Cyclical use of tamoxifen and high-dose medroxyprogesterone acetate in advanced estrogen receptor positive breast cancer

Summary One-hundred and seventy patients with estrogen receptor positive (10 pmol/g protein) advanced breast cancer have been treated in a prospective randomized study either with continuous tamoxifen 30 mg × 1 daily (TAM), or with TAM 30 mg × 1 daily for 8 weeks alternating with medroxyprogesterone acetate 500 mg × 2 daily for 8 weeks (TAM/HD-MPA). The response rate was 62% in the group treated with cyclic TAM/HD-MPA versus 41% in the TAM alone group (p = 0.02). There was no significant difference in duration of remissions or survival.     

Pharmacokinetics and pharmacodynamics of the aromatase inhibitor 3-ethyl-3-(4-pyridyl)piperidine-2,6-dione in patients with postmenopausal breast cancer

Summary The pyridylglutarimide 3-ethyl-3-(4-pyridyl)-piperidine-2,6-dione (PyG) is a novel inhibitor of aromatase that was shown to cause effective suppression of plasma oestradiol levels in postmenopausal patients. In four patients receiving oral doses of PyG (500 mg) twice daily for 3–4 days, oestradiol levels fell to 31.1%±6.3% of baseline values within 48 h and remained suppressed during treatment. Of a further six patients who received oral PyG (1 g) as a single dose, five had quantifiable oestradiol levels. Oestradiol suppression was sustained for 36 h and recovery correlated with a fall of PyG concentrations below a threshold value of ca. 2 g/ml. The pharmacokinetics of PyG were non-linear and, when fitted to the integrated Michaelis-Menten equation, yielded good parameter estimates forC _o (21.7±1.82 g/ml),K _m (2.66±0.68 g/ml) and V_max (0.86±0.06 g ml^–1 h^–1). On subsequent repeated dosing with PyG, both theK _m (4.31±0.48 g/ml) and the V_max (1.83±0.13 g ml^–1 h^–1) values increased and recovery from oestradiol suppression was more rapid, indicating that PyG induces its own metabolism.Abbreviations PyG 3-ethyl-3-(4-pyridyl)piperidine-2,6-dione - AG aminoglutethimide - CSCC cholesterol side-chain cleavage - HPLC high-performance liquid chromatography - AUC area under the concentration versus time curve This study was supported in part by grants to the Institute of Cancer Research (Royal Cancer Hospital) from the Cancer Research Campaign and Medical Research Council     

Norwegian oncologists' expectations of intensity-modulated radiotherapy

Although intensity-modulated radiotherapy (IMRT) may increase the therapeutic ratio of radiotherapy for a range of malignancies, only a few IMRT treatments have yet been performed in the Nordic countries. The scores derived from a national survey to assess Norwegian oncologists' expectations of IMRT are presented. A questionnaire was distributed to all consultants in oncology at Norwegian radiotherapy clinics. Summary scores of daily general radiotherapy workload (DGRTW), acquaintance with IMRT (AI) and expectations of IMRT (EI) were derived. Thirty-nine questionnaires (67%) were returned from a total of 58 oncologists. The oncologists' scores on the AI scale (mean score: 7.5 out of 21) were rather low. Their AI scores were found to be positively correlated with their DGRTW. Higher scores on the EI scale were documented (mean score: 6.2 out of 14): 15 oncologists (39%) rated IMRT as one of the three major contributors to potentially increased cancer survival. Oncologists treating patients with prostate, head and neck, gastrointestinal and CNS tumours had higher EI scores than the other oncologists (7.7 vs. 5.1; p=0.01). The Norwegian radiation oncologists' expectations of IMRT are high in terms of both the potential clinical benefit and the rate of implementation. This should encourage the radiotherapy communities to continue (or rapidly initiate) their efforts in providing the routines required for safe implementation of IMRT.     

Evolution of antithrombin III during the postoperative period

With a view to throwing some light on the age characteristics of platelets released into the blood in response to short-term physical exercise, we conducted exercise experiments on 23 healthy subjects previously injected with different platelet populations labelled with ¹¹¹In and ⁵¹Cr. Based on comparative platelet kinetic studies of pre- and post-exercise platelets and on exercise experiments carried out while labelled-platelet populations of different age composition were circulating, we cannot support the concept that the platelets released into the blood in response to exercise are enriched with young platelets. In addition, we found that simultaneously-injected large and small platelets were released to the same extent in response to exercise, but that the sequestration patterns of large and small platelets seem to be different.     

Imaging of Experimental Rat Gliomas Using a Clinical MR Scanner

Background: Studies of brain tumor development in experimental animal models have to date mostly been based on post-mortem histological examinations. The use of magnetic resonance imaging (MRI) may provide a non-invasive technique for studying tumor growth and treatment effects in such animal models. However, most of these studies have been performed on purpose-dedicated small bore magnetic resonance (MR) systems, of high cost and limited availability. The purpose of this study was thus to obtain high-resolution images of experimental gliomas in the rat brain, using a clinical 1.5T MR scanner. Methods: Anesthesized rats bearing BT₄C brain tumors were positioned into a specially designed immobilizing device, and a small circular coil was positioned onto the skulls. Two T1 weighted series were acquired before and after subcutaneous contrast injections. A T2 weighted series was also obtained. The rats were then sacrified, the brains removed, and the histological tumor volumes were compared to the volumes obtained on MRI. Results: There were visible tumors in 10 of 13 animals scanned on MR. The rim of the tumors were visualized on T1 weighted series without contrast. On T1 images with contrast, the tumors were seen as high signal intensity areas. The T2 weighted images showed peritumoral edema. No necrosis or cystic parts of the tumors were detected. There was a consistency between the MR and the histology findings, showing a high degree of correlation between the two volume determination methods. Conclusions: High-resolution images of experimental rat gliomas can be obtained using a clinical MR scanner and a commercially available RF coil. This MRI technique may also be expanded to extraneural rat tumor models, for studies of tumor development and treatment.