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Biomedical subjects

K Possinger

Publications and source records attributed to K Possinger.

At least 109 records · Page 6Linked to original sources
PubMed1997

Quality monitoring, standardized documentation and management with a computerized system in oncology.

Within the last years the prerequisite was prepared to develop a computerized tumor--patient documentation system including quality monitoring and oncological therapy recommendations for every day use. In medicine today, there is an increasing need for quality oriented low cost and transparent management--what is especially true in the field of oncology. The German Federal Authority of Health demands the documentation of all tumor disorders for the establishment of an cancer registry. For these reasons our study group established the program "OncoDoc" in cooperation with the laboratory for Artificial Intelligence of the University Bremen.

Artificial Intelligence↗
PubMed1997

[Intensification of chemotherapy dosage in metastatic breast carcinoma?].

During the last decades, improvements in the median survival time in patients with metastasized carcinoma of the mamma were hardly achieved. There ist still a lack of evidence that the increase in the rate of remissions due to conventional chemotherapy leads to an improvement in survival time. In 450 female patients with metastasized carcinoma of the mamma, the survival time was analyzed with the begin of the metastatic spread in relation to the treatment success of the first palliative chemotherapy. The survival time of the responder group was not significantly different to the group with a stationary tumor (p = 0.5). As patients with primary hormone therapy were included, this result changed if patients only with prognostically unfavorable characteristics (high-risk group) were selected, which received primarily and exclusively a cytostatic chemotherapy. The responder only (partial and complete responder) are profitting from the chemotherapy with a significant increase in survival time in comparison to the group with a stationary tumor (p = 0.02 and p = 0.006). Therefore, a stationary tumor in the high risk group is a result as bad as tumor progression.

Adult↗
PubMed1996

Clinical experiences with magnetic drug targeting: a phase I study with 4'-epidoxorubicin in 14 patients with advanced solid tumors.

Anticancer drugs reversibly bound to magnetic fluids (ferrofluids) could be concentrated in locally advanced tumors by magnetic fields that are arranged at the tumor surface outside of the organism. If certain requirements are met, systemic toxicity might be minimized, and local tumor efficacy might be increased. We have conducted a Phase I clinical trial using this approach in patients with advanced and unsuccessfully pretreated cancers or sarcomas. Nine such patients received two treatment courses, 3 patients received one course, and 2 patients received three courses of magnetic drug targeting consisting of the infusion of epirubicin in increasing doses (from 5 to 100 mg/m2) that had been chemically bound to a magnetic fluid and the application of magnetic fields to the tumors for 60-120 min. In 2 of 14 patients, the same dose of epirubicin not bound to a magnetic fluid was administered systemically 3 weeks after drug targeting for intraindividual comparisons. Magnetic drug targeting with epirubicin was well tolerated. In one case, a planned second treatment was withdrawn, because of an episode of chills 130 min after infusion of the magnetic drug. Two patients received a third treatment because of good responses after the first two therapies. Based on magnetic resonance tomographic techniques, pharmacokinetics, and the histological detection of magnetites, it was shown that the ferrofluid could be successfully directed to the tumors in about one-half of the patients. Organ toxicity did not increase with the treatment, but epirubicin-associated toxicity appeared at doses greater than 50 mg/m2. Although treatment with magnetic drug targeting seems safe, improvements are necessary to make it more effective and independent of patient- or disease-related problems. A study design to compare conventional treatments with the new treatment form within one patient seems crucial to eliminate interindividual differences.

Adolescent↗
PubMed1996

Induction of TGF-beta by an antiprogestin in the human breast cancer cell line T-47D.

