Possible use of CA-125 level normalization after the third chemotherapy cycle in deciding on chemotherapy regimen in patients with epithelial ovarian cancer: brief report.
ABSTRACT Cancer antigen (CA)-125 is a biomarker widely used in the monitoring of response to chemotherapy in patients with epithelial ovarian cancer (EOC). We hypothesize that normalization of the CA-125 after the third cycle of chemotherapy is an independent prognostic indicator of prolonged progression-free survival (PFS) and overall survival (OS).
A retrospective analysis of patients with a diagnosis of advanced-stage (III-IV) EOC who were treated with cytoreductive surgery and adjuvant platinum-based chemotherapy from January 1999 to June 2009 was conducted. Patient demographics and the prognostic significance of CA-125 level above the discrimination value of 35 U/mL were assessed by univariate and multivariate analyses.
A total of 124 women met the study inclusion criteria. The median PFS for all patients with a CA-125 level of less than 35 U/mL (n = 72) after the third chemotherapy cycle was 18 months versus that of the patients with a CA-125 level of 35 U/mL or greater (n = 52) was 9 months (P < 0.0001). The median OS was 42 and 22 months, respectively (P < 0.0001). Optimal microscopically debulked patients with normalization of CA-125 after the third cycle did significantly better than those who did not normalize (PFS, 48 vs 8.3 months; OS, 59 vs 23.8 months; P < 0.0001). When patients with macroscopic disease and normalization of CA-125 after the third cycle were compared with those with CA-125 of 35 U/mL or greater, a significant difference in OS was seen between the 2 groups (47 vs 29 months, respectively; P < 0.0001). On multivariate analysis, only 2 variables were associated with poor prognosis: (1) the failure of CA-125 level to normalize after the third chemotherapy cycle (hazard ratio, 2.5; confidence interval, 1.3-4.6) and (2) the grade of the tumor (hazard ratio, 7.7; confidence interval, 1.6-37.6).
Although hypothesis generating at this point, normalization of CA-125 level after the third chemotherapy cycle is an independent predictor of survival for patients with advanced EOC regardless of debulking status. We would propose future trials that consider switching regimens in patients who do not normalize their CA-125 after the third cycle to see if such a switch can improve PFS and OS.
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ABSTRACT: Biomarkers play critical roles in early detection, diagnosis and monitoring of therapeutic outcome and recurrence of cancer. Previous biomarker research on ovarian cancer (OC) has mostly focused on the discovery and validation of diagnostic biomarkers. The primary purpose of this study is to identify serum biomarkers for prognosis and therapeutic outcomes of ovarian cancer. Forty serum proteins were analyzed in 70 serum samples from healthy controls (HC) and 101 serum samples from serous OC patients at three different disease phases: post diagnosis (PD), remission (RM) and recurrence (RC). The utility of serum proteins as OC biomarkers was evaluated using a variety of statistical methods including survival analysis. Ten serum proteins (PDGF-AB/BB, PDGF-AA, CRP, sFas, CA125, SAA, sTNFRII, sIL-6R, IGFBP6 and MDC) have individually good area-under-the-curve (AUC) values (AUC = 0.69-0.86) and more than 10 three-marker combinations have excellent AUC values (0.91-0.93) in distinguishing active cancer samples (PD & RC) from HC. The mean serum protein levels for RM samples are usually intermediate between HC and OC patients with active cancer (PD & RC). Most importantly, five proteins (sICAM1, RANTES, sgp130, sTNFR-II and sVCAM1) measured at remission can classify, individually and in combination, serous OC patients into two subsets with significantly different overall survival (best HR = 17, p<10(-3)). We identified five serum proteins which, when measured at remission, can accurately predict the overall survival of serous OC patients, suggesting that they may be useful for monitoring the therapeutic outcomes for ovarian cancer.PLoS ONE 01/2013; 8(11):e78393. · 3.53 Impact Factor