Spontaneous fertility after expectant or surgical management of rectovaginal endometriosis in women with or without ovarian endometrioma: a retrospective analysis.

OBJECTIVE: To investigate spontaneous pregnancy rate (SPRs) of women with rectovaginal endometriosis (RV) with/without ovarian endometrioma (OMA) and treated with the use of expectant or surgical management. DESIGN: Retrospective study. SETTING: University hospital. PATIENT(S): The study included patients with RV with or without OMA who tried to conceive spontaneously for 1 year either without undergoing surgery (group E; n = 284) or after surgery (group S; n = 221). The study population was further divided into four subgroups: women with RV without OMA who directly tried to conceive (group eRV; n = 121) or tried to conceive after surgery (group sRV; n = 96), and women with RV with OMA who directly tried to conceive (group eOMA; n = 163) or tried to conceive after surgery (group sOMA; n = 125). INTERVENTIONS(S): Expectant or surgical management. MAIN OUTCOME MEASURE(S): Crude and cumulative SPRs. RESULT(S): At 1 year, crude and cumulative SPRs were lower in group E (17.3% and 23.8%, respectively) than in group S (35.7% and 39.5%). Similarly, crude and cumulative SPRs were lower in group eRV (24.8% and 30.6%) than in group sRV (42.7% and 45.7%, respectively) and in group eOMA (11.7% and 18.0%) than group sOMA (30.4% and 34.5%). At 1 year, crude and cumulative SPRs were higher in group eRV (24.8% and 30.6%) than in group eOMA (11.7% and 18.0%), and in group sRV (42.7% and 45.7%) than in group sOMA (30.4% and 34.5%). CONCLUSION(S): Crude and cumulative SPRs are lower in women treated with the use of expectant rather than surgical management. The presence of OMAs decreases SPRs independently from the treatment modality adopted.

The role of fulvestrant in endometrial cancer.

INTRODUCTION: Endometrial cancer is the most common malignancy of the female genital tract in industrialized countries. The traditional treatment of endometrial cancer is based on a surgical approach. In recent years, systemic endocrine therapy has demonstrated good efficacy in recurrent or metastatic setting, delaying progression, ameliorating quality of life and palliating symptoms. Areas covered: Phase I and II studies on selective estrogen receptor down-regulators used for the treatment of endometrial cancer treatment have been reviewed. The pharmacokinetic and pharmacodynamic features of selective receptor down-regulators have been also investigated. Expert opinion: Selective estrogen receptor down-regulators may exhibit clinical efficacy in the treatment of gynecological malignancies due to their pure estrogen receptor antagonist properties. However, up to now data are still limited and some unsolved questions remain. Fulvestrant has poor oral bioavailability and low pharmacodynamic characteristics. Further trials are required to examine new selective estrogen receptor down-regulator agents with better pharmacodynamic and pharmacokinetic profiles.

Three-month treatment with ulipristal acetate prior to laparoscopic myomectomy of large uterine myomas: a retrospective study.

OBJECTIVE: To assess the usefulness of 3-month treatment with ulipristal acetate (UPA) before laparoscopic myomectomy of large uterine myomas. STUDY DESIGN: This retrospective analysis of a prospectively collected database included women of reproductive age requiring laparoscopic myomectomy with the following characteristics: FIGO type 3, 4 or 5 myomas; largest diameter of the main myoma ≥10cm; number of myomas ≤3; largest diameters of the other myomas ≤5cm (second myoma) and ≤3cm (third myoma). Patients either underwent direct surgery (group S) or were treated before surgery with UPA for 3 months (group UPA). RESULTS: The mean (±SD) intraoperative blood loss was lower in group UPA (507.1±214.9ml) than in group S (684.2±316.8; p=0.012). The total operative time was lower in group UPA (137.6±26.8min) than in group S (159.7±26.8min; p<0.001); there was no significant difference in the suturing time between the two study groups (p=0.076). Hemoglobin drop was lower in group UPA (1.1±0.5g/dl) than in group S (1.3±0.7g/dl; p=0.034). Six patients in group S and no patient in group UPA required postoperative blood transfusions (p=0.031). Complications were not different between the two groups (p=0.726). Moreover, preoperative treatment with UPA caused a significant increase in hemoglobin levels (11.9±1.6g/dl) compared with baseline (9.1±1.1g/dl; p<0.001). CONCLUSION: A 3-month treatment with UPA before laparoscopy for large uterine myomas decreases intraoperative blood loss, hemoglobin drop, postoperative blood transfusion and length of surgery.

