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Objective: Hormonal imbalance characterized by excessive production of growth hormone (GH) and a low circulating concentration of insulin-like growth factor (IGF)-1 has been demonstrated in individuals with various serious conditions. However, little is known about changes in the GH-IGF-1 axis in cancer patients., Methods: We prospectively examined the circulating levels of several hormones in 58 patients with solid tumors who were classified according to Eastern Cooperative Oncology Group performance status (PS): PS 0-1, n = 15; PS 2, n = 15; PS 3, n = 15; and PS 4, n = 13. The relations of hormone concentrations, with a focus on the GH-IGF-1 system, to PS were evaluated by Spearman's rank correlation test and regression analysis., Results: The circulating levels of IGF-1, IGF-binding protein-3 and thyroid hormones (total T(3) and T(4)) were inversely correlated with PS score. The concentration of GH was increased irrespective of PS but not statistically significant. The ratio of IGF-I to GH was inversely correlated with PS. The levels of GH and IGF-1 in all patients were also inversely correlated., Conclusions: The present study suggests that the GH-IGF-1 axis is disturbed in patients with cancer.

Purpose: Symptomatic sedation is often required in terminally ill cancer patients and could cause significant distress to their families. The aim of this study was to gather vivid family descriptions about their experiences in palliative sedation therapy., Methods: This report is an additional analysis of a multicenter questionnaire survey. We performed content analysis on 48 statements described by 185 bereaved family members of patients who received palliative sedation therapy., Results: Family members reported guilt, helplessness, and physical and emotional exhaustion when patients received palliative sedation therapy. They were concerned about whether sedated patients experienced distress, wished to know that the maximum efforts had been made, wished to prepare for patient death, wished to tell important things to patients before sedation, wished to understand patients' suffering, and wanted medical professionals to treat patients with dignity., Conclusions: To alleviate family distress, clinicians should understand families' emotional distress, ensure that unconscious patients feel no distress, reassure family members that the symptoms are truly refractory despite maximum efforts for symptom relief, give information and coordinate the situation to enable families to prepare for patient death and to tell important things to patients before sedation, help families to share patients' suffering, and treat patients the same as when they remained conscious.

Symptomatic sedation is often required in terminally ill cancer patients, and could cause significant distress to their family. The aims of this study were to clarify the family experience during palliative sedation therapy, including their satisfaction and distress levels, and the determinants of family dissatisfaction and high-level distress. A multicenter questionnaire survey assessed 280 bereaved families of cancer patients who received sedation in 7 palliative care units in Japan. A total of 185 responses were analyzed(response rate, 73%). The families reported that 69% of the patients were considerably or very distressed before sedation. Fifty-five percent of the patients expressed an explicit wish for sedation, and 89% of families were clearly informed. Overall, 78% of the families were satisfied with the treatment, whereas 25% expressed a high level of emotional distress. The independent determinants of low levels of family satisfaction were: poor symptom palliation after sedation, insufficient information-giving, concerns that sedation might shorten the patient's life, and feelings that there might be other ways to achieve symptom relief The independent determinants of high levels of family distress were: poor symptom palliation after sedation, feeling the burden of responsibility for the decision, feeling unprepared for changes in the patient's condition, feeling that the physicians and nurses were not sufficiently compassionate, and shorter interval to patient death. Palliative sedation therapy was principally performed to relieve severe suffering based on family and patient consent. Although the majority of families were comfortable with this practice, clinicians should minimize family distress by regular monitoring of patient distress and timely modification of sedation protocols, providing sufficient information, sharing the responsibility of the decision, facilitating grief and providing emotional support.

