Library

feed icon rss

Your email was sent successfully. Check your inbox.

An error occurred while sending the email. Please try again.

Proceed reservation?

Export
  • 1
    ISSN: 1432-0843
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract A limited sampling model of etoposide after oral administration to estimate the area under the plasma concentration-time curve from 0 to 24 h (AUC) by determination of the drug plasma levels at only two time points was developed by a multiple regression analysis on a training data set of 15 patients receiving oral doses ranging from 54 to 90 mg/m2. The equation describing the model is AUC (μg ml−1 h)=5.183 (μg ml−1 h)+1.193 (h)×C1h (μg/ml)+8.439 (h)×C4h (μg/ml) (R 2=0.93,P=0.0001), whereC 1h andC 4h represent the plasma etoposide concentrations at 1 and 4 h, respectively. The model was validated prospectively on a test data set of 13 patients receiving oral doses ranging from 52 to 87 mg/m2 and, additionally, on a data set of 7 patients receiving oral doses ranging between 176 and 200 mg/m2, investigated in a previous study. Validation on both test data sets gave a relative mean predictive error of 0.1% and a relative root mean square error of 15.8% and 16.7%, respectively. The present study shows that it is possible to obtain a good estimate of the plasma AUC after oral administration of etoposide using a two-time-point sampling model. The model can be used to monitor the etoposide AUC in patients receiving chronic oral treatment.
    Type of Medium: Electronic Resource
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 2
    ISSN: 1432-0843
    Keywords: Key words Phase I ; Methoxymorpholinyl doxorubicin ; Anthracycline analogs ; Hematotoxicology ; Oral chemotherapy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Purpose: The methoxymorpholinyl doxorubicin analogue PNU 152243 was brought into clinical studies because of preclinical observations of its non-cross-resistance in mdr tumor cells, dose-limiting neutropenia, lack of cardiotoxicity, and antitumor activity after oral administration. Methods: PNU 152243 was given orally every 4 weeks to 21 adults with a variety of solid tumors at doses ranging from 59 to 940 μg/m2. Antiemetic prophylaxis with 5-HT3 antagonists and steroids, given i.v. on day 1 and orally on days 2–8, was required beginning with the dose of 118 μg/m2. The plasma pharmacokinetics of PNU 152243 were determined by an HPLC method with fluorescence detection. The in vitro myelotoxic effects on granulocyte macrophage-colony forming cells (GM-CFC) of the plasma from 11 patients, obtained 4 and 6 h after treatment at all dose levels, were also assessed. Results: Neutropenia was the main hematologic toxic effect and the maximum tolerated dose (MTD) for myelotoxicity was 940 μg/m2, with neutropenia grade 3–4 in two of three patients. Dose-dependent nausea and vomiting were dose-limiting and the MTD for gastrointestinal toxicity was fixed at 820 μg/m2, with grade 4 vomiting in one of two patients. Other frequent toxic effects were diarrhea and fatigue. Peak levels of PNU 152243 were achieved 4 h after dosing. Dose-dependent Cmax and AUCExp, and significant interpatient variability of the main pharmacokinetic parameters were found. Very low levels of the 13-dihydrometabolite PNU 155051 were detected only at the highest doses. The hematotoxicity tests showed a 〈70% colony growth inhibition with no correlation between the growth inhibition effect and the degree of myelotoxicity in the same patient. Plasma concentrations of PNU 152243 were 1000 times lower than the concentration inhibiting the growth of 70% of colonies. No objective tumor responses were seen. Conclusions: Owing to the occurrence of severe and prolonged nausea and vomiting, the clinical development of oral PNU 152243 was discontinued. The higher-than-expected neutropenia and its lack of relationship with plasma levels of PNU 152243 and its 13-dihydroderivative PNU 155051 might be related to the formation of potent cytotoxic metabolites present in human plasma at undetectable concentrations and with prolonged half-life, as suggested by hematotoxicity tests performed with plasma from patients in GM-CFC assays.
    Type of Medium: Electronic Resource
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 3
    ISSN: 1432-0843
    Keywords: Key words Clonogenic tests ; Toxicology ; Anthracyclines ; Morpholinyldoxorubicin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Purpose: MMDX {3′-deamino-3′-[2(S)-methoxy-4-morpholinyl] doxorubicin}, an anthracycline derivative active in vitro and in vivo against multdrug-resistant tumors, is currently under investigation in phase I clinical trials. In vivo it is metabolically activated, resulting in more cytotoxic compounds. We determined in vitro the toxic concentration of a 1-h period of exposure to doxorubicin (DX), MMDX, and bioactivated MMDX on hematopoietic progenitors and tumor cell lines. Methods: DX and MMDX were tested on both bone marrow- (BM) and cord blood (hCB)-derived clonogenic cells, whereas the metabolites were tested on hCB only. All substances were tested on seven tumor cell lines. Results: BM cells proved to be twice as sensitive as hCB cells to cytotoxics, and MMDX was twice as toxic as DX against hCB cells; MMDX activated with normal rat-liver microsomes and with dexamethasone-induced rat microsomes were, respectively, 70 and 230 times more toxic than MMDX. A comparison of the cytotoxic concentrations on hematopoietic progenitors and tumor cells, revealed that DX and MMDX had 5-fold stronger activity on tumor cell lines than on granulocyte/macrophage colony-forming cells (GM-CFCs), whereas bioactivated MMDX showed comparable cytotoxicity against tumor cells and hematopoietic progenitors. Conclusions: MMDX metabolites are very potent but display a lower degree of tumor selectivity than MMDX. Strategies to reduce MMDX metabolization should be developed to optimize the therapeutic index of this new anthracycline.
    Type of Medium: Electronic Resource
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 4
    ISSN: 1432-0843
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Twenty-five patients with measurable small cell lung cancer relapsing after first-line chemotherapy were treated with vindesine 3 mg/m2 IV on days 1 and 8 and hexamethylmelamine 100 mg/m2 PO on days 1–14, repeated every 3 weeks. Among 18 fully evaluable patients there was 1 partial remission lasting for 111 days. Two patients had disease stabilization for 127 and 152 days, respectively. Fifteen patients had disease progression. The treatment was well tolerated, myelosuppression being the major side-effect.
