title: Carboplatin and Taxol (paclitaxel) in advanced ovarian carcinoma.
abstract: 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.
authors.affiliation: Fox Chase Cancer Center, Philadelphia, Pennsylvania.
authors.forename: R F
authors.initials: RF
authors.lastname: Ozols
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D016190:Carboplatin / Q000008:administration & dosage*; D017321:Clinical Trials, Phase I as Topic; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D010051:Ovarian Neoplasms / Q000188:drug therapy*; D017239:Paclitaxel / Q000008:administration & dosage
chemical_list: D016190:Carboplatin; D017239:Paclitaxel