11 physical symptoms. Results were tested by paired t test to calculate 95% confidence intervals comparing the mean Support Team Assessment Schedule scores for each symptom from the first time to the last time after palliative care intervention. The study concluded that (1) intervention by a palliative care team in general inpatient units can effectively control pain, nausea, and vomiting in patients up until the terminal stage; (2) it is likely that cough is controllable in the terminal stage with intervention by a palliative care team; (3) mouth dryness, anorexia, constipation, diarrhea, fatigue, and ascites are difficult to alleviate in the long term even with palliative intervention.

Effect of Active Hexose-Correlated Compound in Women Receiving Adjuvant Chemotherapy for Breast Cancer: A Retrospective Study

OBJECTIVES Anthracyclines and taxanes are often used as first-line chemotherapy treatments in patients with breast cancer. There are, however, significant toxicity and side effects associated with these therapies. Previous studies have demonstrated that active hexose-correlated compound (AHCC) reduces such side effects. The present study explored the beneficial effects of AHCC on adverse events in patients receiving adjuvant chemotherapy for breast cancer. SUBJECTS Forty-one women who were treated with anthracyclines and taxanes at Nagumo Clinic in Tokyo from October 2004 to March 2011 were selected for this study. OUTCOME MEASURES We compared the occurrence of adverse events in patients who received AHCC with those who did not receive AHCC. Using Fishers exact tests, we also compared the worst-grade adverse events in each treatment cycle. Generalized estimating equations were employed to compare longitudinal changes, and the use of granulocyte colony-stimulating factor, in the two groups was analyzed using Students t-test. RESULTS We found that, compared to the control group, the AHCC group had significantly fewer neutrophil-related events (odds ratio, 0.30; p=0.016), significantly lower use of granulocyte colony-stimulating factor, and a higher (although not significant) rate of adverse events associated with γ-glutamyl transpeptidase. CONCLUSIONS AHCC has the potential to reduce the severity of neutropenia induced by breast cancer chemotherapy and the use of G-CSF during chemotherapy.

The clinical use of Kampo medicines (traditional Japanese herbal treatments) for controlling cancer patients’ symptoms in Japan: a national cross-sectional survey

BackgroundKampo medicines are traditional Japanese medicines produced from medicinal plants and herbs. Even though the efficacy of Kampo medicines for controlling cancer-related symptoms is being reported, their actual nationwide clinical use has not been comprehensively investigated. We aimed to investigate physicians’ recognition of Kampo medicines and their clinical use for cancer patients in the field of palliative care.MethodsA cross-sectional self-administered anonymous questionnaire was distributed to 549 physicians working in palliative care teams at 388 core cancer treatment hospitals and 161 certified medical institutions that have palliative care units (PCUs).ResultsValid responses were obtained from 311 physicians (response rate, 56.7%) who were evenly distributed throughout the country without significant geographical biases. Kampo medicines were prescribed for controlling cancer-related symptoms by 64.3% of the physicians. The symptoms treated with Kampo medicines were numbness/hypoesthesia (n = 99, 49.5%), constipation (n = 76, 38.0%), anorexia/weight loss (n = 72, 36%), muscle cramps (n = 71, 35.5%) and languor/fatigue (n = 64, 32.0%). Regarding open issues about prescription, 60.7% (n = 173) of the physicians raised the issue that the dosage forms need to be better devised.ConclusionsTo increase the clinical use of Kampo medicines, more evidence from clinical studies is necessary. In addition, their mechanisms of action should be clarified through laboratory studies.

