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Biomedical subjects

L Denis

Publications and source records attributed to L Denis.

At least 127 records · Page 7Linked to original sources

Chemotherapy of metastatic renal cancer.

The appearance of metastatic disease heralds disaster for the vast majority of patients with renal carcinoma. A few spontaneous regressions of established metastases have been reported but no systemic chemotherapeutic treatment withstood the test of time or critical analysis. This analysis requires objective remissions in measurable metastatic disease evaluated against well-defined prognostic factors in relation to survival with quality of life for the patient. No single agent chemotherapy achieved a desired 20% response rate and only a few combination studies, especially with immunotherapy, reported significant clinical results. We recommend that the variable biological potential of renal metastatic disease be harnessed in prospective multicentric phase I/II trials with strict response and prognostic criteria to search for new antineoplastic agents for this disease.

Antineoplastic Agents↗

Current status of intravesical chemotherapy trials in the EORTC Urological Group. An overview.

The EORTC Urological Group is one of the 31 clinical groups and working parties within the European Organization for Research and Treatment of Cancer (EORTC). Intravesical chemotherapy has been used as chemoresection or chemoprophylaxis. Chemoresection has mainly been utilized in phase II studies to demonstrate ablation of existing disease and to study the mechanism of drug action. These studies are usually performed by individual members to obtain relevant information for the preparation of randomized trials. One example is a phase II chemoresection study with 4'-epi-doxorubicin (EPR). The EORTC GU Group extended its phase II trials to study remission in patients with primary carcinoma in situ. A new concept introduced in the prospective, randomized phase III trials includes the evaluation of chemoresection of a marker lesion as a prognostic factor in long-term prophylactic treatment. Chemoprophylaxis in the phase III trials aims to study the disease-free period, the recurrence rate and the long-term survival. So far, a series of five phase III trials, totaling more than 2,000 patients, demonstrated the efficacy of chemoprophylaxis to reduce tumor recurrence rates. The variation in the results of the different trials are due more to the prognostic factors (characteristics of the tumors) than to the related efficacy of the chemoprophylactic drugs. The selection of currently employed drugs, Mitomycin C, Epirubicin and BCG, is based on reported results, lack of toxicity, and drug availability in Europe. The data collected will be of great importance to determine the optimal clinical management of superficial bladder cancer.

Administration, Intravesical↗

Combination chemotherapy with cisplatin and methotrexate in advanced transitional cell cancer of the bladder.

We studied 53 patients with bidimensionally measurable metastases of transitional cell cancer of the bladder who were treated with a planned regimen of 70 mg. per m. cisplatin intravenously on day 1, and 40 mg. per m. methotrexate intravenously on days 8 and 15 every 3 weeks. The toxicity of this regimen, with agranulocytosis and mucositis as the most important side effects, was so severe that only 17 per cent of the patients actually received the protocol regimen without modification. Six patients were ineligible and 47 were evaluable for toxicity, including 43 who were evaluable for response. The response to treatment was assessed after each second treatment cycle. A complete response was achieved in 10 patients (23 per cent) and a partial response was achieved in 10 (23 per cent). The median duration of response was 64 weeks for patients with a complete response and 23 weeks for those with a partial response, while the median duration of survival was 81 and 37 weeks, respectively. The aforementioned regimen with allowance of routine leucovorin rescue is tested as preoperative chemotherapy in patients with stages T3 to T4 nonmetastatic bladder cancer.

Antineoplastic Combined Chemotherapy Protocols↗

Embolization and postinfarction nephrectomy in patients with primary metastatic renal adenocarcinoma.

In a phase-II study of the EORTC GU Group 34 patients with metastatic renal cell carcinoma were treated by angioinfarction and delayed nephrectomy. The mortality of the procedure was 5.8%. One patient had a complete remission. 80% of the patients showed progression within 6 months after nephrectomy. The median survival of the patients was 25 weeks, 65% of the patients died within 1 year after nephrectomy.

Adult↗

Effects of high-dose ketoconazole and dexamethasone on ACTH-stimulated adrenal steroidogenesis in orchiectomized prostatic cancer patients.

