Rechallenge of docetaxel combined with epirubicin given on a weekly schedule in advanced castration-resistant prostate cancer patients previously exposed to docetaxel and abiraterone acetate: a single-institution experience.

The aim of this paper was to evaluate the activity and tolerability of weekly docetaxel (D) combined with weekly epirubicin (EPI) in patients with advanced castrate-resistant prostate cancer (CRPC) previously exposed to D and abiraterone acetate (AA). Locally advanced or metastatic CRPC patients with 0-2 performance status, who had progressed after D and AA therapy, were included in the study. Previous treatment with chemotherapy agent cabazitaxel was also admitted. Treatment consisted of D 30 mg/m(2) intravenously (i.v.) and EPI 30 mg/m(2) i.v., every week (D/EPI). Chemotherapy was administered until disease progression or unacceptable toxicity. In our institution, twenty-six patients received D/EPI: their median age was 72 years (range 59-83 years). Twenty-three (88.5%) patients had bone metastases. A decrease in PSA levels ≥50% was observed in seven patients (26.9%, 95% CI: 0.11-0.47); of these, five had achieved a ≥50% PSA response during prior first-line D and six had achieved a PSA response during prior AA Among the subjects who were symptomatic at baseline, pain was reduced in nine patients (38.1%) with a significant decrease in analgesic use. Median progression-free survival was 4.4 months (95% CI, 3-5.2), and median overall survival was 10.7 months (95% CI, 8.9-18.4). Treatment was well tolerated and no grade 4 toxicities were observed. Our findings suggest that weekly D/EPI is feasible and active in heavily pretreated advanced CRPC patients and seem to support the hypothesis that the addition of EPI to D may lead to overcome the resistance to D in a subgroup of patients.

Docetaxel and epirubicin compared with docetaxel and prednisone in advanced castrate-resistant prostate cancer: a randomised phase II study.

BACKGROUND: This randomised phase II study compared the activity and safety of the combination docetaxel (D)/epirubicin (EPI) with the conventional treatment D/prednisone (P) in advanced castrate-resistant prostate cancer (CRPC) patients. MATERIALS AND METHODS: Patients were randomly assigned to D 30 mg m(-2) as intravenous infusion (i.v.) and EPI 30 mg m(-2) i.v. every week (D/EPI arm), or D 70 mg m(-2) i.v. every 3 weeks and oral P 5 mg twice daily (D/P arm). Chemotherapy was administered until disease progression or unacceptable toxicity. RESULTS: A total of 72 patients were enrolled in the study and randomly assigned to treatment: 37 to D/EPI and 35 to D/P. The median progression-free survival (PFS) was 11.1 months (95% CI 9.2-12.6 months) in the D/EPI arm and 7.7 months (95% CI 5.7-9.4 months) in the D/P arm (P=0.0002). The median survival was 27.3 months (95% CI 22.1-30.8 months) in the D/EPI arm and 19.8 months (95% CI 14.4-24.8 months) in the D/P arm (P=0.003). Both regimens were generally well tolerated. CONCLUSION: The treatment of advanced CRPC with weekly D combined with weekly EPI was feasible and tolerable, and led to superior PFS than the treatment with 3-weekly D and oral P.

Oral metronomic chemo-hormonal-therapy of metastatic breast cancer with cyclophosphamide and megestrol acetate.

Metronomic chemotherapy is an anticancer strategy which uses conventional cytotoxic drugs administered at very low dose in close intervals. We have designed a phase II trial to investigate the safety and antitumor activity of the newest metronomic chemo-hormonal-therapy with daily cyclophosphamide and twice daily megestrol acetate (mCM regimen) in patients with metastatic pretreated breast cancer.Twenty-nine pretreated post-menopausal patients with multiple metastatic sites were enrolled. four patients had a triple negative status, nineteen a positive hormonal ER and PgR status, and three ERB-B2 over-expression. Patients received treatment with cyclophosphamide (50 mg/daily day 1-21/q28) and fractionated megestrol acetate (80 mg twice a day). The overall objective response rate was 31.0%, disease control rate 41.3%, mean time to tumor progression 7.4 months (CI 95%, 3.8-10.88, range 1-48 months) and mean overall survival 13.4 months (CI 95%, 7.24-17.18, range 1-53 months). The mCM regimen was active and well tolerated.

