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Biomedical subjects

R Paridaens

Publications and source records attributed to R Paridaens.

At least 109 records · Page 6Linked to original sources
PubMed1985

Cisplatin plus vindesine in advanced breast cancer: a phase II trial of the EORTC Breast Cancer Cooperative Group.

This phase II clinical trial was conducted in a series of patients with advanced breast cancer, refractory to conventional chemotherapy. The therapeutic regimen consisted of a combination of cisplatin 100 mg/m2, given as a 24-hr infusion on day 1 and vindesine (VDS) 2 mg/m2, i.v. bolus on days 1 and 8. VDS injection was omitted on day 8 in patients with poor bone marrow reserves (prior extensive irradiation). Courses were repeated at 4-week intervals until documented disease progression. Among 46 evaluable patients, there were two complete and seven partial remissions for an overall response rate of 20%. These responses lasted for a median of 21 weeks (range 8-89 weeks). Remission rates according to the predominant metastatic site were as follows: soft tissue, 3/8 (38%); bone, 0/6 (0%); viscera, 6/32 (19%). Transient myelosuppression and gastrointestinal intolerance were almost universal. Renal function impairment and neurologic manifestations were frequently encountered but these adverse reactions were generally mild. Significant antineoplastic activity in far-advanced and heavily pretreated patients warrants further evaluation of this regimen at an earlier stage of the disease.

Adult↗
PubMed1983

Effects of aminoglutethimide on adrenal steroid secretion.

Effects of various doses of aminoglutethimide (AG) alone upon adrenal steroidogenesis were studied in normal postmenopausal women, whereas the effects of combined treatment with aminoglutethimide in variable doses together with 40 mg of hydrocortisone were studied in postmenopausal women with advanced mammary cancer and compared to effects of treatment with cortisol alone. Despite the well known inhibitory effect of AG on cortisol biosynthesis, plasma cortisol levels were unaffected by AG in doses of 150-1000 mg/d, probably due to a compensatory increase in ACTH in subjects with an intact pituitary-adrenal axis. The aromatase system appeared to be very sensitive to inhibition by AG, a clearcut inhibition being shown at doses as low as 150 mg/d. Evaluated from the ratio of plasma oestrone (E1) to plasma androstenedione (AN), treatment with AG at a dose of 150 mg/d appeared to reduce the aromatase activity to 33% of the basal value; 250 mg/d resulted in a reduction to 20% and 1 g/d to 5% of basal values. Whereas AG at 150 mg/d did not appear to affect 11 beta-hydroxylase, the latter was clearly inhibited by 250 mg/d and even more so by 1000 mg/d, as indicated by the increase in plasma 11-desoxycortisol and 17-OH progesterone (17-OHP) levels. Due to the increase of the latter, their biosynthetic precursor, AN and to a lesser degree testosterone (TS) levels increased significantly during AG treatment at a dose of 250 or 1000 mg/d. delta 5 steroid levels remained practically unchanged, probably because 11-(as well as the 21-) hydroxylation concerns essentially the delta 4 pathway. During combined treatment with 500-1000 mg/d of AG and cortisol 40 mg/d, AN and TS were significantly higher than during treatment with cortisol alone, suggesting that cortisol had not completely blocked ACTH secretion. E1 and E2 levels were however lower than during treatment with cortisol alone, a consequence of the inhibition of the aromatase activity. Although at a dose of 500-1000 mg/d AG is a highly effective aromatase inhibitor, oestrogen levels during treatment with AG with or without concomitant administration of cortisol are still significantly different from zero. Therefore if one aims at complete elimination of any oestrogen effect, addition of an antioestrogen to AG treatment may be required.

Adrenal Cortex Hormones↗
PubMed1983

[Relation between estrogen and progesterone receptors and response to hormone therapy].

