[To what extent is it possible to integrated quality of life as a normative, subjective evaluation into scientific medicine?]. / Inwieweit ist Lebensqualität als normative, wertende Grösse in die wissenschaftliche Medizin integrierbar?

Quality of Life is an increasingly popular concept, often associated with a wish to organize therapy along patient-oriented lines. However, determining the quality of life goes beyond a purely descriptive and objective assessment. It is based on subjective evaluation and is influenced by the ability to adapt to miserable conditions. Further conceptual problems consist in the structure of questionnaires and in the fact that there is no consensus about a clear definition of quality of life. The ideal of multidimensionality is restricted by practical limits of acceptable time and tolerable number of questions. Nevertheless most of the modern instruments focus on the patient's well-being and promote the realisation of their individual preferences. The hope is that quality of life will be an additional scale to enhance the established criteria of treatment success like survival time and remission duration. There is the risk to set value-thresholds on life, which appears to be inappropriate. Quality of life assessment may refine the choices of therapeutic aids, but can never solve the difficult moral questions that appertain to the value of life.

[Quality of life and cytokines in oncological therapy]. / Lebensqualität und Zytokine in der onkologischen Therapie.

The development of the hematopoietic growth-factors had a major influence on the treatment of malignant diseases. Quality of Life gets increasingly important in the setting of high-dose chemotherapy and stem cell transplantation. Granulocyte-colony stimulating factor (G-CSF) and erythropoietin (EPO) are two of the most important hematopoietic growth-factors, which contribute to the amelioration of the complications of the malignant disease and the side-effects of the cytostatic treatment. G-CSF reduces the median time of neutrophil recovery, the rate of severe infections and the length of hospitalization. Erythropoietin has a beneficial impact on the quality of life of cancer patients by improving the chronic anemia of cancer, leading to a higher level of physical and social activity, brighter mood, improvement of appetite and general sense of well-being.

Recombinant human erythropoietin for the correction of cancer associated anemia with and without concomitant cytotoxic chemotherapy.

BACKGROUND: Chronic anemia is a common complication in patients with cancer, especially in those with advanced disease or who are under intensive chemotherapy. Because homologous blood transfusions involve some hazards, the safety and efficacy of recombinant human erythropoietin (r-HuEPO) in the treatment of anemic patients with cancer with and without concomitant chemotherapy were studied. METHODS: One-hundred two cancer patients with hemoglobin less than 11 g/dl, ferritin greater than 30 micrograms/l, and creatinine < 220 mumol/l were enrolled in the study, 94 were eligible for efficacy evaluation. Sixty-eight patients received chemotherapy (CT group) and 26 had no cytotoxic cancer treatment (NT group). Recombinant human erythropoietin was administered subcutaneously at a dose of 150 U/kg three times per week for 6 weeks; in nonresponders the dose was doubled for the subsequent 6 weeks. Response was defined as the achievement of a hemoglobin increase of 2g/dl. Clinical and laboratory parameters, including serum erythropoietin (EPO) levels, performance status, and quality of life, were investigated at baseline and monitored at regular intervals thereafter. RESULTS: Response was achieved by 52% and 62% of CT and NT patients, respectively. The highest response rates were observed in patients with lung cancer or with a histology of squamous cell carcinoma (both 80%). In responding patients, the symptoms of anemia subsided. They no longer needed blood transfusions after 4 weeks of therapy; and both their performance status and quality of life improved significantly. The NT patients achieved slightly more favorable results on lower weekly doses: 450 U/kg/week in NT versus 570 U/kg/week in CT patients. Serum EPO levels were higher in nonresponders at baseline and further increased during the course of treatment. Recombinant human erythropoietin was well tolerated by all patients. CONCLUSION: This multicenter study in a large patient collective shows that r-HuEPO treatment represents a safe and effective means to increase the red cell mass and eliminate the need for blood transfusions in approximately 50% of the patients with chronic anemia of cancer. Responding patients not only have increased levels of hemoglobin, but their performance status also improves significantly, and they enjoy a significantly enhanced quality of life.

Prediction of response to erythropoietin treatment in chronic anemia of cancer.

Chronic anemia of cancer can be corrected in approximately 50% of the cases by treatment with recombinant human erythropoietin (rHuEPO). Early prediction of responsiveness would avoid the emotional and financial burden of ineffective medical intervention. Eighty patients with chronic anemia of cancer undergoing treatment with rHuEPO (150 U/kg, 3 times per week by subcutaneous injection; after 6 weeks without response, 300 U/kg) participated in this study. Response was defined as a gain of at least 2 g/dL hemoglobin (Hb) within 12 weeks. Multivariate discriminant analysis and logistic regression analysis of response were performed on routine blood tests; serum levels of EPO, iron, ferritin, transferrin, and its receptor; World Health Organization (WHO) performance status; various cytokines; neopterin; stem cell factor; C-reactive protein; and alpha 1-antitrypsin. At baseline, none of these factors showed sufficient prognostic power. The following predictive algorithm was developed: (1) If after 2 weeks of therapy both the serum EPO level is > or = 100 mU/mL and Hb concentration has not increased by at least 0.5 g/dL, unresponsiveness of the patient is very likely (predictive power, 93%); otherwise, response may be predicted with an accuracy of 80%. (2) If both the serum level of EPO is less than 100 mU/mL and Hb concentration has increased by > or = 0.5 g/dL, response is highly probable (predictive power, 95%). (3) Alternatively, a serum ferritin level of > or = 400 ng/mL after 2 weeks of rHuEPO therapy strongly indicates unresponsiveness (predictive power, 88%), whereas a level less than 400 ng/mL suggests response in 3 of 4 patients.

