Medical treatment for relapsed epithelial ovarian, fallopian tubal, or peritoneal cancer: Platinum-resistant disease
- Michael J Birrer, MD, PhD
Michael J Birrer, MD, PhD
- Professor of Medicine
- Harvard Medical School
- Section Editor
- Barbara Goff, MD
Barbara Goff, MD
- Section Editor — Gynecologic Oncology
- Professor of Gynecologic Oncology
- University of Washington
- Deputy Editor
- Don S Dizon, MD, FACP
Don S Dizon, MD, FACP
- Deputy Editor — Oncology and Palliative Care
- Medical Gynecologic Oncology
- Massachusetts General Hospital
- Gillette Center for Women's Cancers
- Associate Professor, Medicine & Obstetrics and Gynecology
- Warren Alpert Medical School of Brown University
Epithelial cancers of ovarian, fallopian tubal, and peritoneal origin in women exhibit similar clinical characteristics and behavior. As such, these are often combined and define epithelial ovarian cancer (EOC) in clinical trials and clinical practice. This topic will consider all three tumors under the heading EOC.
Despite initial therapy, the majority of women will relapse and require retreatment. Taking into account the frequency of each stage of disease and its projected relapse rate, the overall likelihood of relapse after initial therapy for all stages of disease for women with EOC is 62 percent; it is 80 to 85 percent for women who present with abdominal (stage III) or extra-abdominal (eg, liver or lung involvement, stage IV) disease.
The management of relapsed disease is stratified based upon the amount of time that has elapsed between the completion of platinum-based treatment and the detection of relapse, known as the platinum-free interval (PFI) (see "First-line chemotherapy for advanced (stage III or IV) epithelial ovarian, fallopian tubal, and peritoneal cancer", section on 'Treatment of recurrent disease'):
●Patients with a PFI of six months or longer are considered to have "platinum-sensitive" disease. The management of these patients is discussed separately. (See "Medical treatment for relapsed epithelial ovarian, fallopian tubal, or peritoneal cancer: Platinum-sensitive disease".)
●Patients with a PFI of less than six months are considered to have "platinum-resistant" disease. This includes women who experience disease progression during first-line platinum-based therapy, often referred to as having "platinum-refractory" disease. The management of these patients (collectively referred to as having platinum-resistant EOC) is discussed here.
- Hanker LC, Loibl S, Burchardi N, et al. The impact of second to sixth line therapy on survival of relapsed ovarian cancer after primary taxane/platinum-based therapy. Ann Oncol 2012; 23:2605.
- Peng LH, Chen XY, Wu TX. Topotecan for ovarian cancer. Cochrane Database Syst Rev 2008; :CD005589.
- Seewaldt VL, Greer BE, Cain JM, et al. Paclitaxel (Taxol) treatment for refractory ovarian cancer: phase II clinical trial. Am J Obstet Gynecol 1994; 170:1666.
- Gore ME, Levy V, Rustin G, et al. Paclitaxel (Taxol) in relapsed and refractory ovarian cancer: the UK and Eire experience. Br J Cancer 1995; 72:1016.
- Bruzzone M, Catsafados E, Miglietta L, et al. Salvage chemotherapy with paclitaxel in platinum-resistant advanced ovarian cancer patients. Oncology 1996; 53:349.
- Ezcurdia L, Jovtis SL, Mickiewicz E, et al. Paclitaxel in platinum-resistant ovarian cancer patients. Argentine Multicenter Taxol Group. Semin Oncol 1997; 24:S15.
- Gynecologic Oncology Group, Markman M, Blessing J, et al. Phase II trial of weekly paclitaxel (80 mg/m2) in platinum and paclitaxel-resistant ovarian and primary peritoneal cancers: a Gynecologic Oncology Group study. Gynecol Oncol 2006; 101:436.
- Gordon AN, Fleagle JT, Guthrie D, et al. Recurrent epithelial ovarian carcinoma: a randomized phase III study of pegylated liposomal doxorubicin versus topotecan. J Clin Oncol 2001; 19:3312.
- Gordon AN, Tonda M, Sun S, et al. 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.
- Lorusso D, Naldini A, Testa A, et al. Phase II study of pegylated liposomal doxorubicin in heavily pretreated epithelial ovarian cancer patients. May a new treatment schedule improve toxicity profile? Oncology 2004; 67:243.