Pharmacokinetics, pharmacodynamics and clinical efficacy of ospemifene for the treatment of dyspareunia and genitourinary syndrome of menopause.

INTRODUCTION: Ospemifene is a selective estrogen receptor modulator recently approved by the FDA for the treatment postmenopausal women experiencing moderate-to-severe dyspareunia and by the EMA for the treatment of moderate-to-severe symptomatic genitourinary syndrome of menopause (GSM) in women who are not suitable candidates for local vaginal estrogen therapy. AREAS COVERED: This review offers an explanation of the pharmacodynamics and of the pharmacokinetics of ospemifene, and gives readers a complete overview of Phase II and III studies on the clinical efficacy, tolerability and safety of this agent in the setting of GSM. EXPERT OPINION: Ospemifene is efficacious for improving vaginal dryness or dyspareunia as the patient-identified most bothersome symptom, and Phase III clinical trials (4648 patients) have shown good efficacy in terms of improvement of objective and subjective signs and measures of GSM in postmenopausal women. Future studies with a long-term follow-up are required to better elucidate its safety profile. In particular, on the basis of preclinical and early clinical findings of antagonistic to neutral effect on breast tissue, more research is needed to assess the treatment with ospemifene in breast cancer survivors.

Veliparib for the treatment of ovarian cancer.

INTRODUCTION: Ovarian cancer represents the sixth most commonly diagnosed cancer among women, with an incidence of 6.1 cases per 100.000 women and a cumulative lifetime risk of 0.5%. Treatment is based on debulking surgery and platinum-based chemotherapy, with the potential combination with taxane. However, the recently available data on the genetic basis and aetiology of ovarian cancer has led to the development of new anticancer drugs. Poly(ADP-ribose) polymerase (PARP) inhibitors are one of the most promising new classes of targeted agents currently under investigation for the treatment of ovarian cancer. Veliparib is a small molecule that inhibits both PARP-1 and PARP-2 and was originally shown to be efficacious in BRCA-associated tumors. AREAS COVERED: This manuscript reviews the Phase I and II studies investigating the use of veliparib in ovarian cancer. This article also provides and discusses the pharmacokinetics and pharmacodynamics of veliparib. EXPERT OPINION: It is still being discussed whether PARP inhibitors should be used in a front-line or relapsed setting, alone or in combination with cytotoxic chemotherapy or as maintenance treatment. In terms of veliparib, further investigations are needed to explore its full potential in ovarian cancer. It is hoped that the ongoing phase 3 trials will help to further elucidate it potential as a treatment option.

Bevacizumab for the treatment of cervical cancer.

INTRODUCTION: Cervical cancer is still a major cause of morbidity and mortality in women. Early stages and locally advanced cervical cancer are currently treated respectively with surgery and chemoradiation with good prognosis. Persistent, recurrent and metastatic cervical cancers have a poor prognosis. Angiogenesis has been identified as a crucial factor for cervical cancer growth. Recently, research has increasingly focused on the development of targeted therapies, such as anti-angiogenic drugs. Amongst such drugs, bevacizumab, a recombinant humanized monoclonal antibody has been the subject of extensive investigation, including its use in cervical cancer. This was recently approved for the treatment of patients with metastatic, recurrent, or persistent cervical cancer. AREAS COVERED: The aim of this review is to discuss the role of bevacizumab in both locally advanced and metastatic or recurrent cervical cancer and to analyze the studies that have led to the approval of bevacizumab in cervical cancer. EXPERT OPINION: The use of bevacizumab in combination with other chemotherapies in cervical cancer has been proven safe and effective, with a significant improvement in overall survival of patients with advanced cervical cancer. Combination therapy using bevacizumab has been demonstrated to increase toxicity rates but it does not impair patient's quality of life.

Ulipristal Acetate Before High Complexity Hysteroscopic Myomectomy: A Retrospective Comparative Study.

