Carboplatin/Docetaxel as First-Line Therapy for Gynecologic Cancers

June 1, 2001

Combination chemotherapy with carboplatin (Paraplatin) and docetaxel (Taxotere) is a highly active and generally well-tolerated regimen when used as initial therapy for gynecologic cancers, including cancers of the ovary, fallopian tubes, and the

Combination chemotherapy with carboplatin(Paraplatin) and docetaxel (Taxotere) is a highly activeand generally well-tolerated regimen when used as initial therapy forgynecologic cancers, including cancers of the ovary, fallopian tubes, and theperitoneum, according to a report published in the Journal of Clinical Oncology(19:1901-1905, 2001). The results of this phase II clinical study from theCleveland Clinic Foundation were reported by lead investigator Maurie Markman,MD, and colleagues.

"While there have been improvements over the past 20 yearsin the prognosis of patients with gynecologic cancers, treatment remains lessthan completely satisfactory," said Dr. Markman, who is chairman of thedepartment of hematology/oncology and director of the Cleveland Clinic TaussigCancer Center in Cleveland, Ohio. "Our finding that thecarboplatin/docetaxel combination is safe and effective as first-line therapymerits further exploration of the role of docetaxel in the management ofadvanced ovarian cancer."

Patient Population

The study included 50 women with a histologically confirmeddiagnosis of ovarian cancer (36 patients), fallopian tube cancer (1 patient), orprimary peritoneal cancer (13 patients) who had not previously receivedchemotherapy for their malignancy. Because the latter two cancers are generallyconsidered to be identical to ovarian cancer with respect to the cell of origin,prognosis, and response to chemotherapy, patients with these two malignancieswere deemed to be suitable for enrollment in the trial. Patients with a priorhistory of another malignancy such as skin or breast cancer were also eligible,provided they had been disease-free for at least 2 years prior to enrollment.All study participants had measurable or evaluable disease, were 18 years of ageor older, and had an Eastern Cooperative Oncology Group (ECOG) performancestatus of 0 to 2.

All patients were treated with carboplatin, AUC 6, administeredintravenously over 30 minutes, and docetaxel, 60 mg/m2, administeredintravenously over 1 hour. Treatment was repeated six times, with 3 weeksbetween treatments.

Response and Toxicity

Standard Gynecologic Oncology Group (GOG) response criteria formeasurable disease were employed in this trial. Objective responses wereobserved in 34 (81%) of 42 evaluable patients who received first-linechemotherapy with carboplatin in combination with docetaxel. "Theseresponses were associated with improvement of symptoms of the cancer," saidDr. Markman. In addition, decreases in the level of CA-125 antigen, a proteinthat tends to be increased in women with ovarian cancer, were consideredevidence of response in the absence of other measurable or evaluable disease.

All patients were evaluable for toxicity. In all, 32 patients(64%) experienced severe neutropenia, while 17 (34%) had hypersensitivityreactions that were not severe enough to discontinue treatment. Three patients(6%) developed a peripheral neuropathy. The treatment dose was reduced in 33patients (66%), usually because of severe neutropenia.

"The safety data show that neurotoxicity was not asignificant problem with treatment. And the low incidence of neuropathy isparticularly noteworthy," said Dr. Markman. "The data suggest that apatient at high risk for developing peripheral neuropathy might fare better on adocetaxel-containing chemotherapy combination."