Clinical trial NCT00483782: Carboplatin and Paclitaxel With or Without Bevacizumab in Treating Patients With Newly Diagnosed Ovarian Epithelial Cancer, Fallopian Tube Cancer, or Primary Peritoneal Cavity Cancer
Official title: ICON7 - A Randomised, Two-Arm, Multi-Centre Gynaecologic Cancer InterGroup Trial of Adding Bevacizumab to Standard Chemotherapy (Carboplatin and Paclitaxel) in Patients With Epithelial Ovarian Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Fallopian Tube Cancer
Ovarian Cancer
Primary Peritoneal Cavity Cancer
Keywords: stage IV ovarian epithelial cancer
Brenner tumor
ovarian carcinosarcoma
ovarian clear cell cystadenocarcinoma
ovarian endometrioid adenocarcinoma
ovarian mixed epithelial carcinoma
ovarian mucinous cystadenocarcinoma
ovarian serous cystadenocarcinoma
ovarian undifferentiated adenocarcinoma
stage IA ovarian epithelial cancer
stage IB ovarian epithelial cancer
stage IC ovarian epithelial cancer
stage IIA ovarian epithelial cancer
stage IIB ovarian epithelial cancer
stage IIC ovarian epithelial cancer
stage IIIA ovarian epithelial cancer
stage IIIB ovarian epithelial cancer
stage IIIC ovarian epithelial cancer
stage IA fallopian tube cancer
stage IB fallopian tube cancer
stage IC fallopian tube cancer
stage IIA fallopian tube cancer
stage IIB fallopian tube cancer
stage IIC fallopian tube cancer
stage IIIA fallopian tube cancer
stage IIIB fallopian tube cancer
stage IIIC fallopian tube cancer
stage IV fallopian tube cancer
stage IA primary peritoneal cavity cancer
stage IB primary peritoneal cavity cancer
stage IC primary peritoneal cavity cancer
stage IIA primary peritoneal cavity cancer
stage IIB primary peritoneal cavity cancer
stage IIC primary peritoneal cavity cancer
stage IIIA primary peritoneal cavity cancer
stage IIIB primary peritoneal cavity cancer
stage IIIC primary peritoneal cavity cancer
stage IV primary peritoneal cavity cancer
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2007-06-07
Enrollment: 1520
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Primary purpose: TREATMENT

Brief summary: RATIONALE: Drugs used in chemotherapy, such as carboplatin and paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells or stopping them from dividing. Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Bevacizumab may also stop the growth of tumor cells by blocking blood flow to the tumor. It is not yet known whether giving carboplatin and paclitaxel together with bevacizumab is more effective than carboplatin and paclitaxel alone in treating patients with ovarian epithelial cancer, fallopian tube cancer, or primary peritoneal cavity cancer.

PURPOSE: This randomized phase III trial is studying carboplatin, paclitaxel, and bevacizumab to see how well they work compared with carboplatin and paclitaxel alone in treating patients with newly diagnosed ovarian epithelial cancer, fallopian tube cancer, or primary peritoneal cavity cancer.

Detailed description: OBJECTIVES:

Primary

* Compare the progression-free survival and overall survival of patients with newly diagnosed ovarian epithelial, fallopian tube, or primary peritoneal cavity cancer treated with carboplatin and paclitaxel with vs without bevacizumab.

Secondary

* Compare the response rate in patients treated with these regimens.
* Compare the duration of tumor response in patients treated with these regimens.
* Compare the biological progression-free interval, as measured by increasing CA 125 levels, in patients treated with these regimens.
* Compare the safety (e.g., adverse events, laboratory results, and performance status) of these regimens in these patients.
* Compare the quality of life of patients treated with these regimens.
* Compare the cost-effectiveness of these regimens in these patients.

OUTLINE: This is a multicenter, open-label, randomized, controlled study. Patients are stratified according to FIGO stage (stage I-III with residual disease ≤ 1 cm vs stage I-III with residual disease \> 1 cm vs stage IV disease), intended time to start chemotherapy after surgery (≤ 4 weeks vs \> 4 weeks), and participating center. Patients are randomized to 1 of 2 treatment arms.