STUDY OBJECTIVE: To evaluate the efficacy of preoperative treatment with ulipristal acetate (UPA) in patients undergoing high complexity hysteroscopic myomectomy. DESIGN: Retrospective analysis of a prospectively collected database (Canadian Task Force classification II-2). SETTING: University teaching hospital. PATIENTS: Patients of reproductive age requiring hysteroscopic myomectomy with STEPW (size, topography, extension, penetration, and wall) score 5 or 6. INTERVENTIONS: Patients included in the study either underwent direct surgery (group S) or received a 3-month preoperative treatment with UPA (group UPA). Based on a power calculation, 25 patients were required in each study group. MEASUREMENTS AND MAIN RESULTS: Myoma characteristics were similar in the 2 study groups. The 3-month UPA treatment caused a 21.9% (±10.3%) mean (±SD) percentage decrease in myoma volume. The number of complete resections (primary outcome of the study) was higher in group UPA (92.0%) than in group S (68.0%; p = .034). The operative time was lower in group UPA than in group S (p = .048), whereas there was no significant difference in fluid balance between the 2 study groups (p = .256). The incidence of complications was similar in the 2 groups (p = .609). Patient satisfaction at 3 months from surgery was higher in group UPA than in group S (p = .041). CONCLUSION: A 3-month preoperative treatment with UPA increases the possibility of complete resection in high complexity hysteroscopic myomectomy. It decreases the operative time and improves patient satisfaction at 3 months from surgery.

Three-month treatment with triptorelin, letrozole and ulipristal acetate before hysteroscopic resection of uterine myomas: prospective comparative pilot study.

OBJECTIVE: To compare the usefulness of preoperative treatment with triptorelin, letrozole or ulipristal acetate or no treatment before hysteroscopic removal of uterine submucosal myomas. STUDY DESIGN: Single center prospective non-randomized comparative pilot study. The study included consecutive premenopausal patients undergoing hysteroscopic resection of myomas graded as type 0, type 1 or type 2 according to the FIGO classification with diameter between 20 and 35 mm. Exclusion criteria were: associated polyps, associated non-hysteroscopic surgical procedures, >2 myomas requiring hysteroscopic resection. This study enrolled patients who underwent either direct surgery (group S; n=23) or 3-month preoperative treatment with triptorelin (3.75 mg every 28 days; group T; n=20), letrozole (2.5 mg/day; group L; n=11) or ulipristal acetate (5 mg/day; group U; n=7). Patients underwent hysteroscopic resection of the myomas. RESULTS: All medical treatments caused a significant decrease in the volume of myomas (group T, p<.001; group L, p<.001; group U, p=.006); however, the percentage decrease in myoma volume was lower in group U than in group T (p=.001) and in group L (p=.010). The hysteroscopy time was higher in group S than in group T (p<.001) and in group L (p=.001); there was no significant difference in the hysteroscopy time between group S and group U (p=.206). Fluid absorption was lower in group T than in group S (p=.002) and in group L than in group S (p=.048); fluid absorption was similar in group S and group U (p=.110). Intra- and postoperative complications, postoperative pain, and patient satisfaction were similar in the four study groups. Surgeon's evaluation of operative difficulty was better in group T than in group S (p<.005). CONCLUSIONS: Preoperative treatment with triptorelin and letrozole decreases the hysteroscopy time and the volume of fluid absorbed during hysteroscopic resection of uterine submucosal myomas.

Oxaliplatin for the treatment of ovarian cancer.

INTRODUCTION: Oxaliplatin is an important drug in treatment of several solid tumors. Ovarian cancer (OC) is sensitive to chemotherapy and the overall response rate with primary therapy is about 75%. Unfortunately, 60 - 70% of patients experience recurrence requiring additional treatments and finally die of progressive disease within 5 years of the initial diagnosis. Currently, a platinum-based combination therapy is recommended in platinum-sensitive disease while a non-platinum single-agent therapy is preferred in platinum-resistant disease that is characterized by a low response rate. AREAS COVERED: In this article, the authors review the Phase II and Phase III studies of oxaliplatin as an OC therapy. Furthermore, the authors discuss the pharmacokinetic and pharmacodynamic features of oxaliplatin. EXPERT OPINION: Platinum emerged as the mainstay of OC treatment in frontline therapy, and platinum compounds remain a critical component of chemotherapy also in relapsed disease. Unfortunately, increasing exposure to carboplatin/cisplatin raises the risk of resistance or hypersensitivity to platinum. Several studies have demonstrated the safety and effectiveness of oxaliplatin, both alone and in combination regimens, in relapsed OC, demonstrating a good tolerability profile. Moreover, the therapeutic spectrum of oxaliplatin might be extended to OC patients who experienced hypersensitivity to carboplatin because of its favorable toxicity profile and at least equal efficacy.

