Emerging treatment options for management of malignant ascites in patients with ovarian cancer

Malignant ascites affects approximately 10% of patients with recurrent epithelial ovarian cancer and is associated with troublesome symptoms, including abdominal pressure and distension, dyspnea, bloating, pelvic pain, and bowel/bladder dysfunction. To date, no effective therapy has been identified for the treatment of malignant ascites in patients with recurrent, advanced ovarian cancer. In this article, we discuss currently existing options for the treatment of ascites associated with ovarian cancer, and review the literature as it pertains to novel, targeted therapies. Specifically, preclinical and clinical trials exploring the use of the antiangiogenic agents, bevacizumab and vascular endothelial growth factor-trap, as well as the nonangiogenic agent, catumaxomab, will be reviewed. Despite current limitations in treatment, knowledge regarding management options in the palliation of ascites is critical to practicing physicians. Ultimately, as with all novel therapies, symptom relief and treatment goals must be weighed against patient discomfort and potentially significant adverse events.

[1]  A. Gaya,et al.  A preclinical and clinical review of aflibercept for the management of cancer. , 2012, Cancer treatment reviews.

[2]  J. Sehouli,et al.  First patient treated with a re-challenge of catumaxomab in recurrent malignant ascites: a case report , 2012, Medical Oncology.

[3]  N. Colombo,et al.  A phase II study of aflibercept in patients with advanced epithelial ovarian cancer and symptomatic malignant ascites. , 2012, Gynecologic oncology.

[4]  M. Stewart Aflibercept (VEGF Trap-eye): the newest anti-VEGF drug , 2012, British Journal of Ophthalmology.

[5]  Richard S Levene,et al.  Palliative Chemotherapy for Malignant Ascites Secondary to Ovarian Cancer , 2012, The American journal of hospice & palliative care.

[6]  D. Provencher,et al.  Intravenous aflibercept for treatment of recurrent symptomatic malignant ascites in patients with advanced ovarian cancer: a phase 2, randomised, double-blind, placebo-controlled study. , 2012, The Lancet. Oncology.

[7]  G. Becker,et al.  VEGF Trap for the treatment of malignant ascites. , 2012, The Lancet. Oncology.

[8]  R. Burger,et al.  Antiangiogenic agents should be integrated into the standard treatment for patients with ovarian cancer. , 2011, Annals of oncology : official journal of the European Society for Medical Oncology.

[9]  S. Barni,et al.  A novel perspective for an orphan problem: old and new drugs for the medical management of malignant ascites. , 2011, Critical reviews in oncology/hematology.

[10]  R. Burger,et al.  Overview of anti-angiogenic agents in development for ovarian cancer. , 2011, Gynecologic oncology.

[11]  R. Eskander,et al.  Bevacizumab in the treatment of ovarian cancer , 2011, Biologics : targets & therapy.

[12]  L. Teng,et al.  Clinical Applications of VEGF‐Trap (Aflibercept) in Cancer Treatment , 2010, Journal of the Chinese Medical Association : JCMA.

[13]  V. Gebski,et al.  Pegylated liposomal Doxorubicin and Carboplatin compared with Paclitaxel and Carboplatin for patients with platinum-sensitive ovarian cancer in late relapse. , 2010, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[14]  S. Cannistra Evaluating new regimens in recurrent ovarian cancer: how much evidence is good enough? , 2010, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[15]  P. Murawa,et al.  The trifunctional antibody catumaxomab for the treatment of malignant ascites due to epithelial cancer: Results of a prospective randomized phase II/III trial , 2010, International journal of cancer.

[16]  H. Dickinson,et al.  Management of drainage for malignant ascites in gynaecological cancer. , 2010, The Cochrane database of systematic reviews.

[17]  Lawrence H. Schwartz,et al.  Phase I study of intravenous vascular endothelial growth factor trap, aflibercept, in patients with advanced solid tumors. , 2010, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[18]  C. Bokemeyer,et al.  Intraperitoneal VEGF inhibition using bevacizumab: a potential approach for the symptomatic treatment of malignant ascites? , 2009, The oncologist.

[19]  M. Bookman Trials With Impact on Clinical Management: First Line , 2009, International Journal of Gynecologic Cancer.

[20]  Mildred R. Chernofsky,et al.  Intraperitoneal bevacizumab for the palliation of malignant ascites in refractory ovarian cancer. , 2008, Gynecologic oncology.

[21]  P. Mhawech-Fauceglia,et al.  The use of bevacizumab in refractory ovarian granulosa-cell carcinoma with symptomatic relief of ascites: a case report. , 2008, Gynecologic oncology.

[22]  R. Kimmig,et al.  Effective Relief of Malignant Ascites in Patients with Advanced Ovarian Cancer by a Trifunctional Anti-EpCAM × Anti-CD3 Antibody: A Phase I/II Study , 2007, Clinical Cancer Research.

[23]  K. El-Shami,et al.  Open-label safety and efficacy pilot trial of intraperitoneal bevacizumab as palliative treatment in refractory malignant ascites , 2007 .

[24]  B. Monk,et al.  Salvage bevacizumab (rhuMAB VEGF)-based therapy after multiple prior cytotoxic regimens in advanced refractory epithelial ovarian cancer. , 2006, Gynecologic oncology.

[25]  M. Barnes,et al.  The use of bevacizumab to palliate symptomatic ascites in patients with refractory ovarian carcinoma. , 2006, Gynecologic oncology.