* Arm I (control): Patients receive paclitaxel IV over 3 hours followed by carboplatin IV over 30-60 minutes on day 1. Treatment repeats every 3 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity.
* Arm II: Patients receive bevacizumab IV over 30-90 minutes followed by paclitaxel IV over 3 hours and carboplatin IV over 30-60 minutes on day 1. Treatment repeats every 3 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients then continue to receive bevacizumab alone every 3 weeks for 12 courses.

Quality of life is assessed at baseline, before every course, every 6 weeks for 1 year, every 3 months until disease progression or for up to 2 years, and then at 3 years. Health economic data is assessed periodically, including days of inpatient hospitalization visits, outpatient visits, and use of anticancer therapies.

After completion of study treatment, patients are followed every 3-6 months for 5 years and then annually thereafter.

Peer Reviewed and Funded or Endorsed by Cancer Research UK.

Eligibility criteria: DISEASE CHARACTERISTICS:

* Histologically confirmed ovarian epithelial, fallopian tube, or primary peritoneal cavity cancer

  * Newly diagnosed disease
* Meets 1 of the following staging criteria:

  * High-risk stage I or IIA disease (grade 3 disease or clear cell carcinoma only)
  * Stage IIB-IV disease (all grades and all histological types)
* Must have undergone initial surgery (e.g., debulking cytoreductive surgery or a biopsy if the patient has stage IV disease) within the past 6 weeks

  * Patients with stage IV disease for which initial surgical debulking was not appropriate are eligible provided the following criteria are met:

    * Stage IV disease diagnosed by histology
    * No planned surgery prior to disease progression, including interval debulking surgery
* Patients with prior early-stage ovarian epithelial or fallopian tube carcinoma treated with surgery alone are eligible at the time of diagnosis of abdominopelvic recurrence provided no further interval cytoreductive therapy is planned prior to disease progression
* Synchronous primary endometrial carcinoma or a past history of primary endometrial carcinoma allowed provided the following criteria are met:

  * Disease ≤ stage IB
  * No more than superficial myometrial invasion
  * No lymphovascular invasion
  * Not poorly differentiated (i.e., no grade 3, papillary serous, or clear cell disease)
* Measurable or nonmeasurable disease
* No ovarian nonepithelial cancer, including malignant mixed Müllerian tumors
* No borderline tumors (e.g., tumors of low malignant potential)
* No history or clinical suspicion of brain metastases or spinal cord compression

  * CT scan or MRI of the brain is mandatory (within 4 weeks prior to randomization) in case of suspected brain metastases
  * Spinal MRI is mandatory (within 4 weeks prior to randomization) in case of suspected spinal cord compression

PATIENT CHARACTERISTICS:

* ECOG performance status 0-2
* Life expectancy \> 12 weeks
* ANC ≥ 1,500/mm\^3
* Platelet count ≥ 100,000/mm\^3
* Hemoglobin ≥ 9 g/dL (can be post-transfusion)
* INR ≤ 1.5
* APTT ≤ 1.5 times upper limit of normal (ULN)
* Bilirubin ≤ 1.5 times ULN
* ALT and AST ≤ 2.5 times ULN
* Creatinine ≤ 2.0 mg/dL
* Proteinuria ≤ 1+ by urine dipstick OR ≤ 1 g by 24-hour urine collection
* Not pregnant or nursing
* Negative pregnancy test
* Fertile patients must use effective contraception during and for ≥ 6 weeks after completion of study therapy
* No significant traumatic injury within the past 4 weeks
* No cerebrovascular accident, transient ischemic attack, or subarachnoid hemorrhage within the past 6 months
* No other malignancies within the past 5 years except for adequately treated carcinoma in situ of the cervix, and/or basal cell skin cancer, and/or early endometrial carcinoma
* No pre-existing sensory or motor neuropathy ≥ grade 2
* No history or evidence of CNS disease (e.g., uncontrolled seizures) by neurological examination unless adequately treated with standard medical therapy
* No history or evidence of thrombotic or hemorrhagic disorders
* No uncontrolled hypertension (i.e., blood pressure \> 150/100 mm Hg despite antihypertensive therapy)
* No known hypersensitivity to bevacizumab and its excipients, chemotherapy, or Cremophor EL
* No nonhealing wound, ulcer, or bone fracture

