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
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
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."