NCCN Guidelines Insights: Ovarian Cancer,Version 3.2012
Version 3.2012 © National Comprehensive Cancer Network, Inc. 2012, All rights reserved. The NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN®.
Citation: Journal of the National Comprehensive Cancer Network J Natl Compr Canc Netw 10, 11; 10.6004/jnccn.2012.0140
NCCN Categories of Evidence and Consensus
Category 1: Based upon high-level evidence, there is uniform NCCN consensus that the intervention is appropriate.
Category 2A: Based upon lower-level evidence, there is uniform NCCN consensus that the intervention is appropriate.
Category 2B: Based upon lower-level evidence, there is NCCN consensus that the intervention is appropriate.
Category 3: Based upon any level of evidence, there is major NCCN disagreement that the intervention is appropriate.
All recommendations are category 2A unless otherwise noted.
Clinical trials: NCCN believes that the best management for any cancer patient is in a clinical trial. Participation in clinical trials is especially encouraged.
Overview
The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Ovarian Cancer discuss management of epithelial ovarian cancer, which is the most common type of ovarian cancer. The guidelines also discuss borderline epithelial ovarian cancer (also known as low malignant potential), fallopian tube cancer, and primary peritoneal cancer; these neoplasms occur less frequently but are managed in a similar manner to epithelial ovarian cancer. Less common ovarian histopathologies are also described in the complete version of the NCCN Guidelines (available at NCCN.org), including malignant germ cell neoplasms, carcinosarcomas (malignant mixed Müllerian tumors of the ovary [MMMT], which are also known as poorly differentiated ovarian cancer), and sex cord-stromal tumors.
In 2012, it is estimated that 22,300 new diagnoses and 15,500 deaths from ovarian cancer will occur in the United States.1 The complete version of the NCCN Guidelines for Ovarian Cancer is available on the NCCN Web site (NCCN.org). Patient guidelines for ovarian cancer are also available (NCCN.com).
NCCN Guidelines Insights: Ovarian Cancer,Version 3.2012
Version 3.2012 © National Comprehensive Cancer Network, Inc. 2012, All rights reserved. The NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN®.
Citation: Journal of the National Comprehensive Cancer Network J Natl Compr Canc Netw 10, 11; 10.6004/jnccn.2012.0140
Screening Tests for Diagnosing Ovarian Cancer
Most ovarian cancer is diagnosed at an advanced stage, which accounts for the high mortality rate with this disease. More than 60% of women have advanced-stage disease (stage III–IV)2 at diagnosis; therefore, a screening test to detect early-stage disease would be very useful. Currently, no effective and sensitive screening test for ovarian cancer is available, and none is recommended either by the NCCN Ovarian Cancer Panel or any major organization.3–5
Ongoing trials are assessing different approaches for ovarian cancer screening (eg, UK Collaborative Trial of Ovarian Cancer Screening [UKCTOCS]; Diagnosing Ovarian Cancer Early [DOvE]).6,7 The Prostate, Lung, Colorectal and Ovarian [PLCO] Cancer trial is a large randomized trial involving more than 78,000 women in the United States that assessed screening with transvaginal ultrasonography and serum cancer antigen 125 (CA-125) levels. However, the PLCO trial found that this screening method did not decrease mortality from ovarian cancer.3 In addition, false-positive results led to serious complications in some women (n=163). Although reports suggest that human epididymis protein 4 (HE4) and CA-125 may be useful in detecting ovarian cancer,8,9 recent data show that several markers (including CA-125 and HE4) do not increase early enough to be useful in detecting early-stage ovarian cancer.10,11
Diagnostic Tests for Assessing Pelvic Masses
The FDA has approved the use of OVA1 as a triage diagnostic test for estimating the risk of ovarian cancer in women with a pelvic mass. Note that the OVA1 test is not approved as a screening test for ovarian cancer. The OVA1 diagnostic test assesses several biomarkers (eg, CA-125), although the specific individual levels are not provided. Additional testing must be performed to obtain a CA-125 level.
NCCN Guidelines Insights: Ovarian Cancer,Version 3.2012
Version 3.2012 © National Comprehensive Cancer Network, Inc. 2012, All rights reserved. The NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN®.