- Rose PG, Maxson JH, Fusco N, et al. Liposomal doxorubicin in ovarian, peritoneal, and tubal carcinoma: a retrospective comparative study of single-agent dosages. Gynecol Oncol 2001; 82:323.
- Markman M, Kennedy A, Webster K, et al. Phase 2 trial of liposomal doxorubicin (40 mg/m(2)) in platinum/paclitaxel-refractory ovarian and fallopian tube cancers and primary carcinoma of the peritoneum. Gynecol Oncol 2000; 78:369.
- 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.
- Sehouli J, Stengel D, Harter P, et al. Topotecan Weekly Versus Conventional 5-Day Schedule in Patients With Platinum-Resistant Ovarian Cancer: a randomized multicenter phase II trial of the North-Eastern German Society of Gynecological Oncology Ovarian Cancer Study Group. J Clin Oncol 2011; 29:242.
- Rose PG, Blessing JA, Mayer AR, Homesley HD. Prolonged oral etoposide as second-line therapy for platinum-resistant and platinum-sensitive ovarian carcinoma: a Gynecologic Oncology Group study. J Clin Oncol 1998; 16:405.
- Verschraegen CF, Sittisomwong T, Kudelka AP, et al. Docetaxel for patients with paclitaxel-resistant Müllerian carcinoma. J Clin Oncol 2000; 18:2733.
- Coleman RL, Brady WE, McMeekin DS, et al. A phase II evaluation of nanoparticle, albumin-bound (nab) paclitaxel in the treatment of recurrent or persistent platinum-resistant ovarian, fallopian tube, or primary peritoneal cancer: a Gynecologic Oncology Group study. Gynecol Oncol 2011; 122:111.
- Miller DS, Blessing JA, Krasner CN, et al. Phase II evaluation of pemetrexed in the treatment of recurrent or persistent platinum-resistant ovarian or primary peritoneal carcinoma: a study of the Gynecologic Oncology Group. J Clin Oncol 2009; 27:2686.
- Vergote I, Calvert H, Kania M, et al. A randomised, double-blind, phase II study of two doses of pemetrexed in the treatment of platinum-resistant, epithelial ovarian or primary peritoneal cancer. Eur J Cancer 2009; 45:1415.
- Pujade-Lauraine E, Hilpert F, Weber B, et al. Bevacizumab combined with chemotherapy for platinum-resistant recurrent ovarian cancer: The AURELIA open-label randomized phase III trial. J Clin Oncol 2014; 32:1302.
- Poveda AM, Selle F, Hilpert F, et al. Weekly paclitaxel, pegylated liposomal doxorubicin or topotecan ± bevacizumab in platinum-resistant ovarian cancer: analysis by chemotherapy cohort in the GCIG AURELIA randomised phase III trial. Ann Oncol 2012; 23:ixe17.
- http://www.accessdata.fda.gov/drugsatfda_docs/label/2014/125085s305lbl.pdf (Accessed on November 24, 2014).
- Lortholary A, Largillier R, Weber B, et al. Weekly paclitaxel as a single agent or in combination with carboplatin or weekly topotecan in patients with resistant ovarian cancer: the CARTAXHY randomized phase II trial from Groupe d'Investigateurs Nationaux pour l'Etude des Cancers Ovariens (GINECO). Ann Oncol 2012; 23:346.
- Brewer CA, Blessing JA, Nagourney RA, et al. Cisplatin plus gemcitabine in platinum-refractory ovarian or primary peritoneal cancer: a phase II study of the Gynecologic Oncology Group. Gynecol Oncol 2006; 103:446.
- Pectasides D, Pectasides E, Papaxoinis G, et al. Carboplatin/gemcitabine alternating with carboplatin/pegylated liposomal doxorubicin and carboplatin/cyclophosphamide in platinum-refractory/resistant paclitaxel - pretreated ovarian carcinoma. Gynecol Oncol 2010; 118:52.
- Williams CJ. Tamoxifen for relapse of ovarian cancer. Cochrane Database Syst Rev 2001; :CD001034.
- Smyth JF, Gourley C, Walker G, et al. Antiestrogen therapy is active in selected ovarian cancer cases: the use of letrozole in estrogen receptor-positive patients. Clin Cancer Res 2007; 13:3617.
