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Biomedical subjects

H J Staab

Publications and source records attributed to H J Staab.

At least 19 recordsLinked to original sources
PubMed2005

Randomized phase II study comparing topotecan/cisplatin administration for 5 days versus 3 days in the treatment of extensive stage small cell lung cancer (SCLC).

BACKGROUND: Topotecan (T) is an active drug in SCLC. A combination of topotecan with cisplatin (DDP) was suggested to be highly synergistic. This phase II trial was initiated to assess the activity of T/DDP in chemotherapy-naive patients suffering from extensive disease small cell lung cancer (SCLC) and to compare the conventional 5-day regime with an experimental 3-day schedule. PATIENTS AND METHODS: A total of 86 patients were included. Patients were randomized to receive either T 1.0 mg/m2 d 1-5 and DDP 75 mg/m2 d 5 (arm A) or T 1.5 mg/m2 d 1-3 and DDP 75 mg/m2 d 3 (arm B). Six cycles were given at a 3-week interval. RESULTS: Data of 84 evaluable patients (67 males and 17 females) were analysed. All patients had metastatic disease. The best response rate was 61.9% in arm A and 59.5% in arm B. Median overall survival was 8.7 months in arm A and 7.6 months in arm B (p=0.6809). CONCLUSIONS: Combination of T and DDP is active in ED SCLC. Toxicity and median survival were comparable in both arms. Three days treatment seems to be similar to the 5 days regime.

Adult↗
PubMed2001

Topotecan chemotherapy in patients with breast cancer and brain metastases: results of a pilot study.

BACKGROUND: Symptomatic brain metastases occur in approximately 10-15% of patients suffering from breast cancer and are linked to a clear deterioration of the patient's condition. Although radiotherapy is recommended as a primary therapy, the optimal management remains controversial. To evaluate the role of topotecan as a primary chemotherapy for brain metastases, we performed a pilot study in patients with metastatic breast cancer. PATIENTS AND METHODS: 24 patients with newly diagnosed, bidimensionally measurable brain metastases received topotecan, 1.5 mg/m(2) day, 30-min infusion for 5 days every 3 weeks. A total of 93 courses of therapy were administered (range 1-11, median 3 courses per patient). Prior radiotherapy was excluded. Most of the patients had received prior adjuvant or palliative chemotherapy. RESULTS: 3/24 patients were withdrawn from the study for various reasons, 16/24 patients could be evaluated in terms of their response to therapy; 1 and 5 patients showed complete and partial response to therapy, respectively, and 5 patients had a stable condition. The median time of survival was 6.25 months. Hematologic toxicity was the major side effect, nonhematologic side effects occurred rarely and were tolerable. CONCLUSIONS: Our results demonstrate that primary chemotherapy with topotecan is an effective and well-tolerated treatment for patients with breast cancer and CNS metastases. Based on this pilot study, future clinical protocols should be developed including multimodal treatment strategies (i.e. radiotherapy).

Adult↗
PubMed2000

[A double-blind comparative study of the effectiveness and tolerance of paroxetine and amitriptyline in treatment of breast cancer patients with clinically assessed depression].

OBJECTIVE: In this double-blind, non-placebo controlled study [corrected], 179 patients with treated breast cancer who fulfilled the ICD-10 criteria for an acute depressive episode underwent an 8-week course of antidepressant treatment with either the tricyclic amitriptyline (75-150 mg, n = 87) or the serotonin-reuptake inhibitor paroxetine (20-40 mg, n = 88). METHODS: The change in clinical status relative to baseline was measured with the Montgomery-Asberg Depression Rating Scale (MADRS), the Clinical Global Impression (CGI), the Functional Living Index-Cancer (FLIC) and the Patient Global Evaluation. RESULTS: Both treatment groups showed significant improvement in all parameters at weeks 3, 5 and 8. At no time was there a significant difference in the efficacy of the antidepressants used. Adverse events, most of which were transitory, were reported by 53% of the patients in the paroxetine group and 60% in the amitriptyline group. The 8-week treatment was completed by 81% of the paroxetine and 76% of the amitriptyline patients. CONCLUSIONS: The results of this study show that depression in breast-cancer patients can be correctly diagnosed and adequately treated by non-psychiatrists. The treatment with both medications was carried out in dose ranges which correspond to that employed in physically well patients.

Adaptation, Psychological↗
PubMed1999

Subnuclear distribution of DNA topoisomerase I and Bax protein in normal and xeroderma pigmentosum fibroblasts after irradiation with UV light and gamma rays or treatment with topotecan.