Citation: Journal of the National Comprehensive Cancer Network J Natl Compr Canc Netw 10, 11; 10.6004/jnccn.2012.0140
Currently, the NCCN panel does not recommend the use of the OVA1 test for determining the status of an undiagnosed pelvic mass, because it increases cost without providing much benefit and because of concerns about false-positive results.12–15 The panel recommends using the ACOG/SGO (American College of Obstetricians and Gynecologists/Society of Gynecologic Oncology) criteria to determine whether a pelvic mass is malignant (ie, suspicious) or benign, and thus whether a patient should be referred to a gynecologic oncologist.16 The ACOG/SGO criteria recommend referral for postmenopausal women with 1) elevated CA-125, 2) nodular or fixed pelvic mass, 3) metastatic disease or ascites, or 4) family history of breast or ovarian cancer. Premenopausal women should be referred for 1) CA-125 level greater than 200 units/mL, 2) metastatic disease or ascites, or 3) strong family history of breast or ovarian cancer. However, some feel that a CA-125 level of greater than 50 units/mL (instead of a CA-125 level >200 units/mL) is a better discriminator of cancer versus benign masses for premenopausal women.16
Primary Treatment Using Neoadjuvant Chemotherapy
The NCCN Ovarian Cancer Panel recommends up-front primary debulking (ie, cytoreductive) surgery followed by adjuvant chemotherapy for most patients with resectable advanced ovarian cancer (including epithelial ovarian, fallopian tube, or primary peritoneal cancers).17–19 Upfront cytoreductive surgery (to achieve a gross total resection) is considered the preferred treatment (ie, gold standard) in the United States.20–22 After aggressive cytoreductive surgery, many patients with advanced ovarian cancer (even those with widespread intra-abdominal metastases, or high-grade serous carcinoma) have increased survival.18 Thus, the management of advanced ovarian cancer differs from many other cancers in which surgery is only recommended for early-stage disease.
NCCN Guidelines Insights: Ovarian Cancer,Version 3.2012
Version 3.2012 © National Comprehensive Cancer Network, Inc. 2012, All rights reserved. The NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN®.
Citation: Journal of the National Comprehensive Cancer Network J Natl Compr Canc Netw 10, 11; 10.6004/jnccn.2012.0140
Neoadjuvant chemotherapy (NACT) can be considered (category 1) for patients with bulky stage III (ie, stage IIIC) or IV ovarian cancer who are not surgical candidates. The panel upgraded the option for considering NACT in this setting to a category 1 recommendation based on recent published data.17,18,23–25 If clinically appropriate, NACT can also be considered for patients with stage II–III disease who are not surgical candidates and for select patients with MMMT (ie, poorly differentiated carcinoma) who are not surgical candidates. In select patients, NACT may be followed by interval cytoreduction (eg, NACT is given for 3 cycles followed by interval cytoreduction if possible, and then the remaining NACT regimen is given). For those having interval cytoreduction, approximately 50% of patients undergo complete resection.23,24 NACT is defined as upfront chemotherapy given before surgery or as a stand-alone option if interval cytoreduction is not feasible.
Whether NACT followed by interval cytoreduction is appropriate as primary treatment for patients with potentially resectable disease (eg, those with stage IIIC or IV disease who are surgical candidates) is a matter of controversy.24,26–30 A recent international trial assessed NACT with interval cytoreduction versus up-front primary cytoreduction in patients with extensive stage IIIC/IV ovarian, primary peritoneal, and fallopian tube carcinoma.23 Median overall survival was equivalent in these patients (29 vs. 30 months), but patients receiving NACT with interval cytoreduction had fewer complications.25 Based on the results of this trial, some oncologists feel that NACT is now appropriate for many patients with stage IIIC or IV ovarian cancer.31 However, the panel only recommends NACT for select patients with stage IIIC or IV cancer who are not candidates for up-front aggressive cytoreduction (eg, those with medical comorbidities, advanced age, extra-abdominal disease, and no access to experienced gynecologic oncologist; those for whom optimal cytoreduction is not possible or for whom extensive debilitating surgery would be required to achieve up-front optimal debulking; those who refuse surgery).17,25,32 Patients should be considered for palliative care (rather than definitive surgery and/or chemotherapy) if they have severely impaired renal function, expected survival less than 2 months, and/or performance status greater than 2.