Development of a Personal Digital Assistant (PDA) System To Collect Symptom Information from Home Hospice Patients

PURPOSE Previous studies have found that inappropriate assessment of cancer pain can lead to inadequate pain management. To improve assessment, it may be helpful to collect real-time data in a natural environment using computerized ecological momentary assessment (cEMA). Therefore, the aim of the study was to develop a personal digital assistant (PDA) system to collect information on symptoms such as pain and mood states in patients with cancer using cEMA. METHODS Following a pilot study in inpatients with cancer, the second phase of the study involved patients with terminal cancer receiving home hospice care. These patients were asked to record their symptoms in a PDA (a palm-sized portable device) several times per day for a week when they took rescue medications and when an alarm sounded. At the end of the week, an interview on the usability of the device was conducted and overall response rates were calculated. RESULTS Fifteen patients completed the second phase of the study. Their median age was 64 years and the median survival time after the study period was 22 days. The overall response rates were 90.3% to the sound of the alarm and 80.2% after taking rescue medications. The user-friendliness of the device was rated as 8.8 on a scale of 0 (worst) to 10 (best). CONCLUSIONS The cEMA technique using a PDA might be applicable to patients with cancer in palliative care to evaluate symptoms in a natural setting. This system may also be useful for managing symptoms such as pain and mood states in patients with cancer.

Assessment of Cancer-Related Fatigue, Pain, and Quality of Life in Cancer Patients at Palliative Care Team Referral: A Multicenter Observational Study (JORTC PAL-09)

Introduction Cancer-related fatigue greatly influences quality of life in cancer patients; however, no specific treatments have been established for cancer-related fatigue, and at present, no medication has been approved in Japan. Systematic research using patient-reported outcome to examine symptoms, particularly fatigue, has not been conducted in palliative care settings in Japan. The objective was to evaluate fatigue, pain, and quality of life in cancer patients at the point of intervention by palliative care teams. Materials and Methods Patients who were referred to palliative care teams at three institutions and met the inclusion criteria were invited to complete the Brief Fatigue Inventory, Brief Pain Inventory, and European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 15-Palliative. Results Of 183 patients recruited, the majority (85.8%) were diagnosed with recurrence or metastasis. The largest group (42.6%) comprised lung cancer patients, of whom 67.2% had an Eastern Cooperative Oncology Group Performance Status of 0–1. The mean value for global health status/quality of life was 41.4, and the highest mean European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 15-Palliative symptom item score was for pain (51.0). The mean global fatigue score was 4.1, and 9.8%, 30.6%, 38.7%, and 20.8% of patients’ fatigue severity was classified as none (score 0), mild (1–3), moderate (4–6), and severe (7–10), respectively. Discussion Cancer-related fatigue, considered to occur more frequently in cancer patients, was successfully assessed using patient-reported outcomes with the Brief Fatigue Inventory for the first time in Japan. Results suggested that fatigue is potentially as problematic as pain, which is the main reason for palliative care.

Efficacy of Vitamin E Treatment for Hand-Foot Syndrome in Patients Receiving Capecitabine

