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Stage III and Stage IV Ovarian Epithelial Cancer Treatment

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    Treatment Options for Patients With Suboptimally Cytoreduced Stage III and Stage IV Disease

    Cytoreductive surgery

    The value of interval cytoreductive surgery has been the subject of two large phase III trials. In the first study, performed by the EORTC, patients subjected to debulking after four cycles of cyclophosphamide and cisplatin (with additional cycles given later) had an improved survival rate compared with patients who completed six cycles of this chemotherapy without surgery.[12][Level of evidence: 1iiB] The GOG-0162 trial was designed to answer a very similar question but used the then-standard paclitaxel-plus-cisplatin regimen as the chemotherapy.[13] This trial did not demonstrate any advantage from the use of interval cytoreductive surgery. The divergence of results may be caused by the efficacy of the chemotherapy obscuring any effects of interval cytoreduction, the wider use of maximal surgical effort at the time of diagnosis by U.S. gynecologic oncologists, or unknown factors. Although many patients with stage IV disease also undergo cytoreductive surgery at diagnosis, whether this improves survival has not been established.

    Systemic chemotherapy

    First-line treatment of ovarian cancer is cisplatin, given IV, or its second-generation analog, carboplatin, given either alone or in combination with other drugs. Clinical response rates from these drugs regularly exceed 60%, and median time-to-recurrence usually exceeds 1 year in this subset of suboptimally debulked women. Trials by various cooperative groups in the subsequent 2 decades addressed issues of optimal dose-intensity [14,15,16] for both cisplatin and carboplatin,[17] schedule,[18] and the equivalent results obtained with either of these platinum drugs, usually in combination with cyclophosphamide.[19] With the introduction of the taxane paclitaxel, two trials confirmed the superiority of cisplatin combined with paclitaxel to the previous standard of cisplatin plus cyclophosphamide; however, two trials that compared the agent with either cisplatin or carboplatin as a single agent failed to confirm such superiority in all outcome parameters (i.e., response, time-to-progression, and survival) (see Table 2).

    Table 2. Paclitaxel/Platinum Combinations Versus Comparator Arms in Trials

    TrialTreatment RegimensNo. of Patients% Early CrossoverProgression-free Survival (mo)Overall Survival (mo)
    AUC = area under the curve.
    a Statistically inferior result (P< .001–< .05).
    GOG-132Paclitaxel (135 mg/m2, 24 h) and cisplatin (75 mg/m2)20122%14.226.6
    Cisplatin (100 mg/m2)20040%16.430.2
    Paclitaxel (200 mg/m2, 24 h)21323%11.2a26
    MRC-ICON3[20]Paclitaxel (175 mg/m2, 3 h) and carboplatin AUC 647823%17.336.1
    Carboplatin AUC 694325%16.135.4
    Paclitaxel (175 mg/m2, 3 h) and carboplatin AUC 623223%1740
    Cyclophosphamide (500 mg/m2) and doxorubicin (50 mg/m2) and cisplatin (50 mg/m2)42120%1740
    GOG-111[21]Paclitaxel (135 mg/m2, 24 h) and cisplatin (75 mg/m2)184None1838
    Cyclophosphamide (750 mg/m2) and cisplatin (75 mg/m2)202None13a24a
    EORTC-55931[22]Paclitaxel (175 mg/m2, 3 h) and cisplatin (75 mg/m2)162None15.535.6
    Cyclophosphamide (750 mg/m2) and cisplatin (75 mg/m2)1614%11.5a25.8a
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