A phase II study of weekly paclitaxel/estramustine/carboplatin in hormone-refractory prostate cancer

Purpose

The objective of this phase II study was to determine the response rate in patients with hormone-refractory prostate cancer given paclitaxel/estramustine/carboplatin for weeks 1, 2, and 3 of a 4-week cycle.

Patients and Methods

Eighty-four patients were registered into the trial. Paclitaxel 80 mg/m² and carboplatin area under the curve of 2 were administered intravenously on days 2, 9, and 16, and oral estramustine 280 mg 3 times daily was given on days 1-3, 8-10, and 15-17 for 6 cycles. Eastern Cooperative Oncology Group performance status 0, 1, and 2 was 46%, 41%, and 13%, respectively, and median age was 70 years (range, 53-82 years), with 58 patients (69%) aged > 65 years. The majority of patients (83%) were white. Fifteen patients (18%) had received previous chemotherapy, 61 patients (73%) had undergone previous surgery, and 51 patients (61%) had received previous external-beam radiation therapy.

Results

Intent-to-treat analysis revealed a ≥ 50% prostate-specific antigen decrease rate of 61%. Median survival was 15.3 months. The most frequent grade ≥ 3 toxicities included fatigue (11%), nausea (10%), neutropenia (9%), anemia (6%), and vomiting (6%).

Conclusion

Paclitaxel/estramustine/carboplatin administered in a weekly regimen is highly effective in the treatment of hormone-refractory prostate cancer and can be administered with reasonable safety in an outpatient setting.     

Optimum number of sessions for depression and anxiety

AIM: To examine the relationship between the number of psychological treatment sessions completed by patients (1-5 sessions, 6-8 sessions, >8 sessions) and the change in self-rated depressive and anxiety symptoms using the Hospital Anxiety and Depression Scale (HADS). METHOD: Recording demographic characteristics and various clinical outcome measures for all referrals to the service and examining the relationship between changes in self-reported anxiety and depression symptoms. RESULTS: For depression, the study shows that having 6-8 sessions offers more benefit than 1-5 sessions. Having more than eight sessions does not confer any additional benefit. Indeed, there is little difference between 1-5 sessions and more than eight sessions for depression. For anxiety, symptoms appear to continue to improve with increasing numbers of treatment sessions. CONCLUSION: Beyond eight treatment sessions, there appears to be no additional improvement. This is not the case for anxiety, where continuing treatment sessions appear to reduce symptoms.     

ERp29 induces breast cancer cell growth arrest and survival through modulation of activation of p38 and upregulation of ER stress protein p58IPK

Endoplasmic reticulum protein 29 (ERp29) is an ER luminal protein that has a role in protein unfolding and secretion, but its role in cancer is unclear. Recently, we reported that overexpression of ERp29 significantly inhibited cell proliferation and prevented tumorigenesis in highly proliferative MDA-MB-231 breast cancer cells. Here, we show that ERp29-induced cancer cell growth arrest is modulated by the interplay between the concomitant phosphorylation of p38 and upregulation of the inhibitor of the interferon-induced, double-stranded RNA-activated protein kinase, p58(IPK). In this cell model, ERp29 overexpression significantly downregulates modulators of cell proliferation, namely urokinase plasminogen activator receptor, β(1)-integrin and epidermal growth factor receptor. Furthermore, ERp29 significantly (P<0.001) increases phosphorylation of p38 (p-p38) and reduces matrix metalloproteinase-9 secretion. The role of ERp29 in upregulating cyclin-dependent kinase inhibitors (p15 and p21) and in downregulating cyclin D(2) is demonstrated in slowly proliferating ERp29-overexpressing MDA-MB-231 cells, whereas the opposite response was observed in ERp29-knockdown MCF-7 cells. Pharmacological inhibition of p-p38 downregulates p15 and p21 and inhibits eIF2α phosphorylation, indicating a role for p-p38 in this process. Furthermore, p58(IPK) expression was increased in ERp29-overexpressing MDA-MB-231 cells and highly decreased in ERp29-knockdown MCF-7 cells. This upregulation of p58(IPK) by ERp29 suppresses the activation of p-p38/p-PERK/p-eIF2α by repressing eIF2α phosphorylation. In fact, reduction of p58(IPK) expression by RNA interference stimulated eIF2α phosphorylation. The repression of eIF2α phosphorylation by p58(IPK) prevents ERp29-transfected cells from undergoing ER-dependent apoptosis driven by the activation of ATF4/CHOP/caspase-3. Hence, the interplay between p38 phosphorylation and p58(IPK) upregulation has key roles in modulating ERp29-induced cell-growth arrest and survival.     

Transplantation of an alginate-matrigel matrix containing isolated ovarian cells: first step in developing a biodegradable scaffold to transplant isolated preantral follicles and ovarian cells

For women diagnosed with leukemia, transplantation of cryopreserved ovarian tissue after disease remission is not advisable. Therefore, to restore fertility in these patients, we aim to develop a biodegradable artificial ovary that offers an environment where isolated follicles and ovarian cells (OCs) can survive and grow. Four NMRI mice were ovariectomized and their ovaries used to isolate OCs. Groups of 50,000 OCs were embedded in an alginate-matrigel matrix for further fixation (fresh controls), one week of in vitro culture (IVC) or heterotopic autografting. OC proliferation (Ki67), apoptosis (TUNEL), scaffold degradation, vessel formation (CD34) and inflammation (CD45) were analyzed. Ki67-positive OCs were found in 2.3%, 9.0% and 15.5% cells of cases in fresh, IVC and grafted beads respectively, while cells were TUNEL-positive in 0%, 1.5% and 6.9% of cases. After IVC or grafting, the beads degraded, losing their original round aspect, and infiltrating blood capillaries could be observed in the grafted beads. CD34-positive cells and 22% CD45-positive cells were found around and inside the matrix. In conclusion, our results demonstrate that an alginate-based matrix is a promising proposition to graft isolated OCs. After transplantation, this matrix was able to degrade, allowed vascularization and elicited a low inflammatory response.     

Gastroesophageal reflux disease in primary care. Prevalence, epidemiology and Quality of Life of patients

AIM: To determine the prevalence of typical symptoms of gastroesophageal reflux disease in a large group of patients consulting their general practitioners (GP) for diverse reasons, as well as the quality-of-life (QoL) of patients with such symptoms. PATIENTS AND METHODS: During the same day, participating GPs (N=3 200) systematically asked all of their patients about the presence of heartburn and regurgitation. For all patients who responded positively, the GPs filled in a questionnaire and the patient a specific QoL questionnaire. RESULTS: Among 40 982 patients attending GP consultations, 4 124 (10.1%) had one or both symptoms. Prevalence was higher in men (11.1%) than in women (9.3%, P<0.001), and increased with age up to 50-59 yrs then slowly declined. Symptoms were present on a weekly basis in 72.8% of patients. Smoking, frequent or nocturnal occurrence of symptoms, regurgitation, and esophagitis were significantly linked up with a higher occurrence of extra-digestive symptoms (cough, ENT symptoms, chest pain). QoL declined with increasing frequency of symptoms, which especially affected food intake, psychology, well-being and daily life. CONCLUSION: In France, typical symptoms of gastroesophageal reflux disease are observed in 10% of the adult population, and markedly alter their QoL.