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.