Neo-adjuvant chemotherapy does not increase the rate of complete resection and does not significantly reduce the morbidity of Visceral-Peritoneal Debulking (VPD) in patients with stage IIIC-IV ovarian cancer.

OBJECTIVE: To measure the efficacy and the safety of Visceral-Peritoneal Debulking (VPD) in patients with stage IIIC-IV ovarian cancer and to compare the outcomes before and after chemotherapy. METHODS: Between 2008 and 2013, 200 consecutive patients were offered VPD for stage IIIC/IV ovarian cancer. Exclusion criteria were: metastases in the lungs or 3 liver segments at CT review and/or disease on small bowel serosa or encasing the porta hepatis at explorative laparoscopy. The endpoints were efficacy (rate of complete resection, CR) and safety (morbidity and mortality). The results were compared between patients in group 1 (upfront surgery) and group 2 (during or after chemotherapy). RESULTS: Ninety-eight patients were in group 1 and 102 in group 2. Twenty out of 200 patients (10%) did not have VPD, 180 out of 200 patients (90%) had VPD and CR: 90.8% in group 1, 89.8% in group 2. The mortality (1%) and intra-operative complication rate (3.3%) were similar. Post-operative complications rate was 34.8% in group 1 vs. 30.7% in group 2 (P=0.669). The difference in grade III (15.7% vs. 5.5%, P=0.053) and grade IIIb complications (13.4% vs. 4.4%, P=0.062) approached statistical significance. All other outcomes were not significantly different in the 2 groups. CONCLUSION: VPD achieved CR in 90% of the patients. Neo-adjuvant chemotherapy did not increase the rate of CR and did not significantly decrease the morbidity or the complexity of the surgery.

Angiogenesis inhibitors for the treatment of ovarian cancer.

BACKGROUND: Many women with ovarian cancer eventually develop resistance to conventional chemotherapy drugs, and so novel agents are being developed to target specific molecular pathways. One such class of drugs inhibits angiogenesis (the development of new blood vessels), which is essential for tumour growth. It is important to establish whether the addition of these new drugs to conventional chemotherapy regimens improves survival, and what the side-effects may be. OBJECTIVES: To compare the effectiveness and toxicities of angiogenesis inhibitors in the treatment of ovarian cancer. SEARCH STRATEGY: We sought to identify completed randomised controlled trials (RCTs) by searching The Cochrane Gynaecological Cancer Review Group's Trial Register, The Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2010, Issue 10), MEDLINE and EMBASE (1990 to October 2010). We also searched registers of clinical trials, and contacted investigators of completed and ongoing trials for further information. SELECTION CRITERIA: Randomised controlled studies comparing angiogenesis inhibitors with either standard chemotherapy or no treatment, in women with ovarian cancer. DATA COLLECTION AND ANALYSIS: Two independent authors carried out data collection and extraction. We used a random-effects model for pooling data. MAIN RESULTS: We did not find any fully-published, completed RCTs of angiogenesis inhibitors that met our inclusion criteria. We identified five abstracts of completed RCTs of four different angiogenesis-inhibiting agents, with a total of 3701 participants.Meta-analysis of two trials found no statistically significant difference in overall survival (OS) between women with newly-diagnosed advanced ovarian cancer who received concurrent and maintenance bevacizumab compared to those who received chemotherapy (carboplatin and paclitaxel) alone. However, women who received concurrent and maintenance bevacizumab had their risk of disease progression reduced by a quarter (hazard ratio (HR) 0.75, 95% confidence interval (CI) 0.68 to 0.83; P < 0.001); they also had a significantly increased risk of severe gastrointestinal adverse events, moderate or severe hypertension and severe bleeding.One trial also compared chemotherapy to concurrent (but not maintenance bevacizumab), and found no statistically significant difference in OS or progression-free survival (PFS).  However, the women who received bevacizumab had a significantly higher risk of moderate or severe hypertension.A three-armed RCT, of paclitaxel alone or with low- or high-dose AMG 386, in women with recurrent ovarian cancer, found no statistically significant difference in OS. However, women who received low-dose AMG 386 had a third less risk of disease progression than those who received placebo (HR 0.57, 95% CI 0.36 to 0.91; P = 0.02). The trial found no evidence of increased adverse events in the intervention arms.Two relatively small RCTs (one of VEGF-Trap, the other of BIBF 1120) found no evidence of either significant survival benefit or increased severe adverse events, compared to placebo, but they both lacked statistical power. All five trials had unclear risk of bias, largely because they have only been published in abstract form, and thus many methodological details are unclear. We identified twelve suitable ongoing trials. AUTHORS' CONCLUSIONS: There is, as yet, no fully-published RCT evidence for the efficacy or safety of angiogenesis inhibitors for the treatment of ovarian cancer, but some preliminary results are available from five trials. There is some evidence from a meta-analysis of two trials that the addition of concurrent and maintenance bevacizumab to standard chemotherapy may reduce the risk of disease progression, in women with newly-diagnosed advanced ovarian cancer. There is also some evidence from a single trial that low-dose AMG 386 may reduce the risk of disease progression in women with recurrent ovarian cancer. However, there is currently no evidence that angiogenesis inhibitors improve OS, nor is there enough evidence to justify the routine use of angiogenesis inhibitors in treating women with ovarian cancer. We eagerly await both the more detailed results of these five completed trials, and the preliminary results of the several ongoing trials.

