Combination Chemotherapy in Treating Patients With Advanced Ovarian Epithelial Cancer

Phase II Study of First-Line Therapy of Ovarian Cancer With Sequential Regimens: Cisplatin-Prolonged Oral Topotecan (C-PORT) Followed by Paclitaxel/Carboplatin (PC)

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells.

PURPOSE: Phase II trial to study the effectiveness of combination chemotherapy in treating patients who have advanced ovarian epithelial cancer.

OBJECTIVES:

• Determine the toxicity and tolerance of sequential therapy with prolonged
• Determine the response rate and time to progression in this patient
• Determine the relative pharmacokinetics of IV and prolonged oral administration of topotecan in the same patients and compare the pharmacodynamics of topo-1 inhibition when given by IV or oral route.

OUTLINE:

• Regimen A: Patients receive cisplatin IV over 60-90 minutes on day 1 of each course. Topotecan IV is administered continuously on days 1-14 of course 1. Oral topotecan is administered twice daily on days 1-14 for courses 2, 3, and 4. Treatment repeats every 28 days for 4 courses.
• Regimen B: After completion of regimen A, patients receive paclitaxel IV over 3 hours followed by carboplatin IV over 30 minutes on day 1. Treatment repeats every 21 days for 4 courses.

PROJECTED ACCRUAL: A total of 30 patients (15 per arm) will be accrued for this study.

DISEASE CHARACTERISTICS:

• Histologically confirmed advanced ovarian epithelial carcinoma, regardless of quantity of disease post-surgery

  • Stage IC, II, III, or IV

PATIENT CHARACTERISTICS:

Age:

• 18 and over

Performance status:

• ECOG 0-2

Life expectancy:

• Not specified

Hematopoietic:

• Absolute neutrophil count at least 1,500/mm^3
• Platelet count at least 100,000/mm^3

Hepatic:

• SGOT no greater than 3 times upper limit of normal
• Bilirubin no greater than 2.0 mg/dL
• No clinically significant hepatic disorder

Renal:

• Creatinine no greater than 1.5 mg/dL OR
• Creatinine clearance greater than 60 mL/min
• No clinically significant renal disorder

Cardiovascular:

• No clinically significant cardiovascular condition

Other:

• Normal GI function allowing reliable administration of oral medication
• No active infection requiring systemic medical therapy within past week
• No other clinically significant medical condition (e.g., endocrine/metabolic or autoimmune disorder)
• No other prior malignancy within the past 5 years except nonmelanoma skin cancer or carcinoma in situ of the cervix
• No dementia or altered mental status that would preclude consent
• Not pregnant
• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• Not specified

Chemotherapy:

• No prior chemotherapy for ovarian epithelial carcinoma

Endocrine therapy:

• Not specified

Radiotherapy:

• No prior radiotherapy for ovarian epithelial carcinoma

Surgery:

• See Disease Characteristics