High-Dose Chemotherapy Compared With Standard Chemotherapy in Treating Patients With Stage III or Stage IV Ovarian Epithelial Cancer That Has Been Removed During Surgery

OBJECTIVES:

• Compare the two-year progression-free survival in patients with optimally debulked stage III or IV ovarian epithelial cancer undergoing high-dose sequential chemotherapy vs standard chemotherapy.
• Compare the overall survival, toxicity, and quality of life in this patient population receiving these two treatment regimens.

OUTLINE: This is a randomized, multicenter study. Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients receive 5 courses of sequential high-dose chemotherapy as follows:

• Courses 1 and 2: Patients receive paclitaxel IV over 3 hours and cyclophosphamide IV over 2 hours on day 1 followed by peripheral blood stem cell (PBSC) collection. Patients receive filgrastim (G-CSF) subcutaneously (SC) beginning 24 hours following chemotherapy and continuing until target number of PBSC are reached.
• Courses 3 and 4: Patients receive paclitaxel as in courses 1-2 and carboplatin IV over 4 hours on day 1. At 72 hours following completion of carboplatin, patients receive PBSC infusion. Beginning one day following PBSC infusion, patients receive G-CSF SC until blood counts recover.
• Course 5: Patients receive paclitaxel as in courses 1 and 2 and carboplatin as in courses 3 and 4 and melphalan IV over 15 minutes on day 2 or 3. Patients receive PBSC and G-CSF as in courses 3 and 4.
• Treatment repeats every 3-4 weeks.
• Arm II: Patients receive standard chemotherapy consisting of carboplatin (or cisplatin) and paclitaxel IV over 3 hours every 3 weeks for 6 courses. Patients may receive doxorubicin or epirubicin in addition to the standard chemotherapy every 4 weeks.

Quality of life is assessed prior to therapy, at 4-6 weeks following completion of therapy, and then at 3 months, 9 months, and 15 months.

Patients are followed every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter.

PROJECTED ACCRUAL: A total of 208 patients (104 per treatment arm) will be accrued for this study.

DISEASE CHARACTERISTICS:

• Histologically confirmed stage III or IV ovarian epithelial cancer
• Bilateral salpingo-oophorectomy, hysterectomy, and omentectomy within 6 weeks of study

• Less than 2 cm maximum diameter of residual tumor remaining

PATIENT CHARACTERISTICS:

Age:

• 18 to 65

Performance status:

• ECOG 0-2

Life expectancy:

• Not specified

Hematopoietic:

• Normal hematological function

Hepatic:

• Normal hepatic function

Renal:

• Creatinine clearance greater than 60 mL/min
• GFR greater than 60 mL/min

Cardiovascular:

• No active cardiac disease

Other:

• No other uncontrolled serious medical illness, including hearing problems
• No other malignancy within the past 5 years except basal cell skin cancer or carcinoma in situ of the cervix

PRIOR CONCURRENT THERAPY:

Biologic therapy

• Not specified

Chemotherapy

• No prior chemotherapy

Endocrine therapy

• Not specified

Radiotherapy

• Not specified

Surgery

• See Disease Characteristics