open access: Review - 2010 Targeted Therapies in Epithelial Ovarian Cancer

Review

Targeted Therapies in Epithelial Ovarian Cancer

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Abstract:

Molecularly targeted therapy is relatively new to ovarian cancer despite the unquestionable success with these agents in other solid tumours such as breast and colorectal cancer. Advanced ovarian cancer is chemosensitive and patients can survive several years on treatment. However chemotherapy diminishes in efficacy over time whilst toxicities persist. Newer biological agents that target explicit molecular pathways and lack specific chemotherapy toxicities such as myelosuppression offer the advantage of long-term therapy with a manageable toxicity profile enabling patients to enjoy a good quality of life.

In this review we appraise the emerging data on novel targeted therapies in ovarian cancer. We discuss the role of these compounds in the front-line treatment of ovarian cancer and in relapsed disease; and describe how the development of predictive clinical, molecular and imaging biomarkers will define the role of biological agents in the treatment of ovarian cancer.

Predictive Factors in Relapsed Ovarian Cancer for Complete Tumor Resection

"Results:

Overall, 177 consecutive patients (pts) were analyzed. The median age at first diagnosis was 55 years (range, 23-83 years). The complete tumor resection rate was 44.6%. Predictive factors that correlated with an adverse surgical outcome in terms of residual tumor were ascites <500 ml (Odds ratio, OR=0.3; 95% Confidence interval, CI=0.1-0.8 p<0.05), tumor involvement of the small bowel (OR=0.22; 95% CI=0.07-0.71 p<0.05), tumor spread in the upper abdomen (OR=0.33; 95% CI=0.1-0.9 p<0.05) and platinum resistance (OR=0.1, 95% CI=0.06-0.5 p<0.01).

Serous tumor histology (OR=5.8) appeared to have a protective effect. Age and initial FIGO stage were of no predictive significance.

Conclusion:

Platinum-sensitive patients without ascites, no intestinal tumor involvement, tumor restricted to middle and lower abdomen, and of serous papillary histology have significantly higher complete tumor resection rates. Prospective studies are warranted to evaluate the predictive value of these factors."

Pegylated Liposomal Doxorubicin and Carboplatin Compared With Paclitaxel and Carboplatin for Patients With Platinum-Sensitive Ovarian Cancer in Late Relapse

Pegylated Liposomal Doxorubicin and Carboplatin Compared With Paclitaxel and Carboplatin for Patients With Platinum-Sensitive Ovarian Cancer in Late Relapse  
ABSTRACT  

Purpose This randomized, multicenter, phase III noninferiority trial was designed to test the efficacy and safety of the combination of pegylated liposomal doxorubicin (PLD) with carboplatin (CD) compared with standard carboplatin and paclitaxel (CP) in patients with platinum-sensitive relapsed/recurrent ovarian cancer (ROC).  

Patients and Methods Patients with histologically proven ovarian cancer with recurrence more than 6 months after first- or second-line platinum and taxane-based therapies were randomly assigned by stratified blocks to CD (carboplatin area under the curve [AUC] 5 plus PLD 30 mg/m2) every 4 weeks or CP (carboplatin AUC 5 plus paclitaxel 175 mg/m2) every 3 weeks for at least 6 cycles. Primary end point was progression-free survival (PFS); secondary end points were toxicity, quality of life, and overall survival.  

Results Overall 976 patients were recruited. With median follow-up of 22 months, PFS for the CD arm was statistically superior to the CP arm (hazard ratio, 0.821; 95% CI, 0.72 to 0.94; P = .005); median PFS was 11.3 versus 9.4 months, respectively. Although overall survival data are immature for final analysis, we report here a total of 334 deaths. Overall severe nonhematologic toxicity (36.8% v 28.4%; P < .01) leading to early discontinuation (15% v 6%; P < .001) occurred more frequently in the CP arm. More frequent grade 2 or greater alopecia (83.6% v 7%), hypersensitivity reactions (18.8% v 5.6%), and sensory neuropathy (26.9% v 4.9%) were observed in the CP arm; more hand-foot syndrome (grade 2 to 3, 12.0% v 2.2%), nausea (35.2% v 24.2%), and mucositis (grade 2-3, 13.9% v 7%) in the CD arm.  

Conclusion To our knowledge, this trial is the largest in recurrent ovarian cancer and has demonstrated superiority in PFS and better therapeutic index of CD over standard CP.