Biomedical subjects

S Olbricht

Publications and source records attributed to S Olbricht.

9 recordsLinked to original sources

PubMed2002

Chemotherapy versus hormonal treatment in platinum- and paclitaxel-refractory ovarian cancer: a randomised trial of the German Arbeitsgemeinschaft Gynaekologische Onkologie (AGO) Study Group Ovarian Cancer.

BACKGROUND: The majority of patients with ovarian cancer are not cured by first-line treatment. Until now, no study could demonstrate any substantial benefit when exposing ovarian cancer patients to second-line chemotherapy. However, most treatment regimens induce toxicity, thus negatively influencing the quality of rather limited life spans. Here we evaluate whether a second-line chemotherapy can offer any benefit compared with a less toxic hormonal treatment. PATIENTS AND METHODS: Patients with ovarian cancer progressing during platinum-paclitaxel containing first-line therapy or experiencing relapse within 6 months were eligible. Patients were stratified for response to primary treatment (progression versus no change/response), and measurable versus non-measurable disease. Treatment consisted of either treosulfan 7 g/m5 infused over 30 min or leuprorelin 3.75 mg injected subcutaneously or intramuscularly. Both regimens were repeated every 4 weeks. RESULTS: This study began in late 1996, and after 2.5 years accrual an interim analysis was performed when several investigators reported their concern about a suspected lack of efficacy. Following this analysis the recruitment was stopped early and the 78 patients already enrolled were followed up. The majority of patients received treatment until progressive disease was diagnosed or death occurred. Treatment delay was observed rarely and dose reduction was performed only in the treosulfan arm in 5% of 150 courses. Overall, both treatment arms were well tolerated. No objective responses were observed. The median survival time was 36 and 30 weeks in the treosulfan and leuprorelin arms, respectively. Overall survival did not differ between patients with relapse 3-6 months after first-line chemotherapy compared with patients with progressive disease within 3 months. CONCLUSIONS: The selected patient population represents a subgroup with extremely poor prognosis. Accordingly, results were not impressive. Both treatment arms showed favourable toxicity data, but failed to show remarkable activity, thus adding only limited evidence to the issue of whether patients with refractory ovarian cancer might benefit from second-line chemotherapy. Even stratified analysis did not identify any subgroup of patients in whom the administration of second-line chemotherapy could demonstrate a clinically relevant survival benefit.

Adult↗

PubMed2001

[Electrophysiological studies in breast carcinoma patients with tamoxifen retinopathy].

PURPOSE: Crystalline plaques in the cornea or the retinal nerve fiber layer are well-known side effects of tamoxifen therapy. We investigated whether electrophysiological methods for determining the function of the retinal nerve fiber layer and retinal pigment epithelium demonstrate changes in tamoxifen retinopathy. PATIENTS AND METHODS: We compared the right eyes of four women with breast cancer and mono- or bilateral tamoxifen retinopathy to ten right eyes of age-matched, eyehealthy patients who had not received tamoxifen by means of electrophysiological investigations (e.g., pattern-reversal electroretinography, flash electroretinography for the maximal combined response, electrooculography; ISCEV standard conditions). RESULTS: No significant differences were observed between patients with tamoxifen retinopathy and controls regarding mean visual acuity, basal level of the electro-oculographic standing potential, basal level on the Arden index, or any of the other electrophysiological potentials. CONCLUSIONS: Pattern-reversal electroretinographic measurements revealed no damage of retinal ganglion cells in the presence of crystalline plaques in the retinal nerve fiber layer. Electro-oculography did reveal differences, but these were not statistically significant, possibly due to the small number of cases.

Aged↗

PubMed1999

[In Process Citation]

OBJECTIVE: The objective of the study was to analyse the prognostic impact of several criteria for median survival and recurrence free interval in patients with uterine sarcomas. Factors included to our analysis were the staging according to FIGO, DNA content (ploidy), mitotic index, histology, the kind of primary therapy, grading and menopausal status. MATERIAL AND METHODS: Retrospectively, clinical data of 78 patients (41 leimyosarcomas, 23 carcinosarcomas = homologous malignant mixed Mullerian tumors, 14 endometrial stromal sarcomas--10 low grade, 4 high grade) were analysed. Additionally, in 36 of the cases mitoses were counted. Furthermore, DNA ploidy was determined using image cytometry on paraffine sections stained according to the Feulgen method. Receptor status was determined using immunohistochemical staining. Two and five year survival rates were 22% and 15%. There were 21 cases with local relapse and 27 cases with metastasis. RESULTS: The staging according to FIGO was the main prognostic factor, significantly influencing median survival time (p = 0.001) as well as the recurrence free interval (p = 0.03). There was a significant difference between median survival time compared to mitotic index (p = 0.014) and DNA ploidy (p = 0.02). A mitotic index < 10/10 HPF and diploidy were related with a better prognosis. Receptor status did not have an impact on median survival time. CONCLUSIONS: As our results suggest, DNA ploidy and mitotic index are likely to provide additional information for prognosis in patients with uterine sarcomas and could be used as criteria for selecting patients for adjuvant therapy.