DNA-repair pathway inhibitors for the treatment of ovarian cancer.

BACKGROUND: Ovarian cancer is the sixth most common cancer and seventh most common cause of cancer death in women world-wide.Three-quarters of women present when the disease has spread through-put the abdomen (stage III or IV) and treatment consists of a combination of debulking surgery and platinum-based chemotherapy, with or without taxanes. Although initial responses to chemotherapy are often good, most women will relapse and require further chemotherapy and will eventually develop resistance to chemotherapy agents. Increased understanding about the molecular basis of ovarian cancer has lead to the development of novel agents, which work in different ways to conventional chemotherapy. These include DNA-repair pathway inhibitors, the commonest of which are the PARP (poly (ADP-ribose) polymerase) inhibitors. It is therefore important to compare their effectiveness and side effects of these novel agents to assess their role in the treatment of advanced ovarian cancer, especially as treatment of advanced disease is aiming to improve length of survival and quality of life (QoL). OBJECTIVES: To compare the effectiveness and harmful effects of interventions, which inhibit DNA-repair pathways, in the treatment of ovarian cancer. SEARCH STRATEGY: RCTs were identified by searching The Cochrane Central Register of Controlled Trials (CENTRAL, Issue 2, 2009), The Cochrane Gynaecological Cancer Collaborative Review Group's Trial Register, MEDLINE (1990 to June 2009), EMBASE (1990 to June 2009), ongoing trials on www.controlled-trials.com/rct, www.clinicaltrials.gov, www.cancer.gov/clinicaltrials and the National Research Register (NRR), the FDA database and pharmaceutical industry biomedical literature. SELECTION CRITERIA: Adult women with histologically proven ovarian cancer who were randomised to treatment groups which either compared DNA-repair pathway inhibitors with no treatment or DNA-repair pathway inhibitors together with conventional chemotherapy compared with conventional chemotherapy alone. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed whether potentially relevant studies met the inclusion criteria. Searches for additional data and information were also performed by two independent review authors. No trials were found and therefore no data were analysed, so only information on excluded references was collected. MAIN RESULTS: The search strategy identified 473 unique references of which 461 were excluded on the basis of title and abstract. The remaining 12 articles were retrieved in full, but none satisfied the inclusion criteria. However, two ongoing randomised phase II clinical trials were identified from the clinical trials databases that met our inclusion criteria, but no preliminary data were available. AUTHORS' CONCLUSIONS: There are to date no published RCT data on the effectiveness and side effects of DNA-repair pathways inhibitors used alone or in association with conventional chemotherapy in the treatment of ovarian cancer. On-going trials have been identified and results are awaited and will be included in future updates of this review.

Laparoscopic surgery for gynaecological cancers in obese women.

The use of laparoscopic surgery in the management of gynaecological malignancies has been growing for over a decade. Concomitantly the incidence of obesity has been increasing worldwide. This review summarizes the available studies on minimal invasive surgery in obese women with gynaecological malignancies. We undertook a literature search to identify the differences between traditional open methods and the laparoscopic approach in terms of intra- and postoperative outcome and patient safety. Only eight relevant studies were identified. Six of these focused on endometrial cancer, one study included early stage cervical and ovarian cancers with other benign conditions, while another paper included cervical and endometrial pre-cancers and only a few malignant conditions. Obesity is generally known to increase the risk of intra- and postoperative complications. However, several studies show that obesity, formerly precluding keyhole surgery, seems now to be an indication for the laparoscopic approach. As compared to laparotomy, laparoscopic surgery has a good postoperative outcome, reduced estimated blood loss (EBL) and pain and in some series an increased lymph node count. Laparoscopy has been shown to be cost effective with a shorter hospital stay and return to normal activity. Survival is reported to be the same with both laparotomy and laparoscopy. The benefits of minimal invasive surgery in gynaecological surgery are starting to be found with robotic surgery.

When should surgical cytoreduction in advanced ovarian cancer take place?

Initial surgical management is commonly accepted to date as paramount in the treatment of women presenting with epithelial ovarian cancer and permits the assessment of the disease (staging), the histological confirmation of disease type and grade, and the practice of maximal debulking preceding platinum-based chemotherapy. Many studies have shown that the volume of residual disease after initial surgical cytoreduction inversely correlates with survival. Thus, women with optimal debulking performed by a trained specialist have improved median survival. In this review, we will focus on the answers gleaned from clinical trials on primary and interval surgery, which prompts the question on the timing of surgery in respect to chemotherapy. Interval debulking surgery (IDS) is secondary cytoreduction following primary debulking and is carried out in between the courses of chemotherapy. The major clinical trials and the latest systematic reviews seem unable to give any definitive guidance or recommendation for clinical practice. The choice of aggressive primary cytoreduction or upfront chemotherapy followed by second line surgical cytoreduction seems among others to have to be individualized according to tumour load, prediction of its resectability, and response to chemotherapy. The role of tumour biology must also be kept in mind. Finally, concrete answers are awaited on the timing of surgery from the ongoing prospective randomized control trials (CHORUS and EORTC 55971) though preliminary data from the latter have already been presented at major meetings (IGCS 2008; SGO 2009) and ignited strong debate.