The role of gemcitabine in first-line treatment of advanced ovarian carcinoma.

The combination of paclitaxel and carboplatin is now established as the standard first-line chemotherapy regimen for advanced ovarian cancer. Ways in which this standard therapy can be further improved are being investigated, and several approaches have been taken. One approach is to integrate a different cytotoxic agent into the standard combination. Gemcitabine is one such cytotoxic agent that is of particular interest because it has activity in disease resistant to treatment with paclitaxel plus carboplatin, and also has a different mechanism of action to that of the two agents in the standard combination. Gemcitabine plus cisplatin has shown activity in phase II trials and results are awaited from a phase III trial comparing paclitaxel plus carboplatin with gemcitabine plus carboplatin doublets. Using agents sequentially has been shown to be as effective as using them in combination; therefore, using a gemcitabine plus platinum doublet sequentially with paclitaxel plus carboplatin has also been studied. A phase III trial has closed and results are expected shortly. Triplet combinations have also been shown to be effective in early stage trials, although dose-limiting myelosuppression occurs with gemcitabine plus paclitaxel plus carboplatin. Two phase III trials of this triplet have finished and are awaiting data maturation. Lastly, a sequential triplet of gemcitabine plus paclitaxel plus carboplatin has been investigated, but high pulmonary toxicity led to the study being halted. The role of gemcitabine in first-line advanced ovarian cancer will become much clearer once the results from the various phase III trials are published.