EPA guidance on the role and responsibilities of psychiatrists

Psychiatry is that branch of the medical profession, which deals with the origin, diagnosis, prevention, and management of mental disorders or mental illness, emotional and behavioural disturbances. Thus, a psychiatrist is a trained doctor who has received further training in the field of diagnosing and managing mental illnesses, mental disorders and emotional and behavioural disturbances. This EPA Guidance document was developed following consultation and literature searches as well as grey literature and was approved by the EPA Guidance Committee. The role and responsibilities of the psychiatrist include planning and delivering high quality services within the resources available and to advocate for the patients and the services. The European Psychiatric Association seeks to rise to the challenge of articulating these roles and responsibilities. This EPA Guidance is directed towards psychiatrists and the medical profession as a whole, towards other members of the multidisciplinary teams as well as to employers and other stakeholders such as policy makers and patients and their families

Bevacizumab in combination with metronomic oral cyclophosphamide:An effective and well-tolerated treatment for patients with recurrent ovarian cancer

Purpose of Investigation: In this study the authors describe their clinical experience with metronomic oral cyclophosphamide and bevacizumab in terms of efficacy and tolerability in patients with recurrent ovarian cancer beyond first-line treatment. Materials and Methods: This retrospective, descriptive study included 59 patients with recurrent ovarian cancer. They were treated with intravenous bevacizumab (10 mg/kg, once every three weeks) in combination with oral cyclophosphamide (100 mg once daily). Patients had received at least one line of platinum-based chemotherapy prior to combined bevacizumab and cyclophosphamide treatment. Both platinum sensitive patients and platinum resistant patients were included. Results: Treatment with combined bevacizumab and cyclophosphamide was administered as a third line therapy in 42.4% of patients. The median number of cycles of bevacizumab administered with oral cyclophosphamide was 7 (range 1-40). A response was demonstrated in 37 (62.7%) patients, with a median progression free survival of 6 months (range 0-44). No toxicity was recorded in the medical report of 39% of patients, with only mild toxicities reported in the others. Conclusion: Bevacizumab combined with metronomic cyclophosphamide appears to be a well-tolerated and effective therapy with sustainable remissions in this selective group heavily pretreated ovarian cancer patients. This regimen should be considered in patients who are not suitable or have no need for more toxic systemic treatment

Hyperthermic Intraperitoneal Chemotherapy in Ovarian Cancer

BACKGROUND: Treatment of newly diagnosed advanced-stage ovarian cancer typically involves cytoreductive surgery and systemic chemotherapy. We conducted a trial to investigate whether the addition of hyperthermic intraperitoneal chemotherapy (HIPEC) to interval cytoreductive surgery would improve outcomes among patients who were receiving neoadjuvant chemotherapy for stage III epithelial ovarian cancer. METHODS: In a multicenter, open-label, phase 3 trial, we randomly assigned 245 patients who had at least stable disease after three cycles of carboplatin (area under the curve of 5 to 6 mg per milliliter per minute) and paclitaxel (175 mg per square meter of body-surface area) to undergo interval cytoreductive surgery either with or without administration of HIPEC with cisplatin (100 mg per square meter). Randomization was performed at the time of surgery in cases in which surgery that would result in no visible disease (complete cytoreduction) or surgery after which one or more residual tumors measuring 10 mm or less in diameter remain (optimal cytoreduction) was deemed to be feasible. Three additional cycles of carboplatin and paclitaxel were administered postoperatively. The primary end point was recurrence-free survival. Overall survival and the side-effect profile were key secondary end points. RESULTS: In the intention-to-treat analysis, events of disease recurrence or death occurred in 110 of the 123 patients (89%) who underwent cytoreductive surgery without HIPEC (surgery group) and in 99 of the 122 patients (81%) who underwent cytoreductive surgery with HIPEC (surgery-plus-HIPEC group) (hazard ratio for disease recurrence or death, 0.66; 95% confidence interval [CI], 0.50 to 0.87; P=0.003). The median recurrence-free survival was 10.7 months in the surgery group and 14.2 months in the surgery-plus-HIPEC group. At a median follow-up of 4.7 years, 76 patients (62%) in the surgery group and 61 patients (50%) in the surgery-plus-HIPEC group had died (hazard ratio, 0.67; 95% CI, 0.48 to 0.94; P=0.02). The median overall survival was 33.9 months in the surgery group and 45.7 months in the surgery-plus-HIPEC group. The percentage of patients who had adverse events of grade 3 or 4 was similar in the two groups (25% in the surgery group and 27% in the surgery-plus-HIPEC group, P=0.76). CONCLUSIONS: Among patients with stage III epithelial ovarian cancer, the addition of HIPEC to interval cytoreductive surgery resulted in longer recurrence-free survival and overall survival than surgery alone and did not result in higher rates of side effects. (Funded by the Dutch Cancer Society; ClinicalTrials.gov number, NCT00426257 ; EudraCT number, 2006-003466-34 .)

