Recurrent epithelial ovarian cancer: an update on treatment
An estimated 85% of patients with epithelial ovarian cancer who achieve a full remission following first-line therapy will develop recurrent disease. Although each subsequent line of therapy is characterized by shorter disease-free intervals, median survival for these patients ranges from 12 months...
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| Published in | Oncology (Williston Park, N.Y.) Vol. 27; no. 4; p. 288 |
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| Main Authors | , , |
| Format | Journal Article |
| Language | English |
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United States
Intellisphere, LLC
01.04.2013
MultiMedia Healthcare Inc |
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| Abstract | An estimated 85% of patients with epithelial ovarian cancer who achieve a full remission following first-line therapy will develop recurrent disease. Although each subsequent line of therapy is characterized by shorter disease-free intervals, median survival for these patients ranges from 12 months to 24 months. Emerging therapies in the management of ovarian cancer have resulted in a shift in paradigm, including in the appropriate time to institute therapy, and in the selection of therapy. This review focuses on chemotherapy and emerging biologic agents that present a therapeutic option for patients with recurrent ovarian cancer. |
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| AbstractList | An estimated 85% of patients with epithelial ovarian cancer who achieve a full remission following first-line therapy will develop recurrent disease. Although each subsequent line of therapy is characterized by shorter disease-free intervals, median survival for these patients ranges from 12 months to 24 months. Emerging therapies in the management of ovarian cancer have resulted in a shift in paradigm, including in the appropriate time to institute therapy, and in the selection of therapy. This review focuses on chemotherapy and emerging biologic agents that present a therapeutic option for patients with recurrent ovarian cancer.An estimated 85% of patients with epithelial ovarian cancer who achieve a full remission following first-line therapy will develop recurrent disease. Although each subsequent line of therapy is characterized by shorter disease-free intervals, median survival for these patients ranges from 12 months to 24 months. Emerging therapies in the management of ovarian cancer have resulted in a shift in paradigm, including in the appropriate time to institute therapy, and in the selection of therapy. This review focuses on chemotherapy and emerging biologic agents that present a therapeutic option for patients with recurrent ovarian cancer. An estimated 85% of patients with epithelial ovarian cancer who achieve a full remission following first-line therapy will develop recurrent disease. Although each subsequent line of therapy is characterized by shorter disease-free intervals, median survival for these patients ranges from 12 months to 24 months. Emerging therapies in the management of ovarian cancer have resulted in a shift in paradigm, including in the appropriate time to institute therapy, and in the selection of therapy. This review focuses on chemotherapy and emerging biologic agents that present a therapeutic option for patients with recurrent ovarian cancer. A phase II trial randomly assigning patients with platinum-sensitive recurrences to either single-agent paclitaxel or combination therapy with cisplatin, doxorubicin, and cyclophosphamide documented similar overall response rates between the two regimens (45% vs 55%) but showed that the platinumcontaining combination was associated with a significant increase in response duration (16 vs 9 months) and median survival (35 vs 26 months). [15] This study is limited by its small sample size, phase II design, and the fact that close to 50% of the patients dropped out of the trial at "cross-over." [15, 16] However, the study results are used to advocate the use of platinum first in the management of women with platinum-sensitive recurrent ovarian cancer. [15,16] The choice of whether to use a single platinum agent or a platinumcontaining combination should take into account the individual patients specific circumstances, beyond the disease-free interval for patients on platinum therapy. Combination regimens are associated with a longer response rate and PFI.