Oncological resource allocation in Germany.

BACKGROUND: Oncology is a resource-intensive medical discipline where, so far, effectiveness rather than efficiency of a treatment has stood in the foreground. The aim of our study was, therefore, to determine the resource allocation and to assess the efficiency of oncology in Germany for the period of 2002-2004. MATERIALS AND METHODS: With the aid of the official German Health Report, the expenditures for health in 2004 and the gain in years of life according to ICD 10 disease categories were analyzed. Based on the incremental costs and years of life gained, the cost calculation per year of life gained was made. RESULTS: Malignant neoplasms appear in 5th place in health expenditures at a cost of 15 billion 1. With costs per year of life gained of 140,750 1, malignant neoplasms range ahead of respiratory diseases (52,500 1)digestive diseases (27,455 1), and injuries (14,538 1). Costs involving malignant neoplasm per year of life gained range between 39,000 1(malignancies of the lip, oral cavity, and the pharynx), and 126,000 1(digestive organ cancer). CONCLUSION: In Germany, oncology incurs higher costs per year of life gained as compared to several other diseases. Also, in malignant neoplasm considerable differences can be observed regarding resource allocation and efficiency.

Oral naloxone reverses opioid-associated constipation.

Opioid-related constipation is one of the most frequent side effects of chronic pain treatment. Enteral administration of naloxone blocks opioid action at the intestinal receptor level but has low systemic bioavailability due to marked hepatic first-pass metabolism. The aim of this study was to examine the effects of oral naloxone on opioid-associated constipation in an intraindividually controlled manner. Twenty-two chronic pain patients with oral opioid treatment and constipation were enrolled in this study. Constipation was defined as lack of laxation and/or necessity of laxative therapy in at least 3 out of 6 days. Laxation and laxative use were monitored for the first 6 days without intervention ('control period'). Then, oral naloxone was started and titrated individually between 3x3 to 3x12 mg/day depending on laxation and withdrawal symptoms. After the 4-day titration period, patients were observed for further 6 days ('naloxone period'). The Wilcoxon signed rank test was used to compare number of days with laxation and laxative therapy in the two study periods. Of the 22 patients studied, five patients did not reach the 'naloxone period' due to death, operation, systemic opioid withdrawal symptoms, or therapy-resistant vomiting. In the 6 day 'naloxone' compared to the 'control period', the mean number of days with laxation increased from 2.1 to 3.5 (P<0.01) and the number of days with laxative medication decreased from 6 to 3.8 (P<0.01). The mean naloxone dose in the 'naloxone period' was 17.5 mg/day. The mean pain intensity did not differ between these two periods. Moderate side effects of short duration were observed in four patients following naloxone single dose administrations between 6 and 20 mg, resulting in yawning, sweating, and shivering. Most of the patients reported mild or moderate abdominal propulsions and/or abdominal cramps shortly after naloxone administration. All side effects terminated after 0.5-6 h. This controlled study demonstrates that orally administered naloxone improves symptoms of opioid associated constipation and reduces laxative use. To prevent systemic withdrawal signs, therapy should be started with low doses and patients carefully monitored during titration.

Premenopausal breast cancer: chemotherapy and endocrine therapy.

Modern treatment of premenopausal breast cancer is based on well-established prognostic and predictive factors for disease outcome such as nodal status, hormone receptor expression, tumour size, tumour grading and patient age. The development of strategies according to such individual risk profiles has resulted in significant improvements both in overall and disease-free survival. An abundant number of new prognostic and predictive factors in addition to those already mentioned may help to increase our understanding of the biology of breast cancer and to individualize therapy in premenopausal patients. Although less than 10% of patients directly benefit, it is estimated that approximately each year the life of more than 4000 women in Germany will be saved or prolonged by adjuvant treatment. Whether dose intensive modifications and new antineoplastic drugs can improve disease outcome will be clarified when ongoing studies have increased observation time. At present, hormone ablation via surgical, radiotherapeutical or drug-induced castration in addition to selective estrogen response modifiers (SERM), such as tamoxifen, with or without chemotherapy remains the cornerstone of adjuvant treatment in premenopausal patients with breast cancer. In advanced disease, new highly effective hormonal and other target-oriented antineoplastic agents with few adverse effects have been recently introduced. However, overall survival in metastatic disease remains poor, even when intensive or high-dose chemotherapy is used. Special attention must be given to longer follow up and potential toxic long-term adverse effects of therapy when new regimens are applied in clinical trials.

