Fractionated scheme of oral vinorelbine as single-agent therapy or in combination with cisplatin concomitantly with thoracic radiotherapy in stage III non-small-cell lung cancer: dose-escalation phase I trial.

INTRODUCTION: A dose-determination study was conducted in untreated stage III non-small-cell lung cancer to assess continuous exposure to fractionated oral vinorelbine (NVBo), a radiosensitizer, during the radiotherapy period, either alone (first cohort) or in combination with cisplatin (second cohort). PATIENTS AND METHODS: Three patients with stage IIIAN2/IIIB were expected at each dose level, with 3 additional patients in case of dose-limiting toxicity (DLT). Concomitantly with a 60-Gy total dose of radiotherapy, NVBo was given from 60 mg up to 180 mg total dose per week split on days 1, 3, and 5. Once the maximum tolerated dose (MTD), defined as 2 DLTs in a dose level, was determined and the recommended dose of NVBo alone was established, the trial assessed its recommended dose in combination with cisplatin 80 mg/m(2) every 3 weeks. RESULTS: In the first cohort, 26 patients were enrolled. MTD was 160 mg/wk; there were 3 cases of grade 3 esophagitis and 1 of grade 3 pneumonia as DLT out of 5 patients in this dose level. In the recommended dose level (150 mg/wk), only 1 of 6 patients experienced a DLT. In the second cohort, 11 patients received NVBo weekly doses from 130 mg to 150 mg with cisplatin. Only 2 patients received 150 mg/wk NVBo; the trial closed before MTD was determined. The confirmed response rates were 42% and 55% in the first and second cohort, respectively. CONCLUSION: The recommended dose of this fractionated NVBo scheme as single-agent therapy concomitantly with radiotherapy for 6 weeks is 50 mg on days 1, 3, and 5 (150 mg/wk); combined with cisplatin 80 mg/m(2) every 3 weeks, the dose should be 140 to 150 mg/wk adapted on hematology. The response rate is promising.

[Management of locally advanced prostatic adenocarcinoma in France. OCTAVE observational survey]. / Prise en charge thérapeutique de l'adénocarcinome de la prostate localement avancé en France. Enquête Observationnelle OCTAVE.

OBJECTIVE: To describe the management of patients with locally advanced prostate cancer in France and the changes in this management between 2000 and 2003. MATERIAL AND METHODS: Observational survey on a sample of urologists and radiotherapists throughout France, comprising 2 aspects: a retrospective aspect (patients diagnosed and treated in 2000) and a prospective aspect (patients diagnosed in 2003 during the survey period). Eligible patients presented locally advanced prostate cancer (T3, biopsy pT3, T4, NO-N1-Nx, M0), not treated in the context of a therapeutic trial. Demographic data, prognostic factors and first-line treatments were collected. RESULTS: From September 2003 to January 2004, 1,076 patients with a mean age of 69.2 years were included in 188 centres. The percentage of most favourable stages, T3-pT3, N0-Nx, M0 was 84.6% in 2000 and 90.6% in 2003. The median PSA was 18 ng/ml and 21% of patients had a Gleason score > 7. Lymph node invasion was demonstrated in 9.4% of patients. Changing management practices between 2000 and 2003 were marked by an increased use of the radiotherapy/hormonal therapy combination (p<0.001) rather than exclusive radiotherapy (p< 0.001) and total prostatectomy either alone or combined with another modality (p=0.001). No other treatment was associated with prostatectomy in 70% of operated patients. One quarter of patients received exclusive hormonal therapy, and this rate remained stable between 2000 and 2003. CONCLUSION: Epidemiological data of the survey are concordant with those of the literature with a migration of TNM stages towards less advanced stages. In terms of treatment, there is a growing use of the radiotherapy-hormonal therapy combination, with a predominant place of hormonal therapy. The indication for prostatectomy appears to be optimized and constitutes the only therapeutic procedure in almost 70% of operated patients.

Treatment of central precocious puberty by subcutaneous injections of leuprorelin 3-month depot (11.25 mg).

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.