Capecitabine is a novel oral fluoropyrimidine that is converted within tumor cells to fluorouracil by thymidine phosphorylase [1]. Hand-foot syndrome (HFS) is the most frequent side effect of capecitabine and has been reported in up to 71% of patients receiving a starting dose of 1,250 mg/m2 twice daily [2, 3, 4, 5, 6, 7]. Grade 3 HFS was reported in up to 10–24% of patients. Treatment interruption and, if required, dose reduction usually ameliorate symptoms without compromising efficacy [8, 9]. Supportive treatments such as topical wound care, elevation, and cold compresses may help to relieve pain [10, 11]. Use of systemic corticosteroids, pyridoxine (vitamin B6), and cox-2 inhibitors have been used in patients developing HFS with cytotoxic agents including capecitabine and pegylated liposomal doxorubicin with varying success [11, 12, 13]. Kara et al. [13] from Turkey reported apparent benefit of vitamin E in managing HFS. Therefore we conducted this study to examine the efficacy of vitamin E in managing capecitabine-induced HFS. This retrospective, multicenter study was undertaken between 2005 and 2009 in HER2-negative patients with breast cancer treated with oral capecitabine 828 mg/m2 twice daily on days 1–21 every 4 weeks. Patients with symptoms of grade 2 HFS received oral vitamin E (Tocopherol Acetate, Eisai Pharmaceuticals, Tokyo, Japan) 100 mg/day without chemotherapy dose modification. Patient and treatment-related data, e.g. chemotherapy-related toxicities, dose of vitamin E, severity of symptoms, and tumor response to therapy, were recorded every 4 weeks. Patients underwent a complete der-matological examination at every visit. HFS including pain was graded using the National Cancer Institute Common Terminology Criteria for Adverse Events version 3.0 (NCI-CT-CAE v3.0). Wilcoxon signed rank test was used to examine patient demographics and treatment information. Median time to onset of grade 2 HFS was estimated. Severity of HFS was compared before and after vitamin E administration. We identified 32 patients developing grade 2 HFS during capecitabine therapy between January 2005 and February 2009, who subsequently received vitamin E with or without capecitabine treatment modification. The median time to first onset of HFS was 7.3 months (range 4.1–9.6). The initial starting dose of vitamin E for treatment of HFS was 100 mg/day, and the median dose of vitamin E was 200 mg (range 100–400 mg/day). Vitamin E application had a marked effect on dermatological complications within 7 days of initiation. The effect lasted throughout administration. Desquamation and pain reduced gradually (figs. ​(figs.1]1] and ​and2),2), and the comfort level of the patients improved. Fifteen of 32 patients (46.9%) with HFS experienced symptom improvement with vitamin E (100 mg/day) (p < 0.05; before vs. after 2 months vitamin E administration). Neurological symptoms improved. Thirteen patients still had pain, but this decreased after vitamin E dose escalation to 400 mg/day. The remaining 4 patients had considerable pain interfering with function after vitamin E 100 mg/day, but this reduced after vitamin E dose escalation to 400 mg/day and dose reduction of capecitabine as described previously [14]. Among all 32 patients included, the overall response rate to capecitabine was 37.5%, comprising 2 complete and 10 partial responses. Patients receiving capecitabine and vitamin E (100–400 mg) had longer time to progression than did patients receiving dose reduction of capecitabine (median 10.2 months vs. 6.1 months). Fig. 1 Hand-foot syndrome (HFS) began to disappear after 1 month of vitamin E treatment; 15 of 32 patients (47%) with HFS experienced symptom improvement with vitamin E (100 mg/day) (p < 0.05). Fig. 2 Clinical presentation of hand-foot syndrome. After vitamin E without dose reduction of capecitabine, the skin lesions had disappeared. In this retrospective study, 15 of 32 patients with HFS improved with vitamin E 100 mg/day, suggesting a beneficial effect of vitamin E therapy. Vitamin E is a widely used skin care product and functions as the major lipophilic antioxidant, preventing peroxidation of lipids and resulting in more stable cell membranes. The antioxidant membrane stabilizing effect of vitamin E also includes stabilization of the lysomal membrane, a function shared with glucocorticoids [13]. Systemic vitamin E and glucocorticoids inhibit the inflammatory response and collagen synthesis, thereby possibly impeding the

Oral nutritional support can shorten the duration of parenteral hydration in end-of-life cancer patients: a randomized controlled trial.

Tube feeding or hydration is often considered for end-of-life cancer patients despite the negative effects on quality of life. The efficacy of oral nutritional support in this setting is unknown. We conducted a randomized trial to compare the efficacies of an amino acid jelly, Inner Power® (IP), and a liquid enteral product, Ensure Liquid® (EL), in terminally ill cancer patients. We randomly assigned patients to 3 arms: EL, IP, and EL+IP. The primary endpoint was drip infusion in vein (DIV)-free survival, which was defined as the duration from nutritional support initiation to administration of parenteral hydration. Twenty-seven patients were enrolled in the study, of whom 21 were included in the intention-to-treat analysis. The median age of the subjects was 69 yr. There were significant differences between the arms with regard to the median DIV-free survival (0.5, 6.0, and 4.5 days in the EL, IP, and EL + IP arms, respectively; P = 0.05). The median overall survival was 7, 9, and 8 days in the EL, IP, and EL + IP arms, respectively. IP may shorten the duration of parenteral hydration in terminally ill cancer patients and does not affect their survival.