Future options for first-line therapy of advanced ovarian cancer

Abstract

The current standard of treatment for patients with advanced ovarian cancer has been established in light of the results from various clinical trials. After debulking surgery, a combination of carboplatin and paclitaxel is considered to be the best treatment option in terms of survival and quality of life. However, since most patients on this chemotherapy modality will experience relapse, several studies have explored, and continue to do so, various modifications and alternatives to standard therapy in order to attain improved efficacy. Various modifications of dose, schedule, or route of standard regimens have shown no benefit, apart from intraperitoneal therapy, which has produced mixed results and would benefit from a definitive trial. Studies of maintenance/consolidation therapy have been mainly negative, although a small number of trials have produced enough positive data to prompt two new studies powered to detect survival benefits. Various phase II trials have investigated “targeted therapies,” but until now no positive results have been recorded. Translational studies are needed to identify patients who will benefit from such specific treatment strategies. The current most evaluated modification of standard therapy is the addition of a third non–cross-resistant drug to carboplatin and paclitaxel. Data for the addition of anthracyclines have either been negative (epirubicin) or not yet analyzed (pegylated liposomal doxorubicin), while evaluable data are shortly expected for the addition of topotecan. Data on the addition of gemcitabine are eagerly awaited from two phase III trials.

Survival in ovarian cancer in Wales: prior to introduction of all Wales guidelines

“…Platinum agents were more commonly used in the cancer center than in the peripheral units. Platinum agents remain the gold standard for the management of both early and advanced ovarian cancer (26,27) , with substantial survival benefits associated with single and combined regimens with agents such as paclitaxel (28,29,30) . On a cautionary note, we recognize that our data are retrospective and that elements of inaccuracy and bias may occur despite the best efforts of the investigators to eliminate them.…”

Topotecan Is a Substrate for Multidrug Resistance Associated Protein 4

“…stantial anticancer activity in a wide spectrum of cancer. Both TPT and CPT-11 have become standard therapy for cancer, but poor or variable clinical response is often observed in cancer patients despite the application of doseintensified regimens [124,125]. Thus, it is important to identify the relevant resistant proteins and effective approaches for circumventing such resistance.…”

First-line randomized trials: revisiting the Ptolemaic universe

“…International criteria were adopted to permit using CA-125 to declare progression of disease after completion of primary therapy. Dosing on each arm (including the reference arm) was adjusted to equilibrate toxicity and achieve an equal number of planned (6) AGO, GINECO 635 647 1282 NSGO (7) NSGO, EORTC, NCIC-CTG, GEICO 444 443 887 MITO (8) MITO 170 156 326 AGO-OVAR9 (9) AGO-OVAR, GINECO, NSGO 882 860 1742 NCIC-OV16 (10) NCIC cycles (x8) across all arms, without the use of maintenance or consolidation. Second-look laparotomy was not permitted, but patients with suboptimal disease could elect interval cytoreduction (with stratification for intent).…”