- Argenta PA, Thomas SG, Judson PL, et al. A phase II study of fulvestrant in the treatment of multiply-recurrent epithelial ovarian cancer. Gynecol Oncol 2009; 113:205.
- Tanguay JS, Ansari J, Buckley L, Fernando I. Epithelial ovarian cancer: role of pegylated liposomal Doxorubicin in prolonging the platinum-free interval and cancer antigen 125 trends during treatment. Int J Gynecol Cancer 2009; 19:361.
- Leitao MM Jr, Hummer A, Dizon DS, et al. Platinum retreatment of platinum-resistant ovarian cancer after nonplatinum therapy. Gynecol Oncol 2003; 91:123.
- FDA approves Lynparza to treat advanced ovarian cancer. http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm427554.htm (Accessed on December 20, 2014).
- Kaufman B, Shapira-Frommer R, Schmutzler RK, et al. Olaparib Monotherapy in Patients With Advanced Cancer and a Germline BRCA1/2 Mutation. J Clin Oncol 2015; 33:244.
- Tamussino KF, Lim PC, Webb MJ, et al. Gastrointestinal surgery in patients with ovarian cancer. Gynecol Oncol 2001; 80:79.
- Clarke-Pearson DL, Chin NO, DeLong ER, et al. Surgical management of intestinal obstruction in ovarian cancer. I. Clinical features, postoperative complications, and survival. Gynecol Oncol 1987; 26:11.
- Abu-Rustum NR, Barakat RR, Venkatraman E, Spriggs D. Chemotherapy and total parenteral nutrition for advanced ovarian cancer with bowel obstruction. Gynecol Oncol 1997; 64:493.
- Kobold S, Hegewisch-Becker S, Oechsle K, et al. Intraperitoneal VEGF inhibition using bevacizumab: a potential approach for the symptomatic treatment of malignant ascites? Oncologist 2009; 14:1242.
- Numnum TM, Rocconi RP, Whitworth J, Barnes MN. The use of bevacizumab to palliate symptomatic ascites in patients with refractory ovarian carcinoma. Gynecol Oncol 2006; 102:425.
- Hamilton CA, Maxwell GL, Chernofsky MR, et al. Intraperitoneal bevacizumab for the palliation of malignant ascites in refractory ovarian cancer. Gynecol Oncol 2008; 111:530.
- Ströhlein MA, Heiss MM. The trifunctional antibody catumaxomab in treatment of malignant ascites and peritoneal carcinomatosis. Future Oncol 2010; 6:1387.
- Gotlieb WH, Amant F, Advani S, 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. Lancet Oncol 2012; 13:154.
- Bellati F, Napoletano C, Ruscito I, et al. Complete remission of ovarian cancer induced intractable malignant ascites with intraperitoneal bevacizumab. Immunological observations and a literature review. Invest New Drugs 2010; 28:887.
- Von Hoff DD, Stephenson JJ Jr, Rosen P, et al. Pilot study using molecular profiling of patients' tumors to find potential targets and select treatments for their refractory cancers. J Clin Oncol 2010; 28:4877.
- Sales E, Penson RT, Sullivan LA, et al. A snapshot of potentially personalized care: Molecular diagnostics in gynecologic cancer. J Clin Oncol 30, 2012 (suppl; abstr 5029).
- OVERVIEW OF THE TREATMENT APPROACH
- First-line treatment
- Second- or later-line treatment
- SINGLE-AGENT CHEMOTHERAPY
- Pegylated liposomal doxorubicin
- Other agents
- SINGLE-AGENT CHEMOTHERAPY PLUS BEVACIZUMAB
- ALTERNATIVE OPTIONS
- Combination therapy
- Endocrine therapy
- Heated intraperitoneal chemotherapy
- PROLONGING THE PLATINUM-FREE INTERVAL
- SPECIAL CONSIDERATIONS
- Patients with a BRCA mutation
- Recurrence based on CA-125 only
- Malignant bowel obstruction
- Recurrent ascites
- Genome-wide tumor analysis
- In vitro chemosensitivity and resistance assays
- INFORMATION FOR PATIENTS
- SUMMARY AND RECOMMENDATIONS