NCCN Guidelines Insights: Ovarian Cancer,Version 3.2012
Version 3.2012 © National Comprehensive Cancer Network, Inc. 2012, All rights reserved. The NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN®.
Citation: Journal of the National Comprehensive Cancer Network J Natl Compr Canc Netw 10, 11; 10.6004/jnccn.2012.0140
Most patients in the United States undergoing primary cytoreduction followed by postoperative intravenous chemotherapy for advanced ovarian cancer have better progression-free and overall survivals (overall survival averages 50 months in US trials) than those reported in the international trial.17,33 The median overall survival in the international trial is 20 months lower than that reported in US trials using accepted therapeutic interventions (ie, up-front primary cytoreduction followed by chemotherapy). However, this difference may have occurred because the international trial did not include patients with stage IIIB or earlier-stage cancer. In addition, primary or interval cytoreduction in the international trial may not have been optimal (ie, patients may have had >1 cm of residual disease) or equivalent between the 2 arms.17,26 The NCCN Guidelines recommend optimal cytoreduction (ie, to yield a gross total resection) for patients with ovarian cancer.20–22
NCCN Guidelines Insights: Ovarian Cancer,Version 3.2012
Version 3.2012 © National Comprehensive Cancer Network, Inc. 2012, All rights reserved. The NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN®.
Citation: Journal of the National Comprehensive Cancer Network J Natl Compr Canc Netw 10, 11; 10.6004/jnccn.2012.0140
The panel believes that more data are necessary before NACT can be recommended in patients with potentially resectable ovarian cancer.20 Thus, up-front cytoreductive surgery remains the preferred treatment in the United States for most patients with resectable advanced ovarian cancer (including epithelial, fallopian tube, or primary peritoneal cancer). Note that the authors of the international trial believe that up-front primary cytoreduction should remain the standard of care for patients with stage IIIB or earlier-stage cancer, but that NACT with interval cytoreduction is an option for those with extensive stage IIIC or stage IV disease.23
Primary Adjuvant Treatment Using Bevacizumab in Combination With Chemotherapy
The panel members had a major disagreement about recommending the addition of bevacizumab to up-front therapy with carboplatin/paclitaxel or using bevacizumab as maintenance therapy; this disagreement is reflected as a category 3 recommendation. Most panel members believe that bevacizumab should not be added to up-front chemotherapy in patients with ovarian cancer, because recent data from 2 phase III randomized trials (ie, GOG-0218 and ICON7) have not shown a statistically significant increase in overall survival and/or improved quality of life.34,35 The magnitude of the clinical benefit versus the potential for serious side effects (eg, <3% of patients had gastrointestinal perforation or fistula) and cost were also discussed by the panel, with varying opinions.36,37
The panel recommends (category 3) that if bevacizumab is used with up-front chemotherapy followed by maintenance therapy, then either the GOG-0218 or ICON7 regimen should be used (see OV-D, page 1344).34,35 The only GOG-0218 regimen that is recommended (category 3) is bevacizumab up-front with carboplatin/paclitaxel followed by maintenance bevacizumab. Note that a category 3 recommendation indicates that more than 25% of the panel members believe that the intervention is not appropriate.
The ICON7 and GOG-0218 (phase III, randomized) trials assessed bevacizumab in combination with intravenous carboplatin/paclitaxel as up-front adjuvant therapy (after up-front cytoreductive surgery) compared with carboplatin/paclitaxel alone in patients with stage III–IV ovarian cancer.34,35 In GOG-0218, the median progression-free survival was slightly increased (3.8 months) in patients receiving bevacizumab up-front and as maintenance therapy compared with chemotherapy alone.34 Whether use of maintenance bevacizumab therapy alone in GOG-0218 would have yielded the same progression-free survival results is unclear. Although the progression-free survival data from ICON7 confirm the findings of GOG-0218, the benefits were also modest (1.7 month increase in progression-free survival). Quality of life was similar between the arms in both trials. Overall survival was also similar between the arms in GOG-0218. Mature data regarding overall survival have not been reported yet for ICON7.