Drug safety evaluation of ulipristal acetate in the treatment of uterine fibroids.

INTRODUCTION: Ulipristal acetate (UPA) is a selective progesterone-receptor modulator (SPRM). SPRMs are a new class of progesterone-receptor ligands that exert tissue selective agonist, antagonist or mixed agonist-antagonist activity in target cells. UPA inhibits the proliferation, induces apoptosis of leiomyoma cells in vitro and demonstrates potent progesterone antagonist activity in vitro and in vivo. AREAS COVERED: This manuscript aims to review the available data on safety of UPA in the treatment of uterine fibroids. Data and articles included in this manuscript were obtained via PubMed, Medline and Embase up to November 2014. EXPERT OPINION: UPA is efficacious in the treatment of uterine fibroids before surgery; it decreases leiomyoma volume and uterine bleeding; furthermore, it improves quality of life. Short-term administration of UPA has been shown to be safe at short follow-up (months) and it is associated with minimal adverse side effects; further studies with longer follow-up are required to define the safety profile of UPA on endometrial histology.

Intraoperative Transrectal Ultrasonography for Hysteroscopic Metroplasty: Feasibility and Safety.

The primary objective of this prospective comparative nonrandomized study was to assess the feasibility and safety of intraoperative transrectal ultrasonography (TRUS) during hysteroscopic metroplasty (HM). The secondary objective of the study was to assess whether TRUS facilitates complete removal of the uterine septum. Septate uterus was diagnosed by 3-dimensional transvaginal ultrasonography (3D-TVS) and confirmed by magnetic resonance imaging. In the control group (HM group; n = 18), patients underwent HM according to the traditional standard of operative hysteroscopy. In the study group (HM+TRUS group; n = 27), HM and TRUS were performed simultaneously; the hysteroscopic procedure was continued until a normal uterine fundus was observed. At 6 to 8 weeks after HM, 3D-TVS was performed to identify the numbers of complete resections (residual septum absent or <5 mm), suboptimal resections (residual septum 5-10 mm), and incomplete resections (residual septum > 10 mm). The 2 study groups did not differ significantly in terms of demographic and clinical characteristics, or in the volume of fluid infused and absorbed. There were no severe intraoperative or postoperative complication in either group; 2 patients in the HM+TRUS group and 1 patient in the HM group experienced urinary tract infection (p = .807). At 6 to 8 weeks after HM, the number of suboptimal resections and incomplete resections was higher in the HM group than in the HM+TRUS group (p = .031). Residual septum >10 mm (incomplete resection) was seen in 1 patient in the HM group but in no patients in the HM+TRUS group. Intraoperative TRUS can be performed safely during HM, and may increase the likelihood of complete resection of the uterine septum; however, this finding should be confirmed by larger studies.

Second surgery for recurrent unilateral endometriomas and impact on ovarian reserve: a case-control study.

OBJECTIVE: To investigate the impact on ovarian reserve of second laparoscopic surgery for recurrent unilateral endometriomas. DESIGN: Case-control study. SETTING: University teaching hospital. PATIENT(S): This study included patients who underwent stripping of endometriomas (diameter ≥4 cm) and were followed-up at our institution. Case subjects had second surgery for recurrent unilateral endometriomas (n = 18); control subjects had no recurrence and no second surgery (n = 18). INTERVENTION(S): This case-control study was based on a retrospective analysis of a prospectively collected database including patients who underwent surgery for endometriomas at our institution. MAIN OUTCOME MEASURE(S): The primary outcome of the study was to assess the changes in antimüllerian hormone (AMH) levels in each study group and between the two study groups. The secondary outcomes of the study were to assess the changes in basal FSH, antral follicle count (AFC), and ovarian volume in each study group and between the two study groups. RESULT(S): In both study groups, primary surgery decreased AMH, increased basal FSH, and decreased the AFC of the operated ovary. Before second surgery, case subjects had AMH, basal FSH, and AFC similar to control subjects. After second surgery, case subjects had lower AMH, higher basal FSH, and lower AFC of the affected ovary than before surgery; the volume of the operated ovary was lower than that of the contralateral ovary. CONCLUSION(S): The laparoscopic stripping of recurrent ovarian endometriomas is associated with a high risk of ovarian reserve damage and ovarian failure. CLINICAL TRIAL REGISTRATION NUMBER: NCT02047838.

Current opinion on bevacizumab on endometrial cancer treatment.