    Type of Medium: Electronic Resource
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 5
    Electronic Resource
    Electronic Resource
    Springer
    Annals of oncology 11 (2000), S. 219-222 
    ISSN: 1569-8041
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 6
    Electronic Resource
    Electronic Resource
    Springer
    Breast cancer research and treatment 6 (1985), S. 213-220 
    ISSN: 1573-7217
    Keywords: endocrine therapy ; medroxyprogesterone acetate ; megestrol acetate ; receptor status ; side effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The use of pharmacologic doses of steroid hormones to treat patients with advanced breast cancer has been standard for many years. Recently there has been increased interest in the investigation of progestational agents, largely as a result of their excellent response rate in selected patients and their minimal side effects. In this panel discussion the participants discuss the use of progestin in advanced and early breast cancer. Criteria for patient selection, such as receptor status or response to previous therapies, are analyzed, and dose-response relationship and the side effects are addressed.
    Type of Medium: Electronic Resource
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 7
    ISSN: 1433-7339
    Keywords: Quality of life indicator ; Fatigue and malaise ; Small-cell lung cancer
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract “Fatigue and malaise” (FM) is a frequent, non-specific symptom of cancer patients caused by the disease, its treatment and psychological distress. Since comprehensive quality of life assessment is often not feasible in multicentre clinical trials, short, but clinically relevant, quality of life indicators have to be defined. In a representative subsample of 127 patients in a phase-III randomized small-cell lung cancer trial comparing two different regimens of combination chemotherapy, quality of life was assessed at the beginning of each of the six treatment cycles with a self-rating questionnaire including an early version of the EORTC questionnaire, a mood adjective check list (Bf-S) and a single linear-analogue self-assessment scale (LASA) measuring general well-being. FM, measured with a five-item Likert subscale of the EORTC questionnaire, showed moderate to high intercorrelations with other EORTC subscales assessing disease symptoms, toxicity of treatment, role functioning, personal functioning, restriction of social activity, psychological distress, emotional (Bf-S) and general well-being (LASA). At baseline, FM was one of the most pronounced symptoms. Over the six cycles 43%–31% of the patients complained of moderate to severe fatigue. Over the first two cycles FM tended to decrease, slightly increasing during cycles 3 and 4 and decreasing again before cycle 6. In a multiple regression analysis over the six cycles, 53% of the variance of FM was explained by patient-rated symptoms of disease and toxicity (disease alone: 43%; toxicity alone: 35%). Initial performance status, previous weight loss, treatment arm, cycle number and age predicted the scores of FM over the six cycles. We conclude that, among other disease- and treatment-related scales, FM can be used as a global indicator of quality of life in small-cell lung cancer patients.
    Type of Medium: Electronic Resource
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 8
    ISSN: 1433-7339
    Keywords: Key words Assessment ; Expectations ; Distress and conflict management ; Teaching tool ; Functional status
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Continuous accurate assessment is mandatory for palliative care of good quality. One of the major objectives in palliation is to meet the expectations of patient, family members and care givers. While a number of valid tools for assessing symptoms or function are available, there are unfortunately no recognized instruments for assessing expectations. The mismatch of expectations and the actual situation is a major source of distress and conflict. The present paper describes a simple way of visualizing this distress and conflict graphically. In our experience, this method is helpful in raising awareness of and enabling analysis of distress and conflict in patients, family members, and health care workers. It is also useful in the education of students and members of the palliative care team. It is illustrated with reference to four clinical situations.
    Type of Medium: Electronic Resource
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 9
    Electronic Resource
    Electronic Resource
    Springer
    Investigational new drugs 3 (1985), S. 357-359 
    ISSN: 1573-0646
    Keywords: 4-Demethoxydaunorubicin ; Phase-I ; acute leukaemia
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Eleven patients with heavily pretreated acute leukaemia were treated with 4-demethoxydaunorubicin. Dosages were escalated from 7 mg/m2/d to 15 mg/m2/d for 3 consecutive days. One patient achieved a partial remission and antitumor activity was seen in most other patients. Stomatitis was dose-limiting at 15 mg/m2. Phase II trials are warranted and we propose a schedule of 12 mg/m2/d for 3 consecutive days.
    Type of Medium: Electronic Resource
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 10
    ISSN: 1573-0646
    Keywords: phase II trial ; Nimustine ; ACNU ; small cell lung cancer ; second line treatment
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Thirty-nine previously treated patients received Nimustine in a phase II trial to test the therapeutic activity in refractory small cell lung cancer. Nimustine was given as a direct i.v. injection of 100 mg/m2 with treatments repeated every six weeks. Three partial remissions of 56, 123 and 355 days duration were noted among 34 evaluable patients. Thrombocytopenia was prominent with a median platelet nadir of 47,000/μl. We conclude that Nimustine has minor antitumor-activity in heavily pretreated patients with small cell lung cancer. The definitive value of Nimustine in the treatment of small cell lung cancer, as well as its superiority over its parent compounds remains to be established.
    Type of Medium: Electronic Resource
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
Close ⊗
This website uses cookies and the analysis tool Matomo. More information can be found here...