Ulrich R. Kleeberg

Bio: Ulrich R. Kleeberg is an academic researcher from Praxis. The author has contributed to research in topics: Adjuvant therapy & Breast cancer. The author has an hindex of 32, co-authored 91 publications receiving 3961 citations.

Fulvestrant, Formerly ICI 182,780, Is as Effective as Anastrozole in Postmenopausal Women With Advanced Breast Cancer Progressing After Prior Endocrine Treatment

Abstract: PURPOSE: To compare the efficacy and tolerability of fulvestrant (formerly ICI 182,780) and anastrozole in postmenopausal women with advanced breast cancer progressing after prior endocrine treatment. PATIENTS AND METHODS: Patients (n = 451) with advanced breast cancer were randomized to receive fulvestrant 250 mg as a once-monthly (one × 5 mL) intramuscular injection or an oral dose of anastrozole 1 mg in this open, parallel-group, multicenter trial. The primary end point was time to progression (TTP). Secondary end points included objective response (OR) rates, defined as complete response (CR) or partial response (PR), duration of response (DOR), and tolerability. RESULTS: Patients were followed for a median period of 14.4 months. In terms of TTP, fulvestrant was as effective as anastrozole (hazard ratio, 0.98; confidence interval [CI], 0.80 to 1.21; P = .84). Median TTP was 5.5 months for fulvestrant and 5.1 months for anastrozole. OR rates showed a numerical advantage for fulvestrant (20.7%) over ana...

Fulvestrant versus anastrozole for the treatment of advanced breast carcinoma in postmenopausal women: a prospective combined analysis of two multicenter trials.

Abstract: BACKGROUND Fulvestrant (ICI 182,780) is a new type of estrogen receptor (ER) antagonist that down-regulates the ER and has no known agonist effects. The authors report the prospectively planned combined analysis of data from 2 Phase III trials comparing fulvestrant 250 mg monthly (n = 428) and anastrozole 1 mg daily (n = 423) in postmenopausal women with advanced breast carcinoma (ABC) who previously had progressed after receiving endocrine treatment. METHODS The primary endpoint was time to progression (TTP). Secondary endpoints included objective response (OR), duration of response (DOR), and tolerability. The trials were designed to demonstrate superiority of fulvestrant over anastrozole. Noninferiority of fulvestrant versus anastrozole was determined using a retrospectively applied statistical test. RESULTS At a median follow-up of 15.1 months, ≈ 83% of patients in each treatment arm had progressed. The median TTP was 5.5 months in the fulvestrant group and 4.1 months in the anastrozole group, and the OR rates were 19.2% and 16.5% for fulvestrant and anastrozole, respectively (although the difference between treatments was not statistically significant). In patients who responded, further follow-up (median, 22.1 months) was performed to obtain more complete information on DOR; the median DOR (from randomization to disease progression) in patients who responded to treatment was 16.7 months in the fulvestrant group and 13.7 months in the anastrozole group. In a statistical analysis of DOR (using all randomized patients; from the start of response to disease progression), DOR was significantly longer for patients in the fulvestrant group compared with patients in the anastrozole group. Both drugs were tolerated well; withdrawals due to drug-related adverse events were 0.9% and 1.2% in the fulvestrant group and the anastrozole group, respectively. The incidence of joint disorders was significantly lower in the fulvestrant group (P = 0.0036). CONCLUSIONS Fulvestrant was tolerated well and was at least as effective as anastrozole in the second-line treatment of patients with ABC. This new hormonaltherapy may provide a valuable treatment option for ABC in postmenopausal women. Cancer 2003;98:229–38. © 2003 American Cancer Society.

Malignant melanoma S3-guideline "diagnosis, therapy and follow-up of melanoma".