BACKGROUND: Antiprogestins appear to be a new approach for the endocrine therapy of breast cancer. Most breast cancer cells are growth inhibited by TGF-beta. Any change of tumorcellular TGF-beta secretion could have some impact on tumorcellular growth. We addressed our question to whether the antiprogestin onapristone can induce TGF-beta secretion in breast cancer cells in vitro and whether a possible induction correlates with the antiproliferative effect and the receptor status of the cells. MATERIALS AND METHODS: We examined the ER and PR positive breast cancer cell lines MCF7 and T-47D and an ER and PR negative variant T-47D/x. Hormone receptor levels were determined by EIA, total (LTGF-beta + active TGF-beta) and active TGF-beta by a radioreceptor assay. All cell biological and antiproliferative effects were measured during basal, not estrogen-stimulated growth. RESULTS: To our knowledge, we are the first to describe, that the TGF-beta secretion of tumor cells can be increased by an antiprogestin (total: 4.8-fold, active 2.9-fold). A stimulation was found only in the markedly PR positive T-47D cells, in which onapristone proved to have strong antiproliferative potency. In the MCF7 and T-47D/x cells onapristone showed no induction of TGF-beta. Moreover, those cells were not growth inhibited. Whereas onapristone did not influence the ER-content, it dramatically downregulated the PR-content of the T-47D and MCF7 cells (93% and 65%, respectively). CONCLUSIONS: These observations make it likely, that the antiproliferative potency of the antiprogestin onapristone is at least partly due to the ability of onapristone, to stimulate the strong growth inhibitor TGF-beta. In contrast to the antiprogestin RU 486, onapristone showed no estrogenic activity (stimulation of growth and PR), which could be a decisive advantage in the therapy of breast cancer, taking into account, that many breast carcinomas grow estrogen dependent.

Antineoplastic Agents↗
PubMed1995

[Therapeutic management of patients with metastasized breast carcinoma].

In patients with metastasized breast cancer cure is beyond our therapeutic reach at present. In this situation the main treatment objectives are to improve existing or imminently threatening symptoms caused by the tumor growth, to retain or restore physical ability for as long as possible and, if possible, to prolong survival time. To achieve these treatment aims diphosphonates, hormones and cytotoxic mono- or polychemotherapy can be administered. The individualized administration of these drugs, adapted to the rate of the spread of metastases and tumor-induced symptoms, help to attain long survival without pronounced toxic side effects.

Algorithms↗
PubMed1995

Gemcitabine in advanced breast cancer.

The experience with single-agent gemcitabine in advanced or metastatic breast cancer is reviewed. In all studies, gemcitabine was administered as a 30 min intravenous infusion in cycles once a week for 3 weeks followed by 1 week of rest. In the first European study (gemcitabine 800 mg/m2/week), of 40 evaluable patients, 14 were chemo-naive, 7 had received adjuvant chemotherapy, and 19 had received chemotherapy for metastatic disease. There were 3 complete responders and 7 partial responders (all independently validated by an external Oncology Review Board) for an overall response rate of 25.0% (95% CI: 12.7%-41.2%). The median time to declaration of response was 1.9 months and the median duration of survival for all 40 efficacy-evaluable patients was 11.5 months. Haematological and non-haematological toxicities were particularly mild. WHO grade 3 and 4 toxicities included leukopenia (6.8% and 2.3% of patients), neutropenia (23.3% and 7.0%), AST (6.8% and 2.3%), ALT (18.2% and 0%), infection (0% and 2.3%), nausea and vomiting (25.0% and 2.3%), alopecia (2.3% and 0%). There was no grade 3 or 4 creatinine, proteinuria or haematuria. In the smaller US study (18 evaluable patients, all but one having received prior chemotherapy for stage IV disease) there were no responders. However, the mean dose delivered was very low (577 mg/m2/injection). In an ongoing European trial, with a starting dose of 1000 mg/m2, a number of partial responders have been seen in soft tissue, lung and liver. Gemcitabine's modest toxicity profile and single-agent activity make it an attractive candidate for trial in combination therapy in advanced breast cancer where treatment is currently given to palliate symptoms and improve quality of life.

Adult↗
PubMed1995

Advanced breast cancer: a phase II trial with gemcitabine.

