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Uwe Reinhold

Publications and source records attributed to Uwe Reinhold.

14 recordsLinked to original sources
PubMed2006

In vitro drug sensitivity predicts response and survival after individualized sensitivity-directed chemotherapy in metastatic melanoma: a multicenter phase II trial of the Dermatologic Cooperative Oncology Group.

PURPOSE: In vitro sensitivity assays are promising tools to predict the individual outcome of different chemotherapy regimens. However, a direct association between in vitro and in vivo chemosensitivity has to be shown by clinical studies. This multicenter phase II trial was aimed to investigate the efficacy of a sensitivity-directed, first-line chemotherapy in metastasized melanoma patients, and to prove an association between in vitro sensitivity and therapy outcome. PATIENTS AND METHODS: The primary study end point was objective response; secondary end points were safety, overall survival, and progression-free survival. Viable tumor cells obtained from metastatic lesions were tested for chemosensitivity to seven single drugs and five drug combinations using an ATP-based luminescence viability assay. RESULTS: Out of 82 recruited patients (intention-to-treat), 57 received assay-directed chemotherapy and 53 were evaluable for all study end points (per protocol). The drug combinations used were gemcitabine+treosulfan, paclitaxel+cisplatin, paclitaxel+doxorubicin, and gemcitabine+cisplatin. The per protocol population could be divided into 22 (42%) chemosensitive and 31 (58%) chemoresistant patients by an arbitrary chemosensitivity index. Objective response was 36.4% in chemosensitive patients compared with 16.1% in chemoresistant patients (P=0.114); progression arrest (complete response+partial response+stable disease) was 59.1% versus 22.6% (P=0.01). Chemosensitive patients showed an increased overall survival of 14.6 months compared with 7.4 months in chemoresistant patients (P=0.041). CONCLUSION: In vitro chemosensitivity testing may be worthy of further exploration to see if it could be a useful tool to predict the outcome of melanoma patients treated with a sensitivity-directed chemotherapy. Therefore, these preliminary results will be evaluated by a planned phase III trial using a randomized, standard-regimen controlled setting.

Adult↗
PubMed2006

[Efalizumab--therapy of moderately severe to severe plaque-psoriasis in the dermatologist's practice].

Psoriasis is a chronic immune-mediated skin disease with highly variable patterns of presentation, both between patients and in individuals over time. Its course can be influenced by various triggers. Since there is no cure for psoriasis, patients with moderate-to-severe plaque-type psoriasis often require lifelong therapy to control their disease. Traditional approaches such as cyclosporine or methotrexate are problematic for long-term use because of organ toxicity, other side effects, drug interactions and a loss of efficacy over time. Efalizumab is a recombinant monoclonal IgG1-antibody, approved in Germany for the management of moderate-to-severe plaque-type psoriasis. Its efficacy and safety have been demonstrated in clinical trials with thousands of patients,especially with regard to long-term therapy. Therefore, a change of paradigm from the traditional therapy of inflammatory episodes to continuous control of psoriasis seems possible. This supplement deals with practical aspects of using efalizumab in the outpatient setting.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2005

Continuous low-dose GM-CSF as salvage therapy in refractory recurrent breast or female genital tract carcinoma.