ICON7 had some important differences compared with GOG-0218 (eg, the dose of bevacizumab in ICON7 was decreased by 50% to 7.5 mg/kg).35 After an unplanned post hoc subset analysis in ICON7, an apparent overall survival advantage was reported in patients with stage III suboptimal and stage IV disease (30% of participants). However, this overall survival advantage was not seen in GOG-0218, in which 65% to 70% of patients had similar high-risk features; any potential benefit may have been obscured by the availability of bevacizumab after progression of disease in the United States. This topic is discussed in greater detail in the NCCN Guidelines (available at NCCN.org).
Therapy for Recurrent Disease
Chemotherapy
Most patients (≈75%) respond to initial treatment for ovarian cancer, although they often experience recurrence. Many patients have platinum-sensitive disease. For patients with platinum-sensitive disease, platinum-based combination regimens should be considered for recurrent disease.38 Combination regimens are recommended based on randomized trial data, especially for first relapses (see OV-E, page 1345). Platinum-sensitive refers to disease that recurs more than 6 months after primary treatment, whereas platinum-resistant refers to disease that recurs after less than 6 months (or remains stable). Refractory usually refers to disease that has progressed while on platinum-based chemotherapy or does not respond to treatment. Persistent refers to disease that remains after initial chemotherapy treatment, which can be stable or smaller. Stable indicates that the tumor nodules have not grown or shrunk.
Platinum-resistant epithelial ovarian, fallopian tube, and primary peritoneal cancers are difficult to treat; prognosis is poor because most patients do not respond well to therapy.39,40 The NCCN Guidelines recommend single agents for platinum-resistant disease; the preferred agents are docetaxel, oral etoposide, gemcitabine, liposomal doxorubicin, weekly paclitaxel, or topotecan (see OV-E, page 1345).40 These preferred agents can also be used for persistent and refractory disease.40 The choice of agent for recurrent or persistent platinum-resistant disease is often based on expert opinion (eg, decreased toxicity and/or marginally increased effectiveness).39 Although liposomal doxorubicin is widely used, other agents may also be used.39,41–44 Data are lacking to define the appropriate sequence of agents in this setting. All therapy in this setting is highly individualized and often based on the practice patterns of the physician and preferences of the patient.
Targeted Therapy
Currently, single-agent bevacizumab is recommended in the NCCN Guidelines as a preferred recurrence therapy for patients with epithelial ovarian, fallopian tube cancer, or primary peritoneal cancer.45,46 For example, bevacizumab is a reasonable option for patients with recurrent disease that is platinum-resistant.47 Bevacizumab is active (21%) in both platinum-sensitive and -resistant patients.45 Several trials are assessing combination therapy with bevacizumab for recurrent ovarian cancer (ie, OCEANS, AURE-LIA).48,49 Other therapies are in clinical trials.46,50,51
Management of Drug/Hypersensitivity Reactions
Virtually all drugs have the potential to cause drug/hypersensitivity reactions, either during or after the infusion.52–54 Drugs used in gynecologic oncology treatment that more commonly cause adverse reactions include carboplatin, cisplatin, docetaxel, liposomal doxorubicin, oxaliplatin, and paclitaxel. Drug reactions can occur with either intravenous or intraperitoneal administration of these drugs.55 Most of these drug reactions are mild infusion reactions (ie, skin reactions, cardiovascular reactions, respiratory or throat tightness), but more severe allergic reactions (ie, life-threatening anaphylaxis) can sometimes occur.56,57 Infusion reactions are more common with paclitaxel,58 but mild reactions can also occur with liposomal doxorubicin.59 Allergic/hypersensitivity reactions (ie, true drug allergies) are more common with platinum agents (ie, carboplatin, cisplatin, oxaliplatin).58,60 Although severe reactions to biotherapeutic agents (eg, bevacizumab) are rare, they can also occur.58
Management of drug reactions is discussed in the NCCN Guidelines. New algorithms are now provided for management of mild, severe, and life-threatening reactions after intravenous or intraperitoneal infusion (see OV-C, pages 1340–1343).61 Previously, only an appendix (but no algorithm) appeared for this topic. Typically, the infusion should be stopped in patients experiencing a drug reaction; further management is provided in the new algorithms. In many patients who have experienced drug reactions, desensitization may be used to enable further use of chemotherapy. These drug reaction algorithms are also useful for patients with other cancers (eg, cervical and uterine cancers).