Effect of neoadjuvant epirubicin and total androgen blockade on complete pathological response in patients with clinical stage T3/T4 prostate cancer.

AIMS: Most patients with stage T3-T4 prostate cancer experience disease relapse despite radiation and/or hormonal therapy, and their management remains controversial. We investigated the feasibility of, and the pathological response induced by neoadjuvant chemo-hormonal treatment in men with clinical stage T3/T4. METHODS: Fifteen patients underwent neoadjuvant therapy consisting of weekly intravenous infusions of epirubicin 30mg/m(2) and total androgen blockade (TAB) for three months before undergoing radical prostatectomy, after which all received locoregional conformal radiotherapy (66Gy) and then continued with TAB and three additional months of epirubicin. RESULTS: After neoadjuvant therapy, PSA levels decreased in all 15 patients and became undetectable in two. None of the patients achieved a complete pathological response, but a 35-75% reduction in tumour size was observed in all cases, and all the patients were able to undergo successful prostatectomy. Pathological assessments of the surgical specimens revealed negative margins in 13 patients. After a median follow-up of 34 months (range 11-62), 14 patients (93%) are still clinically and biochemically disease free. No grade 3 or 4 complications occurred. CONCLUSION: This study suggests that neoadjuvant treatment with epirubicin and TAB is feasible and well tolerated in patients with clinical stage T3-T4 prostate cancer.

Exemestane after tamoxifen as adjuvant hormonal therapy in postmenopausal women with breast cancer: effects on body composition and lipids.

Recent studies have shown that administering the aromatase inhibitor exemestane after 2-3 years of tamoxifen therapy significantly improves disease-free survival in postmenopausal women with primary breast cancer in comparison with standard 5-year tamoxifen treatment. Although many of the adverse effects associated with exemestane and tamoxifen have been analysed, there are no comparative data concerning body weight and body composition. The aim of this randomised study was to evaluate the longitudinal changes in body composition and lipid profiles in postmenopausal women switched from tamoxifen to exemestane. In total, 60 overweight or obese postmenopausal patients were enrolled. Their anthropometric data, body composition, including fat mass (FM) and fat-free mass (FFM), and lipid profiles, caloric intake and physical activity were assessed 1 week before randomisation, and 6 and 12 months later. In all, 55 patients (27 on tamoxifen and 28 on exemestane) completed the 1-year study period. Fat mass had significantly decreased by month 12 in the exemestane, but not in the tamoxifen group; the between-group difference was statistically significant (P<0.01). The FFM/FM ratio had significantly increased in the exemestane group, but not the tamoxifen group; the between-group difference was statistically significant (P<0.05). Triglycerides and high-density lipoprotein cholesterol significantly decreased (P<0.01; P<0.05), and low-density lipoprotein cholesterol significantly increased (P<0.01) in the exemestane group at the end of the 1-year study period. Our findings suggest that switching patients to adjuvant exemestane treatment after at least 2 years of tamoxifen therapy may be associated with an advantage over continuing adjuvant tamoxifen treatment in terms of body composition.

[Spontaneous staphylococcal abscess of psoas muscle]. / Ascesso stafilococcico spontaneo del muscolo psoas.

An abscess of the psoas muscle is a rare occurrence and pathogenetic interpretation usually proves difficult. Abscessing of the psoas may be due either to direct diffusion of infections of adjacent structure or to hematogenous spread. However, not uncommonly, a "spontaneous" abscess occurs, which cannot be correlated to other sites of infections or sepsis. The Authors describe two cases of abscesses of the psoas muscle following Staphylococcus aureus sepsis of unknown origin.