The effects of high-dose ketoconazole (i.e. 400 mg every 8 h) therapy on adrenal steroidogenesis were investigated in 7 patients with advanced prostatic cancer who no longer responded to orchiectomy. An ACTH challenge was performed before and on days 14 and 28 of high-dose ketoconazole treatment. During the last 14 days, dexamethasone (0.5 mg twice daily) was administered together with ketoconazole. High-dose ketoconazole alone lowered the basal levels of the androgens by 49-66%. It almost completely inhibited their stimulation by ACTH, whereas plasma progesterone was doubled. Basal cortisol was only slightly lowered, but the response to ACTH stimulation was markedly blunted. Basal and stimulated plasma aldosterone remained unaffected. Both basal and stimulated 11-deoxycortisol, 11-deoxycorticosterone, and, to a lesser extent, corticosterone rose more markedly after ketoconazole than after placebo. The basal and stimulated plasma adrenal androgen levels were further reduced after combined ketoconazole-dexamethasone treatment, whereas plasma corticosterone, 11-deoxycortisol, and 11-deoxycorticosterone were lowered in the same way as cortisol. Aldosterone and progesterone profiles were similar to those observed under high-dose ketoconazole, but plasma 17 alpha-hydroxyprogesterone increased more markedly than after high-dose ketoconazole alone. These results demonstrate that high-dose ketoconazole lowers plasma androgen levels in orchiectomized patients and partly inhibits the gluco- and mineralocorticoid syntheses, especially after ACTH-stimulation. The addition of dexamethasone does not only correct the possible consequence of the impairment of the cortisol production by high-dose ketoconazole, but it further reduces the androgen levels and lowers the plasma concentrations of most precursors, for instance 11-deoxycorticosterone, which has some physiological mineralocorticoid activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Cortex Hormones↗

Ultrasound in urological oncology.

Transabdominal, transrectal and transurethral ultrasonography play a major role in the diagnosis and staging of urological tumors. The practical limitations and possibilities of the several techniques are evaluated in the oncological work-up of tumors of the kidney, bladder, seminal vesicles, prostate and testis. Ultrasonography has become an important diagnostic tool in urological oncology.

Diagnosis, Differential↗

Exercise thallium stress testing compared with coronary angiography in patients without exclusions for suboptimal exercise or cardioactive medications.

From 1293 patients who underwent thallium stress testing and 1099 patients who had coronary angiography, a consecutive series of 122 who had both studies is evaluated. This group includes suboptimally exercised patients and those receiving one or several cardiovascular drugs that were not discontinued prior to exercise. When compared with the EKG stress test, thallium stress imaging was superior in sensitivity (80% vs 68%), specificity (84% vs 49%), accuracy (81% vs 62%), positive predictive value, (92% vs 75%), and negative predictive value (65% vs 45%) in this group, with 71% prevalence of angiographically significant coronary artery disease.

Angiography↗

Biochemical monitoring of carcinoma of prostate treated with an LH-RH analogue (Zoladex).

The levels of prostatic specific antigen (PSA) and prostatic acid phosphatase (PAP), both measured by radioimmunoassay, and two cancer indices given by the ratio of serum alpha-1 acid glycoprotein to prealbumin (AGP:Palb) and alpha-1 acid glycoprotein to alpha-2 HS globulin (AGP:HS) were evaluated as markers to assess the response of prostatic cancer to treatment with Zoladex, an LH-RH agonist. A rise in PSA and PAP occurred in 8/65 patients (12%) during the initial induction phase. In metastatic disease prior to treatment none of these indices was significantly different between patients who attained a sustained response and those whose response was nil or only transient. Responders and non-responders could, however, be distinguished by the levels of various analytes after treatment. At 6 months the median PSA in those who responded was 2.5 ng/ml compared with 51.5 ng/ml in the non-responders. At 12 months the figures were 3.0 and 155 ng/ml respectively. The corresponding median PAP levels were 1.4 and 19 ng/ml at 6 months and 1.3 and 18 ng/ml at 12 months. The AGP:Palb ratio was also significantly different in these two groups at 6 and 12 months. PSA appears to be the most sensitive indicator of the response to treatment. The likelihood of obtaining a prolonged clinical response can be assessed within 6 months of the start of treatment.

Acid Phosphatase↗