Granulocyte-macrophage colony-stimulating factor (GM-CSF, sargramostim [Leukine]) is a powerful cytokine that is able to stimulate the generation of dendritic cells. Adjuvant treatment with continuous low-dose GM-CSF has been shown to prolong survival of stage III/IV melanoma patients. Data on continuous low-dose GM-CSF therapy in tumors other than prostate cancer are still lacking. This pilot trial was initiated in order to evaluate the efficacy and tolerability of continuous low-dose GM-CSF as salvage in various chemotherapy-refractory carcinomas. A total of 19 patients who had failed a median of 4 prior chemotherapies were included. Their malignancies included metastatic breast cancer, recurrent ovarian carcinoma, metastatic endometrial carcinoma, and recurrent squamous cell cancer of the cervix uteri. Continuous low-dose GM-CSF was delivered subcutaneously at a daily starting dose of 125 microg. GM-CSF was increased at 25-microg increments until a maximum of 250 microg was reached or when mild leukocytosis (10-20 g/L) was achieved, providing that the relative eosinophil count did not exceed 15%. Therapy was continued until progression or refusal by the patient. Toxicity was generally mild. Only one patient was withdrawn due to grade 3 fatigue. In three additional patients, temporary dose reduction was necessary because of grade 1 injection site reactions, which recovered spontaneously. Mild to moderate leukocytosis was obvious in 10 patients. Systemic hypersensitivity-like reactions did not occur and no patient required hospitalization for other life-threatening side effects. The objective response rate was 37%: 1 complete and 6 partial responses, 4 disease stabilizations, 8 progression of disease. Median response duration was 6 months. Notably, 6 of 7 responders but only 1 of 8 patients with disease progression developed leukocytosis during therapy. Therefore, we conclude that continuous low-dose GM-CSF has substantial activity in heavily pretreated patients with either metastatic breast cancer or female genital tract cancer. Achievement of mild leukocytosis seems to be a predictor of response.

Breast Neoplasms↗
PubMed2004

Down-regulation of HLA class II and costimulatory CD86/B7-2 on circulating monocytes from melanoma patients.

Antigen-presenting cells are crucial for the induction of an antigen-specific antitumoral immune response. Deteriorations in the expression pattern of cell surface molecules important for the presentation of antigens might therefore be indicative of an impaired immune response status in cancer patients. In the present study we investigated the expression of MHC class I and class II molecules, of the costimulatory molecules CD80/B7-1 and CD86/B7-2, of the adhesion molecule CD11c, and of the marker of activation CD71 on CD14+ peripheral blood monocytes (PBMs) from 144 melanoma patients in different stages of disease and 43 healthy controls, by flow cytometric analysis. We found a decreased expression of HLA-DR (p<0.0005), HLA-DQ (p=0.006), HLA-DP (p<0.0005), and CD86/B7-2 (p=0.001) on PBMs from melanoma patients compared with healthy controls, whereas no significant difference could be detected in the expression of HLA class I antigens and CD80/B7-1. This down-regulated expression was associated with disease progression. In contrast, CD71 expression was stage-dependently increased on PBMs from melanoma patients compared with healthy controls (p=0.024). No correlation was found between the PBM surface expression pattern and age, gender, tumor load, and current mode of therapy of the patients. The observed down-regulation of HLA class II and CD86/B7-2 on melanoma patients' PBMs might reflect an ineffective antigen-presenting function contributing to an impaired antigen-specific immune response in these patients.

Antigens, CD↗
PubMed2003

Chemosensitivity testing in malignant melanoma.

The prognosis of patients with metastatic melanoma remains poor. In patients with distant metastases only low response rates between 10% and 15% have been achieved by the most effective cytostatics in single-agent therapy leading to a mean 5-year survival rate of less than 5%. More aggressive treatment regimens using multidrug chemotherapy yielded response rates of up to 40% but failed to show a significant benefit in overall survival compared to single-agent therapy. However, complete remissions of metastatic lesions after multidrug cytostatic regimens have been reported in some cases of melanoma patients. To evaluate an in vitro test system providing information on the drug sensitivity profile of melanoma cells, we examined tumor tissue specimens from 31 metastatic melanoma patients with an ATP-based chemosensitivity assay (ATP-TCA) testing eight anticancer drugs alone or in different combinations. Chemosensitivity was assessed using a luciferin-luciferase- based luminescence assay providing individual chemosensitivity indices for each test drug. We found a heterogeneous chemosensitivity in the melanoma tissue samples tested. The highest sensitivity was detected for the combination of treosulfan and gemcitabine, with 76% of the tissue samples revealing high sensitivity and 10% resistance, followed by the combination of paclitaxel and doxorubicine (66%/0%), gemcitabine and cisplatin (55%/21%),and paclitaxel and cisplatin (46%/8%). Our data indicate that the ATP-TCA can be used to select patients who might benefit from an individually adapted cytostatic therapy. On the basis of these results a multicenter trial has recently been initiated to evaluate the feasibility and predictive value of an ATP-TCA directed chemotherapy in metastatic melanoma patients.

