Combination chemotherapy with carboplatin(Drug information on carboplatin) (Paraplatin) and docetaxel(Drug information on 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 peritoneum, according to a report published in the Journal of Clinical Oncology (19:1901-1905, 2001). The results of this phase II clinical study from the Cleveland Clinic Foundation were reported by lead investigator Maurie Markman, MD, and colleagues.
"While there have been improvements over the past 20 years in the prognosis of patients with gynecologic cancers, treatment remains less than completely satisfactory," said Dr. Markman, who is chairman of the department of hematology/oncology and director of the Cleveland Clinic Taussig Cancer Center in Cleveland, Ohio. "Our finding that the carboplatin/docetaxel combination is safe and effective as first-line therapy merits further exploration of the role of docetaxel in the management of advanced ovarian cancer."
The study included 50 women with a histologically confirmed diagnosis of ovarian cancer (36 patients), fallopian tube cancer (1 patient), or primary peritoneal cancer (13 patients) who had not previously received chemotherapy for their malignancy. Because the latter two cancers are generally considered to be identical to ovarian cancer with respect to the cell of origin, prognosis, and response to chemotherapy, patients with these two malignancies were deemed to be suitable for enrollment in the trial. Patients with a prior history 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 age or older, and had an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.
All patients were treated with carboplatin, AUC 6, administered intravenously over 30 minutes, and docetaxel, 60 mg/m2, administered intravenously over 1 hour. Treatment was repeated six times, with 3 weeks between treatments.
Response and Toxicity
Standard Gynecologic Oncology Group (GOG) response criteria for measurable disease were employed in this trial. Objective responses were observed in 34 (81%) of 42 evaluable patients who received first-line chemotherapy with carboplatin in combination with docetaxel. "These responses were associated with improvement of symptoms of the cancer," said Dr. Markman. In addition, decreases in the level of CA-125 antigen, a protein that tends to be increased in women with ovarian cancer, were considered evidence 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 hypersensitivity reactions that were not severe enough to discontinue treatment. Three patients (6%) developed a peripheral neuropathy. The treatment dose was reduced in 33 patients (66%), usually because of severe neutropenia.
"The safety data show that neurotoxicity was not a significant problem with treatment. And the low incidence of neuropathy is particularly noteworthy," said Dr. Markman. "The data suggest that a patient at high risk for developing peripheral neuropathy might fare better on a docetaxel-containing chemotherapy combination."