Depot GnRH agonists are widely used for the treatment of precocious puberty. Leuprorelin 3-month depot is currently used in adults but has not been evaluated in children. We evaluated the efficacy of this new formulation (11.25 mg every 3 months), for the suppression of gonadotropic activation and pubertal signs in children with central precocious puberty. We included 44 children (40 girls) with early-onset pubertal development in a 6-month open trial. The inclusion criteria were clinical pubertal development before the age of 8 (girls) or 10 (boys), advanced bone age, enlarged uterus (>36 mm), testosterone more than 1.7 nmol/liter (boys), and pubertal response of LH to GnRH (peak >5 IU/liter). The principal criterion for efficacy assessment, GnRH-stimulated LH peak less than 3 IU/liter, was met in 81 of 85 (95%) of the tests performed at months 3 and 6. The remaining four values were slightly above the threshold. The levels of sex steroids were also significantly reduced and clinical pubertal development was arrested. Plasma leuprorelin levels, measured every 30 d, were essentially stable after d 60. Local intolerance was noted after 10 of 86 injections (12%), and was mild in four cases, moderate in five cases, and severe in one. Among these 10 events, 4 consisted in local pain at injection's site. In conclusion, leuprorelin 3-month depot efficiently inhibits the gonadotropic axis in 95% of children with central precocious puberty studied for a 6-month period. This regimen allows the reduction of the number of yearly injections from 12 to 4.

This randomized phase II study examined the use of vinflunine in combination with gemcitabine or carboplatin as first-line chemotherapy in cisplatin-ineligible patients with advanced urothelial carcinoma. Both doublets were feasible and offered a similar 77% disease control rate. Response rate (44%), overall survival (14 months) and less haematological toxicity favoured vinflunine–gemcitabine.

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Introduction: To assess the effects of intermittent maximal androgen blockade (IMAB) on testosterone (T) levels during on- and off-treatment periods. Materials and Methods: A total of 51 patients with metastatic prostate cancer underwent a 6-months period of continuous maximal androgen blockade (MAB) consisting of leuprorelin (3.75 mg at monthly intervals) plus flutamide (250 mg t.i.d.) followed by IMAB. During each cycle, the cut-off prostate-specific antigen (PSA) levels to stop and resume treatment were 4 and 10 ng/ml, respectively. IMAB continued until progression under treatment occurred. Monthly PSA and T measurements were performed in central laboratories. Results: From the 51 patients included (mean age 67.6 years), 27, 16, 12, 8 and 5 underwent a second, third, fourth, fifth and sixth cycle, respectively (mean follow up: 17 months). Before treatment, 4 patients had a T lower than normal laboratory value but these recovered all to a normal T value at the end of the first cycle. During the 6 cycles, only 8 patients did not recover a normal T at least once during the off-treatment periods (OTP). The mean T values at the end of each OTP did not change during these 6 cycles (Anova test, p = 0.621) with a mean stable recovery delay of 32–43 days (Anova test, p = 0.722). Conclusion: IMAB protocol with an initial 6-month treatment period can result in an intermittent castration with the recovery of normal T levels in most patients during six consecutive cycles of treatment.

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