Triple Cytotoxic Therapy for Advanced Ovarian Cancer: A Failed Application, Not a Failed Strategy

摘要: Recommended standard therapies for the initial treatment of advanced ovarian cancer are carboplatin and paclitaxel, on basis equivalent efficacy but lesser toxicity compared with cisplatin docetaxel, or use a platin analog as single agent subsequent taxane. The good news is that such have increased median overall survival to 3 years, 1-year achieved in era before platinum. bad they still not curative great majority. Long-term follow-up Gynecologic Oncology Group (GOG) 111 study European Canadian Intergroup (OV.10) demonstrated progression-free only 18% patients at 6 years. Efforts improve these poor long-term outcomes resulted variety experimental strategies. One extensively tested approach has beent add third cytotoxic drug. Selection criteria picking drug mechanisms resistance different from platins taxanes, more importantly, evidence some degree non– cross-resistance clinical setting. Gemcitabine, topotecan, liposomal doxorubicin been used this setting because their known reproducible single-agent activity cohort platinum-resistant patients; epirubicin apparent superiority anthracycline-containing platin-based regimens meta-analyses. However, all without benefit nine phase III studies. There was absolutely no statistically significant clinically useful associated three drugs, control arms receiving (area under curve, 5 6) paclitaxel (175 mg/m over hours) every weeks six cycles (Table 1). In fact, when comparing hazard ratios (PFS), were often superior three-drug arms. For example, maximum by adding large, well-conducted GOG 182 an increase PFS 2 (16 16.4 months) 2% absolute years (57% 59%), triplets containing gemcitabine doxorubicin. contrast, sequential doublet topotecan gemcitabine, there 3-week decrement PFS. It essential us understand why triple-drug strategy failed, also, lung cancer. negative consequences resulting abandoning flawed analysis will be significant, already becoming apparent. assumption made it failed strategy, design incorrect choice drugs. pharmaceutical industry moved away developing new cytotoxics now concentrating targeted instead, product pipelines consisting almost exclusively therapies. Similarly, cooperative groups wholeheartedly toward testing therapies, vascular endothelial growth factor inhibition conjunction women newly diagnosed cancer, additional first-line combinations.