title: Paclitaxel combined with carboplatin in the first-line treatment of advanced ovarian cancer.
abstract: In a phase I study to determine the maximum tolerated dose of paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) given as a 3-hour infusion in combination with carboplatin administered every 21 days to women with advanced ovarian cancer, paclitaxel doses were escalated as follows: level 1, 135 mg/m2; level 2, 160 mg/m2; level 3, 185 mg/m2; and level 4,210 mg/m2. The fixed dose of carboplatin at levels 1 through 4 was given to achieve an area under the concentration-time curve (AUC) of 5 using the Calvert formula. In levels 5 and 6 the carboplatin dose was targeted at AUCs of 6 and 7.5, respectively, combined with a fixed paclitaxel dose of 185 mg/m2. To date, 30 previously untreated patients, all with a good performance status (Eastern Cooperative Oncology Group 0 to 2) have been entered into this ongoing study. The dose-limiting toxicity of the combination was myelosuppression (leukopenia, granulocytopenia, and thrombocytopenia). Neurotoxicity was largely moderate. So far, 14 patients are evaluable for response; of these, eight (57%) showed objective (complete or partial) response and disease stabilized in six patients. No patient had disease progression. We conclude that the combination of paclitaxel 185 mg/m2 administered as a 3-hour infusion followed immediately by a 1-hour infusion of carboplatin at an AUC of 6 can be administered safely in a 21-day schedule in the outpatient setting. The recommended dose for phase III studies is paclitaxel 185 mg/m2 and carboplatin AUC 6.
authors.affiliation: Frauenklinik, St-Vincentius-Krankenhäuser, Karlsruhe, Germany.
authors.forename: H G
authors.initials: HG
authors.lastname: Meerpohl
authors.forename: A
authors.initials: A
authors.lastname: du Bois
authors.forename: H
authors.initials: H
authors.lastname: Kühnle
authors.forename: H J
authors.initials: HJ
authors.lastname: Lück
authors.forename: R
authors.initials: R
authors.lastname: Kreienberg
authors.forename: V
authors.initials: V
authors.lastname: Möbus
authors.forename: T
authors.initials: T
authors.lastname: Bauknecht
authors.forename: O
authors.initials: O
authors.lastname: Köchli
authors.forename: H
authors.initials: H
authors.lastname: Bochtler
authors.forename: K
authors.initials: K
authors.lastname: Diergarten
mesh_terms: D000328:Adult; D000368:Aged; D000380:Agranulocytosis / Q000139:chemically induced; D000553:Ambulatory Care; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage* / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D016190:Carboplatin / Q000008:administration & dosage* / Q000009:adverse effects; D018450:Disease Progression; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D007970:Leukopenia / Q000139:chemically induced; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000188:drug therapy*; D017239:Paclitaxel / Q000008:administration & dosage* / Q000009:adverse effects; D010523:Peripheral Nervous System Diseases / Q000139:chemically induced; D012074:Remission Induction; D012449:Safety; D013921:Thrombocytopenia / Q000139:chemically induced
chemical_list: D000970:Antineoplastic Agents; D000972:Antineoplastic Agents, Phytogenic; D016190:Carboplatin; D017239:Paclitaxel