Background: Communication about the ending of anticancer treatment and transition to palliative care is a difficult task for oncologists. The primary aims of this study were to clarify family-reported degree of emotional distress and the necessity for improvement in communication methods when communicating about the ending of anticancer treatment, and to identify factors contributing to the levels of emotional distress and the necessity for improvement., Methods: A multi-center questionnaire survey was conducted on 630 bereaved family members of cancer patents who received specialized palliative care in Japan. A total of 318 responses were analyzed (effective response rate, 62%)., Results: Thirty-nine percent of the bereaved family members reported that they were 'very distressed' in receiving information about the ending of anticancer treatment, and 19% reported 'considerable' or 'much' improvement was necessary in the communication methods. High-level emotional distress was significantly associated with younger patient age, female family gender, the experience of the physician stating she/he could do nothing for the patient, the physician's unwillingness to explore their feelings, and prognostic disclosure of definite survival periods without probabilities or ranges. High levels of perceived necessity for improvement in the communication methods were significantly associated with the experience of the physician stating she/he could do nothing for the patient, physicians not explaining treatment goals in specific terms, physicians not pacing the explanation with the state of family preparation, physicians not being knowledgeable about the most advanced treatments, and the atmosphere not being relaxing enough to ask questions., Conclusions: In receiving the information about ending anticancer treatment, a considerable number of families experienced high levels of emotional distress and felt a need for improvement of the communication methods. The strategies to alleviate family distress could include: (i) assuring that physicians will do their best to achieve specific goals, without saying that they can do nothing for the patient; (ii) providing information, including estimated prognosis, in careful consideration of families' preparation and the uncertainty for each patient; (iii) exploring families' emotions and providing emotional support; (iv) acquiring knowledge about advanced treatments; and (v) making the atmosphere relaxing enough to allow families to ask questions.

About half of patients with cancer will suffer from wasting syndrome, called cancer cachexia, which shows abnormality of homeostasis, nutrition, endocrine function, metabolism, immunity et al. This syndrome is characterized with anorexia and weight loss caused by degradation of skeletal muscle and adipose tissue. Progressive weight loss is responsible not only for a poor quality of life and poor response to anti-cancer drug, but also shorter survival time comparing patient without weight loss. Various factors have been found as mediators of this syndrome base on the development of immunology, biochemistry and molecular and cellular biology. These include several cytokines, proteolysis-inducing factor (PIF), lipid-mobilizing factor (LMF), apoptosis-inducing factor and another factors. Recentry, molecular biological analysis makes clear more detail mechanisms of cancer cachexia syndrome, for example, ubiqutin/proteasome pathway, activation of nuclear transcriptional factors and others. These progresses will contribute not only to establish new treatment but also to carry out "order-made palliative oncology" using DNA-chip and/or Protein-chip in near future.

Hospice palliative care programs are rapidly growing in Japan. Although human science has attached importance comparing with natural science in this field, the latter approaches are recently developed to manage symptoms in terminal patients with advanced cancer. These scientific approaches include basic and clinical studies such as physiology, pharmacology, immunology, biochemistry, molecular biology, medical oncology, psycho-oncology and clinical ethics. These multidisciplinary approaches can clarify not only the mechanisms and relationship between cancer pain, cancer anorexia-cachexia syndrome and neuro-endocrine-immune systems with or without the abnormalities of body fluid, electrocyte balance, glucose-protein-lipid metabolisms but also clinical ethics and decision-making in terminal patients with advanced cancers. Based on these analyses, the strategies to modulate "homeostasis" for improving quality of life and even prolongation of life span could be developed in the near future. Our goal is to establish science-based medical practice for management of symptoms and improving the quality of life through ethical and scientific clinical trials. Hospice-palliative care in cancer would be expected to confirm what the academic area has termed "cancer palliative medicine" or "palliative oncology".

A retrospective analysis was made of elderly cancer patients (pts) who were treated with cancer chemotherapy in our Department of the Cancer Inst. Hosp. There were 180 pts above age 70 years at the start of chemotherapy between July of 1974 and December of 1988. Characteristics of these 180 pts were as follows: (1) 73 years of age in median (70-89 years), (2) 67 pts with malignant lymphoma (37%); 40 with lung ca. (22%), 20 with breast ca. (11%), stomach ca., colorectal ca., multiple myeloma and other; (3) Combination chemotherapy given to 174 pts; (4) OUTCOME: 41 pts (23%) were alive as September of 1989, and autopsy performed in 66 out of 87 pts who died in the hospital (76%). There were no special chemotherapeutic regimens only for elderly pts. Intensity of adequate chemotherapy based on therapeutic protocols was evaluated, dividing pts into two groups: full-dose group and reduced-dose group. Most pts (96%) with small cell lung cancer (SCL) were treated on protocols. For example, 12 elderly pts with SCL were treated with VEC regimen (VCR.VP-16.CTX); eight pts with full-dose and four reduced-dose, and their response rate (CR/PR) of 50%/38% and 25%/75%, respectively, and in 23 younger pts; 20 full-dose and three reduced-dose, and response rate 35%/35% and 33%/33%, respectively. There were 40 pts with acute non-lymphocytic leukemia over 60 years old, treated at Jikei University and in our Department. CR rates of these pts according to age showed a lower percentage with advancing age. Elderly pts with malignancies responsive to chemotherapy should be treated with the same regimen used in younger pts. But doses of each drug have to be adjusted to organ functions of each pt. patients with unresponsive malignancies, must be enrolled in clinical trials, and their responses and toxicities evaluated by age-stratified analysis.

