Adjuvant treatment of clinical stage I seminoma: is a single course of carboplatin sufficient?

OBJECTIVES: Adjuvant radiotherapy produces excellent disease-free rates in clinical Stage I seminoma. However, concern is growing about side effects and late hazards of this treatment. Carboplatin has been suggested to supplant radiotherapy. To date, there is little experience with this drug in the adjuvant treatment of seminoma. In particular, it is unclear whether one or two courses should be administered. METHODS: In a nonrandomized study, 125 patients with pure clinical Stage I seminoma were given adjuvant carboplatin treatment (400 mg/m2). Ninety-three patients received one course and 32 two courses. The median follow-up time was 48 months. To assess gonadal toxicity, serial measurements of follicle-stimulating hormone (FSH) levels were done. To assess myelotoxicity, platelet counts at 3 and 4 weeks after treatment were monitored. RESULTS: There were no relapses after two courses of carboplatin. After one course of carboplatin, eight relapses occurred (8.6%; 95% confidence interval [CI] 3.79% to 16.2%). All the relapses were located in the para-aortic region, and all the patients were rescued with cisplatin-based chemotherapy. The median time to recurrence was 16 months. The 5-year actuarial progression-free survival rate after one course was 91.1% (95% CI 85.25% to 97.01%). Younger patients (age groups: less than 30 years and 31 to 38 years) had relapses more frequently (P = 0.038) than those in the older age group (greater than 38 years). After 3 weeks, 32% of the patients had platelet counts below 150/nL. The median FSH level increased immediately after treatment, reaching a peak of 13.6 U/L. After 20 months, the median FSH level had returned to the normal range. CONCLUSIONS: One adjuvant course of carboplatin was associated with low myelotoxicity and low gonadal toxicity; however, the recurrence rate was almost 9% and thus unsatisfactory. After two courses of carboplatin, no relapse was observed. Thus, the two-course regimen of carboplatin appears to be equivalent to radiotherapy, and because of its favorable toxicity profile, this regimen should be investigated in randomized trials.

Adjuvant carboplatin treatment for seminoma clinical stage I.

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 chlorpropamide alcohol flush. Lack of specificity for familial non-insulin dependent diabetes.

A facial flush provoked by alcohol in chlorpropamide treated diabetics has been described as a genetic marker for a dominantly inherited type of non-insulin dependent diabetes. In this study a chlorpropamide alcohol flush was observed in 16.9% of control subjects (n = 154), 23.3% of insulin dependent diabetics (n = 437) and 16.5% of patients with non-insulin dependent diabetes (n = 145). Among the non-insulin dependent diabetics no difference in the frequency of the chlorpropamide alcohol flush was found between those with and without a family history of diabetes. Specificity was not improved by skin temperature measurement or additional placebo tests. According to these data the chlorpropamide alcohol flush does not seem to be specific for non-insulin dependent diabetes and hypotheses about the aetiology of this type of diabetes based on the chlorpropamide alcohol flush should be regarded with caution.

Prevalence of diabetes among children of insulin-dependent diabetic mothers.

Eight diabetics were found among 464 children, mean age 11.2 years, of 311 unselected insulin-treated mothers. By a method of age correction the total diabetes prevalence among the children at the age of 25 years was calculated as 3.4%. Three children were non-insulin dependent and these patients and their mothers may belong to the autosomal dominant type of diabetes, so-called MODY. In two of the other five families the fathers also had insulin-dependent diabetes; in two more cases first or second degree paternal relatives were insulin-dependent diabetics. Thus the prevalence of insulin-dependent diabetes among the children of insulin dependent mothers married to non-diabetics is calculated as 1.5% at the age of 25 years.