Summary of the Major Updates
Six update topics are discussed in these NCCN Guidelines Insights: 1) screening, 2) diagnostic tests for assessing pelvic masses, 3) primary treatment using NACT, 4) primary adjuvant treatment using bevacizumab in combination with chemotherapy, 5) therapy for recurrent disease, and 6) management of drug/hypersensitivity reactions.
Screening for ovarian cancer is not recommended either by the NCCN Ovarian Cancer Panel or by any major organization.3–5
The panel does not recommend use of the OVA1 test for determining the status of an undiagnosed pelvic mass.12–15 The panel feels that guidelines from ACOG/SGO should be used to assess whether a pelvic mass is malignant or benign, and thus whether a patient should be referred to a gynecologic oncologist.
NACT can be considered (category 1) for patients with bulky stage III (ie, stage IIIC) or IV ovarian cancer who are not surgical candidates. The panel upgraded the option for considering NACT in this setting to a category 1 recommendation.17,18,23–25,62 Previously, NACT was a category 2A recommendation in the guidelines. However, the panel recommends up-front primary debulking (ie, cytoreductive) surgery followed by adjuvant chemotherapy for most patients with resectable advanced ovarian cancer (including epithelial ovarian, fallopian tube, or primary peritoneal cancers).17–19
The panel had a major disagreement about recommending the addition of bevacizumab to up-front therapy with carboplatin/paclitaxel or using bevacizumab as maintenance therapy; this disagreement is reflected as a category 3 recommendation. Most panel members believe that bevacizumab should not be added to up-front chemotherapy in patients with ovarian cancer, because data from GOG-0218 and ICON7 have not shown an increase in overall survival and/or improved quality of life.34,35 However, the panel recommends (category 3) that if bevacizumab is used with up-front chemotherapy, then either the GOG-0218 or ICON7 regimens should be used (see OV-D, page 1344).34,35
Most patients (≈75%) respond to initial treatment for ovarian cancer, although they often experience a recurrence. For patients with platinum-sensitive disease, platinum-based combination regimens are preferred for persistent, recurrent, or refractory disease.38 The NCCN Guidelines recommend single agents for platinum-resistant disease; the preferred chemotherapeutic agents are docetaxel, oral etoposide, gemcitabine, liposomal doxorubicin, weekly paclitaxel, or topotecan.40 These preferred agents can also be used for persistent and refractory disease.40 Currently, bevacizumab is recommended in the NCCN Guidelines as a preferred single-agent targeted therapy for patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancers.45,46 For example, bevacizumab is a reasonable option as second- or third-line therapy in patients with persistent or recurrent disease that is platinum-resistant.47
Management of drug reactions is discussed in the NCCN Guidelines. New algorithms are now provided for management of mild, severe, or life-threatening drug reactions after intravenous or intraperitoneal infusion (see OV-C, pages 1340–1343).61 Drugs used in gynecologic oncology treatment that more commonly cause adverse reactions include carboplatin, cisplatin, docetaxel, liposomal doxorubicin, oxaliplatin, and paclitaxel. In many patients who have had drug reactions, desensitization may be used to enable further use of chemotherapy. These drug reaction guidelines are also useful for patients with other cancers (eg, cervical and uterine cancers).
References
- 2↑
Howlader N, Noone A, Krapcho M et al.. SEER Cancer Statistics Review, 1975-2009 (Vintage 2009 Populations) based on November 2011 SEER data submission. Bethesda, MD: National Cancer Institute; 2012. Available at: http://seer.cancer.gov/csr/1975_2009_pops09/. Accessed October 12, 2012.
- 3↑
Buys SS, Partridge E, Black A et al.. Effect of screening on ovarian cancer mortality: the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Randomized Controlled Trial. JAMA 2011;305:2295–2303.
- 4
Smith RA, Cokkinides V, Brawley OW. Cancer screening in the United States, 2012: a review of current American Cancer Society guidelines and current issues in cancer screening. CA Cancer J Clin, in press.
- 5↑
Clarke-Pearson DL. Clinical practice. Screening for ovarian cancer. N Engl J Med 2009;361:170–177.
- 6↑
Menon U, Gentry-Maharaj A, Hallett R et al.. Sensitivity and specificity of multimodal and ultrasound screening for ovarian cancer, and stage distribution of detected cancers: results of the prevalence screen of the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS). Lancet Oncol 2009;10:327–340.
