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.

Intraperitoneal administration of recombinant human growth hormone in children with end-stage renal disease.

Recombinant human growth hormone (GH) therapy has been shown to be effective in the treatment of growth failure related to growth hormone resistance among children with chronic renal failure. The traditional route of administration is subcutaneous injection. This study was designed to evaluate the effectiveness and tolerability of intraperitoneal (i.p.) administration of GH in prepubertal peritoneal dialysis patients. Nine subjects were enrolled. Eight completed 24 months of therapy with GH. Baseline height standard deviation scores (SDS) and growth velocity for the prior year were used for comparison. Peak serum GH was achieved 4 h after administration and serum half-life was 4.6 h. Mean height SDS was -3.1 at baseline, -2.5 at 1 year, and -2.3 at 2 years (NS) of GH therapy. Mean height velocity increased from a baseline of 4.6 cm/yr to 8.5 cm/yr in year 1 (P < 0.05) and 6.1 cm/yr in year 2 (NS) of i.p. GH therapy. Peritonitis infection rates were not increased from overall center rates. This research suggests that the intraperitoneal route of administration of GH can be utilized in the treatment of short stature among children requiring maintenance peritoneal dialysis therapy.

S-phase fraction related to prognosis in localised prostate cancer. No specific significance of chromosome 7 gain or deletion of 7q31.1.

A flow-cytometric (FCM) and fluorescence in situ hybridization (FISH) study was performed in 153 patients with clinically localised prostate cancer (PC) to evaluate retrospectively the prognostic significance of DNA ploidy, S-phase fraction (SPF) and chromosome 7 copy number. Deletions in 7q31.1 were analysed in a subset of 26 tumours. The mean follow-up time was 6 years (range 4-16 years). Twelve cases of benign prostatic hyperplasia (BPH) were studied as a control. Chromosome 7 enumeration and deletion studies were conducted using the alpha-satellite D7Z1 probe and a cosmid probe specific for the marker D7S522 on 7q31.1. Higher SPF was associated with shorter overall survival and shorter time to local progression and metastasis. Near diploid (DNA index 1.05-1.20) cases had a lower frequency of metastases and lower Gleason scores than aneuploid cases. Increased absolute chromosome 7 copy number (centromere count) was associated with higher Gleason score, higher SPF and shorter local progression-free and prostate cancer survival. Absolute chromosome 7 copy number was concordant with FCM DNA ploidy in the majority (75%) of cases. Relative gain or loss of chromosome 7 (centromere counts compared to ploidy) was infrequent, and no correlation was found with clinical parameters. Deletions in 7q31.1 were infrequent. Our results indicate that in localised PC (i) SPF is a prognostic factor, (ii) absolute chromosome 7 copy number is concordant with the ploidy status of the tumour (relative gain or loss of chromosome 7 is infrequent and has no independent prognostic value) and (iii) the frequency of deletions in 7q31.1 is low and not correlated with clinical outcome.

Langerhans' cell histiocytosis in an adult.

A woman with typical skin lesions of histiocytosis X is reported. Electron microscopic and immunohistochemical investigations revealed a large number of markedly long Birbeck Langerhans' cell granulae. During treatment with Interferon alpha -2b, the patient developed infarctus cerebri and died.

Persistent hypothalamic-pituitary insufficiency following acute meningoencephalitis. A report of two cases.

This report concerns two patients, a 43-year-old woman and a 53-year-old man, who developed clinical as well as laboratory signs of permanent gonodal and thyroid failure following an acute intracranial infection--in the woman a meningoencephalitis of unknown origin, and in the man an encephalitis caused by Coxsackie B5. Endocrine investigations were compatible with hypothalamic-pituitary dysfunction, with some of the results favoring a hypothalamic lesion. Perhaps hormone deficiency of hypothalamic and/or pituitary origin is a more common sequel of acute meningoencephalitis than has hitherto been reported.

Disseminated intravascular coagulation and congenital neuroblastoma.

A newborn infant with congenital neuroblastoma complicated by disseminated intravascular coagulation is described. At birth the infant showed liver and spleen enlargement and shortly thereafter malignant cells were found in the bone marrow. On the fifth day of life the infant started to bleed and coabulation analysis indicated disseminated intravascular coagulation. Heparin therapy corrected the coagulation anomaly and irradiation and chemotherapy temporarily improved the general condition of the infant. The infant finally succumbed from tis primary neoplastic disease.