Toxicity in patients receiving adjuvant docetaxel + hormonal treatment after radical radiotherapy for intermediate or high-risk prostate cancer: a preplanned safety report of the SPCG-13 trial.

BACKGROUND: Radical radiotherapy (RT) combined with androgen deprivation therapy is currently the standard treatment for elderly patients with localized intermediate- or high-risk prostate cancer (PC). To increase the recurrence-free and overall survival, we conducted an adjuvant, randomized trial using docetaxel (T) in PC patients (Scandinavian Prostate Cancer Group trial 13). METHODS: The inclusion criteria are the following: men >18 and ≤75 years of age, WHO/ECOG performance status 0--1, histologically proven PC within 12 months before randomization and one of the following: T2, Gleason 7 (4+3), PSA >10; T2, Gleason 8--10, any PSA; or any T3 tumors. Neoadjuvant/adjuvant hormone therapy is mandatory for all patients. The patients were randomized to receive six cycles of T (75 mgm(-2) d 1. cycle 21 d) or no docetaxel after radical RT (with a minimum tumor dose of 74 Gy). This study identifier number is NTC 006653848 (http://www.clinicaltrials.org). RESULTS: In this preplanned safety analysis of 100 patients, T treatment induced grade (G) 3 adverse events (AEs) in 15 patients (30%) and G4 AEs in 30 patients (60%), mainly due to bone marrow toxicity. Neutropenia G3--4 was observed in 72% of the patients, febrile neutropenia was found in 24% of patients, neutropenic infection in 10% of patients and G3 infection without neutropenia in 4% of patients. Nonhematological G3 AEs were rare: anorexia, diarrhea, mucositis, nausea, pain (1 patient each) and fatigue (5). Other severe serious AEs related to T were pulmonary embolism and renal failure. However, only three patients discontinued T before completing the planned six cycles. No deaths had occurred. No patients in the control arm experienced G3--4 toxicities at 12 weeks after the randomization. CONCLUSIONS: Adjuvant docetaxel chemotherapy after radiotherapy has a higher frequency of neutropenia than previous studies on patients with metastatic disease. Otherwise, the treatment was quite well tolerated.

Pharmacokinetics of finrozole (MPV-2213ad), a novel selective aromatase inhibitor, in healthy men.

AIMS: To investigate the pharmacokinetics of finrozole (MPV-2213ad), a novel competitive aromatase enzyme inhibitor, in healthy male volunteers. METHODS: The study was an open, partly randomized cross-over study including 23 volunteers receiving single doses of 3, 9 mg or 30 mg of finrozole as tablets or solution with 14 days between the administrations. The highest dose was given as tablets only. Serum concentrations of finrozole were determined using high performance liquid chromatography combined with mass spectrometry. RESULTS: The mean time to peak serum concentration ranged from 2.5 to 3.1, and 0.6-0.7 h after tablets and solution, respectively. The Cmax values increased as the dose increased. The calculated apparent mean elimination half-life (t(1/2,z)) was approximately 3 h after the solution, and approximately 8 h after the tablet. The AUC(0,infinity) after finrozole tablets increased proportionally from 3 mg to 9 mg and from 3 to 30 mg. The calculated relative mean bioavailabilities (AUC(0,infinity)-ratio) for the 3 mg and 9 mg doses of finrozole as tablets were 89% and 78%, respectively. CONCLUSIONS: The absorption of finrozole from the tablet formulation was relatively rapid, and the apparent elimination half-life was longer after the tablet than after the solution, probably reflecting overlap of the absorption with the elimination phase.

Outcome of Burch retropubic urethropexy and the effect of concomitant abdominal hysterectomy: a prospective long-term follow-up study.

A prospective follow-up study was performed to evaluate the effect of a concomitant abdominal hysterectomy with Burch colposuspension. Sixty-five women underwent Burch colposuspension (the Burch group) and 78 women colposuspension with concomitant abdominal hysterectomy (the hysterectomy group) during a 1-year period in Turku University Hospital. Subjective outcome was assessed with three questionnaires: at 6 weeks, 1 year, and a mean of 4.9 years after the operation. Complications related to the operation occurred in 19 patients (29.2%) in the Burch group and in 36 (46.2%) in the hysterectomy group (P = 0.038). No statistically significant difference in the frequency of any subgroup of complications was found. Instead, complications cumulated to fewer patients in the Burch group. During postoperative care in the hospital intermittent catheterization to treat transient urinary retention was needed more frequently in the Burch group than in the hysterectomy group (10.8% vs. 1.3%, P = 0.046). No significant difference was found in subjective short- and long-term outcome. In the long-term follow-up 79% were subjectively cured or improved, 77% in the Burch group and 81% in the hysterectomy group.