INTRODUCTION: Advanced or recurrent endometrial cancer is still a challenge for clinicians as it has a poor prognosis despite treatment efforts. Thus, there is an urgent need for new agents with activity in this subset of patients. The increased knowledge of the molecular aspects of endometrial carcinogenesis has led to the development of molecular targeted therapies and in particular anti-angiogenic drugs. One of the most promising of these agents is bevacizumab , a recombinant humanized immunoglobulin monoclonal antibody to VEGF. AREAS COVERED: The objective of this paper is to discuss the role of angiogenesis in endometrial cancer and analyze the rational of bevacizumab use, alone or in combination with other therapies, in endometrial cancer patients. We reviewed the most important preclinical and clinical studies published on this topic up to March 2014. EXPERT OPINION: Bevacizumab in combination with others targeted therapies, chemotherapy or radiotherapy demonstrated promising anti-tumor activity. Despite the good oncological outcomes of these recent clinical experiences, caution must be used in light of significant toxicity reported in this subset of heavily pre-treated patients. The identification of biomarkers able to predict either the efficacy or toxicity of anti-angiogenic drugs is a compelling need.

Preoperative treatment with letrozole in patients undergoing laparoscopic myomectomy of large uterine myomas: a prospective non-randomized study.

OBJECTIVE: To assess the efficacy of preoperative treatment with aromatase inhibitors (AIs) in premenopausal women undergoing laparoscopic myomectomy of large uterine myomas. STUDY DESIGN: Prospective non-randomized assessor-blind comparative trial. RESULTS: This study included 80 patients undergoing laparoscopic myomectomy of large uterine myomas (≥8cm). Forty patients were treated with a combination of oral letrozole (2.5mg/day) and norethindrone acetate (2.5mg/day) continuously in the three months prior to surgery (group A) and 40 patients received no treatment before surgery (group B). The total operative time (mean±SD, range) was significantly lower in group A (121.5±19.9min; 89-181min) than in group B (134.4±16.8min; 111-185min; p<0.001). The time required to close the hysterotomies (mean±SD, range) was lower in group A (27.1±5.1min; 16-39min) than in group B (37.1±9.6min; 17-57min; p<0.001). The intraoperative blood loss (mean±SD, range) was lower in group A (271.0±125.6ml; 95-625ml) than in group B (460.4±205.7ml; 180-1115ml; p<0.001). No major complication occurred in any case. The cleavage plane was better defined in group B compared with group A (p<0.001). The quality of the myometrial scar, defined by ultrasound evaluation, was similar in the two study groups both at one-week (p=0.356) and at 3-month follow-up (p=0.201). CONCLUSIONS: The total operative time, the time required to close the hysterotomies and the intraoperative blood loss significantly decrease after preoperative treatment with letrozole. Future randomized studies should compare the efficacy of preoperative administration of AIs and GnRHa prior to laparoscopic myomectomy.

Aromatase and endometriosis: estrogens play a role.

Endometriosis is an estrogen-dependent inflammatory disease defined by the growth of endometrial stroma and glands outside of the uterus. Epidemiological and clinical studies show that estrogen is essential for the growth of endometriosis. There are several molecular links between estrogen production and inflammation in endometriosis. The enzyme aromatase P450 is expressed aberrantly in endometriosis and is stimulated by prostaglandin E2 , resulting in production of estrogen that induces prostaglandin E2 expression within endometriotic lesions. Furthermore, estrogen promotes the secretion of several inflammatory cytokines and growth factors, which contribute to the progression of endometriosis and stimulate estrogen production. On the basis of the local estrogen biosynthesis in endometriotic implants, nonsteroidal aromatase inhibitors have been successfully used to treat pain symptoms caused by endometriosis. These agents do not cause the disappearance of endometriosis; they cannot be considered routine treatment and should only be administered in adequately controlled clinical studies.

Norethisterone acetate versus norethisterone acetate combined with letrozole for the treatment of ovarian endometriotic cysts: a patient preference study.

