The traditional adjuvant therapy for seminoma stage I is abdominal radiotherapy. Although the relapse rate ranges below 5% this treatment is challenged because concerns about adverse late effects are accumulating. Carboplatin is effective in metastatic seminoma and two pilot studies have indicated effectivity in the adjuvant setting also. As this drug is almost non-toxic in moderate doses it could be an ideal adjuvant treatment for seminoma stage I. A group of 82 patients, mean age 37.5 years (range 22-73 years), with histologically pure seminoma stage I, were given carboplatin 400 mg/m2 after orchiectomy; 60 patients received only one course of carboplatin, and 22 patients received two courses. The median time of observation is 24 months, ranging from 2 to 48 months, and 66 patients have a minimum follow-up of 1 year. There is one relapse so far. Toxicity is rather mild with no severe nausea/emesis. Mean platelet counts were 164/nl after 3 weeks and 208/nl after 4 weeks; thus, myelotoxicity was negligible. Gonadal toxicity was measured by serial follicle-stimulating hormone levels. The mean level was 11.4 U/l before treatment, and 16.2 U/l after 5 weeks, 17.3 U/l after 4 months, 14.5 U/l after 8 months and 13.5 U/l after 12 months. Thus, gonadal toxicity also appeared to be mild. In summary, the efficacies of adjuvant carboplatin and of abdominal radiotherapy seem to be identical. As carboplatin, in the dosage used, involves no severe acute side-effects and probably few late adverse effects, this regimen constitutes a promising new treatment option in seminoma patients stage I that deserves to be studied in randomized trials.
The study of multiple primary neoplasms may provide more insight into the pathogenesis of specific cancers and, secondly, it addresses the issue of treatment-related induction of second tumors. 584 consecutive patients with testicular germ cell tumors treated during 1969-1992 in Berlin were retrospectively analyzed for the prevalence of multiple primary neoplasms. 23 patients (16 pure seminoma, 7 nonseminoma) developing nontesticular malignancies in addition to testis cancer were identified (3.9%, 95 confidence intervals ± 1.6%). The mean age at the time of the testis cancer was 42.8 years, and mean age at the time of nontesticular malignancy was 50.2 years. In 4 cases, the nontesticular malignancy preceded testis cancer, in 3 patients both neoplasms occurred simultaneously, and in 16, nontesticular malignancies developed subsequently to testis cancer. In 4 patients, triple malignancies were observed. Bladder carcinoma and bronchogenic cancer with each 3 cases were the most frequent second neoplasms seen in these patients. 9 consecutive cancers developed within radiation fields, the median latency period in these cases was 12 years. None of the subsequent cancers developed after chemotherapy. It is concluded that genetic predisposition and radiation effects are the most important factors contributing to the occurrence of multiple primary neoplasms in patients with testicular germ cell cancer. The high rate of multiple primary neoplasms in these patients lends further evidence to the theory of genetic anticipation of germ cell cancer.
9 alpha-Fluorocortisol (9 alpha FF) is about 200 times more potent as a mineralocorticoid than cortisol (F) in man, although it binds with the same affinity as F and aldosterone to the human mineralocorticoid receptor. The low mineralocorticoid activity of F has been shown to be due to its rapid conversion by the kidney to cortisone (E), which does not bind to the receptor. Therefore, we compared the conversion of F to E with that of 9 alpha FF to 9 alpha-fluorocortisone (9 alpha FE) by 11-hydroxysteroid dehydrogenases in man in vivo and in vitro. Single oral doses of 9 alpha FF, 9 alpha FE, and F were given to normal males, and the excretion of free 9 alpha FF, 9 alpha FE, F, and E was measured in urine. Human kidney and liver slices were incubated with unlabeled steroids, and the free 11-hydroxy- and 11-oxosteroids were quantitated after high performance liquid chromatography separation by UV absorption. Oral F (5 mg) is excreted 70% as free E and 30% as free F (percentage of free steroids only). Oral 9 alpha FF (5 mg) is excreted 90% as free 9 alpha FF and 10% as free 9 alpha FE. Free 9 alpha FF excretion is 14 times greater than that of F after ingesting an identical dose. Oral 9 alpha FE (4 mg) is also excreted 90% as 9 alpha FF and 10% as 9 alpha FE. Kidney slices convert F much faster to E than 9 alpha FF to 9 alpha FE. The conversion of 9 alpha FE to 9 alpha FF is, on the contrary, much faster than that of E to F. Thus, the equilibrium of the reaction is on the 11-oxo side for F/E and on the 11-hydroxy side for 9 alpha FF/9 alpha FE. The interconversion of both pairs of steroids is inhibited by glycyrrhetinic acid in a dose-dependent manner. Liver slices do not measurably convert 9 alpha FF to 9 alpha FE, but do rapidly convert 9 alpha FE into 9 alpha FF. Reflecting this negligible conversion of 9 alpha FF to 9 alpha FE and the low plasma-protein binding of 9 alpha FF, free urinary 9 alpha FF excretion is much higher than that of F after the same oral dose.(ABSTRACT TRUNCATED AT 400 WORDS)
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