Abstract: This first German evidence-based guideline for cutaneous melanoma was developed under the auspices of the German Dermatological Society (DDG) and the Dermatologic Cooperative Oncology Group (DeCOG) and funded by the German Guideline Program in Oncology. The recommendations are based on a systematic literature search, and on the consensus of 32 medical societies, working groups and patient representatives. This guideline contains recommendations concerning diagnosis, therapy and follow-up of melanoma. The diagnosis of primary melanoma based on clinical features and dermoscopic criteria. It is confirmed by histopathologic examination after complete excision with a small margin. For the staging of melanoma, the AJCC classification of 2009 is used. The definitive excision margins are 0.5 cm for in situ melanomas, 1 cm for melanomas with up to 2 mm tumor thickness and 2 cm for thicker melanomas, they are reached in a secondary excision. From 1 mm tumor thickness, sentinel lymph node biopsy is recommended. For stages II and III, adjuvant therapy with interferon-alpha should be considered after careful analysis of the benefits and possible risks. In the stage of locoregional metastasis surgical treatment with complete lymphadenectomy is the treatment of choice. In the presence of distant metastasis mutational screening should be performed for BRAF mutation, and eventually for CKIT and NRAS mutations. In the presence of mutations in case of inoperable metastases targeted therapies should be applied. Furthermore, in addition to standard chemotherapies, new immunotherapies such as the CTLA-4 antibody ipilimumab are available. Regular follow-up examinations are recommended for a period of 10 years, with an intensified schedule for the first three years.

Melanoma and use of sunscreens: An EORTC case‐control study in germany, belgium and france

Abstract: Use of sunscreens is widely advocated as a preventive measure against sun-induced skin cancers. However, to date, no epidemiologic study has reported a decreased melanoma risk associated with sunscreen use. We have conducted a case-control study aimed at evaluating the influence of sunscreen use on the occurrence of cutaneous malignant melanoma. In 1991 and 1992, 418 melanoma cases and 438 healthy controls were interviewed in Germany, France and Belgium. The questionnaire used differentiated between regular sunscreens, psoralen sunscreen (prepared with 5-methoxypsoralen, a tanning activator and photocarcinogen), and self-tanning cosmetics (which produce a tan without ultraviolet radiation). After adjusting for age, sex, hair colour and holiday weeks spent each year in sunny resorts, the melanoma risk was of 1.50 (95% Cl:1.09-2.06) for regular sunscreens, and of 2.28 (95% Cl: 1.28-4.04) for psoralen sunscreens. No melanoma risk was associated with use of self-tanning cosmetics. Among subjects with a poor ability to tan, psoralen sunscreen users displayed a melanoma risk of 4.45 (95% Cl: 1.25-15.8) when compared with regular sunscreen users. There was a significant negative interaction between regular sunscreen use and sunburns experienced in adulthood. Use of sunscreens, especially psoralen sunscreen, was associated with higher density of pigmented lesions of the skin. Although we cannot exclude the presence of an unknown confounding factor, our results support the hypothesis that sunscreens do not protect against melanoma, probably because of their ability to delay or avoid sunburn episodes, which may allow prolonged exposure to unfiltered ultraviolet radiation. Serious doubts are raised regarding the safety of sunscreens containing psoralens.

Immunological aspects of cancer chemotherapy.

Abstract: Accumulating evidence indicates that the innate and adaptive immune systems make a crucial contribution to the antitumour effects of conventional chemotherapy-based and radiotherapy-based cancer treatments. Moreover, the molecular and cellular bases of the immunogenicity of cell death that is induced by cytotoxic agents are being progressively unravelled, challenging the guidelines that currently govern the development of anticancer drugs. Here, we review the immunological aspects of conventional cancer treatments and propose that future successes in the fight against cancer will rely on the development and clinical application of combined chemo- and immunotherapies.

Choosing the right cell line for breast cancer research

Abstract: Breast cancer is a complex and heterogeneous disease. Gene expression profiling has contributed significantly to our understanding of this heterogeneity at a molecular level, refining taxonomy based on simple measures such as histological type, tumour grade, lymph node status and the presence of predictive markers like oestrogen receptor and human epidermal growth factor receptor 2 (HER2) to a more sophisticated classification comprising luminal A, luminal B, basal-like, HER2-positive and normal subgroups. In the laboratory, breast cancer is often modelled using established cell lines. In the present review we discuss some of the issues surrounding the use of breast cancer cell lines as experimental models, in light of these revised clinical classifications, and put forward suggestions for improving their use in translational breast cancer research.

Melanocyte biology and skin pigmentation

Abstract: Melanocytes are phenotypically prominent but histologically inconspicuous skin cells. They are responsible for the pigmentation of skin and hair, and thereby contribute to the appearance of skin and provide protection from damage by ultraviolet radiation. Pigmentation mutants in various species are highly informative about basic genetic and developmental pathways, and provide important clues to the processes of photoprotection, cancer predisposition and even human evolution. Skin is the most common site of cancer in humans. Continued understanding of melanocyte contributions to skin biology will hopefully provide new opportunities for the prevention and treatment of skin diseases.