Immunohistochemical methods were used to determine abundance and subnuclear distribution of DNA topoisomerase I and the Bax protein in normal and excision-repair-deficient xeroderma pigmentosum (XP) fibroblasts after irradiation of cells with gamma rays or UV light, or exposure to the topoisomerase I inhibitor topotecan. DNA topoisomerase I and Bax were monitored using antisera raised against the human proteins. In addition, topoisomerases IIalpha and IIbeta were made visible with specific antibodies. In untreated cells, DNA topoisomerase I was found to occur in the cytoplasm and in nucleoli. Irradiation with gamma rays (2-12 Gy) or UV light (0.3-1.2 mW/cm2) changed the staining pattern in nuclei such that a multitude of small topoisomerase-I-rich centers occurred, which were evenly distributed over the karyoplasm. Simultaneously nucleoli disintegrated. Treatment of fibroblasts with topotecan (6-100 microM concentrations) resulted in similar alterations although the changes were much more pronounced. Combinations of topotecan and gamma irradiation caused additive effects. We conclude that the increase in the number of topoisomerase-I-positive spots and the high fluorescence intensity of the latter may reflect three biological processes: (i) enhanced transcriptional activity (e.g. of DNA damage response genes), (ii) tagging of damaged DNA sites for repair, or (iii) initiation of apoptosis. In separate assays using normal and XP cells, a dose-dependent increase in protein reacting with Bax antibody was observed in nuclei, following treatment with gamma rays or topotecan. In addition, topotecan induced a netlike arrangement of this Bax protein in nuclei. The meshes of the net structure resembled vesicles. DNA staining with 4',6-diamidino-2-phenylindole dihydrochloride revealed that the vesicle-type structures contained DNA. Upon further incubation with topotecan, cells showing the netlike Bax arrangement eventually died. We conclude that topotecan-induced changes made visible by nuclear Bax protein are associated with apoptosis. XP cells, when treated with topotecan, responded more readily than normal cells with both an increase in nuclear Bax protein and rearrangement of Bax, indicating that UV repair functions may be required to process DNA damage inflicted by topotecan. Monitoring of DNA topoisomerases IIalpha and IIbeta in gamma-irradiated cells with antibodies revealed a dramatic increase in the IIalpha form and a redistribution of the IIbeta form representing fragmentation of nucleoli.

Animals↗
PubMed1997

Dose escalation vs. continued doses of paroxetine and maprotiline: a prospective study in depressed out-patients with inadequate treatment response.

In view of the fact that controlled prospective studies on the benefits of dose escalation of the selective serotonin re-uptake inhibitor (SSRI) paroxetine are lacking, we conducted a double-blind, randomized, parallel-group multicentre study designed to compare the possible benefits of dose escalation of paroxetine and maprotiline in patients suffering from major or minor depression according to modified Research Diagnostic Criteria (RDC) with inadequate treatment response. The study sample consisted of 544 out-patients with different degrees of severity of depression. Patients received either 20 mg paroxetine (n = 271) or 100 mg maprotiline (n = 273) for the first 3 weeks in a double-blind manner. Response after 3 weeks was defined using explicit operationalized criteria. Patients with inadequate treatment response (paroxetine group, n = 86; maprotiline group, n = 88) were again randomized to either continuation of the previous dosage (paroxetine, n = 36; maprotiline, n = 48) or increased doses, i.e. 40 mg paroxetine (n = 50) or 150 mg maprotiline (n = 40), respectively. Intention-to-treat and completer analyses were performed. Defining response as a reduction in Hamilton Depression Rating Scale (17-item version) (HAMD-17) score of at least 50% from baseline, no significant benefits of dose escalation were found for either paroxetine or maprotiline. Stratification according to baseline severity of depression also revealed no significant benefits of dose escalation. After dose escalation, new adverse events that had not been present during treatment with lower doses rarely occurred. Our results support the view that a dose of 20 mg paroxetine is optimal for the acute treatment of depression in the majority of patients.

Adult↗
PubMed1995

Colonic spreading of a non-chlorofluorocarbon mesalazine rectal foam enema in patients with quiescent ulcerative colitis.

