ABSTRACT
BACKGROUND: This trial investigated the hypothesis that the treatment with trabectedin/PLD (TP) to extend the platinum-free interval (TFIp) can improve overall survival (OS) in patients with recurrent ovarian cancer (OC). METHODS: Patients with OC (up to two previous platinum-based lines), with a TFIp of 6-12 months, were randomised to receive carboplatin/PLD (CP) or TP followed by platinum therapy at relapse. The primary endpoint was OS (HR: 0.75). RESULTS: The study enrolled 617 patients. The median TFIp was 8.3 months and 30.3% of patients had received two previous platinum lines. 74% and 73.9% of patients, respectively, received a subsequent therapy (ST) in the CP and TP arm; in the latter TP arm 87.2% of ST was platinum-based, as per protocol. The median OS was 21.4 for CP and 21.9 months for TP (HR 1.13; 95% CI: 0.94-1.35; p = 0.197). Grade 3-5 adverse reactions occurred in 37.1% of patients in the CP arm and 69.7% of patients in the TP arm, and the most frequent were neutropenia (22.8% CP, 39.5% TP), gastrointestinal (7.1% CP, 17.4% TP), hepatic (0.7% CP, 19.1% TP). CONCLUSIONS: This study did not meet the primary endpoint. CP combination remains the standard for patients with recurrent OC and a 6-12 months TFIp; TP is an effective treatment in patients suffering from persistent platinum toxicities. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, number NCT01379989.
Subject(s)
Ovarian Neoplasms , Humans , Female , Carboplatin , Trabectedin , Ovarian Neoplasms/drug therapy , Ovarian Neoplasms/etiology , Platinum/therapeutic use , Neoplasm Recurrence, Local/drug therapy , Neoplasm Recurrence, Local/etiology , Carcinoma, Ovarian Epithelial/drug therapy , Doxorubicin , Polyethylene Glycols , Antineoplastic Combined Chemotherapy Protocols/adverse effectsABSTRACT
PURPOSE: To analyse the possible prognostic importance of a combination of serum CA 125 levels, tumor cell DNA distribution and histopathologic grade in patients with epithelial ovarian cancer. METHOD: The study included 41 patients with ovarian cancer stages II-IV. CA 125 was measured before the start of chemotherapy and after every course. The DNA distribution was analysed by flow cytometry in biopsy specimens from the primary tumour. The histopathologic grading was performed according to WHO criteria. RESULTS: The CA 125 level was of major prognostic significance. All patients with an abnormal value (> 35 U/ml) after three courses died within 16 months. The DNA distribution did not add significant prognostic information, but the histopathologic grade was of significant prognostic importance as investigated by Cox analysis. CONCLUSION: CA 125 is an important prognostic marker in epithelial ovarian cancer. The value after three courses of chemotherapy is significant. The histopathologic grade adds further prognostic information.