Incidence, risk factors and outcome of infection in a 1-year hysterectomy cohort: a prospective follow-up study.

A prospective study was performed following 687 patients who underwent abdominal, vaginal and laparoscopic hysterectomy for benign conditions in Turku University Hospital. This study evaluates and compares infection after hysterectomy and determines risk factors associated with postoperative infection. Infective episodes were recorded during hospital stay, convalescence for 4 to 6 weeks at home and for 1 year of follow-up. Factors found to be statistically significant for hospital-acquired infection on univariate analysis were subsequently assessed by means of multivariate analysis. During the hospital stay 23.7% of the study population became infected, 38.1% after vaginal hysterectomy, 23.4% after abdominal hysterectomy and 3.0% after laparoscopic hysterectomy. Over half of all hospital-acquired infections were lower urinary tract infections. Infection during convalescence occurred in 19.2% of patients: 29.5% in the vaginal hysterectomy group, 17.4% in the abdominal hysterectomy group and 16.7% in the laparoscopic hysterectomy group. One year of follow-up did not find any infection directly attributable to surgery. Five factors were found to be related to in-hospital infection on multivariate analysis. These were lack of antibiotic prophylaxis, blood loss during operation, intermittent catheterization, anaemia and medication for urinary or bowel dysfunction after operation.

Complications and long-term outcomes after adnexal surgery by laparotomy and laparoscopy.

STUDY OBJECTIVE: To assess complications and subjective outcomes after adnexal surgery by laparotomy and laparoscopy. DESIGN: Observational study (Canadian Task Force classification II-2). SETTING: University-affiliated hospital. PATIENTS: Two-hundred twenty-eight women requiring adnexal surgery for benign indications. INTERVENTIONS: The 114 patients who underwent laparotomy and 114 having laparoscopy were followed prospectively for 1 year. Two questionnaire-based evaluations were undertaken to determine subjective outcomes. To evaluate possible later surgical procedures, hospital records were reviewed 4 years after operation. MEASUREMENTS AND MAIN RESULTS: No major complications occurred in the laparotomy group. The two (1.8%) in the laparoscopy group were intestinal injury and aortal injury, both in women who had previously undergone laparotomy. Rates of minor complications were 11.4% for laparotomy and 7.0% for laparoscopy. Two patients in both groups were readmitted. No difference was found between groups in need for additional adnexal procedures up to 4 years after operation. After 1 year, frequencies of subjective complaints and satisfaction with surgical procedure did not differ significantly. Mean hospital cost per patient was less for laparoscopy than for laparotomy. CONCLUSION: No statistically significant differences were seen after adnexal surgery by laparoscopy and laparotomy with regard to frequency of complications and subjective outcomes. Laparoscopy in women who have previously undergone laparotomy may be associated with a slightly greater risk of major complications than another laparotomy.

One-year cohort of abdominal, vaginal, and laparoscopic hysterectomies: complications and subjective outcomes.

BACKGROUND: In the past decade, changes in operative approaches to hysterectomy have resulted in needs to renew study of postoperative morbidity. STUDY DESIGN: This prospective observational study, performed in a university teaching hospital in Finland, was conducted to determine the overall number of complications and subjective outcomes after hysterectomy for benign conditions. The population studied during a 1-year period consisted of 687 women, who underwent 516 abdominal hysterectomies, 105 vaginal hysterectomies, and 66 laparoscopic hysterectomies. Complications arising within 1 year of operations were recorded, and subjective complaints and outcomes were assessed using two questionnaire-based evaluations, the first following a convalescence period of 4 to 6 weeks, the second after 1 year. RESULTS: Intraoperative complications occurred in 16 patients (2.3%), in 9 patients in the abdominal hysterectomy group (1.7%), and in 4 (3.9%) and 3 patients (4.5%) in the vaginal and laparoscopic hysterectomy groups, respectively. During the hospital stay postoperative complications were found in 28.5% of patients, in the vaginal hysterectomy group (41.9%) more often than in the abdominal and laparoscopic hysterectomy groups (28.3% and 9.1%, respectively). Postoperative infection, including urinary infection, was the main problem, during both the stay in the hospital and the convalescence period at home. It was also the principal reason for readmission to the hospital. Despite an increase in incidence of subjective complaints, from 14.9% during the first evaluation to 37.0% during the second (p < 0.001), 95% of respondents remained satisfied with their operation after 1 year. CONCLUSIONS: Vaginal hysterectomy was more often associated with some adverse event, mainly postoperative infection, than abdominal and laparoscopic hysterectomy. Subjective outcomes were not influenced by the type of hysterectomy. Most patients were satisfied with the operation on both short- and longterm followup.