[ 17-21] The paclitaxel-carboplatin combination, for example, has been shown to lead to a longer overall survival (OS) compared with platinum alone. However, combination therapy is more toxic. [17] Selection of singleagent platinum vs combination platinum-containing regimens should also take into account patients' performance status and previously encountered chemotherapy toxicities. The angiogenesis inhibitor bevacizumab (Avastin) has been studied as a treatment option in both first-line ovarian cancer therapy and in patients with recurrent epithelial ovarian cancer. [20-24] The phase III OCEANS study randomized women with platinum-sensitive recurrent ovarian cancer to carboplatin plus gemcitabine with or without bevacizumab for 10 cycles maximum, followed by bevacizumab alone until disease progression or toxicity. [23,24] Compared with chemotherapy plus placebo, bevacizumab with chemotherapy was associated with an improved PFS (12 months with bevacizumab vs 8 months in the placebo group; HR = 0.48; 95% CI, 0.39-0.61), a higher response rate (79% vs 57%, ? < .001) and a higher rate of treatment discontinuation for adverse events (23% vs 5%); the latter included higher rates of serious hypertension (17% vs < 1%), proteinuria > grade 3 (9% vs 1%), and non-central nervous system bleeding (6% vs 1%). Notably, there were no cases of gastrointestinal perforation reported during therapy. Overall survival was similar at 35 months of follow-up (33 vs 35 months). [23,24] The Gynecologic Oncology Group (GOG) is conducting a phase III randomized trial to evaluate the role of carboplatin and paclitaxel, with or without bevacizumab, in platinum -sensitive ovarian cancer. Table 2 summarizes these phase III combination trials in platinum -sensitive recurrent ovarian cancer. Bevacizumab, a humanized monoclonal antibody that targets vascular endothelial growth factor, has been studied in several phase II studies alone and in combination with cytotoxic chemotherapy. It has been shown to be an active agent in patients with recurrent ovarian cancer. [20-24] The risk of gastrointestinal complications, specifically perforations, has been estimated to be 5% to 7%. [20-22] Some have suggested that bevacizumab should be used only in patients without clinical symptoms of bowel obstruction, CT scan evidence of bowel involvement, or evidence of rectosigmoid involvement on pelvic examination. [26] The role of bevacizumab in the management of epithelial ovarian cancer is evolving, with two phase III studies of upfront treatment and the OCEANS study in platinum -sensitive disease showing an improved PFS when bevacizumab is used with chemotherapy and as maintenance therapy. However, these trials have failed to show an OS advantage. Thus, for patients with recurrent platinum -sensitive disease, it may be more appropriate to use combination chemotherapy alone as second-line therapy, rather than combination chemotherapy plus bevacizumab. Bevacizumab may be appropriate to use in combination with single-agent therapy for subsequent lines of treatment or as single-agent therapy. Other agents are the subject of ongoing clinical trials. The folate receptor is overexpressed in approximately 90% of ovarian cancers. Farletuzumab, a humanized monoclonal antibody to the folate receptor alpha, has been the subject of a phase II study. Patients with platinum -sensitive recurrent ovarian cancer were treated with either singleagent farletuzumab or, if symptomatic, a combination regimen of paclitaxel, carboplatin, and farletuzumab. The reported overall response was 70%, with a median PFS of 10.9 months. [51] In a phase III trial, women with measurable, platinum -sensitive recurrent ovarian cancer were randomized to paclitaxel and carboplatin with or without farletuzumab. Farletuzumab in combination with carboplatin and a taxane did not meet the study's primary endpoint of PFS. In the post hoc exploratory analysis, a trend toward improved PFS in some patient subsets was noted. Further analysis of the findings is ongoing. [52] |
| Audience | Professional |
| Author | Rauh-Hain, J Alejandro del Carmen, Marcela G Foley, Olivia W |
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| Snippet | An estimated 85% of patients with epithelial ovarian cancer who achieve a full remission following first-line therapy will develop recurrent disease. Although... A phase II trial randomly assigning patients with platinum-sensitive recurrences to either single-agent paclitaxel or combination therapy with cisplatin,... |
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| SubjectTerms | Antineoplastic Combined Chemotherapy Protocols - therapeutic use Cancer Carcinoma, Ovarian Epithelial Chemotherapy Development and progression Doxorubicin - analogs & derivatives Doxorubicin - therapeutic use Drug therapy Female Guanidines - administration & dosage Health aspects Humans Neoplasm Recurrence, Local - drug therapy Neoplasms, Glandular and Epithelial - drug therapy Ovarian cancer Ovarian Neoplasms - drug therapy Polyethylene Glycols - therapeutic use Relapse Time Factors |
| Title | Recurrent epithelial ovarian cancer: an update on treatment |
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