An analog of diarylsulfonylurea, LY 186641 has a broad spectrum activity against murine solid tumors including Colon 26 and LX-1. Preclinical evaluation of the anticancer activity of LY 186641 using the subrenal capsule assay was performed in fresh human tumor samples derived from 87 patients with various cancers and 70 (80%) samples were evaluable. The overall chemosensitivity rate of LY 186641 was 37% and the average tumor growth inhibition rates (TGIRs) of malignant lymphoma, esophageal cancer and colorectal cancer were 51 +/- 19%, 51 +/- 20% and 48 +/- 12%, respectively. The antitumor effect obtained by LY 186641 was comparable to that of the standard anticancer drugs including adriamycin, 5-fluorouracil and cisplatin evaluated in this assay simultaneously. Based upon these results, LY 186641 is considered to have antitumor activity against some human cancers.

Drug resistant phenomenon to antitumor agents remains a major problem in cancer chemotherapy. In this study, we attempted to overcome drug resistance using high-dose chemotherapy with autologous bone marrow transplantation (ABMT). The main regimen consisted of Cyclophosphamide 60 mg/kg/day and thio-TEPA 6 mg/kg/day which were infused for 3 consecutive days. Three patients with malignant lymphoma, four with breast cancer, two with gastric cancer and one with ovarian cancer. All of whom were refractory to conventional chemotherapies were treated. The overall response rate was 70%. Severe bone marrow suppression, mucositis and diarrhea were observed in all patients, but these were not life-threatening and clinically manageable. Furthermore, the administration of granulocyte colony stimulating factor (G-CSF) has significantly (p less than 0.05) shortened the duration of leukopenia, and has been judged to be useful for reducing severe infections and for shortening the period stayed in clean room. Our results indicates that high-dose chemotherapy with ABMT is an effective method for overcoming drug resistance.

Seventeen patients with advanced malignancy were treated with recombinant human granulocyte colony stimulating factor rhG-CSF (KRN 8601) infused intravenously over a period of 30 minutes once daily at the dose level/25 micrograms, 50 micrograms, 100 micrograms, 200 micrograms, 400 micrograms, 800 micrograms/m2 for 14 consecutive days, and the effect was compared to the period without rhG-CSF treatment. The maximum numbers of peripheral leukocyte (granulocyte) showed a dose-related increase and the nadir of leukocyte counts escalated with shortening of the period. After stopping infusion, the neutrophil count dropped to the base line level within two or three days. RhG-CSF did not affect other components of peripheral blood such as monocyte, lymphocyte, eosinophil, and hemoglobin value and platelet counts. Transient bone pain occurred in two patients receiving a dose of 800 micrograms/m2. The biochemical changes detected were increased total alkaline phosphatase activity in serum, which appeared in parallel with the increase of neutrophil numbers, and less elevation of total uric acid values. We conclude that an optimal dose of rhG-CSF is 100 micrograms/m2 (average maximum peripheral granulocyte count, 10799/microliters; nadir granulocyte count, 3772/microliters; period of neutropenia, 2.6 days), and rhG-CSF is useful for acceleration of neutrophil recovery and prevention of infection from chemotherapy.

SM-5887, a new totally synthetic anthracycline derivative was studied in a phase I setting. Twenty-nine evaluable courses of treatment were conducted in groups at doses increasing from 10 to 130 mg/m2. Myelosuppression was the dose-limiting toxicity and a MTD was 130 mg/m2. At 130 mg/m2 the median lowest white blood cell count was 0.7 x 10(3)/cmm (range: 0.3-1.8) and the median lowest granulocyte count was 0.1 x 10(3)/cmm (range: 0-0.7) and the median lowest platelet count was 57 x 10(3)/cmm (range: 4-176). Non-hematologic side effects were mild gastrointestinal symptoms and hair loss. The recommended dose and schedule for phase II setting is 100 mg/m2 every 3 weeks.