Journal Article↗

PubMed1998

Nodular hidradenoma. A report of three cases and review of the literature.

BACKGROUND: Nodular hidradenoma is a rare adnexal tumor most likely arising from the eccrine gland. OBJECTIVE: We describe three cases of a nodular hidradenoma presenting as an expanding nodule on the forehead (case 1), left lower extremity (case 2), and left neck (case 3). We discuss the clinical and histologic features of this tumor and present a review of the literature. CONCLUSIONS: This report highlights the salient histologic findings that distinguish nodular hidradenomas from other adnexal tumors and emphasizes the benefit of complete local excision to prevent recurrence of these tumors.

Adenoma, Sweat Gland↗

PubMed1998

Immunocytochemical detection of somatostatin receptors sst1, sst2A, sst2B, and sst3 in paraffin-embedded breast cancer tissue using subtype-specific antibodies.

The long-acting somatostatin analogue octreotide (SMS 201-995) inhibits growth of certain breast cancer cell lines in vivo and in vitro. Because the antiproliferative action of octreotide depends on at least the presence of somatostatin receptors, it is crucial to determine the pattern of somatostatin receptor protein expression on the tumor cells. In the present study, we have raised polyclonal antibodies to somatostatin receptor subtypes (ssts) sst1, sst2A, sst2B, and sst3 using peptides corresponding to their COOH-terminal sequences. These antisera were used for immunocytochemical staining of paraffin sections of 33 primary breast cancers. Somatostatin receptor-like immunoreactivity (Li) was predominantly localized to the plasma membrane of the tumor cells. In the vast majority of positively stained tumors, somatostatin receptor-Li was uniformly present on nearly all tumor cells. Both the level and the pattern of expression of ssts varied greatly between individual carcinomas. sst2A-Li and/or sst2B-Li was detectable in 28 tumors (85%); among these, 14 tumors (42%) showed particularly high levels of sst2-Li. sst1-Li was found in 17 (52%) cases and sst3-Li in 16 (48%) cases. The expression of ssts was independent of patient age, menopausal status, diagnosis, histological grade, and levels of estrogen and progesterone receptors. The immunocytochemical determination of somatostatin receptor status allows direct detection of receptor protein on the tumor cells and, hence, may provide more precise information than reverse transcription-PCR for predicting response to octreotide therapy in breast cancer.

Adult↗

PubMed1997

Carboplatin plus paclitaxel as first-line chemotherapy in previously untreated advanced ovarian cancer. German AGO Study Group Ovarian Cancer. Arbeitsgemeinschaft Gynäkologische Onkologie.

Since publication of the results of the Gynecologic Oncology Group (GOG) III study, the combination of cisplatin and paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) has been adopted widely as the new standard for treating advanced ovarian cancer. Further attempts to optimize first-line chemotherapy with platinum and taxanes include substituting carboplatin for cisplatin, individualizing the carboplatin dose by calculating it according to the area under the concentration-time curve, and reducing the length of the paclitaxel infusion. Attempts to optimize platinum/paclitaxel combinations have led to the initiation of several small phase I/II trials evaluating the carboplatin/paclitaxel combination. The promising results of these studies have prompted the initiation of three phase III trials comparing carboplatin/paclitaxel with the standard combination of cisplatin/paclitaxel. An interim analysis after 1 year's accrual to the prospectively randomized German Arbeitsgemeinschaft Gynäkologische Onkologie (AGO) study is presented. Treatment consists of paclitaxel 185 mg/m2 infused over 3 hours on day 1 followed directly by either cisplatin 75 mg/m2 (arm B) or carboplatin dosed to an area under the curve of 6 (arm A). Treatment is repeated every 3 weeks for six courses. Eligibility criteria are epithelial ovarian cancer International Federation of Gynecology and Obstetrics stage IIB through IV, age of consent, written informed consent, Eastern Cooperative Oncology Group performance status < or =2, life expectancy of more than 12 weeks, adequate bone marrow function defined as neutrophil count 1.5 x 10(9)/L and platelet count > or =100 x 10(9)/L, adequate renal function defined as glomerular filtration rate (GFR) > or =60 mL/min, and adequate liver function defined as serum bilirubin levels within 1.25 x upper limit of normal. From October 1995 to December 1996, 442 of 660 planned patients were recruited to the AGO study. The interim analysis is based on data from 353 patients who were enrolled within the first study year. These preliminary data indicate that hematologic toxicity occurred more frequently in arm A (carboplatin/paclitaxel), while nonhematologic toxicity occurred slightly more frequently in arm B. Dose-intensity analysis did not reveal cumulative dose reductions or increasing use of colony-stimulating factors over subsequent courses in either arm. In all, 44 patients with measurable disease following surgery completed chemotherapy and were evaluable for response. The data remain blinded at this time, and results are reported for the group as a whole. So far, there have been 18 (41%) complete responses and 15 (34%) partial responses, for an overall response rate of 75%. Retrospective comparison with the GOG results reveals no significant difference in response rates between patients in the cisplatin/paclitaxel arm of GOG III and those in the AGO study: the GOG study reported a 73% response rate, compared with a preliminary 75% response rate in the AGO study, resulting in a relative risk of 1.03 (95% confidence interval, 0.83 to 1.27). Overall, this interim analysis did not reveal any reason to terminate this study early. Accrual is ongoing and is expected to be completed in 1997.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1997

Carboplatin/paclitaxel versus cisplatin/paclitaxel as first-line chemotherapy in advanced ovarian cancer: an interim analysis of a randomized phase III trial of the Arbeitsgemeinschaft Gynäkologische Onkologie Ovarian Cancer Study Group.

