ABSTRACT
BACKGROUND: The majority of women with ovarian cancer develop recurrent disease. For patients with a platinum-free interval of >6 months, platinum-based chemotherapy is a treatment of choice. The benefit of platinum-based combination chemotherapy in randomized trials varies, and a meta-analysis was carried out to gain more secure information on the size of the benefit of this treatment. MATERIALS AND METHODS: We initiated a systematic review and meta-analysis following a pre-specified protocol to determine whether combination chemotherapy is superior to single-agent platinum chemotherapy in women with relapsed platinum-sensitive ovarian cancer. RESULTS: A total of five potentially eligible randomized trials were identified that had used combination-platinum chemotherapy versus single-agent platinum chemotherapy in women with relapsed platinum-sensitive ovarian cancer. For one trial (190 patients), adequate contact with the investigators could not be established. Therefore, four trials that randomly assigned 1300 patients were included, with a median follow-up of 36.1 months. Overall survival (OS) analyses were based on 865 deaths and demonstrated evidence for the benefit of combination-platinum chemotherapy (HR = 0.80; 95% CI, 0.64-1.00; P = 0.05). Progression-free survival (PFS) analyses were based on 1167 events and demonstrated strong evidence for the benefit of combination-platinum chemotherapy (HR = 0.68; 95% CI, 0.57-0.81; P < 0.001). There was no evidence of a difference in the relative effect of combination-platinum chemotherapy on either OS or PFS in patient subgroups defined by previous paclitaxel (Taxol) treatment (OS, P = 0.49; PFS, P = 0.66), duration of treatment-free interval (OS, P = 0.86; PFS, P = 0.48) or the number of previous lines of chemotherapy (OS, P = 0.21; PFS, P = 0.27). CONCLUSIONS: In this individual patient data (IPD) meta-analysis, we have demonstrated that combination-platinum chemotherapy improves OS and PFS across all subgroups. This provides the strongest evidence to date of the benefit of combination-platinum over single-agent platinum.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Neoplasm Recurrence, Local/drug therapy , Ovarian Neoplasms/drug therapy , Antineoplastic Combined Chemotherapy Protocols/pharmacology , Carboplatin/administration & dosage , Cisplatin/administration & dosage , Disease-Free Survival , Female , Humans , Kaplan-Meier Estimate , Neoplasm Recurrence, Local/mortality , Ovarian Neoplasms/mortality , Randomized Controlled Trials as Topic , Treatment OutcomeSubject(s)
Neoplasm Recurrence, Local/diagnosis , Neoplasm Recurrence, Local/therapy , Neoplasms, Glandular and Epithelial/diagnosis , Neoplasms, Glandular and Epithelial/therapy , Ovarian Neoplasms/diagnosis , Ovarian Neoplasms/therapy , Age Factors , Aging , Angiogenesis Inhibitors/therapeutic use , Antineoplastic Agents/therapeutic use , BRCA1 Protein/genetics , BRCA2 Protein/genetics , Carcinoma, Ovarian Epithelial , Chemotherapy, Adjuvant , Europe/epidemiology , Female , Follow-Up Studies , Humans , Neoplasm Recurrence, Local/epidemiology , Neoplasm Staging , Neoplasms, Glandular and Epithelial/epidemiology , Neovascularization, Pathologic/drug therapy , Ovarian Neoplasms/epidemiology , Risk Assessment , Risk Factors , Treatment OutcomeABSTRACT
Treatment of ovarian cancer remains challenging despite the high complete response rate seen after maximal surgical debulking surgery and platinum-combination chemotherapy. as most patients will relapse and eventually succumb to ovarian cancer, new strategies are urgently required to improve survival. a platinum-taxane combination has been the cornerstone of treatment for >15 years. Better use of these drugs is being explored through scheduling studies, and dose-dense or intraperitoneal (IP) therapies. Further improvements in treatment will most likely come from the integration of optimal chemotherapy with one or more of the hundreds of molecular-targeted agents that could be active in ovarian cancer. The greatest experience has been with anti-angiogenic agents. Two large phase III trials in first-line ovarian cancer have demonstrated a positive effect of bevacizumab when administered concurrently with chemotherapy and then as a maintenance treatment. In this review, we discuss the existing treatments for ovarian cancer and highlight areas of recent progress.
Subject(s)
Adenocarcinoma, Clear Cell/drug therapy , Adenocarcinoma, Mucinous/drug therapy , Cisplatin/therapeutic use , Ovarian Neoplasms/drug therapy , Clinical Trials, Phase III as Topic , Dose-Response Relationship, Drug , Female , Humans , Molecular Targeted Therapy , Neoplasm Staging , Ovarian Neoplasms/pathology , Ovarian Neoplasms/surgery , PrognosisABSTRACT
BACKGROUND: Cediranib is a potent oral vascular endothelial growth factor (VEGF) signalling inhibitor with activity against all three VEGF receptors. The International Collaboration for Ovarian Neoplasia 6 (ICON6) trial was initiated based on evidence of single-agent activity in ovarian cancer with acceptable toxicity. METHODS: The ICON6 trial is a 3-arm, 3-stage, double-blind, placebo-controlled randomised trial in first relapse of platinum-sensitive ovarian cancer. Patients are randomised (2 : 3 : 3) to receive six cycles of carboplatin (AUC5/6) plus paclitaxel (175 mg m(-2)) with either placebo (reference), cediranib 20 mg per day, followed by placebo (concurrent), or cediranib 20 mg per day, followed by cediranib (concurrent plus maintenance). Cediranib or placebo was continued for 18 months or until disease progression. The primary outcome measure for stage I was safety, and the blinded results are presented here. RESULTS: Sixty patients were included in the stage I analysis. A total of 53 patients had received three cycles of chemotherapy and 42 patients had completed six cycles. In all, 19 out of 60 patients discontinued cediranib or placebo during chemotherapy because of adverse events/intercurrent illness (n=9); disease progression (n=1); death (n=3); patient decision (n=1); administrative reasons (n=1); and multiple reasons (n=4). Grade 3 and 4 toxicity was experienced by 30 (50%) and 3 (5%) patients, respectively. No gastrointestinal perforations were observed. CONCLUSION: The addition of cediranib to platinum-based chemotherapy is sufficiently well tolerated to expand the ICON6 trial and progress to stage II.
