Paclitaxel, Cisplatin, and Topotecan With or Without Filgrastim in Treating Patients With Newly Diagnosed Stage III or Stage IV Epithelial Ovarian Cancer

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

• No borderline ovarian carcinoma
• Stage III/IV disease that has been suboptimally or optimally debulked
• The following histologies are eligible:

• Adenocarcinoma (unspecified)
• Mucinous cystadenocarcinoma
• Clear cell adenocarcinoma
• Serous cystadenocarcinoma
• Endometrioid adenocarcinoma
• Transitional cell carcinoma
• Malignant Brenner's tumor
• Undifferentiated carcinoma
• Mixed epithelial carcinoma
• Extraovarian papillary serous cystadenocarcinoma
• 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