Pharmacokinetic and toxicity considerations for the use of anthracyclines in ovarian cancer treatment

none4INTRODUCTION: Safe and effective treatments are needed for ovarian cancer. While there are many drugs currently available, there has recently been a renewed novel interest in the use of anthracyclines. AREAS COVERED: This review summarizes the available evidence on pharmacokinetic (PK) and toxicology implications of anthracyclines and pegylated liposomal doxorubicin (PLD) in the clinical management of women with epithelial ovarian cancer. This article consists of material obtained via Medline, PubMed and EMBASE literature searches, up to September 2010. EXPERT OPINION: PLD is a liposomal formulation of doxorubicin (DXR), with a distinct pharmacokinetic profile, characterized by extended circulation time and a reduced clearance and volume of distribution with respect to the free drug. PLD is effective and well tolerated in relapsed ovarian cancer. The toxicity profile of PLD is characterized by dose-limiting mucosal and cutaneous toxicities, mild myelosuppression and decreased cardiotoxicity compared to free DXR. The good response rate, toxicity profile and pharmacokinetic profile of PLD suggest that PLD could be an option in first-line and second-line treatment in ovarian cancer; especially in those who had experienced taxane-induced toxicity or had a poor performance status.Matteo Morotti;Mario Valenzano Menada;Pier Luigi Venturini;Simone FerreroMatteo, Morotti; VALENZANO MENADA, Mario; Venturini, PIER LUIGI; Ferrero, Simon

Bevacizumab in endometrial cancer treatment

There is a critical need to develop effective new strategies for the management of patients with advanced or recurrent endometrial cancer (EC) and molecular targeted therapies; in particular, antiangiogenic drugs represent an interesting field of pharmacological research. One of the most interesting of these agents is bevacizumab, a monoclonal antivascular endothelial growth factor antibody. AREAS COVERED: Mechanism of action and clinical trials of bevacizumab in EC, and suggestions for its future use are reviewed. The most relevant papers and the meeting abstracts published up to December 2011 were used as sources for this review. The purposes of this manuscript are to discuss the rationale of interfering with the process of tumor angiogenesis in EC, to help readers in understanding the mechanism of action of bevacizumab, and to provide a comprehensive summary of initial preclinical and clinical eesults of this drug in EC patients. EXPERT OPINION: Recent advances in the understanding of the molecular biology of EC have led to development of targeted therapies. Among these, antiangiogenic agents are one of the most promising therapies

Uterine adenomyosis in persistence of dysmenorrhea after surgical excision of pelvic endometriosis and colorectal resection.

OBJECTIVE: To determine whether the presence of uterine adenomyosis may impair the amelioration of pain symptoms after laparoscopic excision of pelvic endometriosis combined with colorectal resection. STUDY DESIGN: This prospective study included 50 women with bowel endometriosis with or without uterine adenomyosis. Presence of uterine adenomyosis was investigated by magnetic resonance imaging. Patients underwent excision of pelvic endometriosis and colorectal resection; some patients with focal adenomyosis underwent uterine surgery. Pain symptoms and gastrointestinal complaints were evaluated before surgery and at 6, 12 and 18 months' follow-up. RESULTS: At 6-month follow-up, dysmenorrhea significantly improved in women without uterine adenomyosis and in those with adenomyosis that was excised at surgery; this improvement persisted at 18 months' followup. No significant improvement in dysmenorrhea was observed in women with adenomyosis not excised at surgery. Deep dyspareunia and chronic pelvic pain significantly improved at follow-up in all study groups. Most of gastrointestinal symptoms improved or disappeared at 6 months' follow-up; the improvement in gastrointestinal function persisted at 18 months' follow-up. CONCLUSION: Excision of pelvic endometriosis combined with bowel resection significantly improves chronic pelvic pain, dyspareunia and gastrointestinal symptoms; however, the presence of uterine adenomyosis may determine persistence of dysmenorrhea

The preoperative diagnosis of borderline ovarian tumors: a review of current literature

PURPOSE: To evaluate the available information on the preoperative diagnosis of borderline ovarian tumors (BOTs). METHODS: Articles were identified through electronic databases (Medline and EMBASE, MEDLINE, PubMed), no date or language restrictions were placed; relevant citations were hand searched. RESULTS: Women with BOTs are more likely to have no symptom than women with invasive ovarian cancers; however, the type of symptoms is similar in patients with BOTs and invasive ovarian cancers. Up to 61% of women with BOTs have elevated CA-125; CA 19.9 and endoglin are not useful for diagnosing BOTs. Further studies are required to determine whether the measurements of calprotectin, oviductal glycoprotein 1 and growth differentiation factor-15 are useful for diagnosing BOTs. Ultrasonography and magnetic resonance imaging (MRI) are the mainstay for the diagnosis of BOTs. Combining MRI and positron emission tomography may facilitate the identification of BOTs. CONCLUSION: After completion of this article, the reader should be aware of the symptoms of BOTs, the potential role and pitfalls of tumor marker measurement. In addition, the reader will understand the appearance of BOTs at imaging techniques; the reader will be able to compare and combine ultrasonography, MRI and positron emission tomography in diagnosing BOTs. In clinical practice, the reader should be better able to assess whether an ovarian mass is a benign tumor, a BOT or an invasive cancer

Transobturator adjustable tape (TOA) in female stress urinary incontinence associated with low maximal urethral closure pressure

Abstract Purpose To determine the success rate of transobturator adjustable tape (TOA, Agency for Medical Innovations, A.M.I., Austria) in stress urinary incontinent patients with maximal urethral closure pressure (MUCP) ·20 cm H 2 O compared to those with MUCP >20 cm H 2 O. Materials and methods In this retrospective study, all female patients with a diagnosis of stress urinary incontinence underwent TOA, from September 2005 to August 2007. All patients had preoperative multichannel urodynamic tests (cystometry, urethral proWle and uroXowmetry). During September 2008, patients were contacted by telephone and the validated short forms of the Urogenital Distress Inventory (UDI-6) questionnaire and the Incontinence Impact Questionnaire (IIQ-7) were administered. Results The chart review identiWed 146 patients (125 with MUCP >20 cm H 2 O and 21 with MUCP ·20 cm H 2 O) who had undergone TOA and who met the inclusion criteria. Of these, 121 patients (82.9%) were contacted by telephone. Results showed a very good quality of life (score 0-7 in the IIQ-7) in 95.9% of patients. Only two (1.6%) patients had persistent signiWcant urine leakage related to physical activity. In the MUCP ·20 cm H 2 O group, 90% of patients could be considered as being very satisWed, with a very good quality of life. Conclusion With the TOA procedure, the obturator route could be used to treat patients with urinary incontinence and also with low MUCP

Selection of patients with high risk endometrial cancer for surgical staging according to the evaluation of pre- and intraoperative risk factors

The aim of this paper was to assess the accuracy of frozen sections histological examination and preoperative CA-125 to select patients with high risk endometrial cancer