[26]  G. Becker,et al.  Malignant ascites: systematic review and guideline for treatment. , 2006, European journal of cancer.

[27]  Napoleone Ferrara,et al.  Angiogenesis as a therapeutic target , 2005, Nature.

[28]  R. Kimmig,et al.  Immunotherapy of malignant ascites with trifunctional antibodies , 2005, International journal of cancer.

[29]  Napoleone Ferrara,et al.  VEGF as a Therapeutic Target in Cancer , 2005, Oncology.

[30]  Anil K Sood,et al.  Vascular Endothelial Growth Factor Trap Combined with Paclitaxel Strikingly Inhibits Tumor and Ascites, Prolonging Survival in a Human Ovarian Cancer Model , 2005, Clinical Cancer Research.

[31]  B. Monk,et al.  Activity of bevacizumab (rhuMAB VEGF) in advanced refractory epithelial ovarian cancer. , 2005, Gynecologic oncology.

[32]  Y. Adam,et al.  Malignant ascites: past, present, and future. , 2004, Journal of the American College of Surgeons.

[33]  Robert S Mannel,et al.  Phase III trial of carboplatin and paclitaxel compared with cisplatin and paclitaxel in patients with optimally resected stage III ovarian cancer: a Gynecologic Oncology Group study. , 2003, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[34]  Jianzhong Huang,et al.  Regression of established tumors and metastases by potent vascular endothelial growth factor blockade , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[35]  Eugene S. Kim,et al.  Potent VEGF blockade causes regression of coopted vessels in a model of neuroblastoma , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[36]  S. Cannistra Is there a "best" choice of second-line agent in the treatment of recurrent, potentially platinum-sensitive ovarian cancer? , 2002, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[37]  P. Ruf,et al.  Induction of a long-lasting antitumor immunity by a trifunctional bispecific antibody. , 2001, Blood.

[38]  B. Wollenberg,et al.  The Fc-region of a new class of intact bispecific antibody mediates activation of accessory cells and NK cells and induces direct phagocytosis of tumour cells , 2000, British Journal of Cancer.

[39]  D. Hicklin,et al.  VEGF/Flk-1 interaction, a requirement for malignant ascites recurrence. , 2000, Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research.

[40]  J. Wood,et al.  Inhibition of malignant ascites and growth of human ovarian carcinoma by oral administration of a potent inhibitor of the vascular endothelial growth factor receptor tyrosine kinases. , 2000, International journal of oncology.

[41]  N. Ferrara Molecular and biological properties of vascular endothelial growth factor , 1999, Journal of Molecular Medicine.

[42]  W. Gotlieb,et al.  Intraperitoneal pressures and clinical parameters of total paracentesis for palliation of symptomatic ascites in ovarian cancer. , 1998, Gynecologic oncology.

[43]  L. Twiggs,et al.  Vascular endothelial growth factor expression in early stage ovarian carcinoma , 1997, Cancer.

[44]  K. Geisinger,et al.  Treatment and prevention of malignant ascites associated with disseminated intraperitoneal malignancies by aggressive combined-modality therapy. , 1997, The American surgeon.

[45]  Janet Rossant,et al.  Failure of blood-island formation and vasculogenesis in Flk-1-deficient mice , 1995, Nature.

[46]  Brygida Berse,et al.  Vascular permeability factor (VPF, VEGF) in tumor biology , 1993, Cancer and Metastasis Reviews.

[47]  R. N. Garrison,et al.  Mechanisms of malignant ascites production. , 1987, The Journal of surgical research.

[48]  Stark Rh,et al.  Surgical treatment of adenocarcinoma of the stomach in a community hospital. , 1985 .

[49]  Ostrowski Mj,et al.  Intracavitary bleomycin in the management of malignant effusions: a multicenter study. , 1982, Cancer treatment reports.

[50]  E. Savlov,et al.  Peritoneovenous shunt for palliation of malignant ascites , 1982, Cancer.

[51]  B. Maat,et al.  DISSEMINATION OF TUMOUR CELLS VIA LEVEEN SHUNT , 1979, The Lancet.

[52]  J. Horton,et al.  Intracavitary bleomycin in the management of malignant effusions , 1976, Cancer.

[53]  G. Pack,et al.  Intracavitary administration of radioactive isotopes in the control of effusions due to cancer: Results in 267 patients , 1966, Cancer.

[54]  A. Jemal,et al.  Cancer statistics, 2012 , 2012, CA: a cancer journal for clinicians.

[55]  Gordon B. Mills,et al.  Markedly Elevated Levels of Vascular Endothelial Growth Factor in Malignant Ascites , 1999, Annals of Surgical Oncology.

[56]  N. Ferrara Vascular endothelial growth factor: molecular and biological aspects. , 1999, Current topics in microbiology and immunology.

[57]  N. Ferrara,et al.  Role of Vascular Endothelial Growth Factor in Regulation of Angiogenesis , 1999 .

[58]  J. Kaufman Care of patients with ascites. , 1994, New England Journal of Medicine.

[59]  N. Dubrawsky Cancer statistics , 1989, CA: a cancer journal for clinicians.

[60]  R. H. Stark,et al.  Surgical treatment of adenocarcinoma of the stomach in a community hospital. , 1985, Surgery, gynecology & obstetrics.

[61]  G. Halsall,et al.  Intracavitary bleomycin in the management of malignant effusions: a multicenter study. , 1982, Cancer treatment reports.