BACKGROUND: Rectal foam enemas provide for drug delivery to the distal colon for treatment of left sided ulcerative colitis. However, currently available formulations contain chlorofluorocarbons which are due to be phased out in the near future. The objective of this study was therefore to determine the degree of dispersion of a newly developed non-chlorofluorocarbon rectal foam preparation in ulcerative colitis patients. METHODS: This was an open label non-controlled study of a single administration of a mesalazine foam enema (two actuations containing 2 g of mesalazine in approximately 120 mL foam) in 10 patients with quiescent ulcerative colitis. Spreading of the 99mTc-labelled foam enema was assessed over a 4-h period by the non-invasive technique of gamma scintigraphy. RESULTS: All patients retained the enema for the full 4-h imaging period. In nine out of the 10 patients, the enema was observed to spread as far as the descending colon and on average 23% of the dose was present in the descending colon at 4 h post-dose. CONCLUSIONS: The extent of spreading observed in the study supports the use of the formulation in the treatment of left sided ulcerative colitis.

Aminosalicylic Acids↗
PubMed1995

[Granisetron, a antiemetic for treatment of cytostatic drug-induced vomiting: results of a practice-oriented study].

The present multicentre Austrian investigation of the prophylactic intravenous administration of granisetron, a serotonin antagonist, routinely for control of cytostatic-induced nausea and emesis was carried out in 102 patients with cancer of various types undergoing different emetogenic cytostatic regimens (232 cycles of chemotherapy). A major therapeutic response, i.e. maximally one vomit over the first 24 hours, was achieved in 78-90% of patients undergoing a single or multiple day regimen of chemotherapy. Delayed emesis, experienced between day 1 and day 4 after chemotherapy, was observed in < 5% of the patients. However, particularly in single day regimens 25% of the patients showed only a moderate response to granisetron in suppressing delayed emesis. Tachyphylaxis to granisetron therapy was not observed in the first 3 consecutive cycles of chemotherapy. The individual global efficacy of emesis control by granisetron (day of chemotherapy over all cycles plus the following 7 days) was very good. An excellent therapeutic response was seen in 53-55% of all cases. The study also demonstrated the economic advantages of granisetron therapy. In the majority of patients (88/102) only a single dose of granisetron (3 mg) was required. The tolerability was also very good. The main adverse events reported were headache (7.8%) and constipation (4.9%).

Adult↗
PubMed1992

Investigations of droloxifene and other hormone manipulations on N-nitrosomethylurea-induced rat mammary tumours. 1. Influence on tumour growth.

The effect of droloxifene, a new anti-oestrogenic drug, on N-nitrosomethylurea-induced mammary tumours of Sprague-Dawley rats was investigated and compared with that of tamoxifen. The response of tumour growth to ovariectomy or to treatment with aminoglutethimide or high doses of oestradiol was also studied. Ovariectomy was by far the most effective treatment for mammary-tumour-bearing animals. More than 75% of the tumours in ovariectomized rats did not grow progressively but remained in remission for up to 12 weeks after castration when the experiment was terminated. The inhibitory effects of droloxifene and tamoxifen on mammary tumour growth were similar, but body weight loss of animals treated with tamoxifen was more marked than that of animals treated with droloxifene at the same dose and schedule.

Animals↗
PubMed1992

Investigations of droloxifene and other hormonal manipulations on N-nitrosomethylurea-induced rat mammary tumours. 2. Influence on oestrogen receptor.

In N-nitrosomethylurea-induced rat mammary tumours, tamoxifen is found to compete at the binding sites of the oestradiol receptor if a receptor determination is performed 1 day following the last drug application to animals. Despite a higher binding affinity of droloxifene (3-OH-tamoxifen) to oestradiol receptor, compared to tamoxifen, its influence on the measurable receptor quantity is only very weak or not demonstrable. Therefore, binding affinity is not a valid explanation for the different influences of the two anti-oestrogens on the receptor. These only can be attributed to different behaviour patterns of both substances in relation to their half-lives and metabolism and accumulation in the organism. Owing to the short half-life of droloxifene, even 1 day after the last application too little drug is available to compete for oestradiol binding sites. In the case of both anti-oestrogenic substances, cessation of drug application for 8 weeks abolished any influence on the oestradiol receptor. Furthermore, failure of aminoglutethimide to influence the oestradiol receptor could be observed because this substance does not act via this receptor. The experiments performed confirm literature data regarding the effect of aminoglutethimide therapy on oestradiol receptors in breast tumour tissue of human beings. In summary: receptor investigations of N-nitrosomethylurea-induced rat mammary tumours, used as a model to test therapy regimens with droloxifene or other drugs with a short half-life, may be of limited value only.

Aminoglutethimide↗
PubMed1991

Clinical pharmacology of the hypocholesterolemic agent K 12.148 (lifibrol) in healthy volunteers.

