PHASE I STUDY OF PACLITAXEL COMBINED WITH TOPOTECAN AND CISPLATIN AND G-CSF IN PATIENTS WITH NEWLY DIAGNOSED ADVANCED OVARIAN EPITHELIAL MALIGNANCIES
PHASE I STUDY OF PACLITAXEL COMBINED WITH TOPOTECAN AND CISPLATIN AND G-CSF IN PATIENTS WITH NEWLY DIAGNOSED ADVANCED OVARIAN EPITHELIAL MALIGNANCIES
Phase I trial to study the effectiveness of paclitaxel, cisplatin, and topotecan with or without filgrastim in treating patients who have newly diagnosed stage III or stage IV epithelial ovarian cancer. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Colony-stimulating factors such as filgrastim may increase the number of immune cells found in bone marrow or peripheral blood and may help a person's immune system recover from the side effects of chemotherapy
PRIMARY OBJECTIVES:
I. Determine the maximum tolerated doses of paclitaxel, cisplatin, and topotecan administered together with or without filgrastim (G-CSF) in patients with newly diagnosed advanced ovarian cancer.
II. Describe and quantitate the clinical toxic effects of combination chemotherapy with paclitaxel, cisplatin, and topotecan with or without G-CSF.
III. Assess preliminary evidence of antitumor activity of this combination chemotherapy in these patients.
OUTLINE: This is a dose escalation study of topotecan.
Patients receive paclitaxel IV over 3 hours and cisplatin IV on day 1, followed by topotecan IV over 30 minutes on days 1-3. Patients receive filgrastim (G-CSF) subcutaneously beginning on day 4 and continuing until blood counts recover. Treatment repeats every 3 weeks in the absence of disease progression or unacceptable toxicity.
Cohorts of 4-6 patients receive escalating doses of topotecan until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose limiting toxicities.
Patients are followed as clinically indicated.
Inclusion Criteria:
Histologically confirmed epithelial ovarian carcinoma
The following histologies are eligible:
Measurable or evaluable disease
Performance status - GOG 0-1
Enabling completion of at least 2 courses of therapy
Absolute neutrophil count at least 1,500/mm^3
Platelet count at least 100,000/mm^3
Bilirubin no greater than 1.5 mg/dL
Creatinine clearance at least 60 mL/min
No myocardial infarction within 6 months
No congestive heart failure
No unstable or uncontrolled angina
No history of cardiac arrhythmia requiring anti-arrhythmia medication
No uncontrolled hypertension
No hypersensitivity to E. coli-derived drug preparation
No active infection
No sensory neuropathy
No other malignancies within the past 5 years except nonmelanomatous skin cancer
No prior chemotherapy
No prior radiotherapy
Recovered from any recent surgery