  * Patients with granulating incisions healing by secondary intention with no evidence of facial dehiscence or infection are eligible but require three weekly wound examinations
* No clinically significant cardiovascular disease, including any of the following:

  * Myocardial infarction or unstable angina within the past 6 months
  * New York Heart Association class II-IV congestive heart failure
  * Poorly controlled cardiac arrhythmia despite medication

    * Rate-controlled atrial fibrillation allowed
  * Peripheral vascular disease ≥ grade 3 (i.e., symptomatic and interfering with activities of daily living requiring repair or revision)
* No evidence of other disease or condition, metabolic dysfunction, physical examination findings, or laboratory findings that would contraindicate the use of an investigational drug or put the patient at high-risk for treatment-related complications

PRIOR CONCURRENT THERAPY:

* See Disease Characteristics
* More than 4 weeks since other prior surgery or open biopsy
* No prior systemic therapy for ovarian cancer (e.g., chemotherapy, monoclonal antibody therapy, tyrosine kinase inhibitor therapy, or hormonal therapy)
* Prior adjuvant chemotherapy allowed for other malignancies (e.g., breast or colorectal carcinoma) if malignancy was diagnosed over 5 years ago with no evidence of subsequent recurrence
* No prior mouse CA 125 antibody
* No prior radiotherapy to the abdomen or pelvis
* More than 10 days since prior and no concurrent chronic use of acetylsalicylic acid (\> 325 mg/day)

  * Low-dose (\< 325 mg/day) acetylsalicylic acid allowed
* More than 10 days since prior and no concurrent full-dose oral or parenteral anticoagulants or thrombolytic agents for therapeutic purposes

  * Use of therapy for line patency allowed provided INR \< 1.5
* More than 30 days since prior and no other concurrent investigational agent or participation in another clinical trial
* No other concurrent systemic antitumor agents
* No concurrent surgery
* No concurrent maintenance chemotherapy or intraperitoneal chemotherapy (including cytotoxic chemotherapy)