- 7↑
Gilbert L, Basso O, Sampalis J et al.. Assessment of symptomatic women for early diagnosis of ovarian cancer: results from the prospective DOvE pilot project. Lancet Oncol 2012;13:285–291.
- 8↑
Drapkin R, von Horsten HH, Lin Y et al.. Human epididymis protein 4 (HE4) is a secreted glycoprotein that is overexpressed by serous and endometrioid ovarian carcinomas. Cancer Res 2005;65:2162–2169.
- 9↑
Nolen B, Velikokhatnaya L, Marrangoni A et al.. Serum biomarker panels for the discrimination of benign from malignant cases in patients with an adnexal mass. Gynecol Oncol 2010;117:440–445.
- 10↑
Cramer DW, Bast RC Jr, Berg CD et al.. Ovarian cancer biomarker performance in prostate, lung, colorectal, and ovarian cancer screening trial specimens. Cancer Prev Res (Phila) 2011;4:365–374.
- 11↑
Anderson GL, McIntosh M, Wu L et al.. Assessing lead time of selected ovarian cancer biomarkers: a nested case-control study. J Natl Cancer Inst 2010;102:26–38.
- 12↑
Jacob F, Meier M, Caduff R et al.. No benefit from combining HE4 and CA125 as ovarian tumor markers in a clinical setting. Gynecol Oncol 2011;121:487–491.
- 13
Molina R, Escudero JM, Auge JM et al.. HE4 a novel tumour marker for ovarian cancer: comparison with CA 125 and ROMA algorithm in patients with gynaecological diseases. Tumour Biol 2011;32:1087–1095.
- 14
Van Gorp T, Cadron I, Despierre E et al.. HE4 and CA125 as a diagnostic test in ovarian cancer: prospective validation of the Risk of Ovarian Malignancy Algorithm. Br J Cancer 2011;104:863–870.
- 15↑
Montagnana M, Danese E, Ruzzenente O et al.. The ROMA (Risk of Ovarian Malignancy Algorithm) for estimating the risk of epithelial ovarian cancer in women presenting with pelvic mass: is it really useful? Clin Chem Lab Med 2011;49:521–525.
- 16↑
Im SS, Gordon AN, Buttin BM et al.. Validation of referral guidelines for women with pelvic masses. Obstet Gynecol 2005;105:35–41.
- 17↑
Chi DS, Musa F, Dao F et al.. An analysis of patients with bulky advanced stage ovarian, tubal, and peritoneal carcinoma treated with primary debulking surgery (PDS) during an identical time period as the randomized EORTC-NCIC trial of PDS vs neoadjuvant chemotherapy (NACT). Gynecol Oncol 2012;124:10–14.
- 18↑
Schorge JO, Bradford LS, Del Carmen MG. Primary cytoreductive surgery for advanced ovarian cancer: is it the past, present, or future? Clin Adv Hematol Oncol 2011;9:912–918.
- 20↑
Dewdney SB, Rimel BJ, Reinhart AJ et al.. The role of neoadjuvant chemotherapy in the management of patients with advanced stage ovarian cancer: survey results from members of the Society of Gynecologic Oncologists. Gynecol Oncol 2010;119:18–21.
- 21
Whitney CW, Spirtos N. Gynecologic Oncology Group Surgical Procedures Manual. Philadelphia, PA: Gynecologic Oncology Group; 2009.
- 22↑
Elattar A, Bryant A, Winter-Roach BA et al.. Optimal primary surgical treatment for advanced epithelial ovarian cancer. Cochrane Database Syst Rev 2011:CD007565.
- 23↑
Vergote I, Trope CG, Amant F et al.. Neoadjuvant chemotherapy or primary surgery in stage IIIC or IV ovarian cancer. N Engl J Med 2010;363:943–953.
- 24↑
Vergote I, Trope CG, Amant F et al.. Neoadjuvant chemotherapy is the better treatment option in some patients with stage IIIc to IV ovarian cancer. J Clin Oncol 2011;29:4076–4078.