In mammary cancers, and more especially at the stage of generalization, the detection of estrogen receptors plays a prominent role in the choice of treatment. Recent studies indicate that nearly half of cancers containing receptors are responsive to various hormone treatments while only a minority of cancers not containing receptors are responsive to the same treatments. The present review emphasizes the benefits of a quantitative dosage of these receptors compared to their simple detection. It also evaluates the predictive value of progesterone receptors as an additional test for hormonodependence. Finally, it analyses the part played by receptors dosage in the current therapeutic strategy as well as in the development of new clinical protocols.

Antineoplastic Agents↗
PubMed1982

N-(phosphonacetyl)-L-aspartate (PALA) in advanced breast cancer: a phase II trial of the EORTC breast cancer cooperative group.

Twenty-nine evaluable patients with extensively pretreated breast cancer received PALA, a new pyrimidine antimetabolite. The drug was given by intravenous infusion over 60 min, at a daily dose of 2.5 g/m2 for 2 consecutive days. Courses were repeated at 2-week intervals and doses were escalated to toxicity. Two objective partial remissions were observed, lasting for 3 and 4.5 months respectively. Toxic effects were dose-related and consisted mainly of mucocutaneous manifestations, i.e., skin rashes, stomatitis, diarrhea, conjunctivitis and corneal ulcerations. Evidence of antitumor potential in far-advanced disease and lack of myelosuppression point to the need for additional trials of PALA in a more favorable selection of patients with breast cancer.

Adult↗
PubMed1980

Clinical significance of the quantitative assessment of estrogen receptors in advanced breast cancer.

The predictive value of the estrogen receptor (ER) assay with regard to the response to hormonal treatment was analyzed in women with advanced breast carcinoma. The significance of ten clinical variables of putative prognostic value was also investigated. A total of 49 courses of endocrine therapy were available for study. The respective merits of using the receptor information as a qualitative or a quantitative variable were compared. Linear logistic regression analysis showed that the quantitative information was significantly related to the therapeutic response (P < 0.0001) and proved to be superior to the qualitative information. Compared with the clinical variables tested with the logistic model, receptor concentration was by far the most important single predictor of response. Nevertheless, introduction of two of these clinical variables (i.e., age and menopausal status) into the model in addition to receptor concentration improved its predictive value. Presented in graphic form, the improved model provides a simple means to estimate the probability that a given patient will respond to endocrine therapy. Successive ER assays were available in a series of patients who had received no systemic treatment. In ER+ cases, there was a significant correlation between receptor concentrations in the consecutive assays. There was no influence of the time interval between tissue samplings. Data were also consistent in ER- patients. These results give support to the practice of routine receptor determination in the primary tumor at the time of mastectomy. It is concluded that the distinction between hormone-responsive and hormone-resistant tumors appears artificial. The therapeutic implications of a continuous gradient of hormone-dependency among breast cancers are discussed.

Adrenalectomy↗
PubMedDate not supplied

Mitomycin C for metastatic prostate cancer: final analysis of a randomized trial.

BACKGROUND: Almost all patients that undergo hormonal manipulation for metastatic prostate cancer will ultimately progress because of hormone resistance. Therefore we assessed the effect of early addition of intravenous Mitomycin C to orchiectomy in patients with newly diagnosed metastatic prostate cancer. PATIENTS AND METHODS: 178 patients with histologically proven and previously untreated metastatic prostate cancer were included in a prospective, randomized multicenter trial. Randomization was done centrally between orchiectomy alone and orchiectomy with Mitomycin C. 148 patients were evaluable. RESULTS: At the final analysis 139 patients have deceased. The remaining 9 patients are still alive, but all present progression. There was no statistically significant difference in the real time to progression, or in the estimated cancer related and overall survival between both groups. Mean time to progression was 29 months in group 1 (orchiectomy alone), and 26 months in group 2 (orchiectomy and Mitomycin C) (p = 0.64). Mean time to cancer related death was 32 months and mean overall survival was 31 months in both groups. CONCLUSIONS: Mitomycin C has no beneficial effect when used in conjunction to orchiectomy in patients with newly diagnosed metastatic prostate cancer.

Aged↗