Primary outcomes:
measure: Progression-free survival
Secondary outcomes:
measure: Duration of overall survival
measure: Objective response rate
measure: Duration of response
measure: Biological progression-free interval as measured by increasing CA 125 levels
measure: Safety as measured by NCI CTAE version 3.0
measure: Quality of life
measure: Health economics
Other outcomes:
Locations:
city: Liverpool
country: Australia
facility: Cancer Therapy Centre at Liverpool Hospital
state: New South Wales
city: Randwick
country: Australia
facility: Prince of Wales Private Hospital
state: New South Wales
city: St. Leonards
country: Australia
facility: Royal North Shore Hospital
state: New South Wales
city: Sydney
country: Australia
facility: Sydney Cancer Centre at Royal Prince Alfred Hospital
state: New South Wales
city: Waratah
country: Australia
facility: Newcastle Mater Misericordiae Hospital
state: New South Wales
city: Wentworthville
country: Australia
facility: Westmead Institute for Cancer Research at Westmead Hospital
state: New South Wales
city: Brisbane
country: Australia
facility: Royal Brisbane and Women's Hospital
state: Queensland
city: South Brisbane
country: Australia
facility: Mater Adult Hospital
state: Queensland
city: Adelaide
country: Australia
facility: Royal Adelaide Hospital Cancer Centre
state: South Australia
city: Hobart
country: Australia
facility: Royal Hobart Hospital
state: Tasmania
city: Box Hill
country: Australia
facility: Box Hill Hospital
state: Victoria
city: Carlton
country: Australia
facility: Royal Women's Hospital
state: Victoria
city: East Melbourne
country: Australia
facility: Mercy Hospital for Women
state: Victoria
city: Frankston
country: Australia
facility: Frankston Hospital
state: Victoria
city: Wodonga
country: Australia
facility: Murray Valley Private Hospital and Cancer Treatment Centre
state: Victoria
city: Perth
country: Australia
facility: Sir Charles Gairdner Hospital - Perth
state: Western Australia
city: Angers
country: France
facility: Centre Paul Papin
city: Avignon
country: France
facility: Institut Sainte Catherine
city: Bordeaux
country: France
facility: Institut Bergonie
city: Bordeaux
country: France
facility: Polyclinique Bordeaux Nord Aquitaine
city: Bordeaux
country: France
facility: Clinique Tivoli
city: Caen
country: France
facility: Centre Regional Francois Baclesse
city: Clermont-Ferrand
country: France
facility: Centre Jean Perrin
city: Colmar
country: France
facility: Hopital Louis Pasteur
city: Grenoble
country: France
facility: CHU de Grenoble - Hopital de la Tronche
city: Grenoble
country: France
facility: Institut Prive de Cancerologie
city: Le Chesnay
country: France
facility: Hopital Andre Mignot
city: Le Mans
country: France
facility: Centre Jean Bernard
city: Lyon
country: France
facility: Centre Leon Berard
city: Montpellier
country: France
facility: Centre Regional de Lutte Contre le Cancer - Centre Val d'Aurelle
city: Nancy
country: France
facility: Centre D'Oncologie De Gentilly
city: Nantes-Saint Herblain
country: France
facility: Centre Regional Rene Gauducheau
city: Nantes
country: France
facility: Centre Catherine de Sienne
city: Paris
country: France
facility: Hopital Europeen Georges Pompidou
city: Paris
country: France
facility: Institut Curie Hopital
city: Paris
country: France
facility: Hotel Dieu de Paris
city: Paris
country: France
facility: Hopital Cochin
city: Paris
country: France
facility: Hopital Tenon
city: Pierre Benite
country: France
facility: Centre Hospitalier Lyon Sud
city: Rouen
country: France
facility: Centre Henri Becquerel
city: Saint Brieuc
country: France
facility: Clinique Armoricaine De Radiologie
city: Saint Cloud
country: France
facility: Centre Rene Huguenin
city: Strasbourg
country: France
facility: Hopital Universitaire Hautepierre
city: Tours
country: France
facility: Centre Hospitalier Universitaire Bretonneau de Tours
city: Vandoeuvre-les-Nancy
country: France
facility: Centre Alexis Vautrin
city: Berlin
country: Germany
facility: Evang. Waldkrankenhaus Spandau
city: Berlin
country: Germany
facility: Charite University Hospital - Campus Virchow Klinikum
city: Bremen
country: Germany
facility: Klinikum Bremen-Mitte
city: Bremen
country: Germany
facility: Praxis Dres. F.& G. Doering
city: Chemnitz
country: Germany
facility: Klinikum Chemnitz gGmbH
city: Dresden
country: Germany
facility: Universitatsklinikum Carl Gustav Carus
city: Ebersberg
country: Germany
facility: Kreiskrankenhaus
city: Essen
country: Germany
facility: Universitaetsklinikum Essen
city: Essen
