Carboplatin and Taxol (paclitaxel) in advanced ovarian carcinoma.

Addressing the need for more effective, less toxic therapies for patients with advanced ovarian cancer, a pilot study was conducted to evaluate the therapeutic potential of combination carboplatin/paclitaxel in previously untreated patients. Several factors provided the rationale for this study: paclitaxel plus cisplatin has been shown to be superior to standard treatment with cyclophosphamide plus cisplatin; carboplatin is equally effective and less toxic than cisplatin in ovarian cancer; paclitaxel plus carboplatin could potentially produce less nonhematologic toxicity than cisplatin plus paclitaxel; dosing of carboplatin based on the area under the carboplatin plasma concentration vs. time curve (AUC) would produce an acceptable degree of thrombocytopenia; and the potential additive neutropenia of carboplatin plus paclitaxel could be managed with the addition of growth factors. This study was designed in two parts: In part I, a fixed dose of paclitaxel (135 mg/m2 by 24-hour infusion every 21 days) was administered to study patients given escalating doses of carboplatin, beginning at an AUC of 5 and increasing to 7.5 and then to 10. Dose escalation was based on toxicity observed in the first treatment cycle, with granulocyte colony-stimulating factor added when dose-limiting toxicity developed. The second part was designed to evaluate carboplatin at the maximum tolerated dose with escalating doses of paclitaxel. Preliminary results of phase I of this study indicate that paclitaxel plus carboplatin can be combined at doses that encompass the therapeutic range of carboplatin given with paclitaxel 135 mg/m2. Subsequent phases of this trial are currently under way.