Since publication of the results of the Gynecologic Oncology Group III study, the combination of cisplatin/paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) has been widely adopted as standard treatment for advanced ovarian cancer. Further attempts to optimize first-line chemotherapy with platinum and taxanes include the substitution of cisplatin with carboplatin, individualization of the carboplatin dose by calculating it according to the area under the concentration-time curve, and reduction of paclitaxel infusion duration. These attempts have led to the initiation of several phase I/II trials evaluating the combination of carboplatin/paclitaxel. The promising results of these small studies have prompted the initiation of three phase III trials comparing carboplatin/paclitaxel with the standard combination of cisplatin/paclitaxel. The interim analysis after 15 months' accrual of the prospectively randomized German Arbeitsgemeinschaft Gynäkologische Onkologie (AGO) study is presented here. As of January 1997, 518 of 660 planned patients have been recruited. The interim analysis is based on data from 449 evaluable patients. The preliminary data indicate that hematologic toxicity occurred more frequently in arm A (carboplatin/paclitaxel), whereas nonhematologic toxicity occurred slightly more frequently in arm B (cisplatin/paclitaxel). Dose-intensity analysis did not reveal cumulative dose reductions or an increased need for colony-stimulating factors over subsequent courses in both arms. Forty-four patients with measurable disease following surgery completed chemotherapy and were evaluable for response, which remains blinded at this time and is reported for the group as a whole. So far, there have been 18 complete responses (41%) and 15 partial responses (34%), for an overall response rate of 75%. Retrospective comparison reveals no significant difference in response rates between patients in the cisplatin/paclitaxel arm of Gynecologic Oncology Group III and those in the Arbeitsgemeinschaft Gynäkologische Onkologie study. Overall, this interim analysis did not reveal any reason for an early termination of this study. Accrual is ongoing and is expected to be completed this year.

Antineoplastic Agents↗

PubMed1996

The dominant T cell clone is present in multiple regressing skin lesions and associated T cell lymphomas of patients with lymphomatoid papulosis.

This study was undertaken to determine the clonality of lymphomatoid papulosis (LyP), its clonal relationship to lymphomas, which occur at high frequency in LyP patients, and to define the cell lineage of Reed-Sternberg-like cells in type A lesions of LyP. Punch biopsies of skin of 11 adult patients with LyP were analyzed for morphologic subtype of LyP, surface antigens, and clonal T-cell receptor (TCR) gene rearrangements. Clonal rearrangements were identified by semiquantitative polymerase chain reaction amplification and sequencing of TCR-beta chain genes in nine patients and TCR-gamma chain genes in two patients. A single dominant clone was detected in multiple separate LyP lesions, often of different histologies, in nine patients. The same clone was detected in LyP lesions and the anaplastic large cell lymphoma (ALCL) of 2 patients and the mycosis fungoides (MF) of 2 other patients. No dominant clone could be detected in one patient with LyP uncomplicated by lymphoma or in a second patient with LyP and MF. A T-cell lineage was evident for RS-like cells in cell culture and in type A lesions. These results show that multiple regressing skin lesions and associated T cell lymphomas (MF and ALCL) are clonally related in most LyP patients, which suggest that the disease in these patients was initiated by a non-random genetic event.

Adult↗

PubMed1987

Clonal composition of T cells in lymphomatoid papulosis.

A cDNA of the C beta 2 gene of the T-cell receptor was used as a probe to investigate the clonal composition of T cells in skin lesions of 5 patients with lymphomatoid papulosis (LyP), a chronic recurrent eruption characterized by morphologically abnormal activated T cells in the cutaneous infiltrate. Clonal T-cell populations, as evidenced by rearranged DNA bands, were demonstrated in the skin lesions of four patients, one of whom has shown clinical progression toward lymphoma. Three of these patients had lesions of type A histology, a type previously shown to be associated with aneuploidy. The remaining patient with clonal lesions appeared to have the same gene rearrangement pattern in DNA obtained from separate lesions taken 11 months apart, providing evidence that the T cells in both sites were derived from the same clone. This patient had lesions of type B histology, which is not associated with aneuploidy. Absence of a rearranged band and deletion or near absence of the 10.8 kb band in Eco RI digests was interpreted as evidence of polyclonal T-cell hyperplasia, accounting for the skin infiltrate of a fifth patient who had a prolonged clinical course without progression to lymphoma. This patient had lesions of type A histology with frequent Ki-1-positive Reed-Sternberg-like cells. Our results show that gene rearrangement analysis provides information that is independent of histology in LyP and may in part explain the variable progression of LyP to lymphoma in 10-20% of patients.

Clone Cells↗