K 12.148 (INN:lifibrol), a new cholesterol synthesis inhibitor, was studied in healthy volunteers to evaluate tolerance/safety, the effects on lipids, and pharmacokinetics. In a sequential block design the doses of 150, 300, 600, or 900 mg, given once daily in the morning for 14 consecutive days, were examined in 40 healthy young males (8 active drug and 2 placebo per group, randomized) under well-controlled conditions. Total and LDL cholesterol serum levels decreased significantly in the 300, 600, and 900 mg groups (-13.4%, -23.8%, -25.6%, and -14.7%, -33.3%, -34.8%, respectively). whereas no significant change was seen with placebo and 150 mg. The antiatherogenic index Apo A-I/B increased in a dose-dependent manner between 300 and 900 mg. Changes in HDL cholesterol and triglycerides were not statistically significant. The study compound was tolerated well, and safety laboratory parameters did not show any relevant alterations, K 12.148 might be a very effective drug for the treatment of hypercholesterolemia.

Adolescent↗
PubMed1986

[The doubling time of circulating CEA as an individual prognostic criterion of recurrence in patients with gastrointestinal cancers].

In a prospective study of 928 patients with gastrointestinal cancer registered for primary resection, the postoperative carcinoembryonic antigen (CEA) time courses were analysed in connection with disease recurrence. Only patients with established diagnosis of disease recurrence and complete follow-up to death entered the evaluation of prognostic criteria of the CEA time course. In this group the CEA time courses of 103/201 patients with recurrent disease exhibited an exponential increase of the serum CEA concentration, i.e. a linear relationship of log CEA and time, which allowed the calculation of the CEA doubling time. All 103 patients developed metastatic spread and generally exhibited CEA doubling times ranging between 10 and 158 days, in patients developing peritoneal carcinosis up to 343 days. The individual CEA doubling times of patients with recurrent disease who received no treatment (n = 71) correlated well with the times of individual survival after the initial CEA increase of the log CEA phase (rs = 0.812; P less than 0.001) thus confirming the results of a previous retrospective study. When the survival time is expressed in multiples of the individual CEA doubling time (IDT), no patient survived longer than 10.8 IDT. The median value of survival was 5.4 IDT. Patients with metastatic spread who underwent various treatments of recurrent disease (n = 32) survived distinctly longer showing survival times up to 32.6 IDT. This could be confirmed by comparing the observed survival after the initial CEA increase of treated and untreated patients (life table method) exhibiting highly significant differences (P less than 0.001).

Carcinoembryonic Antigen↗
PubMed1986

Prognostic value of preoperative serum CEA level compared to clinical staging. IV. Histological grading and tumor type in colorectal and gastric cancer.

In a clinical investigation of observed postoperative survival, 410 patients with colorectal cancer and 269 patients with stomach cancer have been registered for primary surgical treatment connected with a long-term follow up. Histologic grading and tumor typing were examined as potential prognostic factors and compared with the prognostic information covered by operability, tumor extension, and the preoperative CEA level. Statistical treatment of the data revealed no prognostic significance of the tumor types adenocarcinoma, mucinous, and anaplastic tumours in gastric cancer. Histologic grading specified ranges associated with significant differences in survival of gastric and colorectal cancer patients. However, histologic grading did not provide prognostic information in addition to operability and tumor extension. However, histologic grading gave additional prognostic information to preoperative CEA levels in the range of 0-5 micrograms CEA/1 serum but not in the range greater than 5 micrograms CEA/1. The results indicate that the prognostic information of preoperative serum CEA level is not directly linked to the histologic grade of a tumor.

Carcinoembryonic Antigen↗
PubMed1985

[Carcinoembryonic antigen: diagnosis and tumor progression in gastrointestinal tumors].

Tumour progression in 340 patients with resected gastrointestinal primary tumours was monitored using the gradual increase in carcinoembryonic antigen (CEA) in serum. The commencement of the rise in CEA generally preceded clinical detection of the cancer by several months. The degree to which the rise in CEA correlated with the recurrence of cancer was investigated. There was a marked difference in the distribution of the rises in CEA between local tumour growth and distant metastases. CEA increases of more than 1 microgram CEA/l serum in 10 days occurred exclusively in patients with distant metastases. There was a further marked difference in the distribution of the CEA increase between the group with liver metastases and the groups with peritoneal carcinomatosis or other metastases. The site of the primary tumour had no influence on the CEA increase during formation of metastases.

Carcinoembryonic Antigen↗