Quality of life in chronic anemia of cancer during treatment with recombinant human erythropoietin.

BACKGROUND: Improvements in quality of life after treatment with recombinant human erythropoietin (rHuEPO) often have been reported in patients with end-stage renal disease. In patients with chronic anemia of cancer, comparatively few systemic investigations have been performed. METHODS: Various aspects of quality of life were self-reported on linear analogue scales of a slightly modified questionnaire that was first developed to assess toxicity of chemotherapy in patients with breast cancer. Thirty-four patients with chronic anemia of cancer completed 10 items (feelings of well-being, mood, level of activity, pain, nausea, appetite, physical ability, social activities, anxiety, and helpfulness of therapy) before and after 8 and 12 weeks of rHuEPO therapy. RESULTS: Patients with response to the therapy significantly improved after 8 weeks of treatment in some items and after 12 weeks in all items. Patients with no response also had some improvement after 12 weeks of therapy. Hemoglobin levels correlated strongly with mood and appetite. World Health Organization (WHO) performance status improved significantly in patients with response but tended to diminish in those without. Median survival was 4.1 months in patients with no response and 12.0 months in those with response. After 12 weeks of therapy, the scores of the items "physical ability" and "social activities" proved to be significant prognostic factors, which surpassed the prognostic power of the WHO performance status. CONCLUSIONS: The results of rHuEPO therapy in chronic anemia of cancer are far more than cosmetics of laboratory values. They enable the patients with response to lead a physically and socially more active life with less anxiety, brighter moods, and an increased general feeling of well-being.

Recombinant human erythropoietin for the treatment of chronic anemia in multiple myeloma and squamous cell carcinoma.

Recombinant human erythropoietin (rHuEPO) improves chronic anemia of cancer, but the proportion of patients who respond favorably to the treatment varies depending on the type of neoplasia. Preliminary data of the two malignancies with the highest response rates, namely, multiple myeloma and squamous cell carcinoma, are reported. Twenty patients with multiple myeloma and 14 with squamous cell carcinoma, who had presented with hemoglobin levels < 11 g/dl, were treated with rHuEPO, 150 U/kg, three times/week. Response, defined as an increase of at least 2 g/dl hemoglobin within 12 weeks, was achieved by 15 myeloma patients (75%) and 11 patients with squamous cell carcinoma (79%). Tolerance of the treatment was excellent. The WHO performance status and quality of life improved in responders. The remarkably low levels of endogenous EPO in our patients with squamous cell carcinoma, most of whom had been treated with cisplatin-or carboplatin-containing regimens, suggest that anemia in these cases had been at least partly chemotherapy induced. In myeloma patients, the blunted EPO response to the anemic condition may have been partly caused by subclinical tubular insufficiency induced by toxic paraproteins. Future studies should aim to elucidate factors which are responsible for the inability of some patients to respond to rHuEPO treatment, even though in multiple myeloma and squamous cell carcinoma these non-responders are a small minority.

Erythropoietin treatment for chronic anemia of selected hematological malignancies and solid tumors.

BACKGROUND: Neoplasias, especially in their more advanced stages, are often associated with chronic anemia of malignancy which impairs the patient's physical ability and quality of life. PATIENTS AND METHODS: Forty-two patients with chronic anemia associated with hematological malignancies (18 multiple myelomas, 10 myelodysplastic syndromes) or solid tumors (9 breast cancers, 5 colon cancers) were treated with 150-300 units/kg rHuEPO for a median time period of 16 weeks. Response was defined as an increase of the initial hemoglobin level by at least 2 g/dl. RESULTS: The response rates for solid tumors were comparable (44.4% and 40% for breast cancer and colon cancer, respectively), whilst the response in patients with hematological malignancies depended strongly on the disease entity (77.8% for multiple myeloma, 10% for myelodysplastic syndrome). Pretreatment serum levels of endogenous erythropoietin (EPO) were significantly higher in non-responding patients than in responders. During rHuEPO therapy, EPO levels in non-responders increased even further, while they remained basically unchanged in responding patients. In responders, the WHO performance status before the start of rHuEPO therapy was more favorable and showed impressive improvement during the course of treatment. The median survival time of responders was 28.0 months as compared to only 9.2 months for non-responders. Clinical symptoms of anemia subsided or at least considerably improved under successful rHuEPO therapy. With the exception of occasional flu-like symptoms, no undesirable effects of rHuEPO treatment were observed. CONCLUSIONS: In conclusion, rHuEPO treatment corrected anemia of malignancy both in patients with hematologic disease and in those with solid tumors, but responsiveness varied considerably amongst the different disease entities.