- 25↑
Rauh-Hain JA, Rodriguez N, Growdon WB et al.. Primary debulking surgery versus neoadjuvant chemotherapy in stage IV ovarian cancer. Ann Surg Oncol 2012;19:959–965.
- 26↑
Schorge JO, Garrett LA, Goodman A. Cytoreductive surgery for advanced ovarian cancer: quo vadis? Oncology (Williston Park) 2011;25:928–934.
- 27
Chi DS, Bristow RE, Armstrong DK, Karlan BY. Is the easier way ever the better way? J Clin Oncol 2011;29:4073–4075.
- 28
Rose PG, Nerenstone S, Brady MF et al.. Secondary surgical cytoreduction for advanced ovarian carcinoma. N Engl J Med 2004;351:2489–2497.
- 29
van der Burg ME, van Lent M, Buyse M et al.. The effect of debulking surgery after induction chemotherapy on the prognosis in advanced epithelial ovarian cancer. Gynecological Cancer Cooperative Group of the European Organization for Research and Treatment of Cancer. N Engl J Med 1995;332:629–634.
- 30↑
Colombo PE, Mourregot A, Fabbro M et al.. Aggressive surgical strategies in advanced ovarian cancer: a monocentric study of 203 stage IIIC and IV patients. Eur J Surg Oncol 2009;35:135–143.
- 31↑
Hoskins PJ. Which is the better surgical strategy for newly diagnosed epithelial ovarian cancer: primary or interval debulking? Curr Opin Oncol 2011;23:501–506.
- 32↑
Chi DS, Eisenhauer EL, Zivanovic O et al.. Improved progression-free and overall survival in advanced ovarian cancer as a result of a change in surgical paradigm. Gynecol Oncol 2009;114:26–31.
- 33↑
Armstrong DK, Bundy B, Wenzel L et al.. Intraperitoneal cisplatin and paclitaxel in ovarian cancer. N Engl J Med 2006;354:34–43.
- 34↑
Burger RA, Brady MF, Bookman MA et al.. Incorporation of bevacizumab in the primary treatment of ovarian cancer. N Engl J Med 2011;365:2473–2483.
- 35↑
Perren TJ, Swart AM, Pfisterer J et al.. A phase 3 trial of bevacizumab in ovarian cancer. N Engl J Med 2011;365:2484–2496.
- 36↑
Cohn DE, Kim KH, Resnick KE et al.. At what cost does a potential survival advantage of bevacizumab make sense for the primary treatment of ovarian cancer? A cost-effectiveness analysis. J Clin Oncol 2011;29:1247–1251.
- 38↑
Parmar MK, Ledermann JA, Colombo N et al.. Paclitaxel plus platinum-based chemotherapy versus conventional platinum-based chemotherapy in women with relapsed ovarian cancer: the ICON4/AGO-OVAR-2.2 trial. Lancet 2003;361:2099–2106.
- 39↑
Mantia-Smaldone GM, Edwards RP, Vlad AM. Targeted treatment of recurrent platinum-resistant ovarian cancer: current and emerging therapies. Cancer Manag Res 2011;3:25–38.
- 40↑
Griffiths RW, Zee YK, Evans S et al.. Outcomes after multiple lines of chemotherapy for platinum-resistant epithelial cancers of the ovary, peritoneum, and fallopian tube. Int J Gynecol Cancer 2011;21:58–65.
- 41↑
Markman M. Pegylated liposomal doxorubicin: appraisal of its current role in the management of epithelial ovarian cancer. Cancer Manag Res 2011;3:219–225.
- 42
Thigpen JT, Aghajanian CA, Alberts DS et al.. Role of pegylated liposomal doxorubicin in ovarian cancer. Gynecol Oncol 2005;96:10–18.
- 43
Gordon AN, Tonda M, Sun S, Rackoff W. Long-term survival advantage for women treated with pegylated liposomal doxorubicin compared with topotecan in a phase 3 randomized study of recurrent and refractory epithelial ovarian cancer. Gynecol Oncol 2004;95:1–8.
- 44↑
Mutch DG, Orlando M, Goss T et al.. Randomized phase III trial of gemcitabine compared with pegylated liposomal doxorubicin in patients with platinum-resistant ovarian cancer. J Clin Oncol 2007;25:2811–2818.