OBJECTIVE: To compare the efficacy of norethisterone acetate (NETA; group N) or letrozole combined with NETA (group L) in treating endometriotic ovarian cysts. STUDY DESIGN: This patient-preference study included 20 patients in group N and 20 patients in group L. The primary aim of the study was to compare the volume of the endometriomas during and after treatment. The secondary outcome was the evaluation of the changes in pain symptoms during and after treatment. RESULTS: After six months of treatment, the volume of the endometriomas significantly decreased compared with baseline in both study groups; it was smaller in group L than in group N (p=0.026). The rate of satisfied patients at six months of treatment was similar between the study groups (p=0.451). No significant difference was reported between the two study groups in the amelioration of pain symptoms and in the incidence of adverse events. CONCLUSIONS: Letrozole combined with NETA is more efficacious than NETA alone in reducing the volume of endometriotic cysts but in none of the 40 patients included in the study did the endometriomas disappear. The efficacy of aromatase inhibitors, however, should be balanced with the need to administer long-term treatment.

Multidetector computerized tomography enema versus magnetic resonance enema in the diagnosis of rectosigmoid endometriosis.

PURPOSE: To compare the accuracy of multidetector computerized tomography enema (MDCT-e) and magnetic resonance enema (MRI-e) in determining the presence of sigmoid and rectal endometriotic nodules. MATERIALS AND METHODS: 260 women (32.6 ± 4.3 years) with symptoms suggestive of rectosigmoid endometriosis underwent MDCT-e and MRI-e prior to laparoscopy. After retrograde colonic distention and injection of intravenous contrast medium, patients were scanned on a 64-row MDCT scanner. MRI-e was performed on a 1.5T magnet using an 8 channels phased array coil; intestinal distention was achieved by introducing in the rectum 250-300 ml of ultrasonographic gel diluted with saline solution. Radiological findings were compared with surgical and histological results. RESULTS: 176 women had rectosigmoid endometriosis at surgery. There was no significant difference in the accuracy of MDCT-e (98.5%) and MRI-e (96.9%) in the diagnosis of sigmoid and rectal endometriosis (p=0.248). The sensitivity, specificity, positive predictive value, negative predictive value, positive likelihood ratio and negative likelihood ratio of MDCT-e and MRI-e were respectively 98.3%, 98.8%, 99.4%, 96.5%, 81.59, 0.02 and 97.2%, 96.4%, 98.3%, 94.1%, 26.89, 0.03. CONCLUSIONS: Both MDCT-e and MRI-e are accurate in the diagnosis of rectal and sigmoid endometriosis.

The potential of sunitinib as a therapy in ovarian cancer.

INTRODUCTION: Sunitinib malate (SU11248; Sutent®; Pfizer, Inc., New York) is a multi-kinase inhibitor currently approved for use in advanced renal cell carcinoma (RCC), imatinib-resistant/-intolerant gastrointestinal stromal tumours and progressive, well-differentiated pancreatic neuroendocrine tumours in patients with unresectable, locally advanced or metastatic disease. AREAS COVERED: This article describes the mechanism of action and of the pharmacokinetics of sunitinib; further, it summarizes Phase I and II trials on the clinical efficacy, tolerability and safety of this agent in the setting of ovarian cancer (OC) treatment. EXPERT OPINION: On the basis of the current literature, sunitinib has shown modest antitumour activity and acceptable toxicity. Studies investigating the impact of horizontal and vertical combinations should represent a priority of future research. Although clinical Phase II trials on the use of sunitinib in the treatment of OC demonstrated an acceptable profile of AEs, a greater comprehension of the toxicity of this compound is recommended.

Sorafenib for ovarian cancer.

INTRODUCTION: Sorafenib is an unselective inhibitor of multiple kinases which has demonstrated clinical advantage in renal cancer and hepatocellular carcinoma. It inhibits tumor proliferation by targeting receptor accessory factor (Raf) kinase isoforms, inhibiting receptor tyrosine kinases of a variety of pro-angiogenic factors and of several receptor tyrosine kinases involved in neovascularization and tumor development. AREAS COVERED: This review offers an explanation of the mechanism of action and of the pharmacokinetics of sorafenib, and gives readers a complete overview of Phase I and II studies on the clinical efficacy, tolerability and safety of this agent in the setting of ovarian cancer (OC) treatment. EXPERT OPINION: The available results from the studies which investigated the use of sorafenib for OC treatment demonstrated poor clinical benefit either as single agent or in combination therapy. The most promising results have been achieved combining sorafenib with bevacizumab, although overlapping and cumulative toxicities should be taken in consideration. Research should focus its attention to the development of reliable predictive biomarkers to assess response and direct therapy in order to allow patient selection and improving treatment schedules maximizing the clinical benefit and simultaneously minimizing the toxicity related to the chemotherapy. Further studies are needed to evaluate the role of sorafenib in the primary treatment of OC.