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

  • 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