Docetaxel and carboplatin as first-line chemotherapy in patients with advanced gynecological tumors. A phase I/II trial of the Arbeitsgemeinschaft Gynäkologische Onkologie (AGO-OVAR) Ovarian Cancer Study Group.
OBJECTIVE
We performed a phase I-II study in patients with ovarian and other gynecological cancers to determine the dose-limiting toxicities, maximum tolerated dose (MTD) and efficacy of docetaxel/carboplatin.


METHODS
Thirty patients were treated in three cohorts with carboplatin (AUC 5) and escalating docetaxel (60, 75 and 90 mg/m2), administered intravenously on day 1, repeated every 3 weeks. Premedication consisted of 16 mg dexamethasone per os on day -1, and +1 and 4 mg intravenously before docetaxel.


RESULTS
A total of 6, 11 and 12 patients were eligible and treated on dose levels 1, 2 and 3, respectively. At docetaxel 90 mg/m2, febrile and prolonged neutropenia were dose-limiting, and 75 mg/m2 with carboplatin AUC 5 was considered the MTD. Prolonged neutropenia occurred in two, four and nine patients of dose levels 1-3, respectively, and febrile neutropenia in 2, 1, and 2 patients of dose level 1-3. Thrombocytopenia grade 4 was observed in one patient of dose level 1. Non-hematological toxicity including neuropathy was usually mild across all dose levels. Overall response rate was 73%. Median time to progression was 18.0 months, and median overall survival will exceed 24.4 months.


CONCLUSIONS
Docetaxel/carboplatin can be safely administered to patients with gynecological cancer despite substantial myelotoxicity and appears to be active in the treatment of ovarian cancer. Low neurotoxicity offers an option for comparison with paclitaxel-containing regimens.
Pfisterer
J
J
Klinik für Gynäkologie und Geburtshilfe, Campus Kiel Universitätsklinikum Schleswig-Holstein, Germany. jpfisterer@email.uni-kiel.de
du Bois
A
A
Wagner
U
U
Quaas
J
J
Blohmer
J U
JU
Wallwiener
D
D
Hilpert
F
F
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects* / Q000627:therapeutic use*; D016190:Carboplatin / Q000008:administration & dosage / Q000009:adverse effects; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy*; D015331:Cohort Studies; D000077143:Docetaxel; D004305:Dose-Response Relationship, Drug; D005260:Female; D005833:Genital Neoplasms, Female / Q000188:drug therapy*; D006801:Humans; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000188:drug therapy; D043823:Taxoids / Q000008:administration & dosage / Q000009:adverse effects
D043823:Taxoids; D000077143:Docetaxel; D016190:Carboplatin