Hyperthermic Intraperitoneal Chemotherapy in Ovarian Cancer

The majority of patients with ovarian cancer (OC) receive an initial diagnosis of advanced disease that has spread from the ovaries to the peritoneal surface. The most effective treatment for patients with advanced disease is cytoreductive surgery followed by systemic chemotherapy. As an alternative, interval cytoreductive surgery is performed after 3 cycles of chemotherapy. Following these treatments, the primary site of disease recurrence is the peritoneal surface. Delivery of chemotherapy by the intraperitoneal (IP) route enhances drug delivery at the peritoneal surface and eliminates residual microscopic peritoneal disease more efficiently than intravenous administration. Previous trials have shown that after primary cytoreductive surgery combined use of intravenous and IP chemotherapy results in longer overall survival among patients with stage III OC compared with intravenous administration alone. Combined intravenous/IP chemotherapy has several drawbacks that have hampered its adoption in many countries. These include catheter-related problems, increased demands on the patient, and gastrointestinal and renal adverse effects. Most of these drawbacks can be circumvented by delivery of the IP chemotherapy at the end of surgery. Delivery of IP chemotherapy during surgery under hyperthermic conditions—termed hyperthermic IP chemotherapy (HIPEC)—increases the penetration of chemotherapy at the peritoneal surface. Although addition of HIPEC to interval cytoreductive surgery is feasible in women with OC, efficacy data from randomized trials are lacking. This multicenter, randomized, open-label, phase 3 trial was designed to assess the efficacy and safety of interval cytoreductive surgery with HIPEC as compared with interval cytoreductive surgery without HIPEC in patients with stage III epithelial OC. Subjects were patients receiving neoadjuvant chemotherapy who had at least stable disease after 3 cycles of carboplatin (area under the curve of 5–6 mg/mL per minute) and paclitaxel (175 mg/m2 of body surface area). Of these patients, 245 were randomized: 122 to the surgery-plus-HIPEC group and 123 to the surgery-without-HIPEC group. Randomization was performed at the time of surgery in cases in which surgery that would result in complete cytoreduction (no visible disease) or optimal cytoreduction (≥1 residual tumors measuring ≤10 mm in diameter) was deemed to be feasible. Patients received an additional 3 cycles of carboplatin and paclitaxel postoperatively. Recurrence-free survival was the primary study end point. Key secondary end points were overall survival and the side effect profile. Data for recurrence-free and overall survival were analyzed according to intention to treat. Among patients who underwent cytoreductive surgery, disease recurrence or death occurred in 89% (110/123) of patients in the surgery-without-HIPEC group and 81% (99/122) of patients in the surgery-plus-HIPEC group; the hazard ratio for disease recurrence or death was 0.66, with a 95% confidence interval of 0.50 to 0.87, P = 0.003. The median recurrence-free survival was 3.5 months longer in the surgery-plus-HIPEC group than in the surgery-without-HIPEC group (14.2 vs 10.7 months). At a median follow-up of 4.7 years, 62% (76/123) of patients in the surgery-without-HIPEC group and 50% (61/122) in the surgery-plus-HIPEC group had died (hazard ratio, 0.67; 95% confidence interval, 0.48–0.94; P = 0.02). There were no significant differences in the incidence of adverse events of any grade between the 2 groups (25% in the surgery-withoutHIPEC group and 27% in the surgery-plus-HIPEC group, P = 0.76). These data indicate that among patients with stage III epithelial OC addition of HIPEC to interval cytoreductive surgery provides longer recurrence-free survival and overall survival compared with surgery alone and no higher rates of adverse effects

Hyperthermic Intraperitoneal Chemotherapy in Ovarian Cancer

BACKGROUND: Treatment of newly diagnosed advanced-stage ovarian cancer typically involves cytoreductive surgery and systemic chemotherapy. We conducted a trial to investigate whether the addition of hyperthermic intraperitoneal chemotherapy (HIPEC) to interval cytoreductive surgery would improve outcomes among patients who were receiving neoadjuvant chemotherapy for stage III epithelial ovarian cancer. METHODS: In a multicenter, open-label, phase 3 trial, we randomly assigned 245 patients who had at least stable disease after three cycles of carboplatin (area under the curve of 5 to 6 mg per milliliter per minute) and paclitaxel (175 mg per square meter of body-surface area) to undergo interval cytoreductive surgery either with or without administration of HIPEC with cisplatin (100 mg per square meter). Randomization was performed at the time of surgery in cases in which surgery that would result in no visible disease (complete cytoreduction) or surgery after which one or more residual tumors measuring 10 mm or less in diameter remain (optimal cytoreduction) was deemed to be feasible. Three additional cycles of carboplatin and paclitaxel were administered postoperatively. The primary end point was recurrence-free survival. Overall survival and the side-effect profile were key secondary end points. RESULTS: In the intention-to-treat analysis, events of disease recurrence or death occurred in 110 of the 123 patients (89%) who underwent cytoreductive surgery without HIPEC (surgery group) and in 99 of the 122 patients (81%) who underwent cytoreductive surgery with HIPEC (surgery-plus-HIPEC group) (hazard ratio for disease recurrence or death, 0.66; 95% confidence interval [CI], 0.50 to 0.87; P=0.003). The median recurrence-free survival was 10.7 months in the surgery group and 14.2 months in the surgery-plus-HIPEC group. At a median follow-up of 4.7 years, 76 patients (62%) in the surgery group and 61 patients (50%) in the surgery-plus-HIPEC group had died (hazard ratio, 0.67; 95% CI, 0.48 to 0.94; P=0.02). The median overall survival was 33.9 months in the surgery group and 45.7 months in the surgery-plus-HIPEC group. The percentage of patients who had adverse events of grade 3 or 4 was similar in the two groups (25% in the surgery group and 27% in the surgery-plus-HIPEC group, P=0.76). CONCLUSIONS: Among patients with stage III epithelial ovarian cancer, the addition of HIPEC to interval cytoreductive surgery resulted in longer recurrence-free survival and overall survival than surgery alone and did not result in higher rates of side effects. (Funded by the Dutch Cancer Society; ClinicalTrials.gov number, NCT00426257 ; EudraCT number, 2006-003466-34 .)