country: Germany
facility: Elisabeth-Krankenhaus
city: Esslingen
country: Germany
facility: Staedtische Kliniken Esslingen
city: Frankfurt
country: Germany
facility: Onkologie Bethanien
city: Frankfurt
country: Germany
facility: Klinikum der J.W. Goethe Universitaet
city: Frankfurt
country: Germany
facility: Staedtische Kliniken Frankfurt am Main - Hoechst
city: Freiburg
country: Germany
facility: Universitaetsfrauenklinik Freiburg
city: Georgsmarienhuette
country: Germany
facility: Franziskus Hospital Hardenberg
city: Greifswald
country: Germany
facility: Klinik Fuer Innere Medizin, Hematology/Oncology, Ernst Moritz Armdt Universitaet
city: Halle
country: Germany
facility: Universitaetsklinikum Halle
city: Hannover
country: Germany
facility: Henriettenstiftung Frauenklinik
city: Hannover
country: Germany
facility: Medizinische Hochschule Hannover
city: Karlsruhe
country: Germany
facility: St. Vincentius - Kliniken
city: Kassel
country: Germany
facility: Klinikum Kassel
city: Kiel
country: Germany
facility: University Hospital Schleswig-Holstein - Kiel Campus
city: Lahr
country: Germany
facility: Kreiskrankenhaus Lahr
city: Leonberg
country: Germany
facility: Kreiskrankenhaus Leonberg - Frauenklinik
city: Lich
country: Germany
facility: Asklepios Klinik Lich
city: Limburg
country: Germany
facility: St. Vincenz Hospital Limburg
city: Luebeck
country: Germany
facility: Universitaetsklinikum Schleswig-Holstein - Campus Luebeck
city: Lueneburg
country: Germany
facility: Staedtisches Klinikum Lueneburg
city: Magdeburg
country: Germany
facility: Klinik St. Marienstift Magdeburg
city: Mainz
country: Germany
facility: St. Vincenz und Elisabeth Hospital
city: Marburg
country: Germany
facility: Universitaetsklinikum Giessen und Marburg GmbH - Marburg
city: Minden
country: Germany
facility: Klinikum Minden
city: Munich
country: Germany
facility: I. Frauenklinik und Hebammenschule der Ludwig-Maximillians Universitaet Muenchen
city: Munich
country: Germany
facility: Klinikum der Universitaet Muenchen - Grosshadern Campus
city: Munich
country: Germany
facility: Klinikum Rechts Der Isar - Technische Universitaet Muenchen
city: Neunkirchen
country: Germany
facility: Staedtisches Klinikum Neunkirchen gGmbH
city: Neuss
country: Germany
facility: Lukaskrankenhaus Neuss
city: Offenbach
country: Germany
facility: Klinikum Offenback GmbH
city: Paderborn
country: Germany
facility: Saint Vincenz-Krankenhaus Paderborn
city: Quedlinburg
country: Germany
facility: Klinikum Dorothea Christiane Erxleben - Quedlingburg
city: Ravensburg
country: Germany
facility: Krankenhaus St. Elisabeth - Ravensburg
city: Siegen
country: Germany
facility: St. Marien - Krankenhaus Siegen GMBH
city: Sigmaringen
country: Germany
facility: Kliniken Landkreis Sigmaringen GMBH
city: Stuttgart
country: Germany
facility: Robert-Bosch-Krankenhaus
city: Stuttgart
country: Germany
facility: Marienhospital Stuttgart
city: Ulm
country: Germany
facility: Comprehensive Cancer Center Ulm at Universitaetsklinikum Ulm
city: Wiesbaden
country: Germany
facility: Dr. Horst-Schmidt-Kliniken
city: Witten
country: Germany
facility: Marien-Hospital Witten
city: Wolfsburg
country: Germany
facility: Klinikum der Stadt Wolfsburg
city: Wuppertal
country: Germany
facility: Praxis Fuer Haemotologie Und Internistischer Onkologie
city: Oslo
country: Norway
facility: Norwegian Radium Hospital
city: Barnstaple
country: United Kingdom
facility: North Devon District Hospital
state: England
city: Broomfield
country: United Kingdom
facility: Broomfield Hospital
state: England
city: Burton-upon-Trent
country: United Kingdom
facility: Queen's Hospital
state: England
city: Cambridge
country: United Kingdom
facility: Addenbrooke's Hospital
state: England
city: Cheltenham
country: United Kingdom
facility: Gloucestershire Oncology Centre at Cheltenham General Hospital
state: England
city: Exeter
country: United Kingdom
facility: Royal Devon and Exeter Hospital
state: England
city: Gateshead
country: United Kingdom
facility: Queen Elizabeth Hospital
state: England
city: Guildford
country: United Kingdom
facility: St. Luke's Cancer Centre at Royal Surrey County Hospital
state: England
city: Hull
country: United Kingdom
facility: Princess Royal Hospital at Hull and East Yorkshire NHS Trust
state: England
city: Ipswich
country: United Kingdom
facility: Ipswich Hospital
state: England
city: Keighley
country: United Kingdom
facility: Airedale General Hospital
state: England
city: Leeds
country: United Kingdom
facility: Leeds Cancer Centre at St. James's University Hospital
state: England