- 45↑
Burger RA, Sill MW, Monk BJ et al.. Phase II trial of bevacizumab in persistent or recurrent epithelial ovarian cancer or primary peritoneal cancer: a Gynecologic Oncology Group Study. J Clin Oncol 2007;25:5165–5171.
- 46↑
Tagawa T, Morgan R, Yen Y, Mortimer J. Ovarian cancer: opportunity for targeted therapy. J Oncol 2012;2012:682480.
- 47↑
Cannistra SA, Matulonis UA, Penson RT et al.. Phase II study of bevacizumab in patients with platinum-resistant ovarian cancer or peritoneal serous cancer. J Clin Oncol 2007;25:5180–5186.
- 48↑
Aghajanian C, Blank SV, Goff BA et al.. OCEANS: a randomized, double-blind, placebo-controlled phase III trial of chemotherapy with or without bevacizumab in patients with platinum-sensitive recurrent epithelial ovarian, primary peritoneal, or fallopian tube cancer. J Clin Oncol 2012;30:2039–2045.
- 49↑
Pujade-Lauraine E, Hilpert F, Weber B et al.. AURELIA: a randomized phase III trial evaluating bevacizumab (BEV) plus chemotherapy (CT) for platinum (PT)-resistant recurrent ovarian cancer (OC) [abstract]. J Clin Oncol 2012;30(Suppl 15):Abstract LBA5002.
- 50↑
Ledermann J, Harter P, Gourley C et al.. Olaparib maintenance therapy in platinum-sensitive relapsed ovarian cancer. N Engl J Med 2012;366:1382–1392.
- 51↑
Buckanovich RJ, Berger R, Sella A et al.. Activity of cabozantinib (XL184) in advanced ovarian cancer patients (pts): results from a phase II randomized discontinuation trial (RDT) [abstract]. J Clin Oncol 2011;29(Suppl 15):Abstract 5008.
- 52↑
Cernadas JR, Brockow K, Romano A et al.. General considerations on rapid desensitization for drug hypersensitivity—a consensus statement. Allergy 2010;65:1357–1366.
- 53
Romano A, Torres MJ, Castells M et al.. Diagnosis and management of drug hypersensitivity reactions. J Allergy Clin Immunol 2011;127:S67–73.
- 54↑
Castells MC, Tennant NM, Sloane DE et al.. Hypersensitivity reactions to chemotherapy: outcomes and safety of rapid desensitization in 413 cases. J Allergy Clin Immunol 2008;122:574–580.
- 55↑
Dizon DS, Sabbatini PJ, Aghajanian C et al.. Analysis of patients with epithelial ovarian cancer or fallopian tube carcinoma retreated with cisplatin after the development of a carboplatin allergy. Gynecol Oncol 2002;84:378–382.
- 56↑
Sampson HA, Munoz-Furlong A, Campbell RL et al.. Second symposium on the definition and management of anaphylaxis: summary report—second National Institute of Allergy and Infectious Disease/Food Allergy and Anaphylaxis Network symposium. Ann Emerg Med 2006;47:373–380.
- 57↑
Manivannan V, Decker WW, Stead LG et al.. Visual representation of National Institute of Allergy and Infectious Disease and Food Allergy and Anaphylaxis Network criteria for anaphylaxis. Int J Emerg Med 2009;2:3–5.
- 58↑
Lenz HJ. Management and preparedness for infusion and hypersensitivity reactions. Oncologist 2007;12:601–609.
- 59↑
Gabizon AA. Pegylated liposomal doxorubicin: metamorphosis of an old drug into a new form of chemotherapy. Cancer Invest 2001;19:424–436.
- 60↑
Navo M, Kunthur A, Badell ML et al.. Evaluation of the incidence of carboplatin hypersensitivity reactions in cancer patients. Gynecol Oncol 2006;103:608–613.
- 61↑
Markman M, Zanotti K, Peterson G et al.. Expanded experience with an intradermal skin test to predict for the presence or absence of carboplatin hypersensitivity. J Clin Oncol 2003;21:4611–4614.
- 62↑
Vandenput I, Van Calster B, Capoen A et al.. Neoadjuvant chemotherapy followed by interval debulking surgery in patients with serous endometrial cancer with transperitoneal spread (stage IV): a new preferred treatment? Br J Cancer 2009;101:244–249.