PURPOSE: In this phase II study, the efficacy and tolerability of gemcitabine were studied in 44 patients with locally advanced or metastatic breast cancer. PATIENTS AND METHODS: Of 40 patients assessable for response, 14 were chemotherapy-naive, seven had received adjuvant chemotherapy, and 19 had received one prior chemotherapy regimen for metastatic disease. Gemcitabine was administered as a 30-minute intravenous infusion once a week for 3 weeks followed by a 1-week rest every 4 weeks. The mean number of completed cycles administered was 2.7 and the mean dosage delivered was 725 mg/m2 per injection. Eighty-one percent of doses were delivered as scheduled. RESULTS: There were three complete responses and seven partial responses, for an overall response rate of 25.0% (95% confidence interval [CI], 12.7% to 41.2%). Four patients were not assessable for efficacy (one had insufficient therapy, two had no bidimensionally measurable disease, and one had neither). All responses were independently validated by an external oncology review board. Responses were observed early in treatment, with a median time to response of 1.9 months. The median survival duration for all 40 assessable patients was 11.5 months. Hematologic toxicity was generally mild, with World Health Organization (WHO) grade 3 and 4 leukopenia occurring in 6.8% and 2.3% of patients and neutropenia in 23.3% and 7.0%, of patients, respectively. The only other grade 4 toxicities were infection and nausea and vomiting in one patient each. One patient was withdrawn due to shortness of breath, possibly drug-related. Flu-like symptoms, which were mild, transient, and treatable with acetominophen, were reported in 6.8% of patients. Only one patient developed alopecia of severity greater than WHO grade 2. CONCLUSION: In view of the single-agent activity seen in advanced breast cancer, modest toxicity profile, and novel mechanism of action, gemcitabine deserves evaluation in breast cancer and is an ideal candidate for combination therapy.

Adult↗
PubMed1994

Formestane in the treatment of advanced postmenopausal breast cancer.

In a phase II study, 91 women with advanced breast cancer received formestane (Lentaron) 500 mg intramuscularly every 2 weeks for 6 weeks, and then 250 mg every 2 weeks thereafter; all were either postmenopausal or surgically oophorectomized, and most had received previous hormonal treatment and/or chemotherapy. Complete or partial response was seen in 23%, disease stabilization in 29%. Disease-free interval and site of metastatic lesions did not significantly affect response. Patients who had previously responded to tamoxifen showed the best results with formestane. Side effects were generally mild and transient; only 3 patients had to discontinue treatment. Serum estradiol and estrone levels fell significantly after 2 weeks' treatment, and remained suppressed; there were no significant changes in serum cortisol, blood parameters, and liver and kidney function. Formestane thus appears to be an effective, specific and well-tolerated aromatase inhibitor for the treatment of advanced postmenopausal breast cancer.

Adult↗
PubMed1993

Effect of onapristone and medroxyprogesterone acetate on the proliferation and hormone receptor concentration of human breast cancer cells.

We studied the influence of the antiprogestin onapristone (ZK 98.299) and the progestin medroxyprogesterone acetate (MPA) on the proliferation and hormone receptor levels of the following human breast cancer cell lines: the oestrogen receptor (ER) and progesterone receptor (PR) negative cell line MDA-MB-231 and the ER- and PR-positive cell lines T47-D and SK-BR-3. MPA and onapristone both bind to the cellular PR and can inhibit the proliferation of hormone-dependent cells; PR-negative MDA-MB-231 cells are not inhibited. The growth inhibition of the ER- and PR-positive tumour cells induced by onapristone is accompanied by a significant accumulation of cells in the G0/G1 phase and a reduction of S-phase cells, while MPA does not change the distribution of the cell cycle phases. However, MPA reduces the cellular ER content by 27% and the PR content by more than 80%. Conversely, onapristone does not significantly affect ER and PR levels. The extent of growth inhibition by both drugs differs considerably: onapristone inhibits growth of both receptor positive cell lines (T47-D:39%; SK-BR-3:17%), while MPA affected growth in only SK-BR-3 (61%). These results indicate that even though the two drugs act through the PR, the inhibitory effect on the three cell lines of MPA may depend on ER concentration and its down-regulation, while the inhibitory effect of onapristone is mainly correlated to the PR concentration without significantly affecting ER levels. Since tumour cells with low ER concentration are growth suppressed by onapristone, but not by MPA, it remains to be examined whether antiprogestins should preferably be used in PR-positive tumours with a low ER concentration.

