Treatment of recurrent disease: randomized trials of monotherapy versus combination chemotherapy

Recurrent ovarian carcinoma is normally an incurable disease situation in which chemotherapy is the usual treatment for palliation. The probability of response to chemotherapy depends on the time from last chemotherapy and the previous response observed. The issue of combination chemotherapy versus monotherapy is a clinically relevant dilemma for medical and gynecologic oncologist involved in the treatment of recurrent patients. In those patients with platinum-resistant relapse, combination chemotherapy has been associated with higher toxicity without a clear clinical benefit in randomized clinical trials. Therefore, a less toxic sequential monotherapy approach should be the choice for resistant patients. On the other hand, two large randomized clinical trials have proved the superiority of a platinum-based doublet over platinum monotherapy in platinum-sensitive recurrent patients. The ICON-4/AGO-OVAR 2.2 trial demonstrated that the combination of paclitaxel-carboplatin (or cisplatin) is likely to provide a survival benefit compared with carboplatin monotherapy. This benefit was more clear in patients with a treatment free-interval >12 months. Moreover, the AGO-OVAR 2.5 trial, with the cooperation of NCIC CTG and EORTC GCG, has confirmed the advantage in response rate and progression free survival of the doublet carboplatin-gemcitabine compared to carboplatin.