city: London
country: United Kingdom
facility: University College of London Hospitals
state: England
city: London
country: United Kingdom
facility: Guy's Hospital
state: England
city: London
country: United Kingdom
facility: St. George's Hospital
state: England
city: London
country: United Kingdom
facility: Hammersmith Hospital
state: England
city: Maidstone
country: United Kingdom
facility: Mid Kent Oncology Centre at Maidstone Hospital
state: England
city: Manchester
country: United Kingdom
facility: Christie Hospital
state: England
city: Margate
country: United Kingdom
facility: Queen Elizabeth The Queen Mother Hospital
state: England
city: Merseyside
country: United Kingdom
facility: Clatterbridge Centre for Oncology
state: England
city: Middlesbrough
country: United Kingdom
facility: James Cook University Hospital
state: England
city: Newcastle-Upon-Tyne
country: United Kingdom
facility: Northern Centre for Cancer Treatment at Newcastle General Hospital
state: England
city: Northampton
country: United Kingdom
facility: Northampton General Hospital
state: England
city: Northwood
country: United Kingdom
facility: Mount Vernon Cancer Centre at Mount Vernon Hospital
state: England
city: Norwich
country: United Kingdom
facility: Norfolk and Norwich University Hospital
state: England
city: Nottingham
country: United Kingdom
facility: Nottingham City Hospital
state: England
city: Oxford
country: United Kingdom
facility: Churchill Hospital
state: England
city: Plymouth
country: United Kingdom
facility: Derriford Hospital
state: England
city: Poole Dorset
country: United Kingdom
facility: Dorset Cancer Centre
state: England
city: Portsmouth Hants
country: United Kingdom
facility: Portsmouth Oncology Centre at Saint Mary's Hospital
state: England
city: Sheffield
country: United Kingdom
facility: Cancer Research Centre at Weston Park Hospital
state: England
city: Shrewsbury
country: United Kingdom
facility: Royal Shrewsbury Hospital
state: England
city: Shrewsbury
country: United Kingdom
facility: Stoke Mandeville Hospital
state: England
city: Slough, Berkshire
country: United Kingdom
facility: Wexham Park Hospital
state: England
city: Southampton
country: United Kingdom
facility: Southampton General Hospital
state: England
city: Stafford
country: United Kingdom
facility: Staffordshire General Hospital
state: England
city: Sutton
country: United Kingdom
facility: Royal Marsden - Surrey
state: England
city: Swindon
country: United Kingdom
facility: Great Western Hospital
state: England
city: Truro, Cornwall
country: United Kingdom
facility: Royal Cornwall Hospital
state: England
city: Yeovil - Somerset
country: United Kingdom
facility: Yeovil District Hospital
state: England
city: Belfast
country: United Kingdom
facility: Centre for Cancer Research and Cell Biology at Queen's University Belfast
state: Northern Ireland
city: Aberdeen
country: United Kingdom
facility: Aberdeen Royal Infirmary
state: Scotland
city: Dundee
country: United Kingdom
facility: Ninewells Hospital
state: Scotland
city: Edinburgh
country: United Kingdom
facility: Edinburgh Cancer Centre at Western General Hospital
state: Scotland
city: Bangor
country: United Kingdom
facility: Ysbyty Gwynedd
state: Wales
city: Swansea
country: United Kingdom
facility: South West Wales Cancer Institute
state: Wales
Study officials:
affiliation: Leeds Cancer Centre at St. James's University Hospital
name: Tim J. Perren, MD
role: STUDY_CHAIR
References:
citation: Dhillon S. Bevacizumab combination therapy: for the first-line treatment of advanced epithelial ovarian, fallopian tube or primary peritoneal cancer. Drugs. 2012 May 7;72(7):917-30. doi: 10.2165/11208940-000000000-00000.
citation: Perren TJ, Swart AM, Pfisterer J, Ledermann JA, Pujade-Lauraine E, Kristensen G, Carey MS, Beale P, Cervantes A, Kurzeder C, du Bois A, Sehouli J, Kimmig R, Stahle A, Collinson F, Essapen S, Gourley C, Lortholary A, Selle F, Mirza MR, Leminen A, Plante M, Stark D, Qian W, Parmar MK, Oza AM; ICON7 Investigators. A phase 3 trial of bevacizumab in ovarian cancer. N Engl J Med. 2011 Dec 29;365(26):2484-96. doi: 10.1056/NEJMoa1103799.
citation: Vaughan S, Coward JI, Bast RC Jr, Berchuck A, Berek JS, Brenton JD, Coukos G, Crum CC, Drapkin R, Etemadmoghadam D, Friedlander M, Gabra H, Kaye SB, Lord CJ, Lengyel E, Levine DA, McNeish IA, Menon U, Mills GB, Nephew KP, Oza AM, Sood AK, Stronach EA, Walczak H, Bowtell DD, Balkwill FR. Rethinking ovarian cancer: recommendations for improving outcomes. Nat Rev Cancer. 2011 Sep 23;11(10):719-25. doi: 10.1038/nrc3144.