Breast Neoplasms↗
PubMed1991

Oral administration of idarubicin as first line cytostatic therapy in patients with metastasized breast cancer and favourable prognosis. A trial of the phase II study group of the Association for Medical Oncology of the German Cancer Society.

Idarubicin is a new anthracycline derivative with therapeutic efficacy in metastatic breast cancer. In a phase II trial we treated 23 patients with advanced breast carcinoma and favourable prognostic factors. Oral dose of idarubicin was 15 mg/m2 day 1-3 repeated every 3 weeks. All patients were pretreated with hormones. Idarubicin was administered as first line chemotherapy. 20 patients were evaluable for response: 3 patients achieved partial remission, 12 patients stable disease; tumour progression occurred in 5 patients. 3 patients were not evaluable for response because only 1 treatment cycle was administered. Main toxicites were leukopenia (median WHO-grade: 2,r:0-4), nausea and vomiting (median: 1,r:0-4) and alopezia (median: 1,r:0-3). 1 patient died in septic shock: Immediately after the administration of one idarubicine cycle, she was extensively irradiated because of bone metastasis. The fatal course of the disease in this patient does not depend only on the idarubicin therapy, but also on the extensive bone infiltration and on intensive radiation therapy. Idarubicin proved to be an effective drug in metastatic breast cancer with low systemic toxicity and the advantage of oral administration. The drug is an enrichment of therapeutic armament, especially in patients with soft tissue and bone metastasis.

Administration, Oral↗
PubMed1991

Lonidamine versus high-dose tamoxifen in progressive, advanced renal cell carcinoma: results of an ongoing randomized phase II study.

Sixty patients with metastatic renal cell carcinoma were entered into an ongoing randomized phase II study with lonidamine, 350 mg/m2 orally daily (arm A) and high dose tamoxifen, 150 mg/m2 orally daily for 6 months, afterwards 50 mg/m2 (arm B), until tumor progression. All patients had measurable disease and documented tumor progression prior to treatment. There were 1 complete and 1 partial remission among 19 evaluable patients in arm A (10.5%) and 2 complete and 1 partial remission among 25 evaluable patients (12%) in arm B. Objective responses were observed in pulmonary, nodal, and cutaneous metastases. In addition, in 63% and 64% tumor progression could be stopped in arm A and B, respectively. Median response duration was 100 days (range, 20-361) in arm A and 150 days (range, 28-355) in arm B. One year survival rate was 37.5% with lonidamine and 35% with tamoxifen. In arm A patients with tumor progression within 12 weeks after diagnosis of metastatic disease survived significantly shorter than patients with a longer interval (P less than 0.05). Nephrectomy or number and localization of metastatic sites failed to significantly influence probability of remission or survival. Toxicity was mostly mild to moderate. Four patients in the lonidamine arm had to discontinue treatment because of intolerable myalgias, which were immediately reversible. These data suggest that lonidamine and high-dose tamoxifen are moderately effective in widespread renal cell carcinoma where treatment intention is palliative.

Adult↗
PubMed1991

Lonidamine in high-risk breast cancer patients.