Primary tooth ankylosis: report of case with histological analysis.

Two primary molars in infraclusion showing clinical and radiographic signs of ankylosis, were subject to histological examination by bright field and polarization microscopy. The roots revealed signs of ongoing resorptive and reparative processes and in some areas dentin with signs of resorption-or repair cementum-were fused with simple lamellar or osteonic bone. These results suggest that ankylosis of primary molars can result from a disturbance of root resorption, with repair processes prevailing over resorptive ones and leading to excessive deposition of bone besides cementum-as a consequence of bone-inductive properties of dentin.

Microscopical aspects of root resorption of human deciduous teeth.

In order to obtain detailed information on the tissue changes which occur during physiological root resorption, 52 human deciduous teeth at various stages of resorption were studied under light microscopy. The early stage of root resorption was defined as resorption of not more than one third of the root length; the late stage was defined as resorption of more than one third. A close topographical interrelationship was found among che sites of pressure of the permanent tooth, the extent of root resorption and the types of tissue changes. Linear resorption (which reflects suspension or marked slowing down of resorption) and redeposition of hard tissue were more pronounced at the early stage of resorption, while lacunar resorption was more pronounced at the late stage. There were pronounced haemorrhagic and inflammatory infiltrates within the pulp at the late stage of resorption and the subodontoblastic cells disappeared as the infiltrates took over the tooth. False denticles were found frequently, especially at the early stage of resorption. Unexpectedly, acellular cementum was found to be deposited against secondary dentine at the cuspidal tip of the pulp chamber of seven teeth, independently of any sign of resorption nearby. These data indicate that: 1) the pressure exerted by a permanent tooth is the most important factor in the differentiation of odontoclasts. 2) the extent of lacunar (i.e., active) resorption correlates directly with the resorption rate, which is higher at the late stage of root resorption. 3) inflammation is a consequence, rather than a cause, of resorption; it may lead to the loss of subodontoblastic cells and a consequent decrease in the ability of the pulp cells to replace damaged odontoblasts. 4) the pulp of the deciduous tooth might be cementogenic in some way, given that about 13% of the samples were found to be so.

[Morphological analysis of lower permanent incisor roots]. / Analisi morfologica della radice degli incisivi inferiori permanenti.

Using horizontal sections at various levels and subsequent examination through a stereoscopic microscope, the authors examined 144 roots from the same number of mandibular incisors, in order to determine the number of canals in the coronal third, in the medial third and in the apical third of the root. It was found that 36.1% of the sample displayed multiple root canals.

The crown odontoblasts of rat molars from primary dentinogenesis to complete eruption.

The involution of crown odontoblasts after primary dentinogenesis in teeth of limited eruption is discussed. The odontoblasts of rat first lower molars were analyzed morphometrically from the tenth day to the 40th day of age, i.e., from the late phase of primary dentinogenesis to complete eruption. All the organelles underwent atrophy, but at different rates. In particular, the membranes of the endoplasmic reticulum decreased progressively in surface area from day 10 to day 40, whereas those of the Golgi apparatus decreased significantly between day 10 and day 14, and then remained practically unchanged in size. The volume of the lysosome compartment never increased beyond that during primary dentinogenesis. The profile length of the endoplasmic reticulum in each observed cell section was taken as an estimate of secretory activity. At day 40, this organelle was smaller in approximately 95% of the cells than it had been in any cell at day 10. These results suggest that cell atrophy may occur without any increase in the degradation processes of the cytoplasmic components and that the organelles along the secretory pathway may have independent regulatory systems. In the odontoblasts, as in several types of secretory epithelial cells, only a small fraction of the cells is engaged in appreciable secretory activity. This occurs, however, when the overall activity of the same cell population is relatively low.