Double high-dose chemotherapy with adriamycin, paclitaxel, cyclophosphamide, and thiotepa followed by autologous peripheral blood stem cell transplantation in women with metastatic breast cancer.

To determine the feasibility, time to progression, and event-free survival, twenty-two women with metastatic breast cancer received two cycles of high-dose chemotherapy (HDCT) followed by peripheral blood stem cell transplantation (PBSCT) early after first-line induction chemotherapy. The median age of the ten (45.5%) pre- and 12 (54.5%) postmenopausal women was 48 (range: 33-60) years. Sixteen patients (72.7%) had at least two or more metastatic sites involved. Protocol induction and mobilization chemotherapy including granulocyte-colony stimulating-factor (G-CSF) consisted of two cycles with adriamycin (60 mg/m(2)) i.v. and paclitaxel (200 mg/m(2)) i.v. After collection of at least 4 x 10(6)/kg bodyweight peripheral blood stem cells, the first HDCT-course of adriamycin (60 mg/m(2)), paclitaxel (200 mg/m(2)) cyclophosphamide (4 g/m(2)), and thiotepa (800 mg/m(2)) (ATCT) was given to at least stable disease (SD) patients. Six to eight weeks later, the second HDCT-ATCT was administered. Each HDCT-cycle was followed by PBSCT with a median of 3.81 x 10(6)/kg bodyweight CD-34 positive cells (range: 1.85-10.38). All women showed median leukocyte engraftment (>1,000 x 10(9)/l) on day +9.4 (range: 7-13) and median platelet engraftment (>20,000 x 10(9)/l) on day +12.3 (range: 8-15). There were no apparent differences in the clinical course and non-hematologic toxicity between the two HDCT-cycles. Of the 21 patients evaluable for response, eight (38.1%) patients achieved complete remission (CR), ten (47.6%) patients showed a partial remission (PR), two patients (9.5%) no change, and one patient (4.8%) progressive disease. After a median observation time of 36 (range 28-55) months, six (28.6%) women are alive, four (19.0%) of them in continuous CR, including two women with stable bone lesions, respectively, and 15 (71.4%) died due to progressive disease. Median time to progression (TTP) was 8 (range 4-19) months. A high initial response rate of early HDCT, including the most active drugs adriamycin and paclitaxel, can be achieved with tolerable toxicity in metastatic breast cancer. New approaches for maintaining primary tumor response achieved with efficacious high-dose chemotherapy are warranted.

[Brain metastases of colorectal carcinomas]. / Zerebrale Metastasen bei kolorektalen Karzinomen.

BACKGROUND: Patients with brain metastases from colorectal cancer are supposed to have the lowest median survival compared to other locations of metastases from this cancer. Patients with brain metastases usually receive highly palliative treatment and are excluded from studied investigating new therapeutic concepts. However, there appears to be a subgroup of patients with brain metastases originating from colorectal cancer who have a median survival comparable to that of other metastatic sites. PATIENTS AND METHODS: Between November 1996 and October 2000, 13 out of 113 patients from our clinic with colorectal cancer had brain metastases (11.5%). We describe their heterogeneous clinical course and present a review of the literature. RESULTS: The median survival time after the diagnosis of brain metastases was 9.0 months for all patients, less than 1 month for three patients who received only supportive care, 40 months for a patient who was treated with radiosurgical resection, 3 months for two patients who received whole brain radiation, and 10.4 months for seven patients who underwent surgical resection. The median interval between the diagnosis of primary cancer and the diagnosis of brain metastases was 26.5 months (2-84). In one case brain metastasis was the initial manifestation of colorectal cancer. Five patients are still alive with a survival time between 6-40 months. CONCLUSION: The clinical course of our 13 patients varied significantly. Thus, patients with brain metastases of colorectal cancer may profit from modern multimodal therapeutic concepts. A therapeutic nihilism should be avoided.