Lonidamine revealed synergistic effects with anthracyclines and alkylating agents in experimental investigations. It differs from conventional cytostatics by acting on the cell energy metabolism and also lacks their typical side effects; therefore it may be valuable to be combined with established chemotherapeutic regimens. Because in unselected patients the results of randomized studies may be influenced by differences in type and combination of prognostic factors, we defined strict entry criteria: no previous systemic palliative treatment, disease-free interval less than or equal to 2 years, measurable visceral metastases, number of tumor sites less than or equal to 2, no brain or bone metastases, World Health Organization performance status less than or equal to 2, age less than or equal to 55. In an ongoing rate, remission duration, time to treatment failure, and survival time in patients treated with vindesin 3 mg/m2 plus epirubicin 100 mg/m2 plus cyclophosphamide 600 mg/m2 (day 1, intravenous, repeated every 3 weeks) +/- lonidamine 600 mg/day orally. Eight of 12 patients achieved an objective remission (complete response 4, partial response 4), 1 patients had a stable disease, 2 patients experienced tumor progression; 1 patient is not yet evaluable for response. In spite of the intensity of the therapy no treatment interval prolongation was necessary. Main toxicities were myelosuppression, nausea, emesis, alopecia, and in patients treated with lonidamine, mild myalgia. The addition of lonidamine to polychemotherapy did not affect myelosuppression. Differences in remission rates or remission duration due to lonidamine could not yet be demonstrated.

Adult↗
PubMed1990

Randomized clinical trial comparing mitoxantrone with epirubicin and with doxorubicin, each combined with cyclophosphamide in the first-line treatment of patients with metastatic breast cancer.

Two hundred and twenty-four patients with advanced breast cancer were enrolled in a multicenter prospective randomized clinical study and received either doxorubicin (40 mg/m2), or epirubicin (40 mg/m2) or mitoxantrone (12 mg/m2) each combined with cyclophosphamide (600 mg/m2) i.v. In the patient collective the following response rates were observed: complete response 12.1%; partial response 30.6%; stable disease 40.5%; progressive disease 16.8%. A complete response was observed significantly less often in patients where more than one organ site was involved as compared to those patients with only one metastatic site. The mean time period required to reach a best response was 3.7 months. There was no significant difference between the response rates in the three arms. In comparing the observed toxicities in 1,434 treatment cycles, there was a significant difference with regard to leukocytopenia (mitoxantrone arm exhibiting more than either epirubicin and doxorubicin) although infections did not occur more frequently in the mitoxantrone arm; with regard to alopecia, mitoxantrone and epirubicin arms both exhibited less than doxorubicin. It is noteworthy that no patient who had previously received adjuvant chemotherapy achieved a complete response (p = 0.006). The overall significance of these findings can only be clearly evaluated when survival times can be measured.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1990

Aromatase inhibition with 4-hydroxyandrostenedione in the treatment of postmenopausal patients with advanced breast cancer: a phase II study.

Estrogen deprivation by aromatase inhibition is an effective treatment in breast cancer. Between October 1986 and March 1988, 91 postmenopausal patients with advanced breast cancer entered a phase II study performed jointly in three center to investigate the new aromatase inhibitor 4-hydroxyandrostenedione. Patients received 500 mg 4-hydroxyandrostenedione intramuscularly (IM) every 2 weeks for 6 weeks, and 250 mg every 2 weeks thereafter. There were two complete (CRs) and 19 partial remissions (PRs) (response rate, 23%). Disease stabilization (no change; NC) was seen in 26 patients, and in 44 patients (48%), disease progression occurred. Duration of the CRs is 20+ months, median durations of PR and NC are 13+ and 8 months, respectively. Receptor status, relapse-free interval, and sites of metastatic lesions did not appear to influence treatment results. However, efficacy of previous tamoxifen treatment favorably predicted response to 4-hydroxyandrostenedione. Serum estradiol levels decreased significantly in patients after 2 weeks of treatment. Side effects were mostly nonspecific and of low degree, requiring discontinuation of treatment in only 3% of the patients. We conclude that aromatase inhibition with 4-hydroxyandrostenedione is efficacious in the treatment of postmenopausal breast cancer.

Adult↗