Adenosine Triphosphate↗
PubMed2003

[Descriptive analysis of drug-related deaths over a 5-year period].

OBJECTIVE: The purpose of the study was to examine opiate-related deaths in the German town Essen (inhabitants about 600,000) from 1990-1994. Sociodemographic data, psychiatric comorbidity and purity of the used opioids were of focussed interest. METHODS: 189 opiate-related deaths were analysed during the 5-year period. Patient files and police-related documents were used for the retrospective analysis. Purity of opioids was examined in a criminalistic laboratory and correlated with the number of deaths per time interval. RESULTS: The average age to start drug abuse in this cohort of 189 people was about 20, the average time of drug career was about 8.5 years, and the highest number of drug-related deaths was to be found at the age of 29-30. Purity of opioids was correlated statistically significantly (p < 0.05) with the number of deaths per period of time. CONCLUSIONS: After an average start of drug abuse at the age of 20 and a drug career of about a decade the risk of drug-related death seems to be relatively high at the age of about 30 years. Opiate purity seems to be relevant for drug-related death.

Accidents↗
PubMed2003

Treosulfan and gemcitabine in metastatic uveal melanoma patients: results of a multicenter feasibility study.

No effective treatment currently exists for metastatic uveal melanoma. However, recent results obtained by an ATP-based tumor chemosensitivity assay have shown consistent activity of treosulfan+gemcitabine in up to 80% of tumor specimens tested. In this study we describe the first clinical results observed with this drug combination at different European centers in patients with metastatic uveal melanoma. Clinical case series of patients with metastatic uveal melanoma were treated with treosulfan+gemcitabine at seven different centers. Fourteen patients, 13 previously untreated and one pretreated with chemoimmunotherapy, were included in the study. Patients received treosulfan+gemcitabine in four different dose regimens. The response rates, progression-free and overall survival, and toxicity were evaluated. The analysis of 14 patients revealed one complete response, three partial responses and a stable disease in eight cases. The objective response rate was 28.6%, the median overall survival was 61 weeks [95% confidence interval (CI) 54-133 weeks], the progression-free survival was 28.5 weeks (95% CI 13-62 weeks) and the 1-year survival rate was 80%. The drugs were well tolerated. The most common side-effects were leuko- and thrombocytopenia. These preliminary results suggest potential therapeutic benefit of treosulfan+gemcitabine treatment in metastatic uveal melanoma and warrant further controlled studies.

Aged↗
PubMed2003

Second-line chemotherapy of metastatic malignant melanoma with intravenous treosulfan: a phase II multicentre trial.

The purpose of this multicentre phase II trial was to evaluate time to progression, survival time, rate of objective tumour response and toxicity of second-line intravenous treosulfan chemotherapy in stage IV melanoma patients. Thirty-one patients with measurable stage IV malignant melanoma and prior chemotherapy with a dacarbazine-containing regimen were included. Of this group, 26 patients were evaluable. All patients received treosulfan (8 g/m intravenously on day 1; cycle repeated every 28 days up to six courses). Patients were evaluated for tumour response, survival time and toxicity. No objective responses (complete or partial) were observed. Five patients (19%) showed no change and 21 had progressive disease after treosulfan treatment. Four patients experienced a minor or mixed response. The median time to progression was 1.8 months (95% confidence interval [CI] 1.6-2.1 months) and the median overall survival was 6.5 months (95% CI 3.1-10 months). The 1 year survival rate was 33.9% (95% CI 15.4-52.3%). Leukocytopenia and thrombocytopenia (Common Toxicity Criteria grades 3 and 4) occurred in 15% and 18% of cases, respectively. The non-haematological toxicity of this outpatient regimen was mild. In conclusion, intravenous treosulfan treatment does not induce objective response rates when used as a second-line treatment of metastatic malignant melanoma.

Adult↗
PubMed2002

Soluble HLA-DR is a potent predictive indicator of disease progression in serum from early-stage melanoma patients.

Despite numerous therapeutic options, the prognosis of malignant melanoma, once metastasized, is still poor. Thus, the search for reliable methods to identify patients with high risk of disease progression as early as possible is of major importance. In our study, we analyzed the predictive value of soluble HLA-DR (sHLA-DR) in comparison to S100-beta in serum from 183 melanoma patients of different stages of disease and with or without current therapy using immunosorbent assays. sHLA-DR serum levels of 121 healthy individuals served as controls. We found significantly (p < 0.0005) reduced sHLA-DR serum levels in melanoma patients (0.70 +/- 0.08 SEM microg/ml) compared to controls (1.49 +/- 0.10 SEM microg/ml). Reduced sHLA-DR and increased S100-beta levels were associated with advanced disease stages and tumor load. S100-beta was increased under cytostatic therapy (p < 0.0005), whereas sHLA-DR was not influenced by therapy modalities. Univariate analysis showed an association of sHLA-DR < 0.3 microg/ml and S100-beta > 0.12 microg/l with poor overall (p = 0.021 and p = 0.0009) and progression-free survival (p < 0.0005 and p = 0.0025). Multivariate analysis revealed disease stage (p = 0.0093) and tumor burden (p < 0.0005) as independent predictive factors for overall survival, and sHLA-DR (p = 0.0007) and tumor burden (p = 0.0015) for progression-free survival. In contrast to S100-beta, sHLA-DR serum concentrations < 0.3 microg/ml were strongly associated (p = 0.0001) with poor progression-free survival in a subgroup of 60 nonmetastasized patients. In conclusion, our results suggest sHLA-DR as a potent prognostic serum marker in melanoma patients superior to S100-beta in helping to identify early-stage patients at high risk of disease progression.

Disease Progression↗
PubMed2002

Verrucae vulgares in children: successful simulated X-ray treatment (a suggestion-based therapy).

BACKGROUND: Treatment of verrucae vulgares is sometimes difficult. Invasive methods should not be used for young children. OBJECTIVE: Evaluation of a special suggestion therapy for treatment of verrucae vulgares in children. METHODS: Nine children with warts on the hands and/or feet and in the face were treated with a simulated X-ray treatment. RESULTS: Five children showed a complete remission of warts, 3 children a partial remission. For 1 child, there was no response. On average, 3 treatment sessions were needed for children showing a complete remission. CONCLUSION: This therapy offers an easy-to-perform, alternative treatment option. It is noninvasive and does not depend on special psychological techniques for which training is required.

Child↗
PubMed2002

Treatment of genito-anal lesions in inflammatory skin diseases with PUVA cream photochemotherapy: an open pilot study in 12 patients.

BACKGROUND: Localized skin lesions of the genito-anal region such as in lichen sclerosus et atrophicus or in lichen planus are a burden for many patients, and therapeutic efforts, including therapies with potentially hazardous side-effects, are often unsatisfactory. Recently, PUVA bath photochemotherapy has been proven highly effective in the treatment of various inflammatory skin diseases, including localized scleroderma. Another form of topical PUVA therapy, 8-methoxypsoralen-containing cream or gel preparations, has been proven to be as effective as PUVA bath therapy for palmoplantar dermatoses. OBJECTIVE: We evaluated the clinical effects of PUVA cream photochemotherapy in patients with genital lesions of inflammatory skin diseases. METHODS: Twelve patients with lichen sclerosus et atrophicus, lichen planus, vulvar eczema and pruritus vulvae were included in the study. PUVA cream therapy was performed up to 4 times a week. RESULTS: PUVA cream photochemotherapy induced a significant clinical improvement of genital lesions in most patients, as revealed by clinical examination. Clinical improvement (reduction in size of lesions of erythema, and/or of pruritus) was achieved in most patients after 10-20 treatments and was reduced in patients that had only received 5-15 treatments. Cumulative doses ranged between 4.5 and 180 J/cm(2); all patients tolerated PUVA cream phototherapy well without any side-effects. CONCLUSION: PUVA cream phototherapy represents a highly effective therapy that should be further investigated as an alternative treatment